ID AAPK1_HUMAN Reviewed; 559 AA. AC Q13131; A8MTQ6; B2R7E1; O00286; Q5D0E1; Q86VS1; Q9UNQ4; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 28-JUL-2009, sequence version 4. DT 11-NOV-2015, entry version 172. DE RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-1; DE Short=AMPK subunit alpha-1; DE EC=2.7.11.1; DE AltName: Full=Acetyl-CoA carboxylase kinase; DE Short=ACACA kinase; DE EC=2.7.11.27; DE AltName: Full=Hydroxymethylglutaryl-CoA reductase kinase; DE Short=HMGCR kinase; DE EC=2.7.11.31; DE AltName: Full=Tau-protein kinase PRKAA1; DE EC=2.7.11.26; GN Name=PRKAA1; Synonyms=AMPK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP LEU-10. RC TISSUE=Brain, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-559 (ISOFORM 1). RC TISSUE=Mammary gland; RA Yano K.; RT "Nucleotide sequence of cDNA for human AMP-activated protein kinase RT alpha-1."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-559 (ISOFORM 1). RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-559 (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for RT 300 previously undefined genes expressed in CD34+ hematopoietic RT stem/progenitor cells."; RL Genome Res. 10:1546-1560(2000). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 36-209 (ISOFORM 1). RC TISSUE=Intestine; RA Taboada E.N., Hickey D.A.; RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 303-559 (ISOFORMS 1/2). RC TISSUE=Liver; RX PubMed=8557660; DOI=10.1074/jbc.271.2.611; RA Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., RA Teh T., House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E.; RT "Mammalian AMP-activated protein kinase subfamily."; RL J. Biol. Chem. 271:611-614(1996). RN [8] RP DOMAIN AIS. RX PubMed=9857077; DOI=10.1074/jbc.273.52.35347; RA Crute B.E., Seefeld K., Gamble J., Kemp B.E., Witters L.A.; RT "Functional domains of the alpha1 catalytic subunit of the AMP- RT activated protein kinase."; RL J. Biol. Chem. 273:35347-35354(1998). RN [9] RP FUNCTION. RX PubMed=11554766; DOI=10.1006/bbrc.2001.5627; RA Imamura K., Ogura T., Kishimoto A., Kaminishi M., Esumi H.; RT "Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated RT protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D- RT ribofuranoside, in a human hepatocellular carcinoma cell line."; RL Biochem. Biophys. Res. Commun. 287:562-567(2001). RN [10] RP FUNCTION IN PHOSPHORYLATION OF EP300. RX PubMed=11518699; DOI=10.1074/jbc.C100316200; RA Yang W., Hong Y.H., Shen X.Q., Frankowski C., Camp H.S., Leff T.; RT "Regulation of transcription by AMP-activated protein kinase: RT phosphorylation of p300 blocks its interaction with nuclear RT receptors."; RL J. Biol. Chem. 276:38341-38344(2001). RN [11] RP ENZYME REGULATION. RX PubMed=11602624; DOI=10.1172/JCI13505; RA Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., RA Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., RA Goodyear L.J., Moller D.E.; RT "Role of AMP-activated protein kinase in mechanism of metformin RT action."; RL J. Clin. Invest. 108:1167-1174(2001). RN [12] RP FUNCTION IN PHOSPHORYLATION OF CFTR. RX PubMed=12519745; DOI=10.1152/ajpcell.00227.2002; RA Hallows K.R., Kobinger G.P., Wilson J.M., Witters L.A., Foskett J.K.; RT "Physiological modulation of CFTR activity by AMP-activated protein RT kinase in polarized T84 cells."; RL Am. J. Physiol. 284:C1297-C1308(2003). RN [13] RP FUNCTION IN PHOSPHORYLATION OF TSC2. RX PubMed=14651849; DOI=10.1016/S0092-8674(03)00929-2; RA Inoki K., Zhu T., Guan K.L.; RT "TSC2 mediates cellular energy response to control cell growth and RT survival."; RL Cell 115:577-590(2003). RN [14] RP PHOSPHORYLATION AT THR-183, AND ENZYME REGULATION. RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110; RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., RA Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., RA Alessi D.R.; RT "LKB1 is a master kinase that activates 13 kinases of the AMPK RT subfamily, including MARK/PAR-1."; RL EMBO J. 23:833-843(2004). RN [15] RP PHOSPHORYLATION AT THR-183, AND ENZYME REGULATION. RX PubMed=16054095; DOI=10.1016/j.cmet.2005.05.009; RA Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., RA Frenguelli B.G., Hardie D.G.; RT "Calmodulin-dependent protein kinase kinase-beta is an alternative RT upstream kinase for AMP-activated protein kinase."; RL Cell Metab. 2:9-19(2005). RN [16] RP PHOSPHORYLATION AT THR-183, AND ENZYME REGULATION. RX PubMed=15980064; DOI=10.1074/jbc.M503824200; RA Hurley R.L., Anderson K.A., Franzone J.M., Kemp B.E., Means A.R., RA Witters L.A.; RT "The Ca2+/calmodulin-dependent protein kinase kinases are AMP- RT activated protein kinase kinases."; RL J. Biol. Chem. 280:29060-29066(2005). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15866171; DOI=10.1016/j.molcel.2005.03.027; RA Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., RA Birnbaum M.J., Thompson C.B.; RT "AMP-activated protein kinase induces a p53-dependent metabolic RT checkpoint."; RL Mol. Cell 18:283-293(2005). RN [18] RP INTERACTION WITH FNIP1. RX PubMed=17028174; DOI=10.1073/pnas.0603781103; RA Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., RA Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III, RA Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr., RA Linehan W.M., Schmidt L.S., Zbar B.; RT "Folliculin encoded by the BHD gene interacts with a binding protein, RT FNIP1, and AMPK, and is involved in AMPK and mTOR signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006). RN [19] RP DOMAIN AIS, AND MUTAGENESIS OF VAL-307. RX PubMed=17088252; DOI=10.1074/jbc.M605790200; RA Pang T., Xiong B., Li J.Y., Qiu B.Y., Jin G.Z., Shen J.K., Li J.; RT "Conserved alpha-helix acts as autoinhibitory sequence in AMP- RT activated protein kinase alpha subunits."; RL J. Biol. Chem. 282:495-506(2007). RN [20] RP FUNCTION IN PHOSPHORYLATION OF FOXO3. RX PubMed=17711846; DOI=10.1074/jbc.M705325200; RA Greer E.L., Oskoui P.R., Banko M.R., Maniar J.M., Gygi M.P., RA Gygi S.P., Brunet A.; RT "The energy sensor AMP-activated protein kinase directly regulates the RT mammalian FOXO3 transcription factor."; RL J. Biol. Chem. 282:30107-30119(2007). RN [21] RP FUNCTION IN CELL POLARITY. RX PubMed=17486097; DOI=10.1038/nature05828; RA Lee J.H., Koh H., Kim M., Kim Y., Lee S.Y., Karess R.E., Lee S.H., RA Shong M., Kim J.M., Kim J., Chung J.; RT "Energy-dependent regulation of cell structure by AMP-activated RT protein kinase."; RL Nature 447:1017-1020(2007). RN [22] RP FUNCTION IN PHOSPHORYLATION OF HDAC5. RX PubMed=18184930; DOI=10.2337/db07-0843; RA McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., RA Schertzer J.D., Kemp B.E., Hargreaves M.; RT "AMP-activated protein kinase regulates GLUT4 transcription by RT phosphorylating histone deacetylase 5."; RL Diabetes 57:860-867(2008). RN [23] RP INTERACTION WITH FNIP2. RX PubMed=18403135; DOI=10.1016/j.gene.2008.02.022; RA Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., RA Valera V.A., Linehan W.M., Schmidt L.S.; RT "Identification and characterization of a novel folliculin-interacting RT protein FNIP2."; RL Gene 415:60-67(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [26] RP FUNCTION IN PHOSPHORYLATION OF RPTOR. RX PubMed=18439900; DOI=10.1016/j.molcel.2008.03.003; RA Gwinn D.M., Shackelford D.B., Egan D.F., Mihaylova M.M., Mery A., RA Vasquez D.S., Turk B.E., Shaw R.J.; RT "AMPK phosphorylation of raptor mediates a metabolic checkpoint."; RL Mol. Cell 30:214-226(2008). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [28] RP INTERACTION WITH FNIP2. RX PubMed=18663353; DOI=10.1038/onc.2008.261; RA Takagi Y., Kobayashi T., Shiono M., Wang L., Piao X., Sun G., RA Zhang D., Abe M., Hagiwara Y., Takahashi K., Hino O.; RT "Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel RT Fnip1-like (FnipL/Fnip2) protein."; RL Oncogene 27:5339-5347(2008). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-486; THR-490 RP AND SER-496, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32 AND SER-467, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [32] RP FUNCTION IN PHOSPHORYLATION OF KLC1. RX PubMed=20074060; DOI=10.1042/BST0380205; RA McDonald A., Fogarty S., Leclerc I., Hill E.V., Hardie D.G., RA Rutter G.A.; RT "Cell-wide analysis of secretory granule dynamics in three dimensions RT in living pancreatic beta-cells: evidence against a role for AMPK- RT dependent phosphorylation of KLC1 at Ser517/Ser520 in glucose- RT stimulated insulin granule movement."; RL Biochem. Soc. Trans. 38:205-208(2010). RN [33] RP FUNCTION. RX PubMed=20160076; DOI=10.1073/pnas.0913860107; RA Alexander A., Cai S.L., Kim J., Nanez A., Sahin M., MacLean K.H., RA Inoki K., Guan K.L., Shen J., Person M.D., Kusewitt D., Mills G.B., RA Kastan M.B., Walker C.L.; RT "ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response RT to ROS."; RL Proc. Natl. Acad. Sci. U.S.A. 107:4153-4158(2010). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [35] RP PHOSPHORYLATION BY ULK1 AND ULK2. RX PubMed=21460634; DOI=10.4161/auto.7.7.15451; RA Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., RA Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.; RT "Ulk1-mediated phosphorylation of AMPK constitutes a negative RT regulatory feedback loop."; RL Autophagy 7:696-706(2011). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [37] RP FUNCTION IN PHOSPHORYLATION OF ULK1. RX PubMed=21205641; DOI=10.1126/science.1196371; RA Egan D.F., Shackelford D.B., Mihaylova M.M., Gelino S., Kohnz R.A., RA Mair W., Vasquez D.S., Joshi A., Gwinn D.M., Taylor R., Asara J.M., RA Fitzpatrick J., Dillin A., Viollet B., Kundu M., Hansen M., Shaw R.J.; RT "Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase RT connects energy sensing to mitophagy."; RL Science 331:456-461(2011). RN [38] RP INTERACTION WITH PRKAB1 AND PRKAG1, AND ENZYME REGULATION. RX PubMed=21680840; DOI=10.1126/science.1200094; RA Oakhill J.S., Steel R., Chen Z.P., Scott J.W., Ling N., Tam S., RA Kemp B.E.; RT "AMPK is a direct adenylate charge-regulated protein kinase."; RL Science 332:1433-1435(2011). RN [39] RP REVIEW ON FUNCTION. RX PubMed=17307971; DOI=10.1161/01.RES.0000256090.42690.05; RA Towler M.C., Hardie D.G.; RT "AMP-activated protein kinase in metabolic control and insulin RT signaling."; RL Circ. Res. 100:328-341(2007). RN [40] RP REVIEW ON FUNCTION. RX PubMed=17712357; DOI=10.1038/nrm2249; RA Hardie D.G.; RT "AMP-activated/SNF1 protein kinases: conserved guardians of cellular RT energy."; RL Nat. Rev. Mol. Cell Biol. 8:774-785(2007). RN [41] RP DEPHOSPHORYLATION. RX PubMed=23088624; DOI=10.1042/BJ20121201; RA Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., RA Takano-Yamamoto T., Tamura S., Kobayashi T.; RT "N-Myristoylation is essential for protein phosphatases PPM1A and RT PPM1B to dephosphorylate their physiological substrates in cells."; RL Biochem. J. 449:741-749(2013). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-355; SER-496; SER-508; RP SER-524 AND SER-527, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [43] RP VARIANT [LARGE SCALE ANALYSIS] ARG-16. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Catalytic subunit of AMP-activated protein kinase CC (AMPK), an energy sensor protein kinase that plays a key role in CC regulating cellular energy metabolism. In response to reduction of CC intracellular ATP levels, AMPK activates energy-producing pathways CC and inhibits energy-consuming processes: inhibits protein, CC carbohydrate and lipid biosynthesis, as well as cell growth and CC proliferation. AMPK acts via direct phosphorylation of metabolic CC enzymes, and by longer-term effects via phosphorylation of CC transcription regulators. Also acts as a regulator of cellular CC polarity by remodeling the actin cytoskeleton; probably by CC indirectly activating myosin. Regulates lipid synthesis by CC phosphorylating and inactivating lipid metabolic enzymes such as CC ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and CC cholesterol synthesis by phosphorylating acetyl-CoA carboxylase CC (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, CC respectively. Regulates insulin-signaling and glycolysis by CC phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose CC uptake in muscle by increasing the translocation of the glucose CC transporter SLC2A4/GLUT4 to the plasma membrane, possibly by CC mediating phosphorylation of TBC1D4/AS160. Regulates transcription CC and chromatin structure by phosphorylating transcription CC regulators involved in energy metabolism such as CRTC2/TORC2, CC FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, CC p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of CC glucose homeostasis in liver by phosphorylating CRTC2/TORC2, CC leading to CRTC2/TORC2 sequestration in the cytoplasm. In response CC to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), CC leading to promote transcription. Acts as a key regulator of cell CC growth and proliferation by phosphorylating TSC2, RPTOR and CC ATG1/ULK1: in response to nutrient limitation, negatively CC regulates the mTORC1 complex by phosphorylating RPTOR component of CC the mTORC1 complex and by phosphorylating and activating TSC2. In CC response to nutrient limitation, promotes autophagy by CC phosphorylating and activating ATG1/ULK1. AMPK also acts as a CC regulator of circadian rhythm by mediating phosphorylation of CC CRY1, leading to destabilize it. May regulate the Wnt signaling CC pathway by phosphorylating CTNNB1, leading to stabilize it. Also CC has tau-protein kinase activity: in response to amyloid beta A4 CC protein (APP) exposure, activated by CAMKK2, leading to CC phosphorylation of MAPT/TAU; however the relevance of such data CC remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, CC NOS3 and SLC12A1. {ECO:0000269|PubMed:11518699, CC ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, CC ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, CC ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, CC ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, CC ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, CC ECO:0000269|PubMed:21205641}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- CATALYTIC ACTIVITY: ATP + [tau protein] = ADP + [tau protein] CC phosphate. CC -!- CATALYTIC ACTIVITY: ATP + [hydroxymethylglutaryl-CoA reductase CC (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] CC phosphate. CC -!- CATALYTIC ACTIVITY: ATP + [acetyl-CoA carboxylase] = ADP + CC [acetyl-CoA carboxylase] phosphate. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- ENZYME REGULATION: Activated by phosphorylation on Thr-183. CC Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or CC PRKAG3) results in allosteric activation, inducing phosphorylation CC on Thr-183. AMP-binding to gamma subunit also sustains activity by CC preventing dephosphorylation of Thr-183. ADP also stimulates Thr- CC 183 phosphorylation, without stimulating already phosphorylated CC AMPK. ATP promotes dephosphorylation of Thr-183, rendering the CC enzyme inactive. Under physiological conditions AMPK mainly exists CC in its inactive form in complex with ATP, which is much more CC abundant than AMP. AMPK is activated by antihyperglycemic drug CC metformin, a drug prescribed to patients with type 2 diabetes: in CC vivo, metformin seems to mainly inhibit liver gluconeogenesis. CC However, metformin can be used to activate AMPK in muscle and CC other cells in culture or ex vivo (PubMed:11602624). Selectively CC inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]- CC 3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by CC resveratrol, a natural polyphenol present in red wine, and S17834, CC a synthetic polyphenol. {ECO:0000269|PubMed:11602624, CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15980064, CC ECO:0000269|PubMed:16054095, ECO:0000269|PubMed:21680840}. CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit CC (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non- CC catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with CC FNIP1 and FNIP2. {ECO:0000269|PubMed:17028174, CC ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353, CC ECO:0000269|PubMed:21680840}. CC -!- INTERACTION: CC Q9NYB9:ABI2; NbExp=3; IntAct=EBI-1181405, EBI-743598; CC Q08117:AES; NbExp=3; IntAct=EBI-1181405, EBI-717810; CC O14503:BHLHE40; NbExp=3; IntAct=EBI-1181405, EBI-711810; CC O14627:CDX4; NbExp=3; IntAct=EBI-1181405, EBI-10181162; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-1181405, EBI-10171858; CC O95073:FSBP; NbExp=3; IntAct=EBI-1181405, EBI-1059030; CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-1181405, EBI-618309; CC Q6NT76:HMBOX1; NbExp=3; IntAct=EBI-1181405, EBI-2549423; CC Q8IX15-3:HOMEZ; NbExp=3; IntAct=EBI-1181405, EBI-10172004; CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-1181405, EBI-352572; CC Q9UKT9:IKZF3; NbExp=3; IntAct=EBI-1181405, EBI-747204; CC Q8NBZ0:INO80E; NbExp=3; IntAct=EBI-1181405, EBI-769401; CC Q6A162:KRT40; NbExp=3; IntAct=EBI-1181405, EBI-10171697; CC Q96JM7:L3MBTL3; NbExp=3; IntAct=EBI-1181405, EBI-2686809; CC Q5JR59:MTUS2; NbExp=3; IntAct=EBI-1181405, EBI-742948; CC Q8IXK0:PHC2; NbExp=3; IntAct=EBI-1181405, EBI-713786; CC Q96PV4:PNMA5; NbExp=3; IntAct=EBI-1181405, EBI-10171633; CC Q9Y478:PRKAB1; NbExp=6; IntAct=EBI-1181405, EBI-719769; CC O43741:PRKAB2; NbExp=12; IntAct=EBI-1181405, EBI-1053424; CC P54619:PRKAG1; NbExp=10; IntAct=EBI-1181405, EBI-1181439; CC Q93062:RBPMS; NbExp=3; IntAct=EBI-1181405, EBI-740322; CC Q8HWS3:RFX6; NbExp=3; IntAct=EBI-1181405, EBI-746118; CC Q9UFD9:RIMBP3; NbExp=3; IntAct=EBI-1181405, EBI-10182375; CC Q9HAT0:ROPN1; NbExp=3; IntAct=EBI-1181405, EBI-1378139; CC Q9Y2D8:SSX2IP; NbExp=3; IntAct=EBI-1181405, EBI-2212028; CC Q9NVV9:THAP1; NbExp=3; IntAct=EBI-1181405, EBI-741515; CC P14373:TRIM27; NbExp=3; IntAct=EBI-1181405, EBI-719493; CC Q15654:TRIP6; NbExp=3; IntAct=EBI-1181405, EBI-742327; CC Q9Y3Q8:TSC22D4; NbExp=3; IntAct=EBI-1181405, EBI-739485; CC Q5T124:UBXN11; NbExp=3; IntAct=EBI-1181405, EBI-746004; CC Q9H9H4:VPS37B; NbExp=3; IntAct=EBI-1181405, EBI-4400866; CC Q8N1B4:VPS52; NbExp=3; IntAct=EBI-1181405, EBI-2799833; CC O96006:ZBED1; NbExp=3; IntAct=EBI-1181405, EBI-740037; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15866171}. CC Nucleus {ECO:0000269|PubMed:15866171}. Note=In response to stress, CC recruited by p53/TP53 to specific promoters. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13131-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13131-2; Sequence=VSP_035431; CC -!- DOMAIN: The AIS (autoinhibitory sequence) region shows some CC sequence similarity with the ubiquitin-associated domains and CC represses kinase activity. {ECO:0000269|PubMed:17088252, CC ECO:0000269|PubMed:9857077}. CC -!- PTM: Ubiquitinated. {ECO:0000250}. CC -!- PTM: Phosphorylated at Thr-183 by STK11/LKB1 in complex with CC STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also CC phosphorylated at Thr-183 by CAMKK2; triggered by a rise in CC intracellular calcium ions, without detectable changes in the CC AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a CC much lower level. Dephosphorylated by protein phosphatase 2A and CC 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to CC negatively regulate AMPK activity and suggesting the existence of CC a regulatory feedback loop between ULK1, ULK2 and AMPK. CC Dephosphorylated by PPM1A and PPM1B. {ECO:0000269|PubMed:14976552, CC ECO:0000269|PubMed:15980064, ECO:0000269|PubMed:16054095, CC ECO:0000269|PubMed:21460634}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK CC Ser/Thr protein kinase family. SNF1 subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA64850.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAD43027.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAH37303.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=BAA36547.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=BAG35788.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC008810; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC048980; AAH48980.1; -; mRNA. DR EMBL; AB022017; BAA36547.1; ALT_INIT; mRNA. DR EMBL; AK312947; BAG35788.1; ALT_INIT; mRNA. DR EMBL; BC037303; AAH37303.1; ALT_INIT; mRNA. DR EMBL; AF100763; AAD43027.1; ALT_INIT; mRNA. DR EMBL; U22456; AAA64850.1; ALT_INIT; mRNA. DR EMBL; Y12856; CAA73361.1; -; mRNA. DR CCDS; CCDS3932.2; -. [Q13131-1] DR CCDS; CCDS3933.2; -. [Q13131-2] DR PIR; G01743; G01743. DR RefSeq; NP_006242.5; NM_006251.5. [Q13131-1] DR RefSeq; NP_996790.3; NM_206907.3. [Q13131-2] DR UniGene; Hs.43322; -. DR PDB; 4RED; X-ray; 2.95 A; A/B=22-362. DR PDB; 4RER; X-ray; 4.05 A; A=20-559. DR PDB; 4REW; X-ray; 4.58 A; A=20-559. DR PDBsum; 4RED; -. DR PDBsum; 4RER; -. DR PDBsum; 4REW; -. DR ProteinModelPortal; Q13131; -. DR SMR; Q13131; 20-559. DR BioGrid; 111549; 142. DR DIP; DIP-39973N; -. DR IntAct; Q13131; 93. DR MINT; MINT-6771251; -. DR STRING; 9606.ENSP00000346148; -. DR BindingDB; Q13131; -. DR ChEMBL; CHEMBL3038452; -. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB00131; Adenosine monophosphate. DR DrugBank; DB00171; Adenosine triphosphate. DR DrugBank; DB00914; Phenformin. DR GuidetoPHARMACOLOGY; 1541; -. DR PhosphoSite; Q13131; -. DR BioMuta; PRKAA1; -. DR DMDM; 254763436; -. DR MaxQB; Q13131; -. DR PaxDb; Q13131; -. DR PRIDE; Q13131; -. DR DNASU; 5562; -. DR Ensembl; ENST00000354209; ENSP00000346148; ENSG00000132356. [Q13131-2] DR Ensembl; ENST00000397128; ENSP00000380317; ENSG00000132356. [Q13131-1] DR GeneID; 5562; -. DR KEGG; hsa:5562; -. DR UCSC; uc003jmb.3; human. [Q13131-2] DR UCSC; uc003jmc.3; human. [Q13131-1] DR CTD; 5562; -. DR GeneCards; PRKAA1; -. DR H-InvDB; HIX0004832; -. DR HGNC; HGNC:9376; PRKAA1. DR HPA; CAB005050; -. DR HPA; HPA035409; -. DR MIM; 602739; gene. DR neXtProt; NX_Q13131; -. DR PharmGKB; PA33744; -. DR eggNOG; KOG0586; Eukaryota. DR eggNOG; ENOG410XNQ0; LUCA. DR GeneTree; ENSGT00790000122960; -. DR HOGENOM; HOG000233016; -. DR HOVERGEN; HBG050432; -. DR KO; K07198; -. DR OMA; NYRSCQK; -. DR OrthoDB; EOG7RRF6K; -. DR PhylomeDB; Q13131; -. DR TreeFam; TF314032; -. DR BRENDA; 2.7.11.1; 2681. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR SignaLink; Q13131; -. DR ChiTaRS; PRKAA1; human. DR GeneWiki; Protein_kinase,_AMP-activated,_alpha_1; -. DR GenomeRNAi; 5562; -. DR NextBio; 21546; -. DR PRO; PR:Q13131; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; Q13131; -. DR CleanEx; HS_PRKAA1; -. DR ExpressionAtlas; Q13131; baseline and differential. DR Genevisible; Q13131; HS. DR GO; GO:0031588; C:AMP-activated protein kinase complex; ISS:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005622; C:intracellular; IC:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0050405; F:[acetyl-CoA carboxylase] kinase activity; IEA:UniProtKB-EC. DR GO; GO:0047322; F:[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004679; F:AMP-activated protein kinase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; NAS:UniProtKB. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0035174; F:histone serine kinase activity; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0050321; F:tau-protein kinase activity; IEA:UniProtKB-EC. DR GO; GO:0000187; P:activation of MAPK activity; NAS:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; TAS:Reactome. DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl. DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB. DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl. DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0009631; P:cold acclimation; IEA:Ensembl. DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB. DR GO; GO:0019395; P:fatty acid oxidation; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl. DR GO; GO:0035404; P:histone-serine phosphorylation; IBA:GO_Central. DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB. DR GO; GO:0016236; P:macroautophagy; TAS:Reactome. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:2001274; P:negative regulation of glucose import in response to insulin stimulus; IEA:Ensembl. DR GO; GO:0046318; P:negative regulation of glucosylceramide biosynthetic process; NAS:UniProtKB. DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB. DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB. DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; NAS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0045821; P:positive regulation of glycolytic process; ISS:UniProtKB. DR GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Ensembl. DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:2000505; P:regulation of energy homeostasis; ISS:UniProtKB. DR GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0060627; P:regulation of vesicle-mediated transport; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0031000; P:response to caffeine; IEA:Ensembl. DR GO; GO:1901563; P:response to camptothecin; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; ISS:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; NAS:UniProtKB. DR GO; GO:0009411; P:response to UV; IEA:Ensembl. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR InterPro; IPR032270; AMPK_C. DR InterPro; IPR028375; KA1/Ssp2_C. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF16579; AdenylateSensor; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF103243; SSF103243; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Autophagy; KW Biological rhythms; Cholesterol biosynthesis; Cholesterol metabolism; KW Chromatin regulator; Complete proteome; Cytoplasm; KW Fatty acid biosynthesis; Fatty acid metabolism; Kinase; KW Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Serine/threonine-protein kinase; KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; KW Sterol metabolism; Transcription; Transcription regulation; KW Transferase; Ubl conjugation; Wnt signaling pathway. FT CHAIN 1 559 5'-AMP-activated protein kinase catalytic FT subunit alpha-1. FT /FTId=PRO_0000085589. FT DOMAIN 27 279 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 33 41 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 302 381 AIS. FT ACT_SITE 150 150 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 56 56 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 32 32 Phosphothreonine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 183 183 Phosphothreonine; by LKB1 and CaMKK2. FT {ECO:0000250}. FT MOD_RES 269 269 Phosphothreonine. FT {ECO:0000250|UniProtKB:P54645}. FT MOD_RES 355 355 Phosphothreonine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 356 356 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 360 360 Phosphoserine; by ULK1. {ECO:0000250}. FT MOD_RES 368 368 Phosphothreonine; by ULK1. {ECO:0000250}. FT MOD_RES 382 382 Phosphothreonine. FT {ECO:0000244|PubMed:18220336, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 397 397 Phosphoserine; by ULK1. FT {ECO:0000305|PubMed:21460634}. FT MOD_RES 467 467 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 486 486 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 488 488 Phosphothreonine; by ULK1. FT {ECO:0000305|PubMed:21460634}. FT MOD_RES 490 490 Phosphothreonine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 496 496 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 508 508 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 524 524 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 527 527 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT VAR_SEQ 121 121 R -> RKSDVPGVVKTGSTKE (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_035431. FT VARIANT 10 10 M -> L (in dbSNP:rs17855679). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_058401. FT VARIANT 16 16 Q -> R (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035622. FT MUTAGEN 307 307 V->G,Q: Activates the kinase activity. FT {ECO:0000269|PubMed:17088252}. FT CONFLICT 5 5 S -> C (in Ref. 4; BAG35788). FT {ECO:0000305}. FT CONFLICT 9 9 K -> S (in Ref. 5; AAD43027). FT {ECO:0000305}. FT CONFLICT 37 37 T -> A (in Ref. 6; AAA64850). FT {ECO:0000305}. FT CONFLICT 202 202 A -> V (in Ref. 6; AAA64850). FT {ECO:0000305}. FT CONFLICT 208 208 I -> L (in Ref. 6; AAA64850). FT {ECO:0000305}. FT CONFLICT 269 269 T -> S (in Ref. 3; BAA36547). FT {ECO:0000305}. FT STRAND 27 35 {ECO:0000244|PDB:4RED}. FT STRAND 40 49 {ECO:0000244|PDB:4RED}. FT STRAND 52 59 {ECO:0000244|PDB:4RED}. FT HELIX 60 66 {ECO:0000244|PDB:4RED}. FT STRAND 68 70 {ECO:0000244|PDB:4RED}. FT HELIX 71 77 {ECO:0000244|PDB:4RED}. FT STRAND 90 95 {ECO:0000244|PDB:4RED}. FT STRAND 97 105 {ECO:0000244|PDB:4RED}. FT HELIX 112 118 {ECO:0000244|PDB:4RED}. FT HELIX 124 144 {ECO:0000244|PDB:4RED}. FT HELIX 153 155 {ECO:0000244|PDB:4RED}. FT STRAND 156 158 {ECO:0000244|PDB:4RED}. FT STRAND 164 167 {ECO:0000244|PDB:4RED}. FT STRAND 169 171 {ECO:0000244|PDB:4RED}. FT HELIX 193 196 {ECO:0000244|PDB:4RED}. FT HELIX 204 220 {ECO:0000244|PDB:4RED}. FT STRAND 227 229 {ECO:0000244|PDB:4RED}. FT HELIX 231 233 {ECO:0000244|PDB:4RED}. FT HELIX 250 259 {ECO:0000244|PDB:4RED}. FT HELIX 264 266 {ECO:0000244|PDB:4RED}. FT HELIX 270 274 {ECO:0000244|PDB:4RED}. FT HELIX 277 280 {ECO:0000244|PDB:4RED}. FT TURN 296 298 {ECO:0000244|PDB:4RED}. FT HELIX 301 310 {ECO:0000244|PDB:4RED}. FT HELIX 315 323 {ECO:0000244|PDB:4RED}. FT HELIX 330 340 {ECO:0000244|PDB:4RED}. FT TURN 347 351 {ECO:0000244|PDB:4RED}. SQ SEQUENCE 559 AA; 64009 MW; ABAE71FBF912947A CRC64; MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG HKVAVKILNR QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG ELFDYICKNG RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG LSNMMSDGEF LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG IFYTPQYLNP SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD FYLATSPPDS FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ GVRKAKWHLG IRSQSRPNDI MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP VTSTYSKMSL QLYQVDSRTY LLDFRSIDDE ITEAKSGTAT PQRSGSVSNY RSCQRSDSDA EAQGKSSEVS LTSSVTSLDS SPVDLTPRPG SHTIEFFEMC ANLIKILAQ //