BioPAX通路从“AMPK被去磷酸化的”在Reactome数据库转换。 从左到右 3.1.3.16 AMPK是脱去磷酸 正常情况下，在低AMP:ATP条件下，活性AMPK被去磷酸化(可能是通过PP2C)，从而失活。 著作：Katajisto，P，Makela，T，吴，J，2008-11-19 中国海洋大学学报(自然科学版)，2015-05-14 编辑:Jassal, B, 2008-11-19 15:14:38 p-AMPK heterotrimer Reactome DB_ID: 380934 胞质 基因本体论 去:0005829 从EntitySet的在Reactome转换 AMPK伽马 Reactome DB_ID：381851 PRKAG1 AMPKγ 5'- amp激活的蛋白激酶亚基-1 AAKG1_HUMAN Reactome DB_ID: 380946 UniProt: P54619 PRKAG1 PRKAG1 AMP活化蛋白激酶(AMPK)的AMP/ atp结合亚基，是一种在调节细胞能量代谢中起关键作用的能量传感器蛋白激酶。随着细胞内ATP水平的降低，AMPK激活能量产生途径并抑制能量消耗过程:抑制蛋白质、碳水化合物和脂类生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化作用，并通过转录调节因子的磷酸化作用产生长期效应。还可以通过重塑肌动蛋白细胞骨架来调节细胞极性;可能是通过间接激活肌凝蛋白。Gamma非催化亚基介导与AMP、ADP和ATP结合，导致活化或抑制AMPK: AMP结合导致α催化亚基(PRKAA1或PRKAA2)变构活化，通过诱导磷酸化和阻止催化亚基脱磷酸化。ADP也能刺激磷酸化，而不刺激已经磷酸化的催化亚基。ATP促进催化亚基去磷酸化，致使AMPK酶inactive.SUBUNIT AMPK是α催化亚单位的异源（或PRKAA1 PRKAA2），β（PRKAB1或PRKAB2）和伽马非催化亚基（PRKAG1，PRKAG2或PRKAG3）。化与FNIP1和FNIP2。AMPK伪底物motif与AMPK靶蛋白磷酸化位点周围的序列相似，除了存在一个非磷酸化残基代替Ser。 In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.DOMAIN The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.PTM Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK.SIMILARITY Belongs to the 5'-AMP-activated protein kinase gamma subunit family. HOMO SAPIENS. NCBI分类法 9606 UniProt P54619 1 平等的 331 平等的 反应数据库ID版本77 380946 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=380946 Reactome r - hsa - 380946 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-380946.1 Reactome //www.joaskin.com PRKAG2 AMPK GAMMA2（不活动） Reactome DB_ID：200419 UniProt: Q9UGJ0 PRKAG2 PRKAG2 AMP活化蛋白激酶(AMPK)的AMP/ atp结合亚基，是一种在调节细胞能量代谢中起关键作用的能量传感器蛋白激酶。随着细胞内ATP水平的降低，AMPK激活能量产生途径并抑制能量消耗过程:抑制蛋白质、碳水化合物和脂类生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化作用，并通过转录调节因子的磷酸化作用产生长期效应。还可以通过重塑肌动蛋白细胞骨架来调节细胞极性;可能是通过间接激活肌凝蛋白。Gamma非催化亚基介导与AMP、ADP和ATP结合，导致活化或抑制AMPK: AMP结合导致α催化亚基(PRKAA1或PRKAA2)变构活化，通过诱导磷酸化和阻止催化亚基脱磷酸化。ADP也能刺激磷酸化，而不刺激已经磷酸化的催化亚基。ATP促进催化亚基去磷酸化，致使AMPK酶inactive.SUBUNIT AMPK是α催化亚单位的异源（或PRKAA1 PRKAA2），β（PRKAB1或PRKAB2）和伽马非催化亚基（PRKAG1，PRKAG2或PRKAG3）。与FNIP1和FNIP2.TISSUE特异性亚型B交互时，除了在肝脏和胸腺广泛表达。最高级别是在心脏检测，在胎盘和testis.DOMAIN的AMPK假底图案丰富的表情酷似周围磷酸化的AMPK的靶蛋白点的序列，只是一个不可磷酸渣代替丝氨酸的存在。 In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.DOMAIN The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.PTM Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.SIMILARITY Belongs to the 5'-AMP-activated protein kinase gamma subunit family. UniProt Q9UGJ0 1 平等的 569 平等的 反应数据库ID版本77 200419 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=200419 Reactome r - hsa - 200419 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-200419.1 PRKAG3 AMPKγ₃ 5'- amp激活的蛋白激酶亚基-3 AAKG3_HUMAN Reactome DB_ID: 381839 UniProt: Q9UGI9 PRKAG3 PRKAG3 AMPKG3 AMP活化蛋白激酶(AMPK)的AMP/ atp结合亚基，是一种在调节细胞能量代谢中起关键作用的能量传感器蛋白激酶。随着细胞内ATP水平的降低，AMPK激活能量产生途径并抑制能量消耗过程:抑制蛋白质、碳水化合物和脂类生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化作用，并通过转录调节因子的磷酸化作用产生长期效应。还可以通过重塑肌动蛋白细胞骨架来调节细胞极性;可能是通过间接激活肌凝蛋白。Gamma非催化亚基介导与AMP、ADP和ATP结合，导致活化或抑制AMPK: AMP结合导致α催化亚基(PRKAA1或PRKAA2)变构活化，通过诱导磷酸化和阻止催化亚基脱磷酸化。ADP也能刺激磷酸化，而不刺激已经磷酸化的催化亚基。ATP促进催化亚基去磷酸化，致使AMPK酶inactive.SUBUNIT AMPK是α催化亚单位的异源（或PRKAA1 PRKAA2），β（PRKAB1或PRKAB2）和伽马非催化亚基（PRKAG1，PRKAG2或PRKAG3）。与FNIP1和FNIP2相互作用(通过相似性)。组织特异性骨骼肌，心脏和胰腺弱表达。DOMAIN The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.DOMAIN The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.PTM Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.POLYMORPHISM PRKAG3 genetic variants can be associated with increased glycogen content in skeletal muscle [MIM:604976]. Muscle fibers from carriers of variant Trp-225 have approximately 90% more muscle glycogen content than controls and decreased levels of intramuscular triglyceride.SIMILARITY Belongs to the 5'-AMP-activated protein kinase gamma subunit family. UniProt Q9UGI9 1 平等的 489 平等的 反应数据库ID版本77 381839 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=381839 Reactome R-HSA-381839 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-381839.1 反应数据库ID版本77 381851 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=381851 Reactome r - hsa - 381851 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-381851.1 1 从EntitySet的在Reactome转换 AMPKβ Reactome DB_ID：381854 PRKAB1 AMPKβ1的 5'- amp激活的蛋白激酶亚基-1 AAKB1_HUMAN Reactome DB_ID：380968 UniProt的：Q9Y478 PRKAB1 PRKAB1 AMPK ampp活化蛋白激酶(AMPK)的非催化亚基，是一种在调节细胞能量代谢中起关键作用的能量传感器蛋白激酶。随着细胞内ATP水平的降低，AMPK激活能量产生途径并抑制能量消耗过程:抑制蛋白质、碳水化合物和脂类生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化作用，并通过转录调节因子的磷酸化作用产生长期效应。还可以通过重塑肌动蛋白细胞骨架来调节细胞极性;可能是通过间接激活肌凝蛋白。β非催化亚基作为支架，通过其c端连接α (PRKAA1或PRKAA2)和γ亚基(PRKAG1, PRKAG2或PRKAG3)， AMPK复合物在其上组装。亚基AMPK是由α催化亚基(PRKAA1或PRKAA2)、β (PRKAB1或PRKAB2)和非催化亚基(PRKAG1, PRKAG2或PRKAG3)组成的异三聚体。化与FNIP1和FNIP2。糖原结合结构域可能将AMPK定位于糖原，这样其他因素如糖原结合脱分支酶或蛋白磷酸酶可以直接影响AMPK的活性。PTM与催化亚基(PRKAA1或PRKAA2)相结合时磷酸化。由ULK1磷酸化;导致AMPK活性负调控，提示ULK1与AMPK之间存在调节反馈回路。属于5'- amp激活的蛋白激酶β亚基家族。 UniProt Q9Y478 2 平等的 270 平等的 反应数据库ID版本77 380968 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=380968 Reactome R-HSA-380968 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-380968.1 PRKAB2 AMPK β 2(非活性) Reactome DB_ID：200413 UniProt: O43741 PRKAB2 PRKAB2 ampp活化蛋白激酶(AMPK)的非催化亚基，是一种在调节细胞能量代谢中起关键作用的能量传感器蛋白激酶。随着细胞内ATP水平的降低，AMPK激活能量产生途径并抑制能量消耗过程:抑制蛋白质、碳水化合物和脂类生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化作用，并通过转录调节因子的磷酸化作用产生长期效应。还可以通过重塑肌动蛋白细胞骨架来调节细胞极性;可能是通过间接激活肌凝蛋白。β非催化亚基作为支架，通过其c端连接α (PRKAA1或PRKAA2)和γ亚基(PRKAG1, PRKAG2或PRKAG3)， AMPK复合物在其上组装。亚基AMPK是由α催化亚基(PRKAA1或PRKAA2)、β (PRKAB1或PRKAB2)和非催化亚基(PRKAG1, PRKAG2或PRKAG3)组成的异三聚体。PTM与催化亚基(PRKAA1或PRKAA2)相结合时磷酸化。被ULK1和ULK2磷酸化;导致AMPK活性负调控，表明ULK1、ULK2和AMPK之间存在调节反馈回路。属于5'- amp激活的蛋白激酶β亚基家族。 UniProt O43741 1 平等的 272 平等的 反应数据库ID版本77 200413 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=200413 Reactome r - hsa - 200413 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-200413.1 反应数据库ID版本77 381854 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=381854 Reactome r - hsa - 381854 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-381854.1 1 从EntitySet的在Reactome转换 p-AMPKα Reactome DB_ID: 381844 p-T172-PRKAA2 P-T172-AMPKα-2 Reactome DB_ID：200417 UniProt的：P54646 PRKAA2 PRKAA2 AMPK AMPK2 AMP活化蛋白激酶（AMPK）的功能催化亚基，一种能量传感器蛋白激酶在调节细胞能量代谢方面发挥关键作用。随着细胞内ATP水平的降低，AMPK激活能量产生途径并抑制能量消耗过程:抑制蛋白质、碳水化合物和脂类生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化作用，并通过转录调节因子的磷酸化作用产生长期效应。还可以通过重塑肌动蛋白细胞骨架来调节细胞极性;可能是通过间接激活肌凝蛋白。通过磷酸化和灭活脂质代谢酶如Acaca，Acacb，Gys1，HMGCR和Lipe来调节脂质合成;通过磷酸化乙酰-CoA羧化酶（Acaca和Acacb）和激素敏感脂肪酶（LiPE）酶来调节脂肪酸和胆固醇合成。通过磷酸化IRS1，PFKFB2和PFKFB3调节胰岛素 - 信号传导和糖酵解。在胰岛素受体/ INSR内参与（PUBMED：25687571）。AMPK通过增加葡萄糖转运蛋白SLC2A4 / GLUT4至质膜的易位来刺激肌肉中的葡萄糖摄取，可能通过介导TBC1D4 / AS160的磷酸化。 Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45 (PubMed:28561066). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity).ACTIVITY REGULATION Activated by phosphorylation on Thr-172. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172. ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-172, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation.SUBUNIT AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2. Associates with internalized insulin receptor/INSR complexes on Golgi/endosomal membranes; PRKAA2/AMPK2 together with ATIC and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (PubMed:25687571).DOMAIN The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.PTM Ubiquitinated.PTM Phosphorylated at Thr-172 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-172 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by STK11/LKB1).SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. UniProt P54646 172. 平等的 O-磷酸-L-苏氨酸 摩擦 国防部:00047 1 平等的 552 平等的 反应数据库ID版本77 200417 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=200417 Reactome r - hsa - 200417 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-200417.1 p-T183-PRKAA1 p-T183-AMPKα1 Reactome DB_ID：380964 UniProt: Q13131 PRKAA1 PRKAA1 AMPK1 AMP活化蛋白激酶（AMPK）的功能催化亚基，一种能量传感器蛋白激酶在调节细胞能量代谢方面发挥关键作用。随着细胞内ATP水平的降低，AMPK激活能量产生途径并抑制能量消耗过程:抑制蛋白质、碳水化合物和脂类生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化作用，并通过转录调节因子的磷酸化作用产生长期效应。还可以通过重塑肌动蛋白细胞骨架来调节细胞极性;可能是通过间接激活肌凝蛋白。通过磷酸化和灭活脂质代谢酶如Acaca，Acacb，Gys1，HMGCR和Lipe来调节脂质合成;通过磷酸化乙酰-CoA羧化酶（Acaca和Acacb）和激素敏感脂肪酶（LiPE）酶来调节脂肪酸和胆固醇合成。通过磷酸化IRS1，PFKFB2和PFKFB3调节胰岛素 - 信号传导和糖酵解。AMPK通过增加葡萄糖转运蛋白SLC2A4 / GLUT4至质膜的易位来刺激肌肉中的葡萄糖摄取，可能通过介导TBC1D4 / AS160的磷酸化。通过磷酸化转录调节剂来调节转录和染色质结构，如CRTC2 / TORC2，FOXO3，组蛋白H2B，HDAC5，MEF2C，MLXIPP，EP300，HNF4A，P53 / TP53，SREBF1，SREBF2和PPARGC1A。 Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45 (PubMed:28561066). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.ACTIVITY REGULATION Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol.SUBUNIT AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.DOMAIN The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.PTM Ubiquitinated.PTM Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B.SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. UniProt Q13131 183. 平等的 1 平等的 559 平等的 反应数据库ID版本77 380964 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=380964 Reactome r - hsa - 380964 2 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-380964.2 反应数据库ID版本77 381844 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=381844 Reactome R-HSA-381844 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-381844.1 1 反应数据库ID版本77 380934 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=380934 Reactome R-HSA-380934 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-380934.1 水 水 Reactome DB_ID：29356 水(ChEBI: 15377) 水 Chebi. CHEBI：15377 反应数据库ID版本77 29356 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=29356 Reactome R-ALL-29356 5 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-ALL-29356.5 化合物 C00001 额外的信息 心肌梗死 小姐:0361 AMPK异源三聚 Reactome DB_ID：380961 从EntitySet的在Reactome转换 AMPKα Reactome DB_ID: 381845 PRKAA1 AMPK ALPHA1 5'- amp活化蛋白激酶催化亚基α -1 AAPK1_HUMAN Reactome DB_ID: 380935 1 平等的 559 平等的 反应数据库ID版本77 380935 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=380935 Reactome R-HSA-380935 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-380935.1 PRKAA2 AMPK alpha2(不活跃) Reactome DB_ID：200405 1 平等的 552 平等的 反应数据库ID版本77 200405 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=200405 Reactome r - hsa - 200405 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-200405.1 反应数据库ID版本77 381845 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=381845 Reactome R-HSA-381845 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-381845.1 1 1 1 反应数据库ID版本77 380961 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=380961 Reactome R-HSA-380961 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-380961.1 ComplexPortal cpx - 5791 ComplexPortal cpx - 5790 ComplexPortal cpx - 5786 ComplexPortal cpx - 5787 ComplexPortal CPX-5633 ComplexPortal cpx - 5845 ComplexPortal cpx - 5846 ComplexPortal cpx - 5843 ComplexPortal cpx - 5844 ComplexPortal cpx - 5841 ComplexPortal cpx - 5842 ComplexPortal cpx - 5840 π 正磷酸盐 hydrogenphosphate 磷酸 无机磷酸盐 Reactome DB_ID: 29372 hydrogenphosphate (ChEBI: 43474) hydrogenphosphate 磷酸氢 磷酸盐 (警察丙(OH)) (2) 无机磷酸基 HYDROGENPHOSPHATE离子 HPO4 (2 -) [P（OH）O3]（2-） Chebi. CHEBI: 43474 反应数据库ID版本77 29372 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=29372 Reactome r - - 29372 4 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-ALL-29372.4 化合物 C00009 激活 PPM1A Reactome DB_ID: 380928 UniProt的：P35813 PPM1A PPM1A PPPM1A 功能酶具有广泛的特异性。通过负的去磷酸化Smad2和Smad3，导致从SMAD4的Smad蛋白的核出口和终止TGF-β介导的信号的解离自己调节TGF-β信号。去磷酸化PRKAA1和PRKAA2。起着通过去磷酸化和失活IKBKB / IKKB.SUBUNIT单体中的TNF-α介导的NF-κ-B启动终止了重要作用。与SMAD2相互作用;的相互作用去磷酸化SMAD2在其C末端SXS基序导致TGF-β介导的信号传导的SMAD2 / SMAD4复杂，SMAD2核出口和终止中断。与SMAD2相互作用;的相互作用去磷酸化SMAD2在其C末端SXS基序导致TGF-β介导的信号传导的SMAD2 / SMAD4复杂，SMAD2核出口和终止中断。与IKBKB / IKKB.PTM的N-豆蔻酰化的磷酸化形式的相互作用是用于识别其底物的必不可少的dephosphorylation.SIMILARITY属于PP2C家族。 UniProt P35813 2 平等的 382 平等的 反应数据库ID版本77 380928 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=380928 Reactome r - hsa - 380928 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-380928.1 基因本体论 去:0004722 对于细胞功能基因本体项 心肌梗死 小姐:0355 相同的催化剂活性 反应数据库ID版本77 380940 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=380940 反应数据库ID版本77 380949 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=380949 Reactome r - hsa - 380949 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-380949.1 16943194 PubMed. 2006年 剖析5'-AMP在变构刺激、激活和去激活amp激活的蛋白激酶中的作用 苏特尔米 里克•U 图尔克，R Schlattner，U Wallimann，T 诺伊曼,D J Biol Chem 281:32207-16 8549768 PubMed. 1995年 5'-AMP抑制去磷酸化，以及促进磷酸化，所述AMP活化蛋白激酶的。研究使用细菌表达的人蛋白磷酸酶2Cα和天然牛蛋白磷酸酶2AC 戴维斯，SP 帮助,NR 科恩,PT 哈迪，DG 2月列托人377:421-5