BioPAX途径由Reactome数据库中“myg - cdk5r1,2 binding CDK5”转化而来。 MyrG-CDK5R1 2绑定CDK5 MyrG-CDK5R1 2绑定CDK5 CDK5R1是CDK5的神经元特异性调节亚基激活CDK5在来自大鼠PC12细胞中的细胞周期蛋白型方式和CDK5R1和CDK5的共沉淀物和从牛脑（Tsai等人，1994激酶活性;卢等人，1994;原田等人，2001）。CDK5活动所需的神经突增生和CDK5或CDK5R1导致在小鼠中神经元迁移缺陷破坏（Nikolic的等，1996; Xiong等人，1997; Paglini等人，1998）。第二CDK5调节蛋白，CDK5R2（也称为P39）所需的CDK5依赖性神经突长出响应于bFGF的（Tang等人，1995; Xiong等人，1997）。 撰写：Rothfels，克伦族，2019年8月16日 来自：阿莱塔，约翰男，2020年1月17日 编辑:Rothfels, Karen, 2020-02-24 从EntitySet的在Reactome转换 Reactome DB_ID: 9616816 1 等离子体膜 去 0005886 MyrG-CDK5R1,2 [质膜] 从EnticeSet转换在反应中。每个同义词是身份有力的名称，每个XREF都指向一个身体性感性 myrg-cdk5r1（2-307）[血浆膜] Reactome //www.joaskin.com HOMO SAPIENS. NCBI分类学 9606 uniprot. Q15078 Reactome DB_ID：180064 1 cytosol. 去 0005829 UniProt: Q00535 CDK5 CDK5 CDKN5 CDK5 FUNCTION脯氨酸定向用于神经元细胞周期停滞和分化的丝氨酸/苏氨酸 - 蛋白激酶必需的，可以在神经元疾病的细胞凋亡通过触发无效细胞周期重新进入有关。交互与D1和D3型细胞周期蛋白G1。磷酸化SRC，NOS3，VIM /波形蛋白，P35 / CDK5R1，MEF2A，SIPA1L1，SH3GLB1，PXN，PAK1，MCAM / MUC18，SEPT5，SYN1，DNM1，AMPH，SYNJ1，CDK16，RAC1，RHOA，CDC42，TONEBP / NFAT5，MAPT/ TAU，MAP1B，组蛋白H1，P53 / TP53，HDAC1，APEX1，PTK2 / FAK1，亨廷顿/ HTT，ATM，MAP2，NEFH和NEFM。调节几个神经元发育和生理过程，包括神经元的存活，迁移和分化，轴突和神经突生长，突触，少突胶质细胞分化，突触可塑性和神经传递，通过磷酸化的关键蛋白。通过相互作用CDK5R1（P35）和CDK5R2（P39）来激活，尤其是在有丝分裂后的神经元，促进在autostimulation环CDK5R1（P35）的表达。Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.ACTIVITY REGULATION Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by proteasome result in down regulation of kinase activity, during this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Kinase activity is mainly determined by the amount of p35 available and subcellular location; reversible association to plasma membrane inhibits activity. Long-term inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5 triggers cell death. The pro-death activity of hyperactivated CDK5 is suppressed by membrane association of CDK5, via myristoylation of p35. Brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor (NGF), retinoic acid, laminin and neuregulin promote activity. Neurotoxicity enhances nuclear activity, thus leading to MEF2 phosphorylation and inhibition prior to apoptosis of cortical neurons. Repression by GSTP1 via p25/p35 translocation prevents neurodegeneration.SUBUNIT Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only the heterodimer shows kinase activity. Under neurotoxic stress and neuronal injury conditions, p35 is cleaved by calpain to generate p25 that hyperactivates CDK5, that becomes functionally disabled and often toxic. Found in a trimolecular complex with CABLES1 and ABL1. Interacts with CABLES1 and CABLES2 (By similarity). Interacts with AATK and GSTP1. Binds to HDAC1 when in complex with p25. Interaction with myristoylation p35 promotes CDK5 association with membranes. Both isoforms 1 and 2 interacts with beta-catenin/CTNNB1. Interacts with delta-catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons. Interacts with EPHA4; may mediate the activation of NGEF by EPHA4. Interacts with PTK2/FAK1 (By similarity). The complex p35/CDK5 interacts with CLOCK. Interacts with HTR6 (By similarity).TISSUE SPECIFICITY Isoform 1 is ubiquitously expressed. Accumulates in cortical neurons (at protein level). Isoform 2 has only been detected in testis, skeletal muscle, colon, bone marrow and ovary.PTM Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by casein kinase 1 promotes kinase activity. By contrast, phosphorylation at Thr-14 inhibits activity.PTM Phosphorylation at Ser-159 is essential for maximal catalytic activity.MISCELLANEOUS Dysregulation of CDK5 is associated with neurodegenerative disorders such as Alzheimer, Parkinson, and Niemann-Pick type C diseases, ischemia, and amyotrophic lateral sclerosis.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. uniprot. Q00535 链坐标 1 平等的 292 平等的 Reactome DB_ID: 9616817 1 CDK5: MyrG-CDK5R1, 2(质膜) CDK5：MyrG-CDK5R1,2 从EntitySet的在Reactome转换 Reactome DB_ID: 9616816 1 Reactome DB_ID：180064 1 1 平等的 292 平等的 Reactome数据库ID Release 77 9616817 数据库标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9616817 Reactome r - hsa - 9616817 1 Reactome稳定的标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9616817.1 Reactome数据库ID Release 77 9616368 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9616368 Reactome r - hsa - 9616368 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9616368.1 8090222 Pubmed 1994年 一种周期蛋白依赖性激酶5的脑特异性激活物 卢，约翰 黄，契券 齐，钟 Winkfein, RJ Aebersold, Ruedi 亨特，蒂姆 王，杰里^ h 自然371：423-6 11331872 Pubmed 2001 ERK诱导的p35，CDK5的神经元特异的活化剂，通过EGR1的感应 原田，武 诸冈，高屋 ogawa，satoshi Nishida E NAT。细胞生物。3：453-9 8090221 Pubmed 1994年 P35是细胞周期蛋白依赖性激酶5的神经特异性调节亚基 仔，L H Delalle,我 Caviness，Vs的 蔡，T 哈洛，E 自然371:419-23 8846918 Pubmed 1996年 在神经元分化过程中，cdk5/p35激酶在神经突生长中起重要作用 尼科利奇，玛格丽塔 杜德克,亨利克·斯 Kwon年轻T 拉莫斯，约兰德˚F 蔡，李，景辉 基因开发。10：816-25 7592934 Pubmed 1995年 神经元细胞周期蛋白依赖性激酶5（Cdk5的）活化剂的同种型 唐、维 杨,我 李,K Y 松下，男 松井,H 富泽，K 阿,Hatase 王，JH 生物。化学270:26897 - 903 9343422 Pubmed 1997年 细胞周期蛋白在海马永生细胞神经元分化中的作用 熊,温 Pestell，理查德· 罗斯纳，玛莎 - [R 摩尔。细胞。BIOL。17：6585-97 9822744 Pubmed 1998年 证据，神经元特异性CDK5活化剂P35的层粘连蛋白增强轴突生长期间的参与 Paglini，加布里埃拉 Pigino，古斯塔沃 昆达，帕特里夏 Morfini，赫拉尔 Maccioni，里卡多 Quiroga,圣地亚哥 费雷拉，阿德里安娜 卡塞雷斯，阿尔弗雷多 j . > 18:9858 - 69