从反应组数据库中的“p-AMPK磷酸化TSC1:TSC2”转换而来的BioPAX途径。 从左到右 2.7.11.11 p-AMPK磷酸化TSC1: TSC2 活化AMPK（在α亚单位上磷酸化并与AMP结合）使Ser-1387上的TSC2（也称为块茎蛋白）磷酸化，从而激活结节性硬化综合征（TSC）的GTPase激活蛋白（GAP）活性。TSC肿瘤抑制剂是mTORC1复合物的关键上游抑制剂。TSC是一种GTPase激活蛋白，刺激小G蛋白Rheb的内在GTPase活性。这通过刺激Rheb的GTPase活性使其失活。GDP结合型Rheb失去了激活mTORC1复合物激酶活性的能力（Sancak等人，2007年）。TSC1或TSC2的缺失导致mTORC1过度激活 作者：Katajisto，P，Makela，T，Wu，J，2008-11-19 中国海洋大学学报(自然科学版)，2015-05-14 印加，Alberto, 2016-02-04 审查：萨拉扎卡拉，2016-02-04 编辑:Jassal, B, 2008-11-19 15:14:38 TSC1: TSC2 反应数据库ID:165175 胞浆 基因本体 去:0005829 TSC2 块茎 TSC2_HUMAN Reactome DB_ID: 2980548 UniProt: P49815 TSC2 TSC2 TSC4 与TSC1结合，该肿瘤抑制因子通过负调控mTORC1信号抑制营养介导或生长因子刺激的S6K1和EIF4EBP1磷酸化(PubMed:12271141, PubMed:28215400)。作为小型GTPase RHEB的GTPase激活蛋白(GAP)， RHEB是mTORC1蛋白激酶活性的直接激活物(PubMed:15340059)。也可能在微管介导的蛋白质运输中发挥作用(通过相似性)。还刺激ras相关蛋白RAP1A和RAB5的固有GTPase活性(通过相似性)。亚单位可能形成一个复合物，由伴侣蛋白HSP90和HSP70，共伴侣蛋白STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1和客户端蛋白TSC2组成(PubMed:29127155)。可能形成由伴蛋白HSP90、HSP70、伴蛋白CDC37、PPP5C、TSC1和客户端蛋白TSC2、CDK4、AKT、RAF1、NR3C1组成的复合物;该复合物不含STIP1/HOP和PTGES3/p23共伴侣(PubMed:29127155)。形成含HSP90AA1、TSC1和TSC2的复合物;TSC1需要将TCS2吸收到复合物中，从而稳定TSC2 (PubMed:29127155)。与TSC1和HERC1相互作用; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1 (PubMed:9580671, PubMed:10585443, PubMed:15963462, PubMed:16464865). May also interact with the adapter molecule RABEP1 (PubMed:9045618). The final complex may contain TSC2 and RABEP1 linked to RAB5 (PubMed:9045618). Interacts with HSPA1 and HSPA8 (PubMed:15963462). Interacts with DAPK1 (PubMed:18974095). Interacts with FBXW5 (PubMed:18381890). Interacts with NAA10 (via C-terminal domain) (PubMed:20145209). Interacts with RRAGA (polyubiquitinated) (PubMed:25936802). Interacts with WDR45B (PubMed:28561066). Interacts with RPAP3 and URI1 (PubMed:28561026).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus protein UL38; this interaction inhibits cellular stress response mediated by mTORC1.TISSUE SPECIFICITY Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta.PTM Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1462 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it and leads to negative regulation of the mTORC1 complex. Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK1.PTM Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2 independently of its phosphorylation status leading to subsequent degradation; association with TSC1 protects from ubiquitination. 智人 分类学 9606 UniProt P49815 1. 平等的 1807 平等的 Reactome数据库ID Release 77 2980548 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=2980548 Reactome r - hsa - 2980548 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-2980548.1 Reactome //www.joaskin.com 1. TSC1 Reactome DB_ID: 5672338 UniProt: Q92574 TSC1 TSC1 KIAA0243 TSC 与TSC2配合，通过负调控mTORC1信号，抑制营养介导或生长因子刺激的S6K1和EIF4EBP1磷酸化(PubMed:12271141, PubMed:28215400)。似乎不需要TSC2对RHEB的GAP活性(PubMed:15340059)。与肿瘤抑制因子有关。参与微管介导的蛋白质运输，但这似乎是由于未调控的mTOR信号(通过相似性)。作为HSP90AA1的辅伴侣，促进HSP90AA1与激酶、TSC2和糖皮质激素受体NR3C1等蛋白客户端伴发(PubMed:29127155)。增加ATP与HSP90AA1的结合，抑制HSP90AA1 ATP酶活性(PubMed:29127155)。与激活的共伴侣AHSA1竞争，从而与HSP90AA1结合，从而为客户端蛋白的伴发提供一种相互调节机制(PubMed:29127155)。将TSC2招募到HSP90AA1中，通过阻止TSC2与泛素连接酶HERC1的相互作用来稳定TSC2 (PubMed:16464865, PubMed:29127155)。亚单位可能形成一个复合物，由伴侣蛋白HSP90和HSP70，共伴侣蛋白STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1和客户端蛋白TSC2组成(PubMed:29127155)。形成由伴蛋白HSP90、HSP70、伴蛋白CDC37、PPP5C、TSC1和客户端蛋白TSC2、CDK4、AKT、RAF1、NR3C1组成的复合物; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (PubMed:29127155). Interacts (via C-terminus) with the closed form of HSP90AA1 (via the middle domain and TPR repeat-binding motif) (PubMed:29127155). Interacts with TSC2; the interaction stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:15963462, PubMed:16464865, PubMed:9580671, PubMed:9809973, PubMed:29127155, PubMed:28215400). Interacts with DOCK7 (PubMed:15963462). Interacts with FBXW5 (PubMed:18381890). Interacts with TBC1D7 (PubMed:17658474). Interacts with WDR45B (PubMed:28561066). Interacts with RPAP3 and URI1 (PubMed:28561026).TISSUE SPECIFICITY Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.DOMAIN The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.PTM Phosphorylation at Ser-505 does not affect interaction with TSC2. UniProt Q92574 1. 平等的 1164 平等的 Reactome数据库ID Release 77 5672338 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=5672338 Reactome r - hsa - 5672338 1. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5672338.1 1. Reactome数据库ID Release 77 165175 数据库标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=165175 Reactome r - hsa - 165175 1. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-165175.1 三磷酸腺苷 腺苷5 '三磷酸 ATP (4) Reactome DB_ID: 113592 ATP (4 -) (ChEBI: 30616) ATP (4) 三磷酸腺苷 三磷酸腺苷 腺苷5 '三磷酸 车比 车比：30616 Reactome数据库ID Release 77 113592 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=113592 Reactome R-ALL-113592 5. 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-ALL-113592.5 复合物 C00002 补充资料 心肌梗死 MI:0361 TSC1: p-S1387-TSC2 反应数据库ID:381855 等离子体膜 基因本体 GO:0005886 TSC2 p-S1387-TSC2 块茎 TSC2_HUMAN Reactome DB_ID: 3132769 1387 平等的 O-phospho-L-serine 国防部 国防部:00046 1. 平等的 1807 平等的 Reactome数据库ID Release 77 3132769 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=3132769 Reactome r - hsa - 3132769 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-3132769.1 1. TSC1 反应数据库ID:165169 1. 平等的 1164 平等的 Reactome数据库ID Release 77 165169 数据库标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=165169 Reactome R-HSA-165169 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-165169.1 1. Reactome数据库ID Release 77 381855 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=381855 Reactome r - hsa - 381855 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-381855.1 ADP 腺苷5 '磷酸氢盐 ADP (3 -) 反应数据库ID:29370 ADP（3-[ChEBI:456216] ADP (3 -) ADP 事情就让它5,- o - [(phosphonatooxy) phosphinato]腺苷 ADP trianion 车比 CHEBI: 456216 Reactome数据库ID Release 77 29370 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=29370 Reactome r - - 29370 5. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.5 复合物 C00008 激活 p-AMPK heterotrimer: AMP Reactome DB_ID: 380931 p-AMPK heterotrimer Reactome DB_ID: 380934 从Reactome中的EntitySet转换而来 AMPKγ 反应数据库ID:381851 PRKAG1 AMPK gamma1 5'-AMP活化蛋白激酶亚单位γ-1 AAKG1_人类 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促进催化亚基脱磷酸化，使AMPK酶失活。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。与FNIP1和FNIP2相互作用。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 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. UniProt P54619 1. 平等的 331 平等的 Reactome数据库ID Release 77 380946 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=380946 Reactome R-HSA-380946 1. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380946.1 PRKAG2 AMPK gamma2（非活动） Reactome DB_ID: 200419 UniProt:Q9UGJ0 PRKAG2 PRKAG2 AMP活化蛋白激酶（AMPK）的功能AMP/ATP结合亚单位，AMPK是一种能量传感器蛋白激酶，在调节细胞能量代谢中起关键作用。作为对细胞内ATP水平降低的反应，AMPK激活能量产生途径并抑制能量消耗过程：抑制蛋白质、碳水化合物和脂质生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化发挥作用，并通过转录调节因子的磷酸化发挥长期作用。还可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球蛋白。γ非催化亚单位介导与AMP、ADP和ATP的结合，从而激活或抑制AMPK：AMP结合通过诱导磷酸化和阻止催化亚单位的去磷酸化，导致α催化亚单位（PRKAA1或PRKAA2）的变构激活。ADP也刺激磷酸化，而不刺激已经磷酸化的催化亚单位。ATP促进催化亚单位的去磷酸化，使AMPK酶失去活性。AMPK亚单位是α催化亚单位（PRKAA1或PRKAA2）、β（PRKAB1或PRKAB2）和γ非催化亚单位（PRKAG1、PRKAG2或PRKAG3）的异源三聚体。与FNIP1和FNIP2相互作用。除肝脏和胸腺外，组织特异性亚型B广泛表达。最高水平在心脏中检测到，在胎盘和睾丸中大量表达。结构域AMPK假底物基序类似于AMPK靶蛋白磷酸化位点周围的序列，除了存在一个非磷酸化残基代替Ser。在缺乏AMP的情况下，该假底物序列可结合到α亚单位（PRKAA1或PRKAA2）上的活性位点槽，阻止上游激活激酶STK11/LKB1的磷酸化。结构域4个CBS结构域介导与核苷酸的结合。在4个潜在的核苷酸结合位点中，有3个被占据，根据CBS模块指定为位点1、3和4，CBS模块提供酸性残基，以便与AMP核糖的2'-和3'-羟基进行配位。其中，位点4似乎是一个结构位点，它保留着一个紧密固定的AMP分子（AMP3）。剩下的2个位点1和3可以结合AMP、ADP或ATP。位点1（AMP、ADP或ATP 1）是高亲和力结合位点，可能容纳AMP或ADP。位点3（AMP、ADP或ATP 2）是γ亚单位上最弱的核苷酸结合位点，但它对核苷酸水平的变化非常敏感，这使AMPK能够对细胞能量状态的变化迅速作出反应。位点3可能负责通过结合由ULK1磷酸化的AMP或ADP.PTM引起的构象变化保护α催化亚单位激活环中的保守苏氨酸；导致负性调节AMPK活性，提示ULK1和AMPK之间存在调节反馈环。相似性属于5'-AMP活化蛋白激酶γ亚基家族。 UniProt Q9UGJ0 1. 平等的 569 平等的 Reactome数据库ID Release 77 200419 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=200419 Reactome r - hsa - 200419 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-200419.1 PRKAG3 AMPK gamma3 5'-AMP活化蛋白激酶亚单位γ-3 AAKG3_人 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促进催化亚基脱磷酸化，使AMPK酶失活。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。与FNIP1和FNIP2相互作用(通过相似性)。TISSUE SPECIFICITY Skeletal muscle, with weak expression in heart and pancreas.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 Reactome数据库ID Release 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. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-381839.1 Reactome数据库ID Release 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Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-381851.1 1. 从Reactome中的EntitySet转换而来 AMPKβ 反应数据库ID:381854 PRKAB1 AMPKβ1 5'-AMP活化蛋白激酶亚单位β-1 AAKB1_人类 Reactome DB_ID: 380968 UniProt: 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。与FNIP1和FNIP2相互作用。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 Reactome数据库ID Release 77 380968 数据库标识符。使用此URL连接到Reactome中此实例的网页：//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Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380968.1 PRKAB2 AMPK beta 2（非活动） Reactome DB_ID: 200413 UniProt: O43741 PRKAB2 PRKAB2 AMP活化蛋白激酶（AMPK）的功能非催化亚单位，AMPK是一种能量传感器蛋白激酶，在调节细胞能量代谢中起关键作用。作为对细胞内ATP水平降低的反应，AMPK激活能量产生途径并抑制能量消耗过程：抑制蛋白质、碳水化合物和脂质生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化发挥作用，并通过转录调节因子的磷酸化发挥长期作用。还可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球蛋白。β-非催化亚单位作为支架，AMPK复合物通过其连接α（PRKAA1或PRKAA2）和γ亚单位（PRKAG1、PRKAG2或PRKAG3）的C-末端进行组装。AMPK亚单位是α-催化亚单位（PRKAA1或PRKAA2）、β（PRKAB1或PRKAB2）和γ-非催化亚单位的异源三聚体（PRKAG1、PRKAG2或PRKAG3）。PTM与催化亚基（PRKAA1或PRKAA2）结合时磷酸化。被ULK1和ULK2磷酸化；导致负调节AMPK活性，表明ULK1、ULK2和AMPK之间存在调节反馈环。相似性属于5'-AMP活化蛋白激酶β亚单位家族。 UniProt O43741 1. 平等的 272 平等的 Reactome数据库ID Release 77 200413 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=200413 Reactome R-HSA-200413 1. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-200413.1 Reactome数据库ID Release 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. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-381854.1 1. 从Reactome中的EntitySet转换而来 p-AMPKα 反应数据库ID:381844 p-T172-PRKAA2 p-T172-AMPK alpha2 Reactome DB_ID: 200417 UniProt:P54646 PRKAA2 PRKAA2 AMPK AMPK2 AMP活化蛋白激酶（AMPK）的功能催化亚单位，AMPK是一种能量传感器蛋白激酶，在调节细胞能量代谢中起关键作用。作为对细胞内ATP水平降低的反应，AMPK激活能量产生途径并抑制能量消耗过程：抑制蛋白质、碳水化合物和脂质生物合成，以及细胞生长和增殖。AMPK通过代谢酶的直接磷酸化发挥作用，并通过转录调节因子的磷酸化发挥长期作用。还可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球蛋白。通过磷酸化和失活脂质代谢酶，如ACACA、ACACB、GYS1、HMGCR和LIPE，调节脂质合成；分别通过磷酸化乙酰辅酶A羧化酶（ACACA和ACACB）和激素敏感脂肪酶（LIPE）调节脂肪酸和胆固醇的合成。通过磷酸化IRS1、PFKFB2和PFKFB3调节胰岛素信号和糖酵解。参与胰岛素受体/INSR内化（PubMed:25687571）。AMPK通过增加葡萄糖转运体SLC2A4/GLUT4向质膜的易位（可能通过介导TBC1D4/AS160的磷酸化）刺激肌肉中的葡萄糖摄取。通过磷酸化参与能量代谢的转录调节因子，如CRTC2/TORC2、FOXO3、组蛋白H2B、HDAC5、MEF2C、MLXIPL/ChREBP、EP300、HNF4A、p53/TP53、SREBF1、SREBF2和PPARGC1A，调节转录和染色质结构。通过磷酸化CRTC2/TORC2，作为肝脏葡萄糖稳态的关键调节器，导致CRTC2/TORC2在细胞质中隔离。在应激反应中，磷酸化组蛋白H2B（H2BS36ph）的“Ser-36”，从而促进转录。通过磷酸化TSC2、RPTOR和ATG1/ULK1，作为细胞生长和增殖的关键调节者：为应对营养限制，通过磷酸化mTORC1复合物的RPTOR组分以及磷酸化和激活TSC2，负调节mTORC1复合物。作为对营养限制的反应，通过磷酸化和激活ATG1/ULK1促进自噬。在此过程中，还激活WDR45（PubMed:28561066）。AMPK还通过介导CRY1的磷酸化来调节昼夜节律，导致其不稳定。可能通过磷酸化CTNNB1来调节Wnt信号通路，从而使其稳定。还磷酸化CFTR、EEF2K、KLC1、NOS3和SLC12A1。在促自噬（由PIK3C3、BECN1、PIK3R4和UVRAG或ATG14组成）和非自噬（由PIK3C3、BECN1和PIK3R4组成）复合物对葡萄糖饥饿的反应中发挥重要作用。可通过磷酸化PIK3C3抑制非自噬复合物，并通过磷酸化BECN1（通过相似性）激活促自噬复合物。Thr-172上磷酸化激活的活性调节。AMP与非催化γ亚单位（PRKAG1、PRKAG2或PRKAG3）的结合导致变构激活，诱导Thr-172上的磷酸化。AMP与γ亚单位的结合也通过阻止Thr-172的去磷酸化来维持活性。ADP也刺激Thr-172磷酸化，而不刺激已经磷酸化的AMPK。ATP促进Thr-172的去磷酸化，使酶失去活性。在生理条件下，AMPK主要以非活性形式与ATP复合存在，ATP比AMP丰富得多。AMPK被抗高血糖药物二甲双胍激活，二甲双胍是一种用于2型糖尿病患者的药物：在体内，二甲双胍似乎主要抑制肝脏糖异生。然而，二甲双胍可用于在培养或体外激活肌肉和其他细胞中的AMPK（PubMed:11602624）。被化合物C（6-[4-（2-哌啶-1-基-乙氧基）-苯基）]-3-吡啶-4-基-吡唑并[1,5-a]嘧啶选择性抑制。由白藜芦醇（一种存在于红酒中的天然多酚）和S17834（一种合成多酚）激活。水杨酸/阿司匹林主要通过抑制Thr-172去磷酸化直接激活激酶活性。AMPK亚单位是α催化亚单位（PRKAA1或PRKAA2）、β（PRKAB1或PRKAB2）和γ非催化亚单位（PRKAG1、PRKAG2或PRKAG3）的异源三聚体。与FNIP1和FNIP2交互。与高尔基体/内体膜上的胰岛素受体/INSR内化复合物相关；PRKAA2/AMPK2以及ATIC和HACD3/PTPLAD1被认为是调节INSR自身磷酸化和内吞作用的信号网络的一部分（PubMed:25687571）。结构域AIS（自身抑制序列）该区域显示出与泛素相关结构域的一些序列相似性，并抑制激酶活性。PTM泛素化。PTM在Thr-172处被STK11/LKB1与STE20相关适配器α（STRADA）伪激酶和CAB39复合物磷酸化。在Thr-172处也被CAMKK2磷酸化；由细胞内钙离子升高触发，AMP/ATP比率无明显变化。CAMKK1也可以进行磷化处理horylate 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-phospho-L-threonine 国防部 国防部:00047 1. 平等的 552 平等的 Reactome数据库ID Release 77 200417 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=200417 Reactome r - hsa - 200417 1. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-200417.1 p-T183-PRKAA1 p-T183-AMPK字母1 Reactome DB_ID: 380964 UniProt:Q13131 PRKAA1 PRKAA1 AMPK1 ampp活化蛋白激酶(AMPK)的催化亚基，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。通过磷酸化和灭活脂类代谢酶如ACACA, ACACB, GYS1, HMGCR和LIPE调控脂类合成;通过磷酸化乙酰辅酶a羧化酶(ACACA和ACACB)和激素敏感脂肪酶(LIPE)分别调节脂肪酸和胆固醇的合成。通过磷酸化IRS1、PFKFB2和PFKFB3调控胰岛素信号传导和糖酵解。AMPK可能通过介导TBC1D4/AS160的磷酸化，通过增加葡萄糖转运体SLC2A4/GLUT4向质膜的转运来刺激肌肉中的葡萄糖摄取。通过磷酸化参与能量代谢的转录调控因子，如CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2和PPARGC1A，调控转录和染色质结构。 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 Reactome数据库ID Release 77 380964 数据库标识符。使用此URL连接到Reactome中此实例的网页：//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 Reactome数据库ID Release 77 381844 数据库标识符。使用此URL连接到Reactome中此实例的网页：//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. Reactome数据库ID Release 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 1. AMP 5'-单磷酸腺苷 腺嘌呤核苷酸 腺苷酸 5'-安培 5'-腺苷酸 5'-一磷酸腺苷 腺苷5 '磷酸 反应数据库ID:76577 腺苷5’一磷酸(ChEBI: 16027) 5'-单磷酸腺苷 车比 CHEBI: 16027 Reactome数据库ID Release 77 76577 数据库标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=76577 Reactome R-ALL-76577 4. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-76577.4 复合物 C00020 1. Reactome数据库ID Release 77 380931 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=380931 Reactome r - hsa - 380931 1. 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380931.1 基因本体 去:0004679 细胞功能的基因本体术语 心肌梗死 MI:0355 相同的催化剂活性 Reactome数据库ID Release 77 381847 数据库标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=381847 Reactome数据库ID Release 77 380927 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=380927 Reactome r - hsa - 380927 3. 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-380927.3 14651849 Pubmed 2003 TSC2介导细胞能量反应以控制细胞生长和存活 伊诺基，K 朱,T 吉隆坡关 单元格115:577-90 17277771 Pubmed 2007 Akt/PKB底物PRAS40介导的胰岛素向mTOR的信号通路 范德哈尔，E 李,如果 Bandhakavi,年代 格里芬,TJ 金,DH Nat Cell Biol 9:316-23 17386266 Pubmed 2007 PRAS40是胰岛素调节的mTORC1蛋白激酶抑制剂 Sancak Y 索林，抄送 彼得森 林德奎斯特 康萨 斯普纳,E 卡尔,SA 萨巴蒂尼，DM 摩尔细胞25:903-15