BioPAX通路converted from "Metabolism of nucleotides" in the Reactome database. Metabolism of nucleotides Metabolism of nucleotides Nucleotide metabolism This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Nucleobase biosynthesis Nucleobase biosynthesis This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Purine ribonucleoside monophosphate biosynthesis Purine ribonucleoside monophosphate biosynthesis This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 6.3.5.2 XMP + L-Glutamine + ATP + H2O => GMP + L-Glutamate + AMP + pyrophosphate XMP + L-Glutamine + ATP + H2O => GMP + L-Glutamate + AMP + pyrophosphate xanthosine 5'-monophosphate (XMP) + L-glutamine + ATP + H2O => guanosine 5'-monophosphate (GMP) + L-glutamate + adenosine 5'-monophosphate (AMP) + pyrophosphate This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29356 1 cytosol GO 0005829 water [ChEBI:15377] water Reactome //www.joaskin.com ChEBI 15377 Reactome DB_ID: 113592 1 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 111584 1 5'-xanthylic acid [ChEBI:15652] 5'-xanthylic acid ChEBI 15652 Reactome DB_ID: 29472 1 L-glutamine zwitterion [ChEBI:58359] L-glutamine zwitterion (2S)-5-amino-2-ammonio-5-oxopentanoate 146.14450 C5H10N2O3 NC(=O)CC[C@H]([NH3+])C([O-])=O L-glutamine (2S)-5-amino-2-azaniumyl-5-oxopentanoate InChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1 ZDXPYRJPNDTMRX-VKHMYHEASA-N ChEBI 58359 Reactome DB_ID: 29404 1 L-glutamate(1-) [ChEBI:29985] L-glutamate(1-) C5H8NO4 WHUUTDBJXJRKMK-VKHMYHEASA-M (2S)-2-ammoniopentanedioate 146.12136 L-glutamate hydrogen L-glutamate InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/p-1/t3-/m0/s1 L-glutamic acid, ion(1-) [NH3+][C@@H](CCC([O-])=O)C([O-])=O L-glutamic acid monoanion ChEBI 29985 Reactome DB_ID: 113578 1 guanosine 5'-monophosphate [ChEBI:17345] guanosine 5'-monophosphate ChEBI 17345 Reactome DB_ID: 111294 1 diphosphoric acid [ChEBI:29888] diphosphoric acid ChEBI 29888 Reactome DB_ID: 76577 1 adenosine 5'-monophosphate [ChEBI:16027] adenosine 5'-monophosphate ChEBI 16027 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766742 UniProt:Q8IJR9 Plasmodium falciparum NCBI Taxonomy 5833 UniProt Q8IJR9 Chain Coordinates 2 EQUAL 693 EQUAL GO 0003922 GO molecular function Reactome Database ID Release 77 10766743 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766743 Reactome Database ID Release 77 10766745 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766745 Reactome R-PFA-73792 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73792.1 Cytosolic GMP synthase (GMPS) catalyzes the reaction of xanthosine 5'-monophosphate (XMP), ATP, glutamine and water to form guanosine 5'-monophosphate (GMP), AMP, glutamate and pyrophosphate. GMPS is a monomer (Hirst et al. 1994; Nakamura and Lou 1995). 7706277 Pubmed 1995 Biochemical characterization of human GMP synthetase Nakamura, J Lou, L J Biol Chem 270:7347-7353 8089153 Pubmed 1994 Human GMP synthetase. Protein purification, cloning, and functional expression of cDNA Hirst, M Haliday, E Nakamura, J Lou, L J Biol Chem 269:23830-23837 inferred by electronic annotation IEA GO IEA 6.3.4.4 IMP + L-Aspartate + GTP => Adenylosuccinate + GDP + Pi [ADSS] IMP + L-Aspartate + GTP => Adenylosuccinate + GDP + Pi [ADSS] 肌苷5 '一磷酸+ L-aspartate +三磷酸鸟苷= >广告enylosuccinate + guanosine 5'-diphosphate + orthophosphate This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29602 1 IMP [ChEBI:17202] IMP 5'-Inosinate Inosine monophosphate Inosine 5'-phosphate Inosine 5'-monophosphate 5'-Inosine monophosphate 5'-Inosinic acid Inosinic acid ChEBI 17202 Reactome DB_ID: 29448 1 L-aspartate(1-) [ChEBI:29991] L-aspartate(1-) (2S)-2-ammoniobutanedioate L-aspartate L-aspartic acid monoanion CKLJMWTZIZZHCS-REOHCLBHSA-M InChI=1S/C4H7NO4/c5-2(4(8)9)1-3(6)7/h2H,1,5H2,(H,6,7)(H,8,9)/p-1/t2-/m0/s1 132.09478 [NH3+][C@@H](CC([O-])=O)C([O-])=O C4H6NO4 (2S)-2-ammoniosuccinate hydrogen L-aspartate ChEBI 29991 Reactome DB_ID: 29438 1 GTP [ChEBI:15996] GTP Guanosine 5'-triphosphate ChEBI 15996 Reactome DB_ID: 29372 1 hydrogenphosphate [ChEBI:43474] hydrogenphosphate [PO3(OH)](2-) HYDROGENPHOSPHATE ION hydrogen phosphate [P(OH)O3](2-) HPO4(2-) phosphate INORGANIC PHOSPHATE GROUP ChEBI 43474 Reactome DB_ID: 29420 1 GDP [ChEBI:17552] GDP Guanosine 5'-diphosphate Guanosine diphosphate ChEBI 17552 Reactome DB_ID: 35141 1 N(6)-(1,2-dicarboxyethyl)-AMP [ChEBI:15919] N(6)-(1,2-dicarboxyethyl)-AMP ChEBI 15919 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10767378 ADSS, ADSSL1 dimers [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0004019 GO molecular function Reactome Database ID Release 77 10767379 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767379 Reactome Database ID Release 77 10767381 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767381 Reactome R-PFA-111524 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111524.1 Two isoforms of adenylosuccinate synthetase, ADSS and ADSSL1, catalyze the reaction of IMP, aspartate, and GTP to form adenylosuccinate, GDP, and orthophosphate (Powell et al. 1992; Sun et al. 2005). ADSS is a homotetramer (unpublished crystallographic data - PDB 2V40) and ADSSL1 is inferred to be a tetramer likewise. 15786719 Pubmed 2005 Molecular cloning and characterization of a novel muscle adenylosuccinate synthetase, AdSSL1, from human bone marrow stromal cells Sun, H Li, N Wang, X Chen, T Shi, L Zhang, L Wang, J Wan, T Cao, X Mol Cell Biochem 269:85-94 1592113 Pubmed 1992 Cloning and characterization of the cDNA encoding human adenylosuccinate synthetase Powell, SM Zalkin, H Dixon, JE FEBS Lett 303:4-20 inferred by electronic annotation IEA GO IEA INHIBITION Reactome Database ID Release 77 111520 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=111520 Reactome R-MMU-111520 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-111520.1 Reactome DB_ID: 35141 INHIBITION Reactome Database ID Release 77 111531 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=111531 Reactome R-HSA-111531 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-111531.1 Reactome DB_ID: 113578 INHIBITION Reactome Database ID Release 77 111533 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=111533 Reactome R-HSA-111533 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-111533.1 Reactome DB_ID: 30014 beta-D-fructofuranose 1,6-bisphosphate(4-) [ChEBI:32966] beta-D-fructofuranose 1,6-bisphosphate(4-) beta-D-fructose 1,6-bisphosphate beta-D-fructofuranose 1,6-bisphosphate 1,6-di-O-phosphonato-beta-D-fructofuranose ChEBI 32966 INHIBITION Reactome Database ID Release 77 111522 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=111522 Reactome R-MMU-111522 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-111522.1 Reactome DB_ID: 29420 Reactome Database ID Release 77 10780476 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780476 Reactome R-PFA-73817 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73817.1 GO 0009168 GO biological process The purine ribonucleotide inosine 5'-monophosphate (IMP) is assembled on 5-phospho-alpha-D-ribose 1-diphosphate (PRPP), with atoms derived from aspartate, glutamine, glycine, N10-formyl-tetrahydrofolate, and carbon dioxide. Although several of the individual reactions in this sequence are reversible, as indicated by the double-headed arrows in the diagram, other irreversible steps drive the pathway in the direction of IMP synthesis in the normal cell. All of these reactions are thus annotated here only in the direction of IMP synthesis. Guanosine 5'-monophosphate (GMP) and adenosine 5'-monophosphate (AMP) are synthesized from IMP. 1574589 Pubmed 1992 De novo purine nucleotide biosynthesis Zalkin, H Dixon, JE Prog Nucleic Acid Res Mol Biol 42:259-287 inferred by electronic annotation IEA GO IEA Pyrimidine biosynthesis Pyrimidine biosynthesis This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 6.3.5.5 CAD hexamer transforms L-Gln to CAP CAD hexamer transforms L-Gln to CAP L-glutamine + 2 ATP + HCO3- + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + orthophosphate bicarbonate and glutamine combine to form carbamoyl phosphate This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 111627 1 hydrogencarbonate [ChEBI:17544] hydrogencarbonate ChEBI 17544 Reactome DB_ID: 29356 1 Reactome DB_ID: 113592 2 Reactome DB_ID: 29472 1 Reactome DB_ID: 111647 1 carbamoyl phosphate [ChEBI:17672] carbamoyl phosphate ChEBI 17672 Reactome DB_ID: 29404 1 Reactome DB_ID: 29372 1 Reactome DB_ID: 29370 2 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5'-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766639 CAD hexamer [cytosol] CAD hexamer Reactome DB_ID: 10766637 6 UniProt:Q8IEN3 UniProt Q8IEN3 2 EQUAL 2225 EQUAL Reactome Database ID Release 77 10766639 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766639 Reactome R-PFA-73457 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73457.1 GO 0004088 GO molecular function Reactome Database ID Release 77 10766646 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766646 Reactome Database ID Release 77 10766648 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766648 Reactome R-PFA-73577 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73577.1 The synthesis of carbamoyl phosphate from glutamine, bicarbonate, and ATP is catalyzed by the carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity of cytosolic trifunctional CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) protein (Ito and Uchino 1973; Iwahana et al. 1996). The purified human protein is active in several different oligomerization states, as is its Syrian hamster homologue. The most abundant form of the latter is a hexamer, and the active human protein is annotated as a hexamer by inference (Ito and Uchino 1973; Lee et al. 1985). 8619816 Pubmed 1996 Molecular cloning of a human cDNA encoding a trifunctional enzyme of carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase in de Novo pyrimidine synthesis Iwahana, H Fujimura, H Ii, S Kondo, M Moritani, M Takahashi, Y Yamaoka, T Yoshimoto, K Itakura, M Biochem Biophys Res Commun 219:249-255 4684686 Pubmed 1973 Control of pyrimidine biosynthesis in human lymphocytes. Simultaneous increase in activities of glutamine-utilizing carbamyl phosphate synthetase and aspartate transcarbamylase in phytohemagglutinin-stimulated human peripheral lymphocytes and their enzyme co-purification Ito, K Uchino, H J Biol Chem 248:389-392 inferred by electronic annotation IEA GO IEA 2.1.3.2 CAD hexamer transforms CAP to N-carb-L-Asp CAD hexamer transforms CAP to N-carb-L-Asp carbamoyl phosphate + L-aspartate <=> N-carbamoyl L-aspartate + orthophosphate carbamoyl phosphate and L-aspartate combine to form N-Carbamoyl-L-aspartate This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 111647 1 Reactome DB_ID: 29448 1 Reactome DB_ID: 29372 1 Reactome DB_ID: 111628 1 N-carbamoyl-L-aspartic acid [ChEBI:15859] N-carbamoyl-L-aspartic acid ChEBI 15859 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766639 GO 0004070 GO molecular function Reactome Database ID Release 77 10766643 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766643 Reactome Database ID Release 77 10766645 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766645 Reactome R-PFA-73573 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73573.1 The synthesis of N-carbamoyl L-aspartate from carbamoyl phosphate and L-aspartate is catalyzed by the aspartate carbamoyltansferase activity of cytosolic trifunctional CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) protein (Ito and Uchino 1973; Iwahana et al. 1996). The purified human protein is active in several different oligomerization states as is its Syrian hamster homologue. The most abundant form of the latter is a hexamer, and the active human protein is annotated as a hexamer by inference (Ito and Uchino 1973; Lee et al. 1985). 2995985 Pubmed 1985 Oligomeric structure of the multifunctional protein CAD that initiates pyrimidine biosynthesis in mammalian cells Lee, L Kelly, RE Pastra-Landis, SC Evans, DR Proc Natl Acad Sci USA 82:6802-6806 inferred by electronic annotation IEA GO IEA 3.5.2.3 CAD hexamer dehydrates N-carb-L-Asp to (S)-DHO CAD hexamer dehydrates N-carb-L-Asp to (S)-DHO N-carbamoyl L-aspartate + H+ <=> (S)-dihydroorotate + H2O N-Carbamoyl-L-aspartate凝结形成的)-Dihydroorotate (ring closure) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 111628 1 Reactome DB_ID: 70106 1 hydron [ChEBI:15378] hydron ChEBI 15378 Reactome DB_ID: 76630 1 (S)-dihydroorotic acid [ChEBI:17025] (S)-dihydroorotic acid ChEBI 17025 Reactome DB_ID: 29356 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766639 GO 0004151 GO molecular function Reactome Database ID Release 77 10766640 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766640 Reactome Database ID Release 77 10766642 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766642 Reactome R-PFA-73571 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73571.1 The synthesis of dihydroorotate from N-carbamoyl L-aspartate is catalyzed by the dihydroorotase activity of cytosolic trifunctional CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) protein. This activity has not been directly demonstrated in experimental studies of the purified human protein, but has been inferred from the behavior of the purified hamster protein and the high degree of sequence similarity between the cloned hamster and human genes (Iwahana et al. 1996). Also on the basis of this similarity, the active human protein is annotated as a hexamer (Lee et al. 1985). inferred by electronic annotation IEA GO IEA 1.3.5.2 DHODH:FMN oxidises (S)-DHO to orotate DHODH:FMN oxidises (S)-DHO to orotate (S)-dihydroorotate + ubiquinone => orotate + ubiquinol oxidation of (S)-Dihydroorotate to form Orotate This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 76630 1 Reactome DB_ID: 73663 1 mitochondrial inner membrane GO 0005743 coenzyme Q10 [ChEBI:46245] coenzyme Q10 ChEBI 46245 Reactome DB_ID: 76632 1 orotic acid [ChEBI:16742] orotic acid ChEBI 16742 Reactome DB_ID: 76633 1 ubiquinol [ChEBI:17976] ubiquinol QH2 CoQH2 辅酶QH2 ChEBI 17976 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766632 DHODH:FMN [mitochondrial inner membrane] DHODH:FMN Reactome DB_ID: 76629 1 FMN [ChEBI:17621] FMN Flavin mononucleotide Riboflavin-5-phosphate ChEBI 17621 Reactome DB_ID: 10766630 1 UniProt:Q08210 UniProt Q08210 1 EQUAL 395 EQUAL Reactome Database ID Release 77 10766632 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766632 Reactome R-PFA-73534 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73534.1 GO 0004152 GO molecular function Reactome Database ID Release 77 10766633 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766633 Reactome Database ID Release 77 10766635 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766635 Reactome R-PFA-73569 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73569.1 oxidati Dihydroorotate脱氢酶催化on of dihydroorotate to orotate (orotic acid). The enzyme is located in the inner mitochondrial membrane oriented so that cytosolic dihydroorotate molecules have access to it, and orotate is released into the cytosol. The reducing equivalents generated by the reaction are transferred by ubiquinone (Coenzyme Q) to the electron transport chain within the inner mitochondrial membrane. There is no evidence for the involvement of NAD+ as an acceptor of reducing equivalents in this reaction in mammalian cells (Jones 1980). In contrast, the reaction catalyzed by the enzyme isolated from the anaerobic bacterium Clostridium oroticum requires NAD+ as a cofactor but also proceeds strongly in the direction of dihydroorotate synthesis consistent with the greater electronegativity of NAD+ (Lieberman and Kornberg 1953).

Early studies of purified rat liver enzyme by Forman and Kennedy suggested the presence of flavin mononucleotide and iron-sulfur complexes as cofactors. More recent work by Bader, Beuneu, and their colleagues with recombinant human protein expressed in insect cells has confirmed the presence of flavin mononucleotide, at a stoichiometry of one molecule per molecule of apoenzyme but suggests that iron-sulfur complexes, if indeed they are involved in the oxidation and electron transport process, are not an integral part of the dihydroorotate dehydrogenase holoenzyme. 6105839 Pubmed 1980 Pyrimidine nucleotide biosynthesis in animals: genes, enzymes, and regulation of UMP biosynthesis. Jones, ME Annu Rev Biochem 49:253-79 9693067 Pubmed 1998 Expression, purification, and characterization of histidine-tagged rat and human flavoenzyme dihydroorotate dehydrogenase. Bader, B Knecht, W Fries, M Löffler, M Protein Expr Purif 13:414-22 13115431 Pubmed 1953 Enzymic synthesis and breakdown of a pyrimidine, orotic acid. I. Dihydro-orotic dehydrogenase Lieberman, I Kornberg, A Biochim Biophys Acta 12:223-234 165196 Pubmed 1975 Superoxide production and electron transport in mitochondrial oxidation of dihydroorotic acid. Forman, JH Kennedy, J J Biol Chem 250:4322-6 10889450 Pubmed 2000 Indirect inhibition of mitochondrial dihydroorotate dehydrogenase activity by nitric oxide. Beuneu, C Auger, R Löffler, M Guissani, A Lemaire, G Lepoivre, M Free Radic Biol Med 28:1206-13 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780462 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780462 Reactome R-PFA-500753 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-500753.1 GO 0046134 GO biological process The pyrimidine orotate (orotic acid) is synthesized in a sequence of four reactions, deriving its atoms from glutamine, bicarbonate, and aspartate. A single multifunctional cytosolic enzyme catalyzes the first three of these reactions, while the last one is catalyzed by an enzyme associated with the inner mitochondrial membrane. In two further reactions, catalyzed by a bifunctional cytosolic enzyme, orotate reacts with 1-phosphoribosyl 5-pyrophosphate (PRPP) to yield orotidine 5'-monophosphate, which is decarboxylated to yield uridine 5'-monophosphate (UMP). While several individual reactions in this pathway are reversible, other irreversible reactions drive the pathway in the direction of UMP biosynthesis in the normal cell. All reactions are thus annotated here only in the forward direction.

This pathway has been most extensively analyzed at the genetic and biochemical level in hamster cell lines. All three enzymes have also been purified from human sources, however, and the key features of these reactions have been confirmed from studies of this human material (Jones 1980; Webster et al. 2001).

All other pyrimidines are synthesized from UMP. The reactions annotaed here, catalyzed by dCMP deaminase and dUTP diphosphatase yield dUMP, which in turn is converted to TMP by thymidylate synthase. inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780464 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780464 Reactome R-PFA-8956320 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8956320.1 GO 0034404 GO biological process The purine ribonucleotide inosine 5'-monophosphate (IMP) is assembled on 5-phospho-alpha-D-ribose 1-diphosphate (PRPP), with atoms derived from aspartate, glutamine, glycine, N10-formyl-tetrahydrofolate, and carbon dioxide. Although several of the individual reactions in this sequence are reversible, as indicated by the double-headed arrows in the diagram, other irreversible steps drive the pathway in the direction of IMP synthesis in the normal cell. All of these reactions are thus annotated here only in the direction of IMP synthesis. Guanosine 5'-monophosphate (GMP) and adenosine 5'-monophosphate (AMP) are synthesized from IMP (Zalkin & Dixon 1992).

The pyrimidine orotate (orotic acid) is synthesized in a sequence of four reactions, deriving its atoms from glutamine, bicarbonate, and aspartate. A single multifunctional cytosolic enzyme catalyzes the first three of these reactions, while the last one is catalyzed by an enzyme associated with the inner mitochondrial membrane. In two further reactions, catalyzed by a bifunctional cytosolic enzyme, orotate reacts with 1-phosphoribosyl 5-pyrophosphate (PRPP) to yield orotidine 5'-monophosphate, which is decarboxylated to yield uridine 5'-monophosphate (UMP). While several individual reactions in this pathway are reversible, other irreversible reactions drive the pathway in the direction of UMP biosynthesis in the normal cell. All reactions are thus annotated here only in the forward direction.

This pathway has been most extensively analyzed at the genetic and biochemical level in hamster cell lines. All three enzymes have also been purified from human sources, however, and the key features of these reactions have been confirmed from studies of this human material (Jones 1980).

All other pyrimidines are synthesized from UMP. The reactions annotated here, catalyzed by dCMP deaminase and dUTP diphosphatase yield dUMP, which in turn is converted to TMP by thymidylate synthase. inferred by electronic annotation IEA GO IEA Interconversion of nucleotide di- and triphosphates Interconversion of nucleotide di- and triphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 2.7.4.3 AMP + ATP <=> ADP + ADP [AK2] AMP + ATP <=> ADP + ADP [AK2] This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 113592 1 Reactome DB_ID: 76577 1 Reactome DB_ID: 29370 2 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10767185 mitochondrial intermembrane space GO 0005758 UniProt:Q8I1T1 UniProt Q8I1T1 2 EQUAL 239 EQUAL GO 0004017 GO molecular function Reactome Database ID Release 77 10767186 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767186 Reactome Database ID Release 77 10767190 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767190 Reactome R-PFA-110145 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-110145.1 Mitochondrial adenylate kinase 2 (AK2) catalyzes the reaction of AMP and ATP to form two molecules of ADP (Hamade et al. 1982). Localization of AK2 specifically to the mitochondrial intermembrane space is inferred from studies of the homologous rat enzyme (Criss 1970). 5484814 Pubmed 1970 大鼠肝脏的广告enosine triphosphate:adenosine monophosphate phosphotransferase activity. II. Subcellular localization of adenylate kinase isozymes Criss, WE J Biol Chem 245:6352-6356 6182143 Pubmed 1982 Adenosine triphosphate-adenosine-5'-monophosphate phosphotransferase from normal human liver mitochondria. Isolation, chemical properties, and immunochemical comparison with Duchenne muscular dystrophic serum aberrant adenylate kinase Hamada, M Sumida, M Okuda, H Watanabe, T Nojima, M Kuby, SA J Biol Chem 257:13120-13128 inferred by electronic annotation IEA GO IEA 2.7.4.3 ADP + ADP <=> AMP + ATP [AK2] ADP + ADP <=> AMP + ATP [AK2] This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29370 2 Reactome DB_ID: 113592 1 Reactome DB_ID: 76577 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10767185 2 EQUAL 239 EQUAL Reactome Database ID Release 77 10767188 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767188 Reactome R-PFA-110144 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-110144.1 Mitochondrial adenylate kinase 2 (AK2) catalyzes the reaction of two molecules of ADP to form AMP and ATP (Hamade et al. 1982). Localization of AK2 specifically to the mitochondrial intermembrane space is inferred from studies of the homologous rat enzyme (Criss 1970). inferred by electronic annotation IEA GO IEA AK5,7,8,9 phosphorylates (d)NMPs to (d)NDPs AK5,7,8,9 phosphorylates (d)NMPs to (d)NDPs (d)AMP or (d)CMP + ATP <=> (d)ADP or (d)CDP + ADP [AK5] This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 6788778 1 (d)NMPs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dCMP [cytosol] CMP [cytosol] 2'-deoxyadenosine 5'-monophosphate [cytosol] AMP [cytosol] ChEBI 15918 ChEBI 17361 ChEBI 17713 Reactome DB_ID: 113592 1 Converted from EntitySet in Reactome Reactome DB_ID: 6788782 1 (d)NDPs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dADP [cytosol] CDP [cytosol] dCDP [cytosol] ADP [cytosol] ChEBI 16174 ChEBI 17239 ChEBI 28846 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10767178 AK5,7,8,9 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AK8 [cytosol] AK9 [cytosol] AK9 [cytosol] AK9 [cytosol] AK7 [cytosol] AK8 [cytosol] AK8 [cytosol] UniProt Q8IB06 UniProt Q8IJV6 UniProt O97242 GO 0019206 GO molecular function Reactome Database ID Release 77 10767179 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767179 Reactome Database ID Release 77 10767183 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767183 Reactome R-PFA-110138 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-110138.1 腺苷酸激酶(部)是核苷monophosphate kinases, which catalyze the phosphorylation of AMP by using ATP or GTP as phosphate donors. AKs are thus involved in maintaining the homeostasis of cellular nucleotides. CMP, dCMP and dAMP are other substrates phosphorylated with less efficiency by AKs. Cytosolic adenylate kinases 5, 7, 8 and 9 (AK5, 7, 8 and 9) catalyze the reversible phosphorylation of (d)AMP and (d)CMP with ATP to form (d)ADP and (d)CDP, respectively, and ADP. When GTP is the phosphate donor, only AMP and CMP are efficiently phosphorylated (Panayiotou et al. 2011, Amiri et al. 2013). In the body AK5 expression was observed only in brain of nine tissues tested by Northern blotting (Van Rompay et al. 1999). AK5 is inferred to occur as a dimer from unpublished crystallographic data obtained for the catalytically active carboxyterminal third of the protein (PDB 2BWJ). 21080915 Pubmed 2011 The characterization of human adenylate kinases 7 and 8 demonstrates differences in kinetic parameters and structural organization among the family of adenylate kinase isoenzymes Panayiotou, Christakis Solaroli, Nicola Xu, Yunjian Johansson, M Karlsson, A Biochem. J. 433:527-34 10215863 Pubmed 1999 Identification of a novel human adenylate kinase. cDNA cloning, expression analysis, chromosome localization and characterization of the recombinant protein Van Rompay, AR Johansson, M Karlsson, A Eur J Biochem 1999:509-516 23416111 Pubmed 2013 The human adenylate kinase 9 is a nucleoside mono- and diphosphate kinase Amiri, Marjan Conserva, Francesca Panayiotou, Christakis Karlsson, A Solaroli, Nicola Int. J. Biochem. Cell Biol. 45:925-31 inferred by electronic annotation IEA GO IEA (d)ADP or (d)CDP + ADP <=> (d)AMP or (d)CMP + ATP (d)ADP or (d)CDP + ADP <=> (d)AMP or (d)CMP + ATP This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 6788782 1 Reactome DB_ID: 29370 1 Converted from EntitySet in Reactome Reactome DB_ID: 6788778 1 Reactome DB_ID: 113592 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10767178 Reactome Database ID Release 77 10767181 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767181 Reactome R-PFA-110137 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-110137.1 Cytosolic adenylate kinase 5 [AK5] catalyzes the reactions of (d)ADP and (d)CDP with ADP to form (d)AMP and (d)CMP, respectively, and ATP. In the body AK5 expression was observed only in brain of nine tissues tested by Northern blotting (Van Rompay et al. 1999). AK5 is inferred to occur as a dimer from unpublished crystallographic data obtained for the catalytically active carboxyterminal third of the protein (PDB 2BWJ). inferred by electronic annotation IEA GO IEA 2.7.4.4 AK6 phosphorylates (d)NMPs to (d)NDPs AK6 phosphorylates (d)NMPs to (d)NDPs This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29358 1 nucleoplasm GO 0005654 Converted from EntitySet in Reactome Reactome DB_ID: 6788813 1 (d)NMPs [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AMP [nucleoplasm] 2'-deoxycytosine 5'-monophosphate [nucleoplasm] 2'-deoxyadenosine 5'-monophosphate [nucleoplasm] CMP [nucleoplasm] Reactome DB_ID: 113582 1 Converted from EntitySet in Reactome Reactome DB_ID: 6788807 1 (d)NDPs [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dADP [nucleoplasm] ADP [nucleoplasm] CDP [nucleoplasm] dCDP [nucleoplasm] PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10776144 UniProt:Q8I236 UniProt Q8I236 1 EQUAL 172 EQUAL GO 0050145 GO molecular function Reactome Database ID Release 77 10776145 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10776145 Reactome Database ID Release 77 10776147 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10776147 Reactome R-PFA-6788810 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-6788810.1 腺苷酸激酶(部)是核苷monophosphate kinases, which catalyze the phosphorylation of AMP by using ATP or GTP as phosphate donors. AKs are thus involved in maintaining the homeostasis of cellular nucleotides. CMP, dCMP and dAMP are other substrates phosphorylated with less efficiency by AKs. When GTP is the phosphate donor, only AMP and CMP are efficiently phosphorylated. Adenylate kinase 6 (AK6) is thought to mediate nucleotide homeostasis in the nucleoplasm (Ren et al. 2005). 15630091 Pubmed 2005 The crystal structure of human adenylate kinase 6: An adenylate kinase localized to the cell nucleus Ren, Hui Wang, L Bennett, Matthew Liang, Yuhe Zheng, Xiaofeng Lu, Fei Li, Lanfen Nan, Jie Luo, M Eriksson, S Zhang, Chuanmao Su, Xiao-Dong Proc. Natl. Acad. Sci. U.S.A. 102:303-8 inferred by electronic annotation IEA GO IEA 2.7.4.8 (d)GMP + ATP <=> (d)GDP + ADP (GUK1) (d)GMP + ATP <=> (d)GDP + ADP (GUK1) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 113592 1 Converted from EntitySet in Reactome Reactome DB_ID: 500071 1 (d)GMP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 2'-deoxyguanosine 5'-monophosphate [cytosol] GMP [cytosol] ChEBI 16192 Converted from EntitySet in Reactome Reactome DB_ID: 500077 1 (d)GDP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GDP [cytosol] dGDP [cytosol] ChEBI 28862 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766734 UniProt:Q8I2M1 UniProt Q8I2M1 2 EQUAL 197 EQUAL GO 0004385 GO molecular function Reactome Database ID Release 77 10766735 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766735 Reactome Database ID Release 77 10766737 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766737 Reactome R-PFA-73788 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73788.1 Cytosolic guanylate kinase 1 (GUK1) catalyzes the reversible reactions of GMP and dGMP with ATP to form GDP and dGDP respectively and ADP. While native gel electrophoretic studies of whole cell extracts suggested the existence of multiple human enzymes with guanylate kinase activity (Jamil et al. 1975), only one has been purified and biochemically characterized (Agarwal et al. 1978; Brady et al. 1996). The enzyme is of clinical importance as it is a target of antitumor drugs and antiviral drugs such as acyclovir (Miller and Miller 1980). 177353 Pubmed 1975 Studies on the properties and tissue distribution of the isozymes of guanylate kinase in man Jamil, T Fisher, RA Harris, H Human Hered 25:402-413 6248551 Pubmed 1980 Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase Miller, WH Miller, RL J Biol Chem 255:7204-7207 8663313 Pubmed 1996 Cloning, characterization, and modeling of mouse and human guanylate kinases Brady, WA Kokoris, MS Fitzgibbon, M 黑色的,我 J Biol Chem 271:16734-40 211390 Pubmed 1978 Guanylate kinases from human erythrocytes, hog brain, and rat liver Agarwal, KC Miech, RP Parks, Jr, RE Methods Enzymol 51:483-491 inferred by electronic annotation IEA GO IEA 2.7.4.8 (d)GDP + ADP <=> (d)GMP + ATP (GUK1) (d)GDP + ADP <=> (d)GMP + ATP (GUK1) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 500077 1 Reactome DB_ID: 29370 1 Reactome DB_ID: 113592 1 Converted from EntitySet in Reactome Reactome DB_ID: 500071 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766734 2 EQUAL 197 EQUAL Reactome Database ID Release 77 10767146 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767146 Reactome R-PFA-110133 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-110133.1 Cytosolic guanylate kinase 1 (GUK1) catalyzes the reversible reactions of GDP and dGDP with ADP to form GMP and dGMP respectively and ATP. While native gel electrophoretic studies of whole cell extracts suggested the existence of multiple human enzymes with guanylate kinase activity (Jamil et al. 1975), only one has been purified and biochemically characterized (Agarwal et al. 1978; Brady et al. 1996). The enzyme is of clinical importance as it is a target of antitumor drugs and antiviral drugs such as acyclovir (Miller and Miller 1980). inferred by electronic annotation IEA GO IEA 2.7.4.4 (d)CMP or UMP + ATP <=> (d)CDP or UDP + ADP (CMPK1) (d)CMP or UMP + ATP <=> (d)CDP or UDP + ADP (CMPK1) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 500009 1 (d)CMP, UMP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dCMP [cytosol] CMP [cytosol] UMP [cytosol] ChEBI 16695 Reactome DB_ID: 113592 1 Converted from EntitySet in Reactome Reactome DB_ID: 500006 1 (d)CDP, UDP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity UDP [cytosol] CDP [cytosol] dCDP [cytosol] ChEBI 17659 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766622 UniProt:Q8I231 UniProt Q8I231 1 EQUAL 196 EQUAL Reactome Database ID Release 77 10766623 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766623 Reactome Database ID Release 77 10766625 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766625 Reactome R-PFA-73548 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73548.1 Cytosolic UMP-CMP kinase (CMPK1) catalyzes the reversible reaction of CMP, dCMP, or UMP and ATP to form CDP, dCDP, or UDP and ADP (Liou et al. 2002; Scott and Wright 1979). 11912132 Pubmed 2002 Characterization of human UMP/CMP kinase and its phosphorylation of D- and L-form deoxycytidine analogue monophosphates. Liou, JY Dutschman, GE Lam, W Jiang, Z Cheng, YC Cancer Res 62:1624-31 40615 Pubmed 1979 Kinetics and equilibria of pyrimidine nucleoside monophosphate kinase from human erythrocytes Scott, EM Wright, RC Biochim Biophys Acta 571:45-54 inferred by electronic annotation IEA GO IEA 2.7.4.4 (d)CDP or UDP + ADP <=> (d)CMP or UMP + ATP (CMPK1) (d)CDP or UDP + ADP <=> (d)CMP or UMP + ATP (CMPK1) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 500006 1 Reactome DB_ID: 29370 1 Converted from EntitySet in Reactome Reactome DB_ID: 500009 1 Reactome DB_ID: 113592 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766622 1 EQUAL 196 EQUAL Reactome Database ID Release 77 10766903 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766903 Reactome R-PFA-75125 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-75125.1 Cytosolic UMP-CMP kinase (CMPK1) catalyzes the reversible reaction of CDP, dCDP, or UDP and ADP to form CMP, dCMP, or UMP and ATP (Liou et al. 2002; Scott and Wright 1979). inferred by electronic annotation IEA GO IEA 6.3.4.2 UTP + glutamine + ATP + H2O => CTP + glutamate + ADP + orthophosphate [CTPS] UTP + glutamine + ATP + H2O => CTP + glutamate + ADP + orthophosphate [CTPS] amination of uridine 5'-triphosphate (UTP) to form cytidine 5'-triphosphate (CTP) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29356 1 Reactome DB_ID: 113592 1 Reactome DB_ID: 29494 1 UTP [ChEBI:15713] UTP Uridine triphosphate uridine 5'-triphosphate ChEBI 15713 Reactome DB_ID: 29472 1 Reactome DB_ID: 29404 1 Reactome DB_ID: 29372 1 Reactome DB_ID: 110614 1 CTP [ChEBI:17677] CTP cytidine 5'-triphosphate Cytidine triphosphate ChEBI 17677 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766716 CTPS tetramer [cytosol] CTPS tetramer Reactome DB_ID: 10766714 4 UniProt:Q8ILZ3 UniProt Q8ILZ3 1 EQUAL 591 EQUAL Reactome Database ID Release 77 10766716 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766716 Reactome R-PFA-504052 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-504052.1 GO 0003883 GO molecular function Reactome Database ID Release 77 10766717 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766717 Reactome Database ID Release 77 10766719 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766719 Reactome R-PFA-73647 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73647.1 Cytosolic CTP synthase 1 (CTPS) catalyzes the reaction of UTP, glutamine, ATP and water to form CTP, glutamate, ADP, and orthophosphate (Han et al. 2005). The active form of the enzyme is a tetramer (Kursala et al. 2006). Both CTPS and a second human gene product, CPTS2, have CTP synthase activity in various test systems; their relative contributions to CTP metabolism in the body is not clear. 16179339 Pubmed 2005 Expression of Human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A Han, GS Sreenivas, A Choi, MG Chang, YF Martin, SS Baldwin, EP Carman, GM J Biol Chem 280:38328-36 16820675 Pubmed 2006 Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy Kursula, P Flodin, S Ehn, M Hammarström, M Schüler, H Nordlund, Par Stenmark, Pål Acta Crystallogr Sect F Struct Biol Cryst Commun 62:613-7 inferred by electronic annotation IEA GO IEA 6.3.4.2 UTP + glutamine + ATP + H2O => CTP + glutamate + ADP + orthophosphate [CTPS2] UTP + glutamine + ATP + H2O => CTP + glutamate + ADP + orthophosphate [CTPS2] amination of uridine 5'-triphosphate (UTP) to form cytidine 5'-triphosphate (CTP) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29356 1 Reactome DB_ID: 113592 1 Reactome DB_ID: 29494 1 Reactome DB_ID: 29472 1 Reactome DB_ID: 29404 1 Reactome DB_ID: 29372 1 Reactome DB_ID: 110614 1 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10770765 CTPS2 tetramer [cytosol] CTPS2 tetramer Reactome DB_ID: 10770763 4 1 EQUAL 586 EQUAL Reactome Database ID Release 77 10770765 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770765 Reactome R-PFA-504058 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-504058.1 Reactome Database ID Release 77 10770766 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770766 Reactome Database ID Release 77 10770768 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770768 Reactome R-PFA-504054 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-504054.1 Cytosolic CTP synthase 2 (CTPS) catalyzes the reaction of UTP, glutamine, ATP and water to form CTP, glutamate, ADP, and orthophosphate (Han et al. 2005; van Kuilenberg et al. 2000). Unpublished X-ray crystallographic data suggest that the enzyme is a tetramer (PDB 3IHL). Both CTPS2 and a second human gene product, CPTS, have CTP synthase activity in various test systems; their relative contributions to CTP metabolism in the body is not clear. 10899599 Pubmed 2000 Identification of a cDNA encoding an isoform of human CTP synthetase van Kuilenberg, AB Meinsma, R Vreken, P Waterham, HR van Gennip, AH Biochim Biophys Acta 1492:548-52 inferred by electronic annotation IEA GO IEA RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin) RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin) NDP + reduced glutaredoxin => dNDP + oxidized glutaredoxin + H2O This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 8866401 1 nucleoside 5'-diphosphate(3-) [ChEBI:57930] nucleoside 5'-diphosphate(3-) ChEBI 57930 Reactome DB_ID: 10767386 1 UniProt:Q9NLB2 UniProt Q9NLB2 2 EQUAL 106 EQUAL Reactome DB_ID: 29356 1 Reactome DB_ID: 10767389 1 Intra-chain Crosslink via L-cystine (cross-link) at 23 and 26 (in Homo sapiens) 23 EQUAL L-cystine (cross-link) 2 EQUAL 106 EQUAL Reactome DB_ID: 8866399 1 2'-deoxyribonucleoside 5'-diphosphate(3-) [ChEBI:73316] 2'-deoxyribonucleoside 5'-diphosphate(3-) a 2'-deoxynucleoside 5'-diphosphate ChEBI 73316 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10767412 RNR (M1M2) [cytosol] RNR (M1M2) Reactome DB_ID: 10767410 1 RRM2 dimer [cytosol] RRM2 dimer Converted from EntitySet in Reactome Reactome DB_ID: 10767408 2 Homologues of RRM2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity RRM2 [cytosol] RRM2 [cytosol] UniProt Q8IJN8 UniProt Q8IM38 Reactome DB_ID: 111736 2 iron(3+) [ChEBI:29034] iron(3+) Ferric ion ferric iron iron, ion (Fe(3+)) Fe3+ FE (III) ION Fe(III) Fe(3+) ChEBI 29034 Reactome Database ID Release 77 10767410 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767410 Reactome R-PFA-111737 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111737.1 Reactome DB_ID: 10767396 1 RRM1 dimer [cytosol] RRM1 dimer Reactome DB_ID: 10767394 2 UniProt:Q8IL94 UniProt Q8IL94 1 EQUAL 792 EQUAL Reactome Database ID Release 77 10767396 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767396 Reactome R-PFA-111735 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111735.1 Reactome Database ID Release 77 10767412 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767412 Reactome R-PFA-73640 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73640.1 GO 0036175 GO molecular function Reactome Database ID Release 77 10767413 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767413 Reactome Database ID Release 77 10767415 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767415 Reactome R-PFA-111742 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111742.1 Ribonucleotide reductase (RNR (M1M2)) catalyzes the reduction of adenine, guanine, cytidine, and uridine ribonucleoside 5'-diphosphates (NDPs) to form the corresponding deoxyribonucleoside 5'-diphosphates, coupled to the oxidation of glutaredoxin (Eklund et al. 2001). The enzyme complex is cytosolic (Pontarin et al. 2008). The form of ribonucleotide reductase annotated here is a tetramer of two large (M1) and two small (M2) subunits (Zhou et al. 2005). Expression of RNR (M1M2) is confined to the S phase of the cell cycle by restriction of the expression of the M1 gene and by degradation of the M1 gene product at the end of S phase. The overall activity of the enzyme is regulated allosterically: ATP binding is stimulatory while dATP binding is inhibitory (Reichard et al. 2000).

The reducing equivalents needed for ribonucleotide reductase activity can be provided by either of two small proteins, glutaredoxin or thioredoxin (Holmgren 1989; Sun et al. 1998; Zahedi Avval & Holmgren 2009). Both are re-reduced with NADPH as the donor of reducing equivalents. The relative contributions of glutaredoxin and thioredoxin in vivo are unknown. 10884394 Pubmed 2000 Cross-talk between the allosteric effector-binding sites in mouse ribonucleotide reductase Reichard, Peter A Eliasson, Rolf Ingemarson, Rolf Thelander, Lars J Biol Chem 275:33021-33026 19176520 Pubmed 2009 Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for Mammalian s phase ribonucleotide reductase Zahedi Avval, Farnaz Holmgren, Arne J. Biol. Chem. 284:8233-40 11796141 Pubmed 2001 Structure and function of the radical enzyme ribonucleotide reductase Eklund, Hans Uhlin, Ulla Farnegardh, Mathias Logan, Derek T Nordlund, Par Prog Biophys Mol Biol 77:177-268 9677297 Pubmed 1998 The NMR solution structure of human glutaredoxin in the fully reduced form Sun, Chaohong Berardi, Marcelo J Bushweller, John H J Mol Biol 280:687-701 16373698 Pubmed 2005 A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases Zhou, Bingsen Shao, Jimin Su, Leila Yuan, Yate-Ching Qi, Christina Shih, Jennifer Xi, Bixin Chu, Bernard Yen, Yun Mol Cancer Ther 4:1830-6 2668278 Pubmed 1989 Thioredoxin and glutaredoxin systems Holmgren, Arne J Biol Chem 264:13963-13966 18997010 Pubmed 2008 Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage Pontarin, Giovanna Fijolek, Artur Pizzo, Paola Ferraro, Paola Rampazzo, Chiara Pozzan, Tullio Thelander, Lars Reichard, Peter A Bianchi, Vera Proc. Natl. Acad. Sci. U.S.A. 105:17801-6 inferred by electronic annotation IEA GO IEA ACTIVATION Reactome Database ID Release 77 9619145 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9619145 Reactome DB_ID: 113592 INHIBITION Reactome Database ID Release 77 8866421 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8866421 Reactome R-HSA-8866421 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8866421.2 Reactome DB_ID: 110644 dATP [ChEBI:16284] dATP 2'-deoxyadenosine 5'-triphosphate Deoxyadenosine triphosphate Deoxyadenosine 5'-triphosphate ChEBI 16284 1.17.4.1 RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (thioredoxin) RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (thioredoxin) NDP + reduced thioredoxin => dNDP + oxidized thioredoxin + H2O This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10766687 1 UniProt:Q4VWQ3 trx3 UniProt Q4VWQ3 2 EQUAL 105 EQUAL Reactome DB_ID: 8866401 1 Reactome DB_ID: 29356 1 Reactome DB_ID: 8866399 1 Reactome DB_ID: 10766685 1 Intra-chain Crosslink via L-cystine (cross-link) at 32 and 35 (in Homo sapiens) 32 EQUAL 2 EQUAL 105 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10767412 GO 0004748 GO molecular function Reactome Database ID Release 77 10767419 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767419 Reactome Database ID Release 77 10767421 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767421 Reactome R-PFA-111751 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111751.1 Ribonucleotide reductase (RNR (M1M2)) catalyzes the reduction of adenine, guanine, cytidine, and uridine ribonucleoside 5'-diphosphates (NDPs) to form the corresponding deoxyribonucleoside 5'-diphosphates, coupled to the oxidation of thioredoxin (Eklund et al. 2001). The enzyme complex is cytosolic (Pontarin et al. 2008). The form of ribonucleotide reductase annotated here is a tetramer of two large (M1) and two small (M2) subunits (Zhou et al. 2005). Expression of RNR (M1M2) is confined to the S phase of the cell cycle by restriction of the expression of the M1 gene and by degradation of the M1 gene product at the end of S phase. The overall activity of the enzyme is regulated allosterically: ATP binding is stimulatory while dATP binding is inhibitory (Reichard et al. 2000).

The reducing equivalents needed for ribonucleotide reductase activity can be provided by either of two small proteins, glutaredoxin or thioredoxin (Holmgren 1989; Sun et al. 1998; Zahedi Avval & Holmgren 2009). Both are re-reduced with NADPH as the donor of reducing equivalents. The relative contributions of glutaredoxin and thioredoxin in vivo are unknown. inferred by electronic annotation IEA GO IEA ACTIVATION Reactome DB_ID: 113592 INHIBITION Reactome DB_ID: 110644 RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin) RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin) NDP + reduced glutaredoxin => dNDP + oxidized glutaredoxin + H2O This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 8866401 1 Reactome DB_ID: 10767386 1 2 EQUAL 106 EQUAL Reactome DB_ID: 29356 1 Reactome DB_ID: 10767389 1 Intra-chain Crosslink via L-cystine (cross-link) at 23 and 26 (in Homo sapiens) 23 EQUAL 2 EQUAL 106 EQUAL Reactome DB_ID: 8866399 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10767427 RNR (M1M2B) [cytosol] RNR (M1M2B) Reactome DB_ID: 10767425 1 RRM2B dimer [cytosol] RRM2B dimer Reactome DB_ID: 10767423 4 UniProt:Q8IM38 1 EQUAL 351 EQUAL Reactome DB_ID: 111736 2 Reactome Database ID Release 77 10767425 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767425 Reactome R-PFA-111794 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111794.1 Reactome DB_ID: 10767396 1 Reactome Database ID Release 77 10767427 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767427 Reactome R-PFA-111795 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111795.1 Reactome Database ID Release 77 10779113 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10779113 Reactome Database ID Release 77 10779115 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10779115 Reactome R-PFA-8866405 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8866405.1 核苷酸还原酶(RNR (M1M2B)催化the reduction of adenine, guanine, cytidine, and uridine ribonucleoside 5'-diphosphates (NDPs) to form the corresponding deoxyribonucleoside 5'-diphosphates, coupled to the oxidation of glutaredoxin (Eklund et al. 2001). The enzyme complex is cytosolic (Pontarin et al. 2008). The form of ribonucleotide reductase annotated here is a tetramer of two large (M1) and two small (M2B) subunits (Shao et al. 2004; Zhou et al. 2005). M2B protein is stable throughout the cell cycle, unlike M2, and is induced by TP53 (Guittet et al. 2001; Tanaka et al. 2000). The RNR (M1M2B) complex can thus provide dNDPs for DNA repair in interphase and quiescent cells. Studies of mitochondrial instability in cells from patients deficient in M2 protein indicate that RNR (M1M2B) likewise provides dNDPs for mitochondrial DNA replication (Pontarin et al. 2012). The overall activity of the enzyme is regulated allosterically: ATP binding is stimulatory while dATP binding is inhibitory (Reichard et al. 2000).

The reducing equivalents needed for ribonucleotide reductase activity can be provided by either of two small proteins, glutaredoxin or thioredoxin (Holmgren 1989; Sun et al. 1998; Zahedi Avval & Holmgren 2009). Both are re-reduced with NADPH as the donor of reducing equivalents. The relative contributions of glutaredoxin and thioredoxin in vivo are unknown. 14729598 Pubmed 2004 In vitro characterization of enzymatic properties and inhibition of the p53R2 subunit of human ribonucleotide reductase Shao, Jimin Zhou, Bingsen Zhu, Lijun Qiu, Weihua Yuan, Yate-Ching Xi, Bixin Yen, Yun Cancer Res 64:1-6 22847445 Pubmed 2012 Mammalian ribonucleotide reductase subunit p53R2 is required for mitochondrial DNA replication and DNA repair in quiescent cells Pontarin, Giovanna Ferraro, Paola Bee, Leonardo Reichard, Peter A Bianchi, Vera Proc. Natl. Acad. Sci. U.S.A. 109:13302-7 11517226 Pubmed 2001 Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells Guittet, Olivier Hakansson, Pelle Voevodskaya, Nina Fridd, Susan Graslund, Astrid Arakawa, Hirofumi Nakamura, Yusuke Thelander, Lars J Biol Chem 276:40647-40651 10716435 Pubmed 2000 A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage Tanaka, Hiroshi Arakawa, Hirofumi Yamaguchi, Tatsuya Shiraishi, Kenji Fukuda, Seisuke Matsui, Kuniko Takei, Yoshiki Nakamura, Yusuke Nature 404:42-49 inferred by electronic annotation IEA GO IEA ACTIVATION Reactome DB_ID: 113592 INHIBITION Reactome DB_ID: 110644 1.17.4.1 RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (thioredoxin) RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (thioredoxin) NDP + reduced thioredoxin => dNDP + oxidized thioredoxin + H2O This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10766687 1 2 EQUAL 105 EQUAL Reactome DB_ID: 8866401 1 Reactome DB_ID: 29356 1 Reactome DB_ID: 8866399 1 Reactome DB_ID: 10766685 1 Intra-chain Crosslink via L-cystine (cross-link) at 32 and 35 (in Homo sapiens) 32 EQUAL 2 EQUAL 105 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10767427 Reactome Database ID Release 77 10767428 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767428 Reactome Database ID Release 77 10767430 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767430 Reactome R-PFA-111804 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111804.1 核苷酸还原酶(RNR (M1M2B)催化the reduction of adenine, guanine, cytidine, and uridine ribonucleoside 5'-diphosphates (NDPs) to form the corresponding deoxyribonucleoside 5'-diphosphates, coupled to the oxidation of thioredoxin (Eklund et al. 2001). The enzyme complex is cytosolic (Pontarin et al. 2008). The form of ribonucleotide reductase annotated here is a tetramer of two large (M1) and two small (M2B) subunits (Shao et al. 2004; Zhou et al. 2005). M2B protein is stable throughout the cell cycle, unlike M2, and is induced by TP53 (Guittet et al. 2001; Tanaka et al. 2000). The RNR (M1M2B) complex can thus provide dNDPs for DNA repair in interphase and quiescent cells. Studies of mitochondrial instability in cells from patients deficient in M2 protein indicate that RNR (M1M2B) likewise provides dNDPs for mitochondrial DNA replication (Pontarin et al. 2012). The overall activity of the enzyme is regulated allosterically: ATP binding is stimulatory while dATP binding is inhibitory (Reichard et al. 2000).

The reducing equivalents needed for ribonucleotide reductase activity can be provided by either of two small proteins, glutaredoxin or thioredoxin (Holmgren 1989; Sun et al. 1998; Zahedi Avval & Holmgren 2009). Both are re-reduced with NADPH as the donor of reducing equivalents. The relative contributions of glutaredoxin and thioredoxin in vivo are unknown. inferred by electronic annotation IEA GO IEA ACTIVATION Reactome DB_ID: 113592 INHIBITION Reactome DB_ID: 110644 glutaredoxin (oxidized) + glutathione (reduced) => glutaredoxin (reduced) + glutathione (oxidized) glutaredoxin (oxidized) + glutathione (reduced) => glutaredoxin (reduced) + glutathione (oxidized) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 10767389 1 Intra-chain Crosslink via L-cystine (cross-link) at 23 and 26 (in Homo sapiens) 23 EQUAL 2 EQUAL 106 EQUAL Reactome DB_ID: 29450 1 glutathione [ChEBI:16856] glutathione ChEBI 16856 Reactome DB_ID: 111745 1 glutathione disulfide [ChEBI:17858] glutathione disulfide ChEBI 17858 Reactome DB_ID: 10767386 1 2 EQUAL 106 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10767389 Intra-chain Crosslink via L-cystine (cross-link) at 23 and 26 (in Homo sapiens) 23 EQUAL 2 EQUAL 106 EQUAL GO 0015038 GO molecular function Reactome Database ID Release 77 10767416 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767416 Reactome Database ID Release 77 10767418 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767418 Reactome R-PFA-111746 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-111746.1 Cytosolic glutaredoxin (oxidized) and glutathione (reduced) react to form glutaredoxin (reduced) and glutathione (oxidized) (Padilla et al. 1995). 7851394 Pubmed 1995 Purification from placenta, amino acid sequence, structure comparisons and cDNA cloning of human glutaredoxin Padilla, CA Martinez-Galisteo, Emilia Barcena, J Antonio Spyrou, G Holmgren, Arne Eur J Biochem 227:27-34 inferred by electronic annotation IEA GO IEA 1.8.1.9 thioredoxin, oxidized + NADPH + H+ => thioredoxin, reduced + NADP+ thioredoxin, oxidized + NADPH + H+ => thioredoxin, reduced + NADP+ regeneration of active (reduced) Thioredoxin This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29364 1 NADPH [ChEBI:16474] NADPH TPNH ChEBI 16474 Reactome DB_ID: 10766685 1 Intra-chain Crosslink via L-cystine (cross-link) at 32 and 35 (in Homo sapiens) 32 EQUAL 2 EQUAL 105 EQUAL Reactome DB_ID: 70106 1 Reactome DB_ID: 29366 1 NADP(+) [ChEBI:18009] NADP(+) ChEBI 18009 Reactome DB_ID: 10766687 1 2 EQUAL 105 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766706 TNXRD1:FAD dimer [cytosol] TNXRD1:FAD dimer Converted from EntitySet in Reactome Reactome DB_ID: 10766704 2 Homologues of TXNRD1 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity TXNRD1 [cytosol] trxr2 [cytosol] GR3 [cytosol] UniProt A0A144A3W0 UniProt P61076 UniProt O15770 Reactome DB_ID: 29386 2 FAD [ChEBI:16238] FAD Flavin adenine dinucleotide ChEBI 16238 Reactome Database ID Release 77 10766706 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766706 Reactome R-PFA-73532 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73532.1 GO 0004791 GO molecular function Reactome Database ID Release 77 10766707 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766707 Reactome Database ID Release 77 10766709 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766709 Reactome R-PFA-73646 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73646.1 Cytosolic thioredoxin reductase catalyzes the reaction of thioredoxin, oxidized and NADPH + H+ to form thioredoxin, reduced and NADP+ (Urig et al. 2006). 16750198 Pubmed 2006 Truncated mutants of human thioredoxin reductase 1 do not exhibit glutathione reductase activity Urig, S Lieske, J Fritz-Wolf, K Irmler, A Becker, K FEBS Lett 580:3595-600 inferred by electronic annotation IEA GO IEA 2.7.4.6 (d)NDP + ATP <=> (d)NTP + ADP (NME1,2,3) (d)NDP + ATP <=> (d)NTP + ADP (NME1,2,3) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 482627 1 (d)NDP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity TDP [cytosol] dUDP [cytosol] UDP [cytosol] dADP [cytosol] CDP [cytosol] dCDP [cytosol] GDP [cytosol] dGDP [cytosol] ChEBI 18075 ChEBI 28850 Reactome DB_ID: 113592 1 Converted from EntitySet in Reactome Reactome DB_ID: 482625 1 (d)NTP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dATP [cytosol] dCTP [cytosol] UTP [cytosol] dGTP [cytosol] TTP [cytosol] CTP [cytosol] dUTP [cytosol] GTP [cytosol] ChEBI 16311 ChEBI 16497 ChEBI 18077 ChEBI 17625 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10770718 NME1,2 hexamers [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0004550 GO molecular function Reactome Database ID Release 77 10770719 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770719 Reactome Database ID Release 77 10770721 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770721 Reactome R-PFA-482619 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-482619.1 Cytosolic nucleoside diphosphate kinases catalyze the reversible reaction of ribonucleoside and deoxyribonucleoside 5'-diphosphates with ATP to form the corresponding nucleoside 5'-triphosphates and ADP. These kinases are ubiquitously expressed enzymes with broad substrate specificities (Berg and Joklik 1954; Parks and Agarwal 1973). Three human cytosolic nucleoside diphosphate kinase proteins, NME1, 2, and 3, have been characterized biochemically (Gilles et al. 1991; Schaertl et al. 1998; Erent et al. 2001; Chen et al. 2003). All are catalytically active as hexamers: homohexamers of NME1, 2, and 3 have been described, as have heterohexamers containing all possible combinations of NME1 and 2 (Gilles et al. 1991; Erent et al. 2001).

While cytosolic nucleoside diphosphate kinases can efficiently use several nucleotide triphosphates as a phosphate donor, the high concentrations of ATP relative to other nucleoside triphosphates in vivo makes it the likely major phosphate donor in these reactions and only reactions with ATP as the phosphate donor are annotated. All of these phosphorylation reactions are freely reversible in vitro (Parks and Agarwal 1973; Schaertl et al. 1998), but the high ratio of ATP to ADP concentrations in the cytosol should favor the conversion of (d)NDP and ATP to (d)NTP and ADP. 12972261 Pubmed 2003 Nucleotide binding to nucleoside diphosphate kinases: X-ray structure of human NDPK-A in complex with ADP and comparison to protein kinases Chen, Y Gallois-Montbrun, S Schneider, B Veron, M Moréra, S Deville-Bonne, D Janin, J J Mol Biol 332:915-26 13211603 Pubmed 1954 Enzymatic phosphorylation of nucleoside diphosphates Berg, P Joklik, WK J Biol Chem 210:657-672 9488696 Pubmed 1998 Substrate specificity of human nucleoside-diphosphate kinase revealed by transient kinetic analysis Schaertl, S Konrad, M Geeves, MA J Biol Chem 273:5662-5669 0121227022 国际标准图书编号 1973 Nucleoside diphosphokinases Parks, Jr, RE Agarwal, RP The Enzymes, 3rd ed (Book): 307-333 11277919 Pubmed 2001 Structural and catalytic properties and homology modelling of the human nucleoside diphosphate kinase C, product of the DRnm23 gene Erent, M Gonin, P Cherfils, J Tissier, P Raschella, G Giartosio, A Agou, F Sarger, C Lacombe, ML Konrad, M Lascu, I Eur J Biochem 268:1972-1981 1851158 Pubmed 1991 Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme Gilles, Anne-Marie Presecan, E Vonica, A Lascu, I J Biol Chem 266:8784-8789 inferred by electronic annotation IEA GO IEA 2.7.4.6 (d)NTP + ADP <=> (d)NDP + ATP (NME1,2,3) (d)NTP + ADP <=> (d)NDP + ATP (NME1,2,3) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 482625 1 Reactome DB_ID: 29370 1 Converted from EntitySet in Reactome Reactome DB_ID: 482627 1 Reactome DB_ID: 113592 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10770718 Reactome Database ID Release 77 10770723 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770723 Reactome R-PFA-482621 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-482621.1 Cytosolic nucleoside diphosphate kinases catalyze the reversible reaction of ribonucleoside and deoxyribonucleoside 5'-diphosphates with ADP to form the corresponding nucleoside 5'-diphosphates and ATP. These kinases are ubiquitously expressed enzymes with broad substrate specificities (Berg and Joklik 1954; Parks and Agarwal 1973). Three human cytosolic nucleoside diphosphate kinase proteins, NME1, 2, and 3, have been characterized biochemically (Gilles et al. 1991; Schaertl et al. 1998; Erent et al. 2001; Chen et al. 2003). All are catalytically active as hexamers: homohexamers of NME1, 2, and 3 have been described, as have heterohexamers containing all possible combinations of NME1 and 2 (Gilles et al. 1991; Erent et al. 2001).

While the high ratio of ATP to ADP concentrations in the cytosol normally favors the conversion of (d)NDP and ATP to (d)NTP and ADP, the reversibility of the reactions and the overlapping substrate specificities of the enzymes suggest that this group of reverse reactions can buffer the intracellular nucleotide pool and regulate the relative concentrations of individual nucleoside di- and tri-phosphates in the pool. inferred by electronic annotation IEA GO IEA 2.7.4.6 (d)NDP + ATP <=> (d)NTP + ADP (NME4) (d)NDP + ATP <=> (d)NTP + ADP (NME4) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 482803 1 mitochondrial matrix GO 0005759 (d)NDP [mitochondrial matrix] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity TDP [mitochondrial matrix] dGDP [mitochondrial matrix] dCDP [mitochondrial matrix] dADP [mitochondrial matrix] dUDP [mitochondrial matrix] CDP [mitochondrial matrix] GDP [mitochondrial matrix] UDP [mitochondrial matrix] Reactome DB_ID: 113593 1 Converted from EntitySet in Reactome Reactome DB_ID: 482807 1 (d)NTP [mitochondrial matrix] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity TTP [mitochondrial matrix] dATP [mitochondrial matrix] CTP [mitochondrial matrix] GTP [mitochondrial matrix] UTP [mitochondrial matrix] dGTP(线粒体基质) dUTP [mitochondrial matrix] dCTP [mitochondrial matrix] Reactome DB_ID: 113581 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10770751 NME4 hexamer [mitochondrial inner membrane] NME4 hexamer Converted from EntitySet in Reactome Reactome DB_ID: 10770749 6 Homologues of NME4 [mitochondrial inner membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity NME4 [mitochondrial inner membrane] NME4 [mitochondrial inner membrane] UniProt Q8ID43 UniProt C6KSQ4 Reactome Database ID Release 77 10770751 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770751 Reactome R-PFA-110636 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-110636.1 Reactome Database ID Release 77 10770752 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770752 Reactome Database ID Release 77 10770754 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770754 Reactome R-PFA-482804 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-482804.1 核苷二磷酸激酶NME4联系在一起the inner mitochondrial membrane (Tokarska-Schlattner et al. 2008) catalyzes the reversible reaction of ribonucleoside and deoxyribonucleoside 5'-diphosphates with ATP to form the corresponding nucleoside 5'-triphosphates and ADP. The active form of the enzyme is a hexamer of NME4 polypeptides whose amino-terminal 33 residues, a mitochondrial translocation signal, have been removed (Milon et al. 2000). The substrate specificity of NME4 has not been examined in detail but is inferred to be broad like that of the homologous NME1, 2, and 3 kinases (Schaertl et al. 1998). 18635542 Pubmed 2008 The nucleoside diphosphate kinase D (NM23-H4) binds the inner mitochondrial membrane with high affinity to cardiolipin and couples nucleotide transfer with respiration Tokarska-Schlattner, M Boissan, M Munier, A Borot, C Mailleau, C Speer, O Schlattner, U Lacombe, ML J Biol Chem 283:26198-207 10799505 Pubmed 2000 The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase Milon, L Meyer, P Chiadmi, M Munier, A Johansson, M Karlsson, A Lascu, I Capeau, J Janin, J Lacombe, ML J Biol Chem 275:14264-14272 inferred by electronic annotation IEA GO IEA 2.7.4.6 (d)NTP + ADP <=> (d)NDP + ATP (NME4) (d)NTP + ADP <=> (d)NDP + ATP (NME4) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 482807 1 Reactome DB_ID: 113581 1 Converted from EntitySet in Reactome Reactome DB_ID: 482803 1 Reactome DB_ID: 113593 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10770751 Reactome Database ID Release 77 10770756 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770756 Reactome R-PFA-482812 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-482812.1 核苷二磷酸激酶NME4联系在一起the inner mitochondrial membrane (Tokarska-Schlattner et al. 2008) catalyzes the reversible reaction of ribonucleoside and deoxyribonucleoside 5'-diphosphates with ADP to form the corresponding nucleoside 5'-diphosphates and ATP. The active form of the enzyme is a hexamer of NME4 polypeptides whose amino-terminal 33 residues, a mitochondrial translocation signal, have been removed (Milon et al. 2000). The substrate specificity of NME4 has not been examined in detail, but is inferred to be broad like that of the homologous NME1, 2, and 3 kinases (Schaertl et al. 1998). inferred by electronic annotation IEA GO IEA 2.7.4.6 NME1:NME3 heterohexamer, NME2P1 phosphorylate NDPs to NTPs NME1:NME3 heterohexamer, NME2P1 phosphorylate NDPs to NTPs This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 113592 1 Reactome DB_ID: 6806885 1 nucleoside diphosphate [ChEBI:16862] nucleoside diphosphate NDP nucleoside diphosphates ChEBI 16862 Reactome DB_ID: 6806881 1 nucleoside triphosphate [ChEBI:17326] nucleoside triphosphate nucleoside triphosphates NTP ChEBI 17326 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10777725 NME1:NME3 heterohexamer, NME2P1 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 77 10777726 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10777726 Reactome Database ID Release 77 10777728 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10777728 Reactome R-PFA-6806877 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-6806877.1 核苷二磷酸激酶(nm)发挥惩罚学生rtant role in the reversible phosphorylation of nuceloside diphosphates (NDP) other than ADP to form nuceloside triphosphates (NTP). The gamma phosphate of ATP is transferred to the beta phosphate on NDP via a ping-pong mechanism, using a phosphorylated active-site intermediate. Nucleoside diphosphate kinase 3 (NME3, aka nm23-H3) can readily form mixed hexamers with NME1, consistent with well-characterised NME family members. The overexpression of the NME3 gene inhibits differentiation and induces the apoptosis of myeloid precursor cell lines (Erent et al. 2001). A putative nucleoside diphosphate kinase (NME2P1) is proposed to perform the same NDPK function as NME1:NME3 heterohexamer based on sequence similarity. inferred by electronic annotation IEA GO IEA 3.6.1.23 dUTP +水= >转储+焦磷酸 dUTP +水= >转储+焦磷酸 hydrolysis of 2'-deoxyuridine 5'-triphosphate to form 2'-deoxyuridine 5'-phosphate This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 500739 1 dUTP [ChEBI:17625] dUTP 2'-deoxyuridine 5'-triphosphate Reactome DB_ID: 113518 1 Reactome DB_ID: 113541 1 Reactome DB_ID: 500742 1 dUMP [ChEBI:17622] dUMP 2'-Deoxyuridine 5'-phosphate Deoxyuridylic acid Deoxyuridine 5'-phosphate Deoxyuridine monophosphate ChEBI 17622 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766726 DUT trimer [nucleoplasm] DUT trimer Reactome DB_ID: 10766724 3 UniProt:Q8II92 UniProt Q8II92 70 EQUAL 252 EQUAL Reactome Database ID Release 77 10766726 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766726 Reactome R-PFA-500745 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-500745.1 GO 0004170 GO molecular function Reactome Database ID Release 77 10766727 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766727 Reactome Database ID Release 77 10766729 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766729 Reactome R-PFA-73666 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73666.1 Deoxyuridine triphosphatase (DUT) catalyzes the hydrolysis of dUTP to form dUMP and pyrophosphate. Two isoforms of DUT are expressed, generated by alternative splicing. The major one, annotated here, is localized to the nucleoplasm (Ladner et al. 1996). The enzyme is a homotrimer (Mol et al. 1996). In the cell, this reaction depletes the supply of dUTP, preventing its incorporation into DNA, while generating dUMP, the immediate precursor of thymidine nucleotides. 8805593 Pubmed 1996 Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits Mol, CD Harris, JM McIntosh, EM Tainer, JA Structure 4:1077-92 8631816 Pubmed 1996 Characterization of distinct nuclear and mitochondrial forms of human deoxyuridine triphosphate nucleotidohydrolase Ladner, RD McNulty, DE Carr, SA Roberts, GD Caradonna, SJ J Biol Chem 271:7745-51 inferred by electronic annotation IEA GO IEA 2.1.1.45 dUMP + N5,N10-methylene tetrahydrofolate => TMP + dihydrofolate dUMP + N5,N10-methylene tetrahydrofolate => TMP + dihydrofolate conversion of dUMP to dTMP This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 111355 1 (6S)-5,6,7,8-tetrahydrofolic acid [ChEBI:15635] (6S)-5,6,7,8-tetrahydrofolic acid ChEBI 15635 Reactome DB_ID: 109382 1 Reactome DB_ID: 109366 1 dTMP [ChEBI:17013] dTMP Deoxythymidine 5'-phosphate Thymidylic acid 5'-Thymidylic acid Thymidylate Thymidine 5'-phosphate Thymidine monophosphate Deoxythymidylic acid ChEBI 17013 Reactome DB_ID: 73604 1 dihydrofolic acid [ChEBI:15633] dihydrofolic acid ChEBI 15633 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766676 TS dimer [cytosol] TS dimer Reactome DB_ID: 10766674 2 UniProt:Q8I1R6 UniProt Q8I1R6 2 EQUAL 313 EQUAL Reactome DB_ID: 29926 2 magnesium(2+) [ChEBI:18420] magnesium(2+) ChEBI 18420 Reactome Database ID Release 77 10766676 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766676 Reactome R-PFA-73519 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73519.1 GO 0004799 GO molecular function Reactome Database ID Release 77 10766677 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766677 Reactome Database ID Release 77 10766679 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766679 Reactome R-PFA-73605 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73605.1 Cytosolic thymidylate synthase catalyzes the reaction of dUMP and N5,N10-methylene tetrahydrofolate to form TMP and dihydrofolate (Davisson et al. 1989). The enzyme is a homodimer (Phan et al. 2001). 2656695 Pubmed 1989 Expression of human thymidylate synthase in Escherichia coli Davisson, VJ Sirawaraporn, W Santi, DV J Biol Chem 264:9145-8 11278511 Pubmed 2001 Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors Phan, J Steadman, DJ Koli, S Ding, WC Minor, W Dunlap, RB Berger, SH Lebioda, L J Biol Chem 276:14170-7 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780458 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780458 Reactome R-PFA-499943 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-499943.1 GO 0015949 GO biological process An array of kinases catalyze the reversible phosphorylation of nucleotide monophosphates to form nucleotide diphosphates and triphosphates.

Nucleoside monophosphate kinases catalyze the reversible phosphorylation of nucleoside and deoxynucleoside 5'-monophosphates to form the corresponding nucleoside 5'-diphosphates. Most appear to have restricted specificities for nucleoside monophosphates, and to use ATP preferentially (Van Rompay et al. 2000; Anderson 1973; Noda 1973). The total number of human enzymes that catalyze these reactions in vivo is not clear. In six cases, a well-defined biochemical activity has been associated with a purified protein, and these are annotated here. However, additional nucleoside monophosphate kinase-like human proteins have been identified in molecular cloning studies whose enzymatic activities are unknown, and several distinctive nucleoside monophosphate kinase activities detected in cell extracts, e.g., a GTP-requiring adenylate kinase activity (Wilson et al. 1976) and one or more guanylate kinase activities (Jamil et al. 1975) have not been unambiguously associated with specific human proteins.

The nucleoside monophosphates against which each of the six well-characterized enzymes is active is shown in the table (Van Rompay et al. 2000). All six efficiently use ATP as a phosphate donor, but have some activity with other nucleoside triphosphates as well in vitro. The high concentrations of ATP relative to other nucleoside triphosphates in vivo makes it the likely major phosphate donor in these reactions under most conditions.

All of these phosphorylation reactions are freely reversible in vitro when carried out with purified enzymes and substrates, having equilibrium constants near 1. In vivo, high ratios of ATP to ADP are likely to favor the forward direction of these reactions, i.e., the conversion of (d)NMP and ATP to (d)NDP and ADP. At the same time, the reversibility of the reactions and the overlapping substrate specificities of the enzymes raises the possibility that this group of reactions can buffer the intracellular nucleotide pool and regulate the relative concentrations of individual nucleotides in the pool: if any one molecule builds up to unusually high levels, multiple routes appear to be open not only to dispose of it but to use it to increase the supply of less abundant nucleotides.

Ribonucleotide reductase catalyzes the synthesis of deoxyribonucleotide diphosphates from ribonucleotide diphosphates. 0121227022 国际标准图书编号 1973 Nucleoside and nucleotide kinases Anderson, EP The Enzymes, 3rd ed (Book): 49-96 5940 Pubmed 1976 Adenylate kinases in man: evidence for a third locus Wilson, Jr, DE Povey, S Harris, H Ann Hum Genet 39:305-313 11008000 Pubmed 2000 Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases Van Rompay, AR Johansson, M Karlsson, A Pharmacol Ther 87:189-198 0121227022 国际标准图书编号 1973 Adenylate kinase Noda, L The Enzymes, 3rd ed (Book): 279-305 inferred by electronic annotation IEA GO IEA Nucleotide salvage Nucleotide salvage This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Purine salvage Purine salvage This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 3.5.4.6 AMP + H2O => IMP + NH4+ (AMPD) AMP + H2O => IMP + NH4+ (AMPD) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29356 1 Reactome DB_ID: 76577 1 Reactome DB_ID: 29602 1 Reactome DB_ID: 31633 1 ammonium [ChEBI:28938] ammonium ChEBI 28938 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10767048 AMPD tetramers [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0003876 GO molecular function Reactome Database ID Release 77 10767049 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767049 Reactome Database ID Release 77 10767051 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10767051 Reactome R-PFA-76590 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-76590.1 Cytosolic AMP deaminase (AMPD) catalyzes the hydrolysis of AMP to yield IMP and ammonia. Three isoforms of AMPD, E, L, and M, have been identified that differ in their expression patterns in the body. All occur as tetramers and all have qualitatively the same catalytic activity, however (Bausch-Jurken et al. 1992; Mahnke-Zizelman et al. 1998). 1429593 Pubmed 1992 Molecular cloning of AMP deaminase isoform L. Sequence and bacterial expression of human AMPD2 cDNA Bausch-Jurken, MT Mahnke-Zizelman, DK Morisaki, T Sabina, RL J Biol Chem 267:22407-13 9857047 Pubmed 1998 Novel aspects of tetramer assembly and N-terminal domain structure and function are revealed by recombinant expression of human AMP deaminase isoforms Mahnke-Zizelman, DK Tullson, PC Sabina, RL J Biol Chem 273:35118-25 inferred by electronic annotation IEA GO IEA 2.4.2.8 guanine or hypoxanthine + PRPP => GMP or IMP + PPi (HPRT1) guanine or hypoxanthine + PRPP => GMP or IMP + PPi (HPRT1) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 500259 1 Gua, Hyp [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Hyp [cytosol] Gua [cytosol] ChEBI 17368 ChEBI 16235 Reactome DB_ID: 73566 1 5-O-phosphono-alpha-D-ribofuranosyl diphosphate [ChEBI:17111] 5-O-phosphono-alpha-D-ribofuranosyl diphosphate ChEBI 17111 Reactome DB_ID: 111294 1 Converted from EntitySet in Reactome Reactome DB_ID: 500260 1 GMP, IMP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GMP [cytosol] IMP [cytosol] PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766756 HGPRT tetramer [cytosol] HGPRT tetramer Reactome DB_ID: 10766754 4 UniProt:Q8IJS1 UniProt Q8IJS1 2 EQUAL 218 EQUAL Reactome DB_ID: 29926 8 Reactome Database ID Release 77 10766756 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766756 Reactome R-PFA-74208 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-74208.1 GO 0004422 GO molecular function Reactome Database ID Release 77 10766757 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766757 Reactome Database ID Release 77 10766759 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766759 Reactome R-PFA-74215 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-74215.1 Cytosolic hypoxanthine-guanine phosphoribosyltransferase (HPRT1) tetramer catalyzes the reactions of guanine or hypoxanthine with PRPP to form GMP ir IMP and pyrophosphate (Holden and Kelley 1978; Jolly et al. 1983). 6300847 Pubmed 1983 Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase Jolly, DJ Okayama, H Berg, P Esty, AC Filpula, D Bohlen, P Johnson, GG Shively, JE Hunkapillar, T Friedmann, T Proc Natl Acad Sci U S A 80:477-81 inferred by electronic annotation IEA GO IEA 3.5.4.4 (2'-deoxy)adenosine + H2O => (2'-deoxy)inosine + NH4+ (ADA) (2'-deoxy)adenosine + H2O => (2'-deoxy)inosine + NH4+ (ADA) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 500173 1 Ade-Rib, dA [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dA [cytosol] Ade-Rib [cytosol] ChEBI 17256 ChEBI 16335 Reactome DB_ID: 29356 1 Converted from EntitySet in Reactome Reactome DB_ID: 500172 1 Ino, dI [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Ino [cytosol] dI [cytosol] ChEBI 17596 ChEBI 28997 Reactome DB_ID: 31633 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10766764 UniProt:Q8IJA9 ADA UniProt Q8IJA9 2 EQUAL 363 EQUAL GO 0004000 GO molecular function Reactome Database ID Release 77 10766765 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766765 Reactome Database ID Release 77 10766767 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766767 Reactome R-PFA-74241 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-74241.1 Cytosolic adenosine deaminase (ADA) catalyzes the hydrolysis of 2'deoxyadenosine and adenosine to yield deoxyinosine and inosine, respectively, plus ammonia (Akeson et al. 1988). Unpublished crystallographic data (PDB 3IAR) indicate that the human enzyme is a monomer. 3182793 Pubmed 1988 Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts Akeson, AL Wiginton, DA Dusing, MR States, JC Hutton, JJ J Biol Chem 263:16291-6 inferred by electronic annotation IEA GO IEA 1.7.1.7 GMP + NADPH + H+ => IMP + NADP+ + NH4+ (GMPR,GMPR2) GMP + NADPH + H+ => IMP + NADP+ + NH4+ (GMPR,GMPR2) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29364 1 Reactome DB_ID: 113578 1 Reactome DB_ID: 70106 1 Reactome DB_ID: 29366 1 Reactome DB_ID: 29602 1 Reactome DB_ID: 31633 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10770814 GMPR四聚体(细胞溶质) Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0003920 GO molecular function Reactome Database ID Release 77 10770815 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770815 Reactome Database ID Release 77 10770817 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10770817 Reactome R-PFA-514604 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-514604.1 Cytosolic GMP reductase (GMPR) catalyzes the reaction of GMP and NADPH + H+ to yield IMP and NADP+ + NH4+ (Spector et al. 1979; Deng et al. 2002). Two GMPR proteins have been identified, GMPR and GMPR2. Both proteins form homotetramers (GMPR - unpublished crstallographic data PDB 2BLE; GMPR2 - Li et al. 2006). 12009299 Pubmed 2002 NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression, purification, and kinetic properties Deng, Y Wang, Z Ying, K Gu, S Ji, C Huang, Y Gu, X Wang, Y Xu, Y Li, Y Xie, Y Mao, Y Int J Biochem Cell Biol 34:1035-50 218932 Pubmed 1979 Reaction mechanism and specificity of human GMP reductase. Substrates, inhibitors, activators, and inactivators Spector, T Jones, TE Miller, RL J Biol Chem 254:2308-15 16359702 Pubmed 2006 Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP Li, J Wei, Z Zheng, M Gu, X Deng, Y Qiu, R Chen, F Ji, C Gong, W Xie, Y Mao, Y J Mol Biol 355:980-8 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780486 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780486 Reactome R-PFA-74217 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-74217.1 GO 0043101 GO biological process Nucleosides and free bases generated by DNA and RNA breakdown are converted back to nucleotide monophosphates, allowing them to re-enter the pathway of purine biosynthesis and interconversiohn. Under normal conditions, DNA turnover is limited and deoxyribonucleotide salvage operates at a correspondingly low level (Watts 1974). 4620886 Pubmed 1974 Molecular variation in relation to purine metabolism Watts, RW J Clin Pathol Suppl (R Coll Pathol) 8:48-63 inferred by electronic annotation IEA GO IEA Pyrimidine salvage Pyrimidine salvage This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 2.4.2.3 uracil + (deoxy)ribose 1-phosphate <=> (deoxy)uridine + orthophosphate [UPP] uracil + (deoxy)ribose 1-phosphate <=> (deoxy)uridine + orthophosphate [UPP] This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 83962 1 uracil [ChEBI:17568] uracil ChEBI 17568 Converted from EntitySet in Reactome Reactome DB_ID: 500244 1 R1P, dRibP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dRibP [cytosol] R1P [cytosol] ChEBI 28542 ChEBI 35425 Converted from EntitySet in Reactome Reactome DB_ID: 500430 1 (d)Ura [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dU [cytosol] Ura-Rib(胞质) ChEBI 16450 ChEBI 16704 Reactome DB_ID: 29372 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10766778 UPP1, UPP2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PNP [cytosol] UniProt Q8I3X4 GO 0004850 GO molecular function Reactome Database ID Release 77 10766779 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766779 Reactome Database ID Release 77 10766781 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766781 Reactome R-PFA-74372 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-74372.1 Cytosolic uridine phosphorylase (isoforms UPP1 and UPP2) catalyzes the reversible reactions of uracil with ribose 1-phosphate or deoxyribose 1-phosphate to yield uridine or deoxyuridine and orthophosphate (Watanabe and Uchida 1995; Johansson, 2003). The active form of UPP1 is a dimer (Rooslid et al. 2009). 19291308 Pubmed 2009 Implications of the structure of human uridine phosphorylase 1 on the development of novel inhibitors for improving the therapeutic window of fluoropyrimidine chemotherapy Roosild, TP Castronovo, S Fabbiani, M Pizzorno, G BMC Struct Biol 9:14 12849978 Pubmed 2003 Identification of a novel human uridine phosphorylase Johansson, M Biochem Biophys Res Commun 307:41-6 7488099 Pubmed 1995 Cloning and expression of human uridine phosphorylase Watanabe, SI Uchida, T Biochem Biophys Res Commun 216:265-272 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780490 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780490 Reactome R-PFA-73614 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73614.1 GO 0043097 GO biological process In pyrimidine salvage reactions, nucleosides and free bases generated by DNA and RNA breakdown are converted back to nucleotide monophosphates, allowing them to re-enter the pathways of pyrimidine biosynthesis and interconversion. inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780488 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780488 Reactome R-PFA-8956321 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8956321.1 GO 0043173 GO biological process Nucleosides and free bases generated by RNA and DNA breakdown are converted back to nucleotide monophosphates, allowing them to re-enter the pathways of nucleotide biosynthesis and interconversion. Under normal conditions, DNA turnover is limited and deoxyribonucleotide salvage operates at a correspondingly low level (Watts 1974). inferred by electronic annotation IEA GO IEA Nucleobase catabolism Nucleobase catabolism This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Purine catabolism Purine catabolism This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Phosphate bond hydrolysis by NUDT proteins Phosphate bond hydrolysis by NUDT proteins This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 3.6.1.55 NUDT1 hydrolyses 8-oxo-dGTP to 8-oxo-dGMP NUDT1 hydrolyses 8-oxo-dGTP to 8-oxo-dGMP 8-oxo-dGTP + H2O => 8-oxo-dGMP + PPi (NUDT1) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2395852 1 8-oxo-dGTP [ChEBI:63220] 8-oxo-dGTP 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate 8-oxo-7,8-dihydro-2'-dGTP 8-oxodeoxyguanosine triphosphate ChEBI 63220 Reactome DB_ID: 29356 1 Reactome DB_ID: 111294 1 Reactome DB_ID: 2395817 1 8-oxo-dGMP [ChEBI:63223] 8-oxo-dGMP 8-hydroxydeoxyguanosine 5'-monophosphate 8-OH-Dgmp 2'-deoxy-7,8-dihydro-8-oxo-5'-guanylic acid 8-oxo-2'-deoxyguanosine-5'-monophosphate 2'-deoxy-7,8-dihydro-8-oxoguanosine 5'-monophosphate ChEBI 63223 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10772885 NUDT1 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0035539 GO molecular function Reactome Database ID Release 77 10772889 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772889 Reactome Database ID Release 77 10772891 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772891 Reactome R-PFA-2395849 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2395849.1 NUDT1 (MTH1) catalyzes the reaction of 8-oxo-dGTP and water to form 8-oxo-dGMP and PPi (pyrophosphate). Four NUDT1 proteins have been identified, encoded by a single gene with alternative start codons (Oda et al. 1999). The shortest of these, NUDT1 p18, has been biochemically (Sakumi et al. 1993; Takagi et al. 2012) and structurally (Mishima et al. 2004) characterized and shown to catalyze hydrolysis of 8-oxo-dGTP. The active enzyme is a monomer associated with a magnesium ion (Mishima et al. 2004). The longer isoforms all consist of the p18 polypeptide with aminoterminal extensions and are presumed to be active as well but have not been experimentally characterized. The p18 isoform is predominantly cytosolic (Kang et al. 1995). Its expression prevents the accumulation of oxo-guanine bases in DNA in mutant mouse cells lacking endogenous NUDT1 activity (Yoshimura et al. 2003).

Together, these data support the hypothesis that by cleaving 8-oxo-dGTP and thus preventing its incorporation into DNA NUDT1 provides a physiologically important defense against mutagenesis due to oxidative stress. This hypothesis is further supported by the demonstration that mice lacking NUDT1 show an increased lifetime incidence of liver and other tumors compared to normal controls, and that rapidly metabolizing tumor cells in culture are killed under conditions where synthesis of NUDT1 protein is suppressed or its catalytic activity is inhibited (Gad et al. 2014; Huber et al. 2014). 24695224 Pubmed 2014 MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool Gad, Helge Koolmeister, Tobias Jemth, Ann-Sofie Eshtad, Saeed Jacques, Sylvain A Ström, Cecilia E Svensson, Linda M Schultz, Niklas Lundbäck, Thomas Einarsdottir, Berglind Osk Saleh, Aljona Göktürk, Camilla Baranczewski, Pawel Svensson, Richard Berntsson, Ronnie P-A Gustafsson, Robert Strömberg, Kia Sanjiv, Kumar Jacques-Cordonnier, Marie-Caroline Desroses, Matthieu Gustavsson, Anna-Lena Olofsson, Roger Johansson, Fredrik Homan, Evert J Loseva, Olga Bräutigam, Lars Johansson, Lars Höglund, Andreas Hagenkort, Anna Pham, Therese Altun, Mikael Gaugaz, Fabienne Z Vikingsson, Svante Evers, Bastiaan Henriksson, Martin Vallin, Karl S A Wallner, Olov A Hammarström, Lars G J Wiita, Elisee Almlöf, Ingrid Kalderén, Christina Axelsson, Hanna Djureinovic, Tatjana Puigvert, Jordi Carreras Häggblad, Maria Jeppsson, Fredrik Martens, Ulf Lundin, Cecilia Lundgren, Bo Granelli, Ingrid Jensen, Annika Jenmalm Artursson, Per Nilsson, Jonas A Stenmark, Pål Scobie, Martin Berglund, Ulrika Warpman Helleday, Thomas Nature 508:215-21 8226881 Pubmed 1993 Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis Sakumi, Kunihiko Furuichi, Masato Tsuzuki, Teruhisa Kakuma, Tetsuya Kawabata, Shun-ichiro Maki, Hisaji Sekiguchi, Mutsuo J. Biol. Chem. 268:23524-30 15133035 Pubmed 2004 Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates Mishima, Masaki Sakai, Yasunari Itoh, Noriyuki Kamiya, Hiroyuki Furuichi, Masato Takahashi, Masayuki Yamagata, Yuriko Iwai, Shigenori Nakabeppu, Yusaku Shirakawa, Masahiro J. Biol. Chem. 279:33806-15 24695225 Pubmed 2014 Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy Huber, Kilian V M Salah, Eidarus Radic, Branka Gridling, Manuela Elkins, JM Stukalov, Alexey Jemth, Ann-Sofie Göktürk, Camilla Sanjiv, Kumar Strömberg, Kia Pham, Therese Berglund, Ulrika Warpman Colinge, Jacques Bennett, Keiryn L Loizou, Joanna I Helleday, Thomas Knapp, Stefan Superti-Furga, Giulio Nature 508:222-7 10536140 Pubmed 1999 Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism Oda, Hisanobu Taketomi, Akinobu Maruyama, Riichiroh Itoh, Riyoko Nishioka, Kenichi Yakushiji, Hiroyuki Suzuki, Tomokazu Sekiguchi, Mutsuo Nakabeppu, Yusaku Nucleic Acids Res. 27:4335-43 22556419 Pubmed 2012 Human MTH3 (NUDT18) Protein Hydrolyzes Oxidized Forms of Guanosine and Deoxyguanosine Diphosphates: COMPARISON WITH MTH1 AND MTH2 Takagi, Yasumitsu Setoyama, Daiki Ito, Riyoko Kamiya, Hiroyuki Yamagata, Yuriko Sekiguchi, Mutsuo J. Biol. Chem. 287:21541-9 7782328 Pubmed 1995 Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria Kang, Dongchon Nishida, Jun-ichi Iyama, Akihiro Nakabeppu, Yusaku Furuichi, Masato Fujiwara, Toshiyuki Sekiguchi, Mutsuo Takeshige, Koichiro J. Biol. Chem. 270:14659-65 12857738 Pubmed 2003 An oxidized purine nucleoside triphosphatase, MTH1, suppresses cell death caused by oxidative stress Yoshimura, Daisuke Sakumi, Kunihiko Ohno, Mizuki Sakai, Yasunari Furuichi, Masato Iwai, Shigenori Nakabeppu, Yusaku J. Biol. Chem. 278:37965-73 inferred by electronic annotation IEA GO IEA NUDT1 hydrolyses 2-OH-dATP to 2-OH-dAMP NUDT1 hydrolyses 2-OH-dATP to 2-OH-dAMP 2-hydroxy-dATP + H2O => 2-hydroxy-dAMP + PPi This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2395822 1 2-hydroxy-dATP [ChEBI:63208] 2-hydroxy-dATP d(isoGTP) 2'-deoxy-2-hydroxyadenosine 5'-(tetrahydrogen triphosphate) 2-OH-dATP 2'-deoxyisoguanosine triphosphate 2-HO-dATP 2'-deoxy-2-hydroxyadenosine triphosphate ChEBI 63208 Reactome DB_ID: 29356 1 Reactome DB_ID: 111294 1 Reactome DB_ID: 2395855 1 2-hydroxy-dAMP [ChEBI:63211] 2-hydroxy-dAMP 2-HO-dAMP 2'-deoxy-2-hydroxyadenosine 5'-(dihydrogen phosphate) 2'-deoxyisoguanosine monophosphate 2-OH-dAMP ChEBI 63211 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10772885 GO 0106378 GO molecular function Reactome Database ID Release 77 10772886 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772886 Reactome Database ID Release 77 10772888 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772888 Reactome R-PFA-2395818 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2395818.1 NUDT1 (MTH1) catalyzes the reaction of 2-hydroxy-dATP and water to form 2-hydroxy-dAMP and PPi (pyrophosphate). Four NUDT1 proteins have been identified, encoded by a single gene with alternative start codons (Oda et al. 1999). The shortest of these, NUDT1 p18, has been shown to catalyze hydrolysis of 2-hydroxy-dATP (Fujikawa et al. 1993; Sakai et al. 2002). The active enzyme is a monomer associated with a magnesium ion (Mishima et al. 2004). The longer isoforms all consist of the p18 polypeptide with aminoterminal extensions and are presumed to be active as well but have not been experimentally characterized. The p18 isoform is predominantly cytosolic (Kang et al. 1995). Its expression prevents the accumulation of modified adenosine bases in DNA in mutant mouse cells lacking endogenous NUDT1 activity (Yoshimura et al. 2003).

Together, these data support the hypothesis that by cleaving 2-hydroxy-dATP and thus preventing its incorporation into DNA, NUDT1 provides a physiologically important defense against mutagenesis due to oxidative stress. This hypothesis is further supported by the demonstration that mice lacking NUDT1 show an increased lifetime incidence of liver and other tumors compared to normal controls, and that rapidly metabolizing tumor cells in culture are killed under conditions where synthesis of NUDT1 protein is suppressed or its catalytic activity is inhibited (Gad et al. 2014; Huber et al. 2014). 10373420 Pubmed 1999 The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein Fujikawa, Katsuyoshi Kamiya, Hiroyuki Yakushiji, Hiroyuki Fujii, Yoshimitsu Nakabeppu, Yusaku Kasai, Hiroshi J. Biol. Chem. 274:18201-5 11756418 Pubmed 2002 A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1 Sakai, Yasunari Furuichi, Masato Takahashi, Masayuki Mishima, Masaki Iwai, Shigenori Shirakawa, Masahiro Nakabeppu, Yusaku J. Biol. Chem. 277:8579-87 inferred by electronic annotation IEA GO IEA NUDT1 hydrolyses 2-OH-ATP to 2-OH-AMP NUDT1 hydrolyses 2-OH-ATP to 2-OH-AMP 2-hydroxy-ATP + H2O => 2-hydroxy-AMP + PPi This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29356 1 Reactome DB_ID: 2395868 1 2-hydroxy-ATP [ChEBI:65119] 2-hydroxy-ATP ChEBI 65119 Reactome DB_ID: 111294 1 Reactome DB_ID: 2395878 1 2-hydroxy-AMP [ChEBI:65129] 2-hydroxy-AMP ChEBI 65129 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10772885 GO 0106377 GO molecular function Reactome Database ID Release 77 10772892 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772892 Reactome Database ID Release 77 10772894 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772894 Reactome R-PFA-2395872 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2395872.1 NUDT1 (MTH1) catalyzes the reaction of 2-hydroxy-ATP and water to form 2-hydroxy-AMP and PPi (pyrophosphate). Four NUDT1 proteins have been identified, encoded by a single gene with alternative start codons (Oda et al. 1999). The shortest of these, NUDT1 p18, has been shown to catalyze hydrolysis of 2-hydroxy-ATP (Fujikawa et al. 2001). The active enzyme is a monomer associated with a magnesium ion (Mishima et al. 2004). The longer isoforms all consist of the p18 polypeptide with aminoterminal extensions and are presumed to be active as well, but have not been experimentally characterized. The p18 isoform is predominantly cytosolic (Kang et al. 1995). 11139615 Pubmed 2001 Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP Fujikawa, Katsuyoshi Kamiya, Hiroyuki Yakushiji, Hiroyuki Nakabeppu, Yusaku Kasai, Hiroshi Nucleic Acids Res. 29:449-54 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10781160 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10781160 Reactome R-PFA-2393930 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2393930.1 GO 0055086 GO biological process Enzymes that belong to the NUDT (Nudix) superfamily catalyze the hydrolysis of phosphodiester bonds in molecules including nucleoside triphosphates and diphosphates and nucleotide sugars. Family members are defined by the presence of an amino acid sequence motif shared with the E. coli MutT gene product, and are involved in diverse physiological processes (Mildvan et al. 2005; McLennan 2006).

The hydrolysis of nucleoside di and triphosphates whose purine bases have been oxidized or deaminated may protect the cell from the mutational damage that would occur if modified deoxyribonucleotides were incorporated into DNA and from the aberrant protein synthesis that would occur if modified ribonucleotides were incorporated into mRNA (Iyama et al. 2010; Takagi et al. 2012). The hydrolysis of ADP ribose may prevent the aberrant spontaneous ADP ribosylation of cellular proteins that could occur were this molecule to accumulate to high levels in the cell (Perraud et al. 2003; Shen et al. 2003). This hypothesis is further supported by the demonstration that mice lacking NUDT1 show an increased lifetime incidence of liver and other tumors compared to normal controls, and that rapidly metabolizing tumor cells in culture are killed under conditions where synthesis of NUDT1 protein is suppressed or its catalytic activity is inhibited (Gad et al. 2014; Huber et al. 2014). 20385596 Pubmed 2010 NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest Iyama, Teruaki Abolhassani, Nona Tsuchimoto, Daisuke Nonaka, Mari Nakabeppu, Yusaku Nucleic Acids Res. 38:4834-43 16378245 Pubmed 2006 The Nudix hydrolase superfamily McLennan, Alexander G Cell. Mol. Life Sci. 63:123-43 15581572 Pubmed 2005 Structures and mechanisms of Nudix hydrolases Mildvan, A S Xia, Z Azurmendi, H F Saraswat, V Legler, P M Massiah, M A Gabelli, S B Bianchet, M A Kang, L-W Amzel, L Mario Arch. Biochem. Biophys. 433:129-43 12948489 Pubmed 2003 The crystal structure and mutational analysis of human NUDT9 Shen, Betty W Perraud, Anne-Laure Scharenberg, Andrew M Stoddard, Barry L J. Mol. Biol. 332:385-98 12427752 Pubmed 2003 NUDT9, a member of the Nudix hydrolase family, is an evolutionarily conserved mitochondrial ADP-ribose pyrophosphatase Perraud, Anne-Laure Shen, Betty W Dunn, Christopher A Rippe, Karsten Smith, Megan K Bessman, Maurice J Stoddard, Barry L Scharenberg, Andrew M J. Biol. Chem. 278:1794-801 inferred by electronic annotation IEA GO IEA ITPA hydrolyses ITP to IMP ITPA hydrolyses ITP to IMP ITP + H2O => IMP + PPi This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29356 1 Reactome DB_ID: 2509836 1 ITP [ChEBI:16039] ITP Inosine 5'-triphosphate Inosine triphosphate Inosine tripolyphosphate ChEBI 16039 Reactome DB_ID: 111294 1 Reactome DB_ID: 29602 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10772904 ITPA dimer [cytosol] ITPA dimer Reactome DB_ID: 10772902 2 UniProt:Q8IBP3 UniProt Q8IBP3 2 EQUAL 194 EQUAL Reactome Database ID Release 77 10772904 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772904 Reactome R-PFA-2509833 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2509833.1 GO 0036220 GO molecular function Reactome Database ID Release 77 10772905 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772905 Reactome Database ID Release 77 10772907 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772907 Reactome R-PFA-2509827 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2509827.1 Cytosolic ITPA dimer catalyzes the reaction of ITP and water to form IMP and PPi (pyrophosphate). Mg++ is required for enzymatic activity. The hydrolysis of ITP is thought to prevent its incorporation into mRNA, which would lead to aberrant protein synthesis (Lin et al. 2001; Abolhassani et al. 2010). 20081199 Pubmed 2010 NUDT16 and ITPA play a dual protective role in maintaining chromosome stability and cell growth by eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals Abolhassani, Nona Iyama, Teruaki Tsuchimoto, Daisuke Sakumi, Kunihiko Ohno, Mizuki Behmanesh, Mehrdad Nakabeppu, Yusaku Nucleic Acids Res. 38:2891-903 11278832 Pubmed 2001 Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene Lin, Shengrong McLennan, Alexander G Ying, K Wang, Z Gu, S Jin, Hua Wu, Chaoqun Liu, Weiping Yuan, Youzhong Tang, Rong Xie, Y Mao, Y J. Biol. Chem. 276:18695-701 inferred by electronic annotation IEA GO IEA ACTIVATION Reactome Database ID Release 77 449940 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=449940 Reactome R-HSA-449940 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-449940.1 Reactome DB_ID: 29926 3.6.1.66 ITPA hydrolyses XTP to XMP ITPA hydrolyses XTP to XMP XTP + H2O => XMP + PPi This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 29356 1 Reactome DB_ID: 2509848 1 XTP [ChEBI:10049] XTP Xanthosine 5'-triphosphate O(5')-(tetrahydroxytriphosphoryl)xanthosine Xanthosine triphosphate triphopsphoric acid 1-xanthosin-5'-yl ester ChEBI 10049 Reactome DB_ID: 111294 1 Reactome DB_ID: 111584 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10772904 GO 0036222 GO molecular function Reactome Database ID Release 77 10772908 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772908 Reactome Database ID Release 77 10772910 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772910 Reactome R-PFA-2509831 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2509831.1 Cytosolic ITPA dimer catalyzes the reaction of XTP and water to form XMP and PPi (pyrophosphate). Mg++ is required for enzymatic activity. The hydrolysis of XTP is thought to prevent its incorporation into mRNA, which would lead to aberrant protein synthesis (Lin et al. 2001; Abolhassani et al. 2010). inferred by electronic annotation IEA GO IEA ACTIVATION Reactome DB_ID: 29926 3.6.1.66 ITPA hydrolyses dITP to dIMP ITPA hydrolyses dITP to dIMP dITP + H2O => dIMP + PPi This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2509835 1 dITP [ChEBI:28807] dITP 2'-Deoxyinosine 5'-triphosphate 2'-Deoxyinosine-5'-triphosphate ChEBI 28807 Reactome DB_ID: 29356 1 Reactome DB_ID: 111294 1 Reactome DB_ID: 109330 1 2'-deoxyinosine-5'-monophosphate [ChEBI:28806] 2'-deoxyinosine-5'-monophosphate ChEBI 28806 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10772904 GO 0035870 GO molecular function Reactome Database ID Release 77 10772911 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772911 Reactome Database ID Release 77 10772913 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10772913 Reactome R-PFA-2509838 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-2509838.1 Cytosolic ITPA dimer catalyzes the reaction of dITP and water to form dIMP and PPi (pyrophosphate). Mg++ is required for enzymatic activity. The hydrolysis of dITP is thought to prevent its incorporation into DNA, which would be mutagenic (Lin et al. 2001; Abolhassani et al. 2010). inferred by electronic annotation IEA GO IEA ACTIVATION Reactome DB_ID: 29926 Reactome Database ID Release 77 10781162 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10781162 Reactome R-PFA-74259 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-74259.1 GO 0006195 GO biological process The purine bases guanine and hypoxanthine (derived from adenine by events in the purine salvage pathways) are converted to xanthine and then to urate uric acid, which is excreted from the body (Watts 1974). The end-point of this pathway in humans and hominoid primates is unusual. Most other mammals metabolize uric acid further to yield more soluble end products, and much speculation has centered on possible roles for high uric acid levels in normal human physiology. inferred by electronic annotation IEA GO IEA Pyrimidine catabolism Pyrimidine catabolism This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 2.4.2.3 (deoxy)uridine + orthophosphate <=> uracil + (deoxy)ribose 1-phosphate (UPP) (deoxy)uridine + orthophosphate <=> uracil + (deoxy)ribose 1-phosphate (UPP) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 500430 1 Reactome DB_ID: 29372 1 Reactome DB_ID: 83962 1 Converted from EntitySet in Reactome Reactome DB_ID: 500244 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10766778 Reactome Database ID Release 77 10766783 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10766783 Reactome R-PFA-74376 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-74376.1 Cytosolic uridine phosphorylase (isoforms UPP1 and UPP2) catalyzes the reversible reactions of uridine or deoxyuridine with orthophosphate to yield uracil and ribose 1-phosphate or deoxyribose 1-phosphate (Watanabe and Uchida 1995; Johansson, 2003). The active form of UPP1 is a dimer (Rooslid et al. 2009). inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780492 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780492 Reactome R-PFA-73621 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-73621.1 GO 0046135 GO biological process In parallel sequences of three reactions each, thymine is converted to beta-aminoisobutyrate and uracil is converted to beta-alanine. Both of these molecules are excreted in human urine and appear to be normal end products of pyrimidine catabolism (Griffith 1986; Webster et al. 2001). Mitochondrial AGXT2, however, can also catalyze the transamination of both molecules with pyruvate, yielding 2-oxoacids that can be metabolized further by reactions of branched-chain amino acid and short-chain fatty acid catabolism (Tamaki et al. 2000). The importance of these reactions in normal human pyrimidine catabolism has not been well worked out. 10989446 Pubmed 2000 Purification, properties, and sequencing of aminoisobutyrate aminotransferases from rat liver Tamaki, Nanaya Sakata, SF Matsuda, K Methods Enzymol 324:376-89 3090932 Pubmed 1986 Beta-amino acids: mammalian metabolism and utility as alpha-amino acid analogues Griffith, OW Annu Rev Biochem 55:855-878 inferred by electronic annotation IEA GO IEA Phosphate bond hydrolysis by NTPDase proteins Phosphate bond hydrolysis by NTPDase proteins This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 3.6.1.15 NTPDase1 hydrolyzes nucleoside triphosphates NTPDase1 hydrolyzes nucleoside triphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 8870907 1 extracellular region GO 0005576 Reactome DB_ID: 109276 1 Reactome DB_ID: 8870906 1 Reactome DB_ID: 109277 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778665 plasma membrane GO 0005886 NTPDase1:Ca2+,Mg2+ [plasma membrane] NTPDase1:Ca2+,Mg2+ Reactome DB_ID: 10778663 1 NTPDase1 [plasma membrane] NTPDase1 Converted from EntitySet in Reactome Reactome DB_ID: 10778661 2 Homologues of ENTPD1 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ENTPD1 [plasma membrane] ENTPD1 [plasma membrane] UniProt Q8ILE7 UniProt Q8IE96 Reactome Database ID Release 77 10778663 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778663 Reactome R-PFA-8850847 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8850847.1 Converted from EntitySet in Reactome Reactome DB_ID: 8850849 1 Ca2+,Mg2+ [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Mg2+ [extracellular region] Ca2+ [extracellular region] ChEBI 29108 Reactome Database ID Release 77 10778665 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778665 Reactome R-PFA-8850845 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8850845.1 GO 0017111 GO molecular function Reactome Database ID Release 77 10778666 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778666 Reactome Database ID Release 77 10778668 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778668 Reactome R-PFA-8850846 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8850846.1 NTPDase1 (CD39) is a plasma membrane-bound ectonucleotidase encoded by the ENTPD1 gene that hydrolyzes extracellular NTPs to NMPs, via corresponding NDP intermediates (Lemmens et al. 2000, Kukulski et al. 2005). NTPDase1 is expressed on endothelial cells, smooth muscle cells and most leukocytes. The vascular endothelial NTPDase1 regulates platelet aggregation and thrombosis (Kaczmarek et al. 1996, Enjoyji et al. 1999). In mice, NTPDase1 is expressed at the surface of epidermal dendritic cells (Langerhans cells) and is involved in regulation of immune response to skin irritants (Mizumoto et al. 2002). NTPDase1 expressed in vascular smooth muscle cells regulates vasomotion (Kauffenstein et al. 2010, reviewed by Kukulski et al. 2011). In regulatory T lymphocytes (Tregs) and other leukocytes NTPDase1 regulates inflammatory processes (Deaglio et al. 2007). 8955160 Pubmed 1996 Identification and characterization of CD39/vascular ATP diphosphohydrolase Kaczmarek, E Koziak, K Sévigny, J Siegel, JB Anrather, J Beaudoin, AR Bach, FH Robson, SC J Biol Chem 271:33116-22 17502665 Pubmed 2007 腺苷生成催化CD39和CD73交货pressed on regulatory T cells mediates immune suppression Deaglio, Silvia Dwyer, Karen M Gao, Wenda Friedman, David Usheva, Anny Erat, Anna Chen, Jiang-Fan Enjyoji, Keiichii Linden, Joel Oukka, Mohamed Kuchroo, Vijay K Strom, Terry B Robson, Simon C J. Exp. Med. 204:1257-65 10866813 Pubmed 2000 Distribution, cloning, and characterization of porcine nucleoside triphosphate diphosphohydrolase-1 Lemmens, R Vanduffel, L Kittel, A Beaudoin, A R Benrezzak, O Sévigny, J Eur. J. Biochem. 267:4106-14 10470077 Pubmed 1999 Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation Enjyoji, K Sévigny, J Lin, Y Frenette, P S Christie, P D Esch, J S Imai, M Edelberg, J M Rayburn, H Lech, M Beeler, D L Csizmadia, E Wagner, D D Robson, S C Rosenberg, R D Nat. Med. 5:1010-7 11927941 Pubmed 2002 CD39 is the dominant Langerhans cell-associated ecto-NTPDase: modulatory roles in inflammation and immune responsiveness Mizumoto, Norikatsu Kumamoto, Tadashi Robson, Simon C Sévigny, Jean Matsue, Hiroyuki Enjyoji, Keiichi Takashima, Akira Nat. Med. 8:358-65 21586362 Pubmed 2011 Impact of ectoenzymes on p2 and p1 receptor signaling Kukulski, Filip Lévesque, Sébastien A Sévigny, Jean Adv. Pharmacol. 61:263-99 18404504 Pubmed 2005 Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8 Kukulski, F Lévesque, S A Lavoie, E G Lecka, J Bigonnesse, F Knowles, A F Robson, S C Kirley, T L Sévigny, J Purinergic Signal. 1:193-204 19640930 Pubmed 2010 NTPDase1 (CD39) controls nucleotide-dependent vasoconstriction in mouse Kauffenstein, Gilles Drouin, Annick Thorin-Trescases, Nathalie Bachelard, Hélène Robaye, Bernard D'Orléans-Juste, Pedro Marceau, François Thorin, Eric Sévigny, Jean Cardiovasc. Res. 85:204-13 inferred by electronic annotation IEA GO IEA 3.6.1.6 NTPDase1 hydrolyzes nucleoside diphosphates NTPDase1 hydrolyzes nucleoside diphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 8870906 1 Reactome DB_ID: 109276 1 Reactome DB_ID: 8870962 1 ribonucleoside monophosphate [ChEBI:26558] ribonucleoside monophosphate ribonucleoside monophosphates ChEBI 26558 Reactome DB_ID: 109277 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778665 GO 0017110 GO molecular function Reactome Database ID Release 77 10778669 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778669 Reactome Database ID Release 77 10778671 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778671 Reactome R-PFA-8850854 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8850854.1 NTPDase1 (CD39), a plasma membrane-bound nucleotide phosphatase encoded by the ENTPD1 gene, hydrolyzes extracellular NDPs to corresponding NMPs (Lemmens et al. 2000, Kukulski et al. 2005) which contributes to inhibition of platelet aggregation and thrombosis (Kaczmarek et al. 1996, Enjyoji et al. 1999, Marcus et al. 2003). 14675084 Pubmed 2003 Heterologous cell-cell interactions: thromboregulation, cerebroprotection and cardioprotection by CD39 (NTPDase-1) Marcus, A J Broekman, M J Drosopoulos, J H F Islam, N Pinsky, D J Sesti, C Levi, R J. Thromb. Haemost. 1:2497-509 inferred by electronic annotation IEA GO IEA 3.6.1.15 NTPDase2 hydrolyzes nucleoside triphosphates NTPDase2 hydrolyzes nucleoside triphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 8936166 1 ATP,GTP,CTP,ITP,UTP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity UTP [extracellular region] CTP [extracellular region] ITP [extracellular region] GTP [extracellular region] ATP [extracellular region] Reactome DB_ID: 109276 1 Converted from EntitySet in Reactome Reactome DB_ID: 8851092 1 ADP,GDP,CDP,IDP,UDP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity IDP [extracellular region] ADP [extracellular region] CDP [extracellular region] GDP [extracellular region] UDP [extracellular region] ChEBI 17808 Reactome DB_ID: 109277 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778679 NTPDase2:Ca2+,Mg2+ [plasma membrane] NTPDase2:Ca2+,Mg2+ Converted from EntitySet in Reactome Reactome DB_ID: 10778677 1 Homologues of ENTPD2 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ENTPD2 [plasma membrane] ENTPD2 [plasma membrane] Converted from EntitySet in Reactome Reactome DB_ID: 8850849 1 Reactome Database ID Release 77 10778679 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778679 Reactome R-PFA-8851095 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851095.1 Reactome Database ID Release 77 10778680 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778680 Reactome Database ID Release 77 10778682 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778682 Reactome R-PFA-8851089 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851089.1 NTPDase2 (CD39L1), encoded by the ENTPD2 gene, is an ectonucleoside triphosphate diphosphohydrolase that is expressed at the plasma membrane where it hydrolyzes extracellular nucleoside triphosphates (ATP, GTP, CTP, ITP, UTP) to the respective nucleoside diphosphate (ADP, GDP, CDP, IDP, UDP) in the presence of Ca2+ of Mg2+ ions. NTPDase2 is only marginally active in hydrolyzing nucleoside diphosphates, such as ADP and UDP (Kegel et al. 1997, Kirley et al. 1997, Mateo et al. 1999). The alpha splicing isoform of NTPDase2 is expressed at the plasma membrane, while beta and gamma isoforms are expressed in the endoplasmic reticulum (Mateo et al. 2003). NTPDase2 may oligomerize and the oligomerization state may affect substrate specificity (Failer et al. 2003).

NTPDase2 may contribute to vascular hemostasis by exerting an opposing role to NTPDase1 (Sévigny et al. 2002). 12888562 Pubmed 2003 Requirement of Cys399 for processing of the human ecto-ATPase (NTPDase2) and its implications for determination of the activities of splice variants of the enzyme Mateo, Jesús Kreda, Silvia Henry, Christopher E Harden, T Kendall Boyer, José L J. Biol. Chem. 278:39960-8 12694193 Pubmed 2003 Determination of native oligomeric state and substrate specificity of rat NTPDase1 and NTPDase2 after heterologous expression in Xenopus oocytes Failer, Bernd U Aschrafi, Armaz Schmalzing, Günther Zimmermann, H Eur. J. Biochem. 270:1802-9 11929769 Pubmed 2002 Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation Sévigny, Jean Sundberg, Christian Braun, Norbert Guckelberger, Olaf Csizmadia, Eva Qawi, Imrana Imai, Masato Zimmermann, H Robson, Simon C Blood 99:2801-9 8995405 Pubmed 1997 Complementary DNA cloning and sequencing of the chicken muscle ecto-ATPase. Homology with the lymphoid cell activation antigen CD39 Kirley, T L J. Biol. Chem. 272:1076-81 10510450 Pubmed 1999 Functional expression of a cDNA encoding a human ecto-ATPase Mateo, J Harden, T K Boyer, J L Br. J. Pharmacol. 128:396-402 9364474 Pubmed 1997 ecto-ATPase和ecto-ATP diphosphohydrolaseare expressed in rat brain Kegel, B Braun, N Heine, P Maliszewski, C R Zimmermann, H Neuropharmacology 36:1189-200 inferred by electronic annotation IEA GO IEA 3.6.1.15 NTPDase3 hydrolyzes nucleoside triphosphates NTPDase3 hydrolyzes nucleoside triphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 8870907 1 Reactome DB_ID: 109276 1 Reactome DB_ID: 8870906 1 Reactome DB_ID: 109277 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778690 NTPDase3:Ca2+,Mg2+ [plasma membrane] NTPDase3:Ca2+,Mg2+ Converted from EntitySet in Reactome Reactome DB_ID: 10778688 1 Homologues of ENTPD3 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ENTPD3 [plasma membrane] ENTPD3 [plasma membrane] Converted from EntitySet in Reactome Reactome DB_ID: 8850849 1 Reactome Database ID Release 77 10778690 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778690 Reactome R-PFA-8851105 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851105.1 Reactome Database ID Release 77 10778691 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778691 Reactome Database ID Release 77 10778693 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778693 Reactome R-PFA-8851110 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851110.1 NTPDase3 (CD39L3), encoded by the ENTPD3 gene, is a plasma membrane-bound ectonucleotidase that hydrolyzes extracellular NTPs to NMPs via corresponding NDP intermediates (Smith and Kirley 1998, Lavoie et al. 2004, Kukulski et al. 2005). NTPDase3 is about 3 times more efficient in hydrolyzing ATP than ADP (Smith and Kirley 1998). NTPDase3 is expressed in some neurons (Belcher et al. 2006, Lavoie et al. 2010) where it may be involved in sleep-wake behaviour (Belcher et al. 2006). NTPDase3 is also expressed in islet cells where it may regulate insulin secretion (Lavoie et al. 2010). 16338080 Pubmed 2006 的Immunolocalization ecto-nucleoside三磷酸diphosphohydrolase 3 in rat brain: implications for modulation of multiple homeostatic systems including feeding and sleep-wake behaviors Belcher, S M Zsarnovszky, A Crawford, P A Hemani, H Spurling, L Kirley, T L Neuroscience 137:1331-46 9675246 Pubmed 1998 Cloning, sequencing, and expression of a human brain ecto-apyrase related to both the ecto-ATPases and CD39 ecto-apyrases1 Smith, T M Kirley, T L Biochim. Biophys. Acta 1386:65-78 20682839 Pubmed 2010 Identification of the ectonucleotidases expressed in mouse, rat, and human Langerhans islets: potential role of NTPDase3 in insulin secretion Lavoie, Elise G Fausther, Michel Kauffenstein, Gilles Kukulski, Filip Künzli, Beat M Friess, Helmut Sévigny, Jean Am. J. Physiol. Endocrinol. Metab. 299:E647-56 15130768 Pubmed 2004 Cloning and characterization of mouse nucleoside triphosphate diphosphohydrolase-3 Lavoie, Elise G Kukulski, Filip Lévesque, Sébastien A Lecka, Joanna Sévigny, Jean Biochem. Pharmacol. 67:1917-26 inferred by electronic annotation IEA GO IEA 3.6.1.6 NTPDase3 hydrolyzes nucleoside diphosphates NTPDase3 hydrolyzes nucleoside diphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 8870906 1 Reactome DB_ID: 109276 1 Reactome DB_ID: 8870962 1 Reactome DB_ID: 109277 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778690 Reactome Database ID Release 77 10778694 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778694 Reactome Database ID Release 77 10778696 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778696 Reactome R-PFA-8851129 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851129.1 NTPDase3 (CD39L3), encoded by the ENTPD3 gene, is a plasma membrane-bound ectonucleotidase that hydrolyzes extracellular NDPs to corresponding NMPs (Smith and Kirley 1998, Lavoie et al. 2004, Vorhoff et al. 2005, Kukulski et al. 2005). 18404510 Pubmed 2005 Cloning and characterization of the ecto-nucleotidase NTPDase3 from rat brain: Predicted secondary structure and relation to other members of the E-NTPDase family and actin Vorhoff, Thomas Zimmermann, H Pelletier, Julie Sévigny, Jean Braun, Norbert Purinergic Signal. 1:259-70 inferred by electronic annotation IEA GO IEA 3.6.1.15 NTPDase4 hydrolyzes nucleoside triphosphates NTPDase4 hydrolyzes nucleoside triphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 8851233 1 Golgi lumen GO 0005796 UTP,GTP,CTP,dTTP [Golgi lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity UTP [Golgi lumen] dTTP [Golgi lumen] CTP(高尔基腔) GTP [Golgi lumen] Reactome DB_ID: 2022884 1 Converted from EntitySet in Reactome Reactome DB_ID: 8851224 1 UDP,GDP,CDP,dTDP [Golgi lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dTDP [Golgi lumen] GDP [Golgi lumen] CDP [Golgi lumen] UDP [Golgi lumen] Reactome DB_ID: 8851226 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778704 Golgi membrane GO 0000139 NTPDase4:Ca2+ [Golgi membrane] NTPDase4:Ca2+ Converted from EntitySet in Reactome Reactome DB_ID: 10778702 1 Homologues of ENTPD4 [Golgi membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ENTPD4 [Golgi membrane] ENTPD4 [Golgi membrane] Reactome DB_ID: 167012 1 calcium(2+) [ChEBI:29108] calcium(2+) Reactome Database ID Release 77 10778704 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778704 Reactome R-PFA-8851222 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851222.1 Reactome Database ID Release 77 10778708 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778708 Reactome Database ID Release 77 10778710 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778710 Reactome R-PFA-8851234 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851234.1 NTPDase4 (UDPase), encoded by the ENTPD4 gene, is an E-NTPDase family member that localizes to the Golgi membrane and can hydrolyze nucleoside triphosphates UTP, GTP, CTP and TTP to nucleoside diphosphates UDP, GDP, CDP and TDP, respectively, in the Golgi lumen. NTPDase4 hydrolyzes nucleoside triphosphates less efficiently than nucleoside diphosphates. Ca2+ is needed for NTPDase4 activity (Wang and Guidotti 1998). 9556635 Pubmed 1998 Golgi localization and functional expression of human uridine diphosphatase Wang, T F Guidotti, G J. Biol. Chem. 273:11392-9 inferred by electronic annotation IEA GO IEA 3.6.1.6 NTPDase4 hydrolyzes nucleoside diphosphates NTPDase4 hydrolyzes nucleoside diphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 8851224 1 Reactome DB_ID: 2022884 1 Reactome DB_ID: 8851226 1 Converted from EntitySet in Reactome Reactome DB_ID: 8851227 1 UMP,GMP,CMP,dTMP [Golgi lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dTMP [Golgi lumen] CMP [Golgi lumen] guanosine 5'-monophosphate [Golgi lumen] uridine 5'-monophosphate [Golgi lumen] PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778704 Reactome Database ID Release 77 10778705 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778705 Reactome Database ID Release 77 10778707 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778707 Reactome R-PFA-8851225 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851225.1 NTPDase4 (UDPase), encoded by the ENTPD4 gene, belongs to the E-NTPDase family of nucleotide phosphatases. NTPDase4 localizes to the Golgi membrane, with active site on the Golgi lumen side. In the presence of Ca2+, NTPDase4 hydrolyzes nucleoside diphosphates UDP, GDP, CDP and dTDP to nucleoside monophosphates UMP, GMP, CMP and dTMP, respectively (Wang and Guidotti 1998). inferred by electronic annotation IEA GO IEA 3.6.1.6 NTPDase5 hydrolyzes nucleoside diphosphates NTPDase5 hydrolyzes nucleoside diphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 109276 1 Converted from EntitySet in Reactome Reactome DB_ID: 8936165 1 ADP,GDP,CDP,UDP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ADP [extracellular region] CDP [extracellular region] GDP [extracellular region] UDP [extracellular region] Converted from EntitySet in Reactome Reactome DB_ID: 8851369 1 AMP,GMP,CMP,UMP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AMP [extracellular region] CMP [extracellular region] GMP [extracellular region] UMP [extracellular region] Reactome DB_ID: 109277 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778714 NPTDase5:Ca2+,Mg2+ [extracellular region] NPTDase5:Ca2+,Mg2+ Reactome DB_ID: 10778712 1 UniProt:Q8ILE7 25 EQUAL 428 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 8850849 1 Reactome Database ID Release 77 10778714 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778714 Reactome R-PFA-8851367 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851367.1 Reactome Database ID Release 77 10778715 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778715 Reactome Database ID Release 77 10778717 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778717 Reactome R-PFA-8851356 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851356.1 NTPDase5 (CD39L4), encoded by the ENTPD5 gene, is an E-NTPDase family member that is secreted to the extracellular space where it hydrolyzes nucleoside diphosphates UDP, GDP, CDP and ADP (listed in the order of preference) to nucleoside monophosphates UMP, GMP, CMP and AMP, respectively. In vitro, NTPDase5 can hydrolyze nucleoside triphosphates GTP, CTP, UTP and ATP to corresponding nucleoside diphosphates but with very low efficiency. NTPDase5 requires Ca2+ or Mg2+ for catalytic activity (Mulero et al. 1999). NTPDase5 is most catalytically active as a monomer, although it can also form disulfide-linked dimers (Mulero et al. 2000).

NTPDase5 may function in the endoplasmic reticulum (ER), where its UDPase activity could contribute to protein glycosylation and folding. NTPDase5 may alleviate ER stress induced by protein overload caused by oncogenic PI3K/AKT signaling in cancer cells. NTPDase5 is over-expressed in tumors with activated AKT and is known as the PCPH oncogene. The underlying mechanism of NTPDase5 over-expression may be AKT-mediated inhibition of FOXO proteins, which are probable transcriptional repressors of the ENTPD5 gene (Fang et al. 2010, Shen et al. 2011). 21074248 Pubmed 2010 The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway Fang, Min Shen, Zhirong Huang, Song Zhao, Liping Chen, She Mak, Tak W Wang, Xiaodong Cell 143:711-24 10400613 Pubmed 1999 CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates Mulero, J J Yeung, G Nelken, S T Ford, J E J. Biol. Chem. 274:20064-7 22169232 Pubmed 2011 ENTPD5, an endoplasmic reticulum UDPase, alleviates ER stress induced by protein overloading in AKT-activated cancer cells Shen, Z Huang, S Fang, M Wang, Xiahong Cold Spring Harb. Symp. Quant. Biol. 76:217-23 11041857 Pubmed 2000 Biochemical characterization of CD39L4 Mulero, J J Yeung, G Nelken, S T Bright, J M McGowan, D W Ford, J E Biochemistry 39:12924-8 inferred by electronic annotation IEA GO IEA 3.6.1.6 NTPDase6 hydrolyzes nucleoside diphosphates NTPDase6 hydrolyzes nucleoside diphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 109276 1 Converted from EntitySet in Reactome Reactome DB_ID: 8851462 1 CDP,GDP,IDP,UDP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity IDP [extracellular region] CDP [extracellular region] GDP [extracellular region] UDP [extracellular region] Converted from EntitySet in Reactome Reactome DB_ID: 8851461 1 CMP,GMP,IMP,UMP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity IMP [extracellular region] CMP [extracellular region] GMP [extracellular region] UMP [extracellular region] Reactome DB_ID: 109277 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778725 NTPDase6:Ca2+,Mg2+ [extracellular region] NTPDase6:Ca2+,Mg2+ Converted from EntitySet in Reactome Reactome DB_ID: 10778723 1 Homologues of ENTPD6 (77-484) [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ENTPD6 (77-484) [extracellular region] ENTPD6 (77-484) [extracellular region] Converted from EntitySet in Reactome Reactome DB_ID: 8850849 1 Reactome Database ID Release 77 10778725 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778725 Reactome R-PFA-8851467 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851467.1 Reactome Database ID Release 77 10778726 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778726 Reactome Database ID Release 77 10778728 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778728 Reactome R-PFA-8851396 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851396.1 NTPDase6 (CD39L2), encoded by the ENTPD6 gene, is an ectonucleotide phosphatase of the E-NTPDase family that can be secreted (Yeung et al. 2000). Secretion involves the removal of the first 77 amino acids at the N-terminus by an unknown peptidase. Secreted NTPDase6 hydrolyzes nucleoside diphosphates GDP, IDP and, less efficiently, UDP and CDP to nucleoside monophosphates GMP, IMP, UMP and CMP, respectively. Secreted NTPDase6 hydrolyzes ADP to AMP and nucleoside triphosphates GTP, ITP, UTP and CTP to corresponding nucleoside diphosphates with very low efficacy (Hicks-Berger et al. 2000, Yeung et al. 2000, Ivanenkov et al. 2003). NTPDase6 requires Ca2+ or Mg2+ for catalytic activity (Hicks-Berger et al. 2000, Ivanenkov et al. 2003).

NTPDase6 may also be able to function as a membrane-bound enzyme, but its catalytic rate is very low and accounts for up to 10% of NTPDase6 activity (Hicks-Berger et al. 2000). 14529283 Pubmed 2003 Bacterial expression, characterization, and disulfide bond determination of soluble human NTPDase6 (CD39L2) nucleotidase: implications for structure and function Ivanenkov, Vasily V Murphy-Piedmonte, Deirdre M Kirley, Terence L Biochemistry 42:11726-35 11041856 Pubmed 2000 CD39L2, a gene encoding a human nucleoside diphosphatase, predominantly expressed in the heart Yeung, G Mulero, J J McGowan, D W Bajwa, S S Ford, J E Biochemistry 39:12916-23 10948193 Pubmed 2000 Expression and characterization of soluble and membrane-bound human nucleoside triphosphate diphosphohydrolase 6 (CD39L2) Hicks-Berger, C A Chadwick, B P Frischauf, A M Kirley, T L J. Biol. Chem. 275:34041-5 inferred by electronic annotation IEA GO IEA 3.6.1.15 NTPDase7 hydrolyzes nucleoside triphosphates NTPDase7 hydrolyzes nucleoside triphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Converted from EntitySet in Reactome Reactome DB_ID: 8851509 1 endocytic vesicle lumen GO 0071682 CTP,GTP,UTP [endocytic vesicle lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CTP [endocytic vesicle lumen] GTP [endocytic vesicle lumen] UTP [endocytic vesicle lumen] Reactome DB_ID: 8851517 1 Converted from EntitySet in Reactome Reactome DB_ID: 8851518 1 CDP,GDP,UDP [endocytic vesicle lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GDP [endocytic vesicle lumen] UDP [endocytic vesicle lumen] CDP [endocytic vesicle lumen] Reactome DB_ID: 8851513 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778736 endocytic vesicle membrane GO 0030666 NTPDase7:Ca2+ [endocytic vesicle membrane] NTPDase7:Ca2+ Reactome DB_ID: 8851519 1 Converted from EntitySet in Reactome Reactome DB_ID: 10778734 1 Homologues of ENTPD7 [endocytic vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ENTPD7 [endocytic vesicle membrane] ENTPD7 [endocytic vesicle membrane] Reactome Database ID Release 77 10778736 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778736 Reactome R-PFA-8851512 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851512.1 Reactome Database ID Release 77 10778737 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778737 Reactome Database ID Release 77 10778739 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778739 Reactome R-PFA-8851494 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851494.1 NTPDase7 (LALP1), encoded by the ENTPD7 gene, is a cytoplasmic vesicle membrane-bound nucleotide phosphatase that hydrolyzes nucleoside triphosphates CTP, GTP and UTP to nucleoside diphosphates CDP, GDP and UDP, respectively. NTPDase7 may have a low activity towards ATP and nucleoside diphosphates (Shi et al. 2001). NTPDase7 requires Ca2+ for catalytic activity (Shi et al. 2001). In mice, NTPDase7 was shown to regulate development of IL17-secreting Th17 cells in the small intestine, possibly by regulating extracellular ATP levels (Kusu et al. 2013). 23241884 Pubmed 2013 Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine Kusu, Takashi Kayama, Hisako Kinoshita, Makoto Jeon, Seong Gyu Ueda, Yoshiyasu Goto, Yoshiyuki Okumura, Ryu Saiga, Hiroyuki Kurakawa, Takashi Ikeda, Kayo Maeda, Yuichi Nishimura, J Arima, Yasunobu Atarashi, Koji Honda, K Murakami, Masaaki Kunisawa, Jun Kiyono, Hiroshi Okumura, Meinoshin Yamamoto, M Takeda, Kiyoshi J. Immunol. 190:774-83 11278936 Pubmed 2001 Molecular cloning and characterization of a novel mammalian endo-apyrase (LALP1) Shi, J D Kukar, T Wang, C Y Li, Q Z Cruz, P E Davoodi-Semiromi, A Yang, P Gu, Y Lian, W Wu, D H She, J X J. Biol. Chem. 276:17474-8 inferred by electronic annotation IEA GO IEA 3.6.1.15 NTPDase8 hydrolyzes nucleoside triphosphates NTPDase8 hydrolyzes nucleoside triphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 109276 1 Converted from EntitySet in Reactome Reactome DB_ID: 9726184 1 三磷酸腺苷、三磷酸鸟苷,ITP, CTP, TTP, UTP(细胞外地区) Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CTP [extracellular region] UTP [extracellular region] TTP [extracellular region] ITP [extracellular region] GTP [extracellular region] ATP [extracellular region] Converted from EntitySet in Reactome Reactome DB_ID: 9726189 1 ADP,GDP,IDP,CDP,TDP,UDP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity IDP [extracellular region] ADP [extracellular region] CDP [extracellular region] GDP [extracellular region] UDP [extracellular region] TDP [extracellular region] Reactome DB_ID: 109277 1 Reactome DB_ID: 351626 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778679 Reactome Database ID Release 77 10778741 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778741 Reactome R-PFA-8851538 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851538.1 NTPDase8, encoded by the ENTPD8 gene, is an E-NTPDase family ectonucleotide phosphatase that, in the presence of Ca2+ or Mg2+, hydrolyzes NTPs to NMPs, via corresponding NDP intermediates. NTPDase8 is more efficient in hydrolyzing NTPs than NDPs. NTPDase8 provides the main ectonucleotide phosphatase activity in rat and porcine livers (Sevigny et al. 2000, Fausther et al. 2007). 17095758 Pubmed 2007 Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8 Fausther, Michel Lecka, Joanna Kukulski, Filip Lévesque, Sébastien A Pelletier, Julie Zimmermann, H Dranoff, Jonathan A Sévigny, Jean Am. J. Physiol. Gastrointest. Liver Physiol. 292:G785-95 10681547 Pubmed 2000 Identification and characterization of a novel hepatic canalicular ATP diphosphohydrolase Sévigny, J Robson, S C Waelkens, E Csizmadia, E Smith, R N Lemmens, R J. Biol. Chem. 275:5640-7 inferred by electronic annotation IEA GO IEA 3.6.1.6 NTPDase8 hydrolyzes nucleoside diphosphates NTPDase8 hydrolyzes nucleoside diphosphates This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 109276 1 Converted from EntitySet in Reactome Reactome DB_ID: 9726189 1 Converted from EntitySet in Reactome Reactome DB_ID: 9726186 1 AMP,GMP,IMP,CMP,TMP,UMP [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity IMP [extracellular region] AMP [extracellular region] CMP [extracellular region] GMP [extracellular region] TMP [extracellular region] UMP [extracellular region] Reactome DB_ID: 109277 1 Reactome DB_ID: 351626 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10778679 Reactome Database ID Release 77 10778742 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778742 Reactome Database ID Release 77 10778744 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10778744 Reactome R-PFA-8851550 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8851550.1 NTPDase8, encoded by the ENTPD8 gene, is the main liver ectonucleotide phosphatase. NTPDase8 belongs to the E-NTPDase family of nucleotide phosphatases and can hydrolyze NDPs to corresponding NMPs (Sévigny et al. 2000, Bigonnesse et al. 2004, Fausther et al. 2007). 15122917 Pubmed 2004 Cloning and characterization of mouse nucleoside triphosphate diphosphohydrolase-8 Bigonnesse, François Lévesque, Sébastien A Kukulski, Filip Lecka, Joanna Robson, Simon C Fernandes, MJ Sévigny, Jean Biochemistry 43:5511-9 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10781404 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10781404 Reactome R-PFA-8850843 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8850843.1 GO 0034656 GO biological process The ectonucleoside triphosphate diphosphatase (E-NTPDase family) of ectonucleotidases includes 8 enzymes: NTPDase1 (encoded by the ENTPD1 gene), NTPDase2 (encoded by the ENTPD2 gene), NTPDase3 (encoded by the ENTPD3 gene), NTPDase4 (encoded by the ENTPD4 gene), NTPDase5 (encoded by the ENTPD5 gene), NTPDase6 (encoded by the ENTPD6 gene), NTPDase7 (encoded by the ENTPD7 gene) and NTPDase8 (encoded by the ENTPD8 gene). NTPDases hydrolyze nucleoside triphosphates and nucleoside diphosphates, producing the corresponding nucleoside monophosphates as final products. Different family members show different specificity for particular nucleotides. NTPDases are involved in various biological processes, such as hemostasis, immune response and development of the nervous system.
The catalytic domain of NTPDases is contained within the loop formed by a cluster of apyrase conserved regions (ACRs). All family members require divalent cations, such as calcium (Ca2+) or magnesium (Mg2+) ions, for catalytic activity. The hydrolysis involves a nucleophilic attack of a water molecule on the terminal phosphate of a nucleotide substrate.
All E-NTPDase family members are transmembrane proteins, associated with either plasma membrane (NTPDase1, NTPDase2, NTPDase3 and NTPDase8) or organelle membranes (NTPDase4 and NTPDase7). Two family members, NTPDase5 and NTPDase6, can be secreted into extracellular space following a proteolytic cleavage from the plasma membrane. NTPDases hydrolyze exocytoplasmic nucleotides, thus regulating the availability of ligands for purinergic receptors. Glycosylation and oligomerization are involved in the regulation of NTPDases, but have not been thoroughly studied.

For reviews of the NTPDase family, please refer to Robson et al. 2006 and Zimmermann et al. 2012. 18404480 Pubmed 2006 The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance Robson, Simon C Sévigny, Jean Zimmermann, H Purinergic Signal. 2:409-30 22555564 Pubmed 2012 Cellular function and molecular structure of ecto-nucleotidases Zimmermann, H Zebisch, Matthias Sträter, Norbert Purinergic Signal. 8:437-502 inferred by electronic annotation IEA GO IEA 3.1.5 SAMHD1:Zn2+ tetramer hydrolyzes dNTP to nucleoside and triphosphate SAMHD1:Zn2+ tetramer hydrolyzes dNTP to nucleoside and triphosphate This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 8866574 1 2'-deoxyribonucleoside 5'-triphosphate(4-) [ChEBI:61560] 2'-deoxyribonucleoside 5'-triphosphate(4-) dNTP(4-) deoxyribonucleoside triphosphate(4-) 2'-deoxyribonucleoside 5'-triphosphate ChEBI 61560 Reactome DB_ID: 113518 1 Reactome DB_ID: 8866567 1 triphosphate(5-) [ChEBI:18036] triphosphate(5-) ChEBI 18036 Reactome DB_ID: 8866608 1 2'-deoxyribonucleoside [ChEBI:18274] 2'-deoxyribonucleoside a 2'-deoxynucleoside 2-Deoxy-D-ribosyl-base 2'-deoxyribonucleosides 2'-Deoxynucleoside Deoxynucleoside ChEBI 18274 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10779122 SAMHD1:Zn2+ tetramer [nucleoplasm] SAMHD1:Zn2+ tetramer Reactome DB_ID: 200493 4 zinc(2+) [ChEBI:29105] zinc(2+) ChEBI 29105 Reactome DB_ID: 10779120 4 UniProt:Q8I533 UniProt Q8I533 1 EQUAL 626 EQUAL Reactome Database ID Release 77 10779122 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10779122 Reactome R-PFA-8866615 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8866615.1 GO 0016793 GO molecular function Reactome Database ID Release 77 10779123 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10779123 Reactome Database ID Release 77 10779125 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10779125 Reactome R-PFA-8866601 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8866601.1 GO 0009264 GO biological process SAMHD1:Zn2+ tetramer (Deoxynucleoside triphosphate triphosphohydrolase SAMHD1, also known as SAM domain and HD domain-containing protein 1) catalyzes the hydrolysis of dNTPs (2'-deoxynucleoside 5'-triphosphates) to form 2'-deoxynucleosides and PPPi (triphosphate) (Goldstone et al. 2011; Powell et al. 2011). The active form of the enzyme is a tetramer with one Zn2+ ion associated with each monomer subunit (Yan et al. 2013; Zhu et al. 2013) localized in the nucleus (Franzolin et al. 2013; Rice et al. 2009). The enzyme is activated by dGTP (Powell et al. 2011).

SAMHD1 activity may play a role in regulating the size of the nuclear pools of dNTPs and dissipating these pools at the end of the S phase of the cell cycle (Franzolin et al. 2013) and it may play a role as well in regulating cellular antiviral responses (Goldstone et al. 2011; Rice et al. 2009). 22056990 Pubmed 2011 HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase Goldstone, David C Ennis-Adeniran, Valerie Hedden, Joseph J Groom, Harriet C T Rice, Gillian I Christodoulou, Evangelos Walker, Philip A Kelly, Geoff Haire, Lesley F Yap, Melvyn W de Carvalho, Luiz Pedro S Stoye, Jonathan P Crow, Yanick J Taylor, Ian A Webb, Michelle Nature 480:379-82 22069334 Pubmed 2011 Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase Powell, Rebecca D Holland, Paul J Hollis, Thomas Perrino, Fred W J. Biol. Chem. 286:43596-600 23426366 Pubmed 2013 Tetramerization of SAMHD1 is required for biological activity and inhibition of HIV infection Yan, Junpeng Kaur, Sarabpreet DeLucia, Maria Hao, Caili Mehrens, Jennifer Wang, Chuanping Golczak, Marcin Palczewski, Krzysztof Gronenborn, Angela M Ahn, Jinwoo Skowronski, Jacek J. Biol. Chem. 288:10406-17 23858451 Pubmed 2013 The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA precursor pools in mammalian cells Franzolin, Elisa Pontarin, Giovanna Rampazzo, Chiara Miazzi, Cristina Ferraro, Paola Palumbo, Elisa Reichard, Peter A Bianchi, Vera Proc. Natl. Acad. Sci. U.S.A. 110:14272-7 19525956 Pubmed 2009 Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response Rice, Gillian I Bond, Jacquelyn Asipu, Aruna Brunette, Rebecca L Manfield, Iain W Carr, Ian M Fuller, Jonathan C Jackson, Richard M Lamb, Teresa Briggs, Tracy A Ali, Manir Gornall, Hannah Couthard, Lydia R Aeby, Alec Attard-Montalto, Simon P Bertini, Enrico Bodemer, Christine Brockmann, Knut Brueton, Louise A Corry, Peter C Desguerre, Isabelle Fazzi, Elisa Cazorla, Angels Garcia Gener, Blanca Hamel, Ben C J Heiberg, Arvid Hunter, Matthew van der Knaap, Marjo S Kumar, Ram Lagae, Lieven Landrieu, Pierre G Lourenco, Charles M Marom, Daphna McDermott, Michael F van der Merwe, William Orcesi, Simona Prendiville, Julie S Rasmussen, Magnhild Shalev, Stavit A Soler, Doriette M Shinawi, Marwan Spiegel, Ronen Tan, Tiong Y Vanderver, Adeline Wakeling, Emma L Wassmer, Evangeline Whittaker, Elizabeth Lebon, Pierre Stetson, Daniel B Bonthron, David T Crow, Yanick J Nat. Genet. 41:829-32 24217394 Pubmed 2013 Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase Zhu, Chunfeng Gao, Wenying Zhao, Ke Qin, Xiaohong Zhang, Yinjie Peng, Xin Zhang, Lei Dong, Yuhui Zhang, Wenyan Li, Peng Wei, Wei Gong, Yong Yu, Xiao-Fang Nat Commun 4:2722 inferred by electronic annotation IEA GO IEA ACTIVATION Reactome Database ID Release 77 8866639 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8866639 Reactome R-HSA-8866639 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8866639.1 Reactome DB_ID: 29892 dGTP [ChEBI:16497] dGTP Deoxyguanosine 5'-triphosphate 2'-deoxyguanosine 5'-triphosphate Deoxyguanosine triphosphate Reactome Database ID Release 77 10780494 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780494 Reactome R-PFA-8956319 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-8956319.1 The purine bases guanine and hypoxanthine (derived from adenine by events in the purine salvage pathways) are converted to xanthine and then to uric acid, which is excreted from the body (Watts 1974). The end-point of this pathway in humans and hominoid primates is unusual. Most other mammals metabolize uric acid further to yield more soluble end products, and much speculation has centered on possible roles for high uric acid levels in normal human physiology.

In parallel sequences of three reactions each, the pyrimidines thymine and uracil are converted to beta-aminoisobutyrate and beta-alanine respectively. Both of these molecules are excreted in human urine and appear to be normal end products of pyrimidine catabolism (Griffith 1986). Mitochondrial AGXT2, however, can also catalyze the transamination of both molecules with pyruvate, yielding 2-oxoacids that can be metabolized further by reactions of branched-chain amino acid and short-chain fatty acid catabolism (Tamaki et al. 2000).

Hydrolysis of phosphate bonds in nucleotides catalyzed by members of the NUDT and NTPD families of enzymes have been grouped here as well, although the physiological roles of these groups of catabolic reactions are diverse. inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10780460 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10780460 Reactome R-PFA-15869 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-PFA-15869.1 Nucleotides and their derivatives are used for short-term energy storage (ATP, GTP), for intra- and extra-cellular signaling (cAMP; adenosine), as enzyme cofactors (NAD, FAD), and for the synthesis of DNA and RNA. Most dietary nucleotides are consumed by gut flora; the human body's own supply of these molecules is synthesized de novo. Additional metabolic pathways allow the interconversion of nucleotides, the salvage and reutilization of nucleotides released by degradation of DNA and RNA, the catabolism of excess nucleotides, and the transport of these molecules between the cytosol and the nucleus (Rudolph 1994). These pathways are regulated to control the total size of the intracellular nucleotide pool, to balance the relative amounts of individual nucleotides, and to couple the synthesis of deoxyribonucleotides to the onset of DNA replication (S phase of the cell cycle).

These pathways are also of major clinical interest as they are the means by which nucleotide analogues used as anti-viral and anti-tumor drugs are taken up by cells, activated, and catabolized (Weilin and Nordlund 2010). As well, differences in nucleotide metabolic pathways between humans and aplicomplexan parasites like Plasmodium have been exploited to design drugs to attack the latter (Hyde 2007).

The movement of nucleotides and purine and pyrimidine bases across lipid bilayer membranes, mediated by SLC transporters, is annotated as part of the module "transmembrane transport of small molecules". 17266529 Pubmed 2007 Targeting purine and pyrimidine metabolism in human apicomplexan parasites Hyde, JE Curr Drug Targets 8:31-47 8283301 Pubmed 1994 The biochemistry and physiology of nucleotides Rudolph, FB J Nutr 124:124S-127S 20494131 Pubmed 2010 Understanding specificity in metabolic pathways--structural biology of human nucleotide metabolism Welin, M Nordlund, Par Biochem Biophys Res Commun 396:157-63 inferred by electronic annotation IEA GO IEA