AAPK1_HUMAN
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 03-AUG-2022, entry version 229.
DE RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-1;
DE Short=AMPK subunit alpha-1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:32029622};
DE AltName: Full=Acetyl-CoA carboxylase kinase;
DE Short=ACACA kinase;
DE EC=2.7.11.27 {ECO:0000250|UniProtKB:P54645};
DE AltName: Full=Hydroxymethylglutaryl-CoA reductase kinase;
DE Short=HMGCR kinase;
DE EC=2.7.11.31 {ECO:0000250|UniProtKB:P54645};
DE AltName: Full=Tau-protein kinase PRKAA1;
DE EC=2.7.11.26 {ECO:0000250|UniProtKB:P54645};
GN Name=PRKAA1; Synonyms=AMPK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., 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 project:
RT 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 alpha-
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT 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., Teh T.,
RA 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-activated
RT 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 receptors.";
RL J. Biol. Chem. 276:38341-38344(2001).
RN [11]
RP ACTIVITY 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., Goodyear L.J.,
RA Moller D.E.;
RT "Role of AMP-activated protein kinase in mechanism of metformin 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 kinase
RT 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 ACTIVITY REGULATION.
RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110;
RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J.,
RA Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily,
RT including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [15]
RP PHOSPHORYLATION AT THR-183, AND ACTIVITY 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 upstream
RT kinase for AMP-activated protein kinase.";
RL Cell Metab. 2:9-19(2005).
RN [16]
RP PHOSPHORYLATION AT THR-183, AND ACTIVITY 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-activated
RT 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., Birnbaum M.J.,
RA 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., Iwamatsu A.,
RA Esposito D., Gillette W.K., Hopkins R.F. III, Hartley J.L., Furihata M.,
RA Oishi S., Zhen W., Burke T.R. Jr., 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-activated
RT 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., Gygi S.P.,
RA 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 protein
RT 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., Schertzer J.D.,
RA 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., Valera V.A.,
RA 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 BY
RP 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., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT 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 the
RT 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., Zhang D.,
RA 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 AND
RP SER-496, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 BY
RP 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., Rutter G.A.;
RT "Cell-wide analysis of secretory granule dynamics in three dimensions in
RT living pancreatic beta-cells: evidence against a role for AMPK-dependent
RT phosphorylation of KLC1 at Ser517/Ser520 in glucose-stimulated insulin
RT 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., Inoki K.,
RA Guan K.L., Shen J., Person M.D., Kusewitt D., Mills G.B., Kastan M.B.,
RA Walker C.L.;
RT "ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to
RT 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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 regulatory
RT 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., Buerckstuemmer T.,
RA 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 connects
RT energy sensing to mitophagy.";
RL Science 331:456-461(2011).
RN [38]
RP INTERACTION WITH PRKAB1 AND PRKAG1, AND ACTIVITY 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., 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 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., Takano-Yamamoto T.,
RA Tamura S., Kobayashi T.;
RT "N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to
RT dephosphorylate their physiological substrates in cells.";
RL Biochem. J. 449:741-749(2013).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32; THR-382; SER-486; THR-490
RP AND SER-496, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-355; SER-496; SER-508;
RP SER-524 AND SER-527, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [44]
RP FUNCTION.
RX PubMed=28561066; DOI=10.1038/ncomms15637;
RA Bakula D., Mueller A.J., Zuleger T., Takacs Z., Franz-Wachtel M.,
RA Thost A.K., Brigger D., Tschan M.P., Frickey T., Robenek H., Macek B.,
RA Proikas-Cezanne T.;
RT "WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling
RT circuits in the control of autophagy.";
RL Nat. Commun. 8:15637-15637(2017).
RN [45]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32029622; DOI=10.1126/science.aay0542;
RA Zhao P., Sun X., Chaggan C., Liao Z., In Wong K., He F., Singh S.,
RA Loomba R., Karin M., Witztum J.L., Saltiel A.R.;
RT "An AMPK-caspase-6 axis controls liver damage in nonalcoholic
RT steatohepatitis.";
RL Science 367:652-660(2020).
RN [46]
RP FUNCTION.
RX PubMed=34077757; DOI=10.1016/j.molcel.2021.05.005;
RA Liu R., Lee J.H., Li J., Yu R., Tan L., Xia Y., Zheng Y., Bian X.L.,
RA Lorenzi P.L., Chen Q., Lu Z.;
RT "Choline kinase alpha 2 acts as a protein kinase to promote lipolysis of
RT lipid droplets.";
RL Mol. Cell 81:2722-2735(2021).
RN [47]
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., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Catalytic subunit of AMP-activated protein kinase (AMPK), an
CC energy sensor protein kinase that plays a key role in regulating
CC cellular energy metabolism (PubMed:17307971, PubMed:17712357). In
CC response to reduction of intracellular ATP levels, AMPK activates
CC energy-producing pathways and inhibits energy-consuming processes:
CC inhibits protein, carbohydrate and lipid biosynthesis, as well as cell
CC growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts
CC via direct phosphorylation of metabolic enzymes, and by longer-term
CC effects via phosphorylation of transcription regulators
CC (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by
CC phosphorylating and inactivating lipid metabolic enzymes such as ACACA,
CC ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol
CC synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB)
CC and hormone-sensitive lipase (LIPE) enzymes, respectively (By
CC similarity). Promotes lipolysis of lipid droplets by mediating
CC phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757).
CC Regulates insulin-signaling and glycolysis by phosphorylating IRS1,
CC PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in
CC muscle by increasing the translocation of the glucose transporter
CC SLC2A4/GLUT4 to the plasma membrane, possibly by mediating
CC phosphorylation of TBC1D4/AS160 (By similarity). Regulates
CC transcription and chromatin structure by phosphorylating transcription
CC regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3,
CC histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53,
CC SREBF1, SREBF2 and PPARGC1A (PubMed:11554766, PubMed:11518699,
CC PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key
CC regulator of glucose homeostasis in liver by phosphorylating
CC CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By
CC similarity). In response to stress, phosphorylates 'Ser-36' of histone
CC H2B (H2BS36ph), leading to promote transcription (By similarity). Acts
CC as a key regulator of cell growth and proliferation by phosphorylating
CC TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation,
CC negatively regulates the mTORC1 complex by phosphorylating RPTOR
CC component of the mTORC1 complex and by phosphorylating and activating
CC TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076,
CC PubMed:21205641). In response to nutrient limitation, promotes
CC autophagy by phosphorylating and activating ATG1/ULK1
CC (PubMed:21205641). In that process also activates WDR45/WIPI4
CC (PubMed:28561066). Phosphorylates CASP6, thereby preventing its
CC autoprocessing and subsequent activation (PubMed:32029622). In response
CC to nutrient limitation, phosphorylates transcription factor FOXO3
CC promoting FOXO3 mitochondrial import (By similarity). Also acts as a
CC regulator of cellular polarity by remodeling the actin cytoskeleton;
CC probably by indirectly activating myosin (PubMed:17486097). AMPK also
CC acts as a regulator of circadian rhythm by mediating phosphorylation of
CC CRY1, leading to destabilize it (By similarity). May regulate the Wnt
CC signaling pathway by phosphorylating CTNNB1, leading to stabilize it
CC (By similarity). Also has tau-protein kinase activity: in response to
CC amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to
CC phosphorylation of MAPT/TAU; however the relevance of such data remains
CC unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1,
CC NOS3 and SLC12A1 (PubMed:20074060, PubMed:12519745).
CC {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47,
CC ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766,
CC ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849,
CC ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097,
CC ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930,
CC ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060,
CC ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641,
CC ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622,
CC ECO:0000269|PubMed:34077757, ECO:0000303|PubMed:17307971,
CC ECO:0000303|PubMed:17712357}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:32029622};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P54645};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[acetyl-CoA carboxylase] = ADP + H(+) + O-
CC phospho-L-seryl-[acetyl-CoA carboxylase]; Xref=Rhea:RHEA:20333,
CC Rhea:RHEA-COMP:13722, Rhea:RHEA-COMP:13723, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.27;
CC Evidence={ECO:0000250|UniProtKB:P54645};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A
CC reductase] = ADP + H(+) + O-phospho-L-seryl-[3-hydroxy-3-
CC methylglutaryl-coenzyme A reductase]; Xref=Rhea:RHEA:23172,
CC Rhea:RHEA-COMP:13692, Rhea:RHEA-COMP:13693, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.31;
CC Evidence={ECO:0000250|UniProtKB:P54645};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC Evidence={ECO:0000250|UniProtKB:P54645};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26; Evidence={ECO:0000250|UniProtKB:P54645};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-183. Binding
CC of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3)
CC results in allosteric activation, inducing phosphorylation on Thr-183.
CC AMP-binding to gamma subunit also sustains activity by preventing
CC dephosphorylation of Thr-183. ADP also stimulates Thr-183
CC phosphorylation, without stimulating already phosphorylated AMPK. ATP
CC promotes dephosphorylation of Thr-183, rendering the enzyme inactive.
CC Under physiological conditions AMPK mainly exists in its inactive form
CC in complex with ATP, which is much more abundant than AMP. AMPK is
CC activated by antihyperglycemic drug metformin, a drug prescribed to
CC patients with type 2 diabetes: in vivo, metformin seems to mainly
CC inhibit liver gluconeogenesis. However, metformin can be used to
CC activate AMPK in muscle and other cells in culture or ex vivo
CC (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-
CC Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a]
CC pyrimidine. Activated by resveratrol, a natural polyphenol present in
CC red wine, and S17834, a synthetic polyphenol.
CC {ECO:0000269|PubMed:11602624, ECO:0000269|PubMed:14976552,
CC ECO:0000269|PubMed:15980064, ECO:0000269|PubMed:16054095,
CC ECO:0000269|PubMed:21680840}.
CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1
CC or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic
CC subunits (PRKAG1, PRKAG2 or PRKAG3) (PubMed:21680840). Interacts with
CC FNIP1 and FNIP2 (PubMed:17028174, PubMed:18403135, PubMed:18663353).
CC {ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18403135,
CC ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:21680840}.
CC -!- INTERACTION:
CC Q13131; Q9NYB9: ABI2; NbExp=5; IntAct=EBI-1181405, EBI-743598;
CC Q13131; O14503: BHLHE40; NbExp=3; IntAct=EBI-1181405, EBI-711810;
CC Q13131; O14627: CDX4; NbExp=3; IntAct=EBI-1181405, EBI-10181162;
CC Q13131; Q13363-2: CTBP1; NbExp=3; IntAct=EBI-1181405, EBI-10171858;
CC Q13131; O95073: FSBP; NbExp=3; IntAct=EBI-1181405, EBI-1059030;
CC Q13131; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1181405, EBI-618309;
CC Q13131; Q6NT76: HMBOX1; NbExp=3; IntAct=EBI-1181405, EBI-2549423;
CC Q13131; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-1181405, EBI-10172004;
CC Q13131; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1181405, EBI-352572;
CC Q13131; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-1181405, EBI-747204;
CC Q13131; Q8NBZ0: INO80E; NbExp=3; IntAct=EBI-1181405, EBI-769401;
CC Q13131; Q6A162: KRT40; NbExp=3; IntAct=EBI-1181405, EBI-10171697;
CC Q13131; Q96JM7: L3MBTL3; NbExp=3; IntAct=EBI-1181405, EBI-2686809;
CC Q13131; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-1181405, EBI-742948;
CC Q13131; Q8IXK0: PHC2; NbExp=3; IntAct=EBI-1181405, EBI-713786;
CC Q13131; Q96PV4: PNMA5; NbExp=4; IntAct=EBI-1181405, EBI-10171633;
CC Q13131; Q9Y478: PRKAB1; NbExp=9; IntAct=EBI-1181405, EBI-719769;
CC Q13131; O43741: PRKAB2; NbExp=16; IntAct=EBI-1181405, EBI-1053424;
CC Q13131; P54619: PRKAG1; NbExp=14; IntAct=EBI-1181405, EBI-1181439;
CC Q13131; Q93062: RBPMS; NbExp=3; IntAct=EBI-1181405, EBI-740322;
CC Q13131; Q8HWS3: RFX6; NbExp=3; IntAct=EBI-1181405, EBI-746118;
CC Q13131; Q9UFD9: RIMBP3; NbExp=3; IntAct=EBI-1181405, EBI-10182375;
CC Q13131; Q9HAT0: ROPN1; NbExp=4; IntAct=EBI-1181405, EBI-1378139;
CC Q13131; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-1181405, EBI-2212028;
CC Q13131; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-1181405, EBI-741515;
CC Q13131; Q08117: TLE5; NbExp=3; IntAct=EBI-1181405, EBI-717810;
CC Q13131; P14373: TRIM27; NbExp=3; IntAct=EBI-1181405, EBI-719493;
CC Q13131; Q15654: TRIP6; NbExp=3; IntAct=EBI-1181405, EBI-742327;
CC Q13131; Q9Y3Q8: TSC22D4; NbExp=3; IntAct=EBI-1181405, EBI-739485;
CC Q13131; Q5T124: UBXN11; NbExp=3; IntAct=EBI-1181405, EBI-746004;
CC Q13131; Q9H9H4: VPS37B; NbExp=3; IntAct=EBI-1181405, EBI-4400866;
CC Q13131; Q8N1B4: VPS52; NbExp=3; IntAct=EBI-1181405, EBI-2799833;
CC Q13131; P46937: YAP1; NbExp=3; IntAct=EBI-1181405, EBI-1044059;
CC Q13131; O96006: ZBED1; NbExp=3; IntAct=EBI-1181405, EBI-740037;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15866171}. Nucleus
CC {ECO:0000269|PubMed:15866171}. Note=In response to stress, recruited by
CC p53/TP53 to specific promoters. {ECO:0000269|PubMed:15866171}.
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 sequence
CC similarity with the ubiquitin-associated domains and represses kinase
CC activity. {ECO:0000269|PubMed:17088252, ECO:0000269|PubMed:9857077}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q5EG47}.
CC -!- PTM: Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-
CC 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 AMP/ATP
CC ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower
CC level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and
CC PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate
CC AMPK activity and suggesting the existence of a regulatory feedback
CC loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B.
CC {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15980064,
CC ECO:0000269|PubMed:16054095, ECO:0000269|PubMed:21460634}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA64850.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD43027.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH37303.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA36547.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG35788.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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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 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 PDB; 5EZV; X-ray; 2.99 A; A/C=359-401.
DR PDB; 6C9F; X-ray; 2.92 A; A=22-559.
DR PDB; 6C9G; X-ray; 2.70 A; A=22-559.
DR PDB; 6C9H; X-ray; 2.65 A; A=22-559.
DR PDB; 6C9J; X-ray; 3.05 A; A=22-559.
DR PDB; 7JHG; EM; 3.47 A; A=22-559.
DR PDB; 7JHH; EM; 3.92 A; A=22-559.
DR PDB; 7JIJ; X-ray; 5.50 A; A=22-559.
DR PDBsum; 4RED; -.
DR PDBsum; 4RER; -.
DR PDBsum; 4REW; -.
DR PDBsum; 5EZV; -.
DR PDBsum; 6C9F; -.
DR PDBsum; 6C9G; -.
DR PDBsum; 6C9H; -.
DR PDBsum; 6C9J; -.
DR PDBsum; 7JHG; -.
DR PDBsum; 7JHH; -.
DR PDBsum; 7JIJ; -.
DR AlphaFoldDB; Q13131; -.
DR SMR; Q13131; -.
DR BioGRID; 111549; 241.
DR ComplexPortal; CPX-5633; AMPK complex, alpha1-beta1-gamma1 variant.
DR ComplexPortal; CPX-5786; AMPK complex, alpha1-beta1-gamma2 variant.
DR ComplexPortal; CPX-5791; AMPK complex, alpha1-beta2-gamma1 variant.
DR ComplexPortal; CPX-5841; AMPK complex, alpha1-beta2-gamma3 variant.
DR ComplexPortal; CPX-5842; AMPK complex, alpha1-beta1-gamma3 variant.
DR ComplexPortal; CPX-5846; AMPK complex, alpha1-beta2-gamma2 variant.
DR CORUM; Q13131; -.
DR DIP; DIP-39973N; -.
DR IntAct; Q13131; 121.
DR MINT; Q13131; -.
DR STRING; 9606.ENSP00000346148; -.
DR BindingDB; Q13131; -.
DR ChEMBL; CHEMBL4045; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB00131; Adenosine phosphate.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00914; Phenformin.
DR DrugBank; DB00273; Topiramate.
DR DrugCentral; Q13131; -.
DR GlyGen; Q13131; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13131; -.
DR PhosphoSitePlus; Q13131; -.
DR BioMuta; PRKAA1; -.
DR DMDM; 254763436; -.
DR EPD; Q13131; -.
DR jPOST; Q13131; -.
DR MassIVE; Q13131; -.
DR MaxQB; Q13131; -.
DR PaxDb; Q13131; -.
DR PeptideAtlas; Q13131; -.
DR PRIDE; Q13131; -.
DR ProteomicsDB; 59180; -. [Q13131-1]
DR ProteomicsDB; 59181; -. [Q13131-2]
DR ABCD; Q13131; 1 sequenced antibody.
DR Antibodypedia; 3564; 1478 antibodies from 46 providers.
DR DNASU; 5562; -.
DR Ensembl; ENST00000354209.7; ENSP00000346148.3; ENSG00000132356.12. [Q13131-2]
DR Ensembl; ENST00000397128.7; ENSP00000380317.2; ENSG00000132356.12. [Q13131-1]
DR GeneID; 5562; -.
DR KEGG; hsa:5562; -.
DR MANE-Select; ENST00000397128.7; ENSP00000380317.2; NM_006251.6; NP_006242.5.
DR UCSC; uc003jmb.4; human. [Q13131-1]
DR CTD; 5562; -.
DR DisGeNET; 5562; -.
DR GeneCards; PRKAA1; -.
DR HGNC; HGNC:9376; PRKAA1.
DR HPA; ENSG00000132356; Low tissue specificity.
DR MIM; 602739; gene.
DR neXtProt; NX_Q13131; -.
DR OpenTargets; ENSG00000132356; -.
DR PharmGKB; PA33744; -.
DR VEuPathDB; HostDB:ENSG00000132356; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000158865; -.
DR HOGENOM; CLU_000288_59_3_1; -.
DR OMA; HHFTRPH; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q13131; -.
DR TreeFam; TF314032; -.
DR BRENDA; 2.7.11.1; 2681.
DR BRENDA; 2.7.11.31; 2681.
DR PathwayCommons; Q13131; -.
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 Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-9619483; Activation of AMPK downstream of NMDARs.
DR SignaLink; Q13131; -.
DR SIGNOR; Q13131; -.
DR BioGRID-ORCS; 5562; 25 hits in 1107 CRISPR screens.
DR ChiTaRS; PRKAA1; human.
DR GeneWiki; Protein_kinase,_AMP-activated,_alpha_1; -.
DR GenomeRNAi; 5562; -.
DR Pharos; Q13131; Tclin.
DR PRO; PR:Q13131; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q13131; protein.
DR Bgee; ENSG00000132356; Expressed in calcaneal tendon and 176 other tissues.
DR ExpressionAtlas; Q13131; baseline and differential.
DR Genevisible; Q13131; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IPI:ComplexPortal.
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:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; NAS:ARUK-UCL.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0015721; P:bile acid and bile salt transport; IEA:Ensembl.
DR GO; GO:0038183; P:bile acid signaling pathway; IEA:Ensembl.
DR GO; GO:0061762; P:CAMKK-AMPK signaling cascade; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:ARUK-UCL.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR GO; GO:0042149; P:cellular response to glucose starvation; IDA:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:ARUK-UCL.
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; IDA:ComplexPortal.
DR GO; GO:0071417; P:cellular response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:ARUK-UCL.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0009631; P:cold acclimation; IEA:Ensembl.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
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:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:1905691; P:lipid droplet disassembly; IDA:UniProtKB.
DR GO; GO:0061744; P:motor behavior; IGI:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0046318; P:negative regulation of glucosylceramide biosynthetic process; NAS:UniProtKB.
DR GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; IDA:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Ensembl.
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:1904428; P:negative regulation of tubulin deacetylation; ISS:ARUK-UCL.
DR GO; GO:0070050; P:neuron cellular homeostasis; IGI:ARUK-UCL.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:ParkinsonsUK-UCL.
DR GO; GO:0008284; P:positive regulation of cell population 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:1903109; P:positive regulation of mitochondrial transcription; IEA:Ensembl.
DR GO; GO:2000758; P:positive regulation of peptidyl-lysine acetylation; ISS:ARUK-UCL.
DR GO; GO:1903829; P:positive regulation of protein localization; ISS:ARUK-UCL.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; IEA:Ensembl.
DR GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Ensembl.
DR GO; GO:1990044; P:protein localization to lipid droplet; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0120188; P:regulation of bile acid secretion; IEA:Ensembl.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:ARUK-UCL.
DR GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0062028; P:regulation of stress granule assembly; IEA:Ensembl.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; IEA:Ensembl.
DR GO; GO:1904486; P:response to 17alpha-ethynylestradiol; 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:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd12199; AMPKA1_C; 1.
DR CDD; cd14403; UBA_AID_AAPK1; 1.
DR InterPro; IPR032270; AMPK_C.
DR InterPro; IPR039137; AMPKA1_C.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR028797; PRKAA1_UBA.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; Cytoplasm; Fatty acid biosynthesis;
KW Fatty acid metabolism; Kinase; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Wnt signaling pathway.
FT CHAIN 1..559
FT /note="5'-AMP-activated protein kinase catalytic subunit
FT alpha-1"
FT /id="PRO_0000085589"
FT DOMAIN 27..279
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 302..381
FT /note="AIS"
FT REGION 485..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 33..41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 32
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 183
FT /note="Phosphothreonine; by LKB1 and CaMKK2"
FT /evidence="ECO:0000250|UniProtKB:Q5EG47"
FT MOD_RES 269
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P54645"
FT MOD_RES 355
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 360
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P54645"
FT MOD_RES 368
FT /note="Phosphothreonine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P54645"
FT MOD_RES 382
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54645"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 488
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P54645"
FT MOD_RES 490
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 121
FT /note="R -> RKSDVPGVVKTGSTKE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035431"
FT VARIANT 10
FT /note="M -> L (in dbSNP:rs17855679)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_058401"
FT VARIANT 16
FT /note="Q -> R (in a breast cancer sample; somatic mutation;
FT dbSNP:rs928784854)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035622"
FT MUTAGEN 307
FT /note="V->G,Q: Activates the kinase activity."
FT /evidence="ECO:0000269|PubMed:17088252"
FT CONFLICT 5
FT /note="S -> C (in Ref. 4; BAG35788)"
FT /evidence="ECO:0000305"
FT CONFLICT 9
FT /note="K -> S (in Ref. 5; AAD43027)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="T -> A (in Ref. 6; AAA64850)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="A -> V (in Ref. 6; AAA64850)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="I -> L (in Ref. 6; AAA64850)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="T -> S (in Ref. 3; BAA36547)"
FT /evidence="ECO:0000305"
FT STRAND 27..34
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:6C9G"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:6C9H"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 60..65
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 69..81
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:6C9J"
FT HELIX 112..119
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 124..143
FT /evidence="ECO:0007829|PDB:6C9H"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:7JHG"
FT HELIX 180..186
FT /evidence="ECO:0007829|PDB:7JHG"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 204..220
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:4RED"
FT HELIX 230..239
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:7JHG"
FT HELIX 250..259
FT /evidence="ECO:0007829|PDB:6C9H"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 270..275
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:6C9G"
FT HELIX 298..305
FT /evidence="ECO:0007829|PDB:6C9H"
FT TURN 323..325
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 330..345
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:6C9H"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 375..379
FT /evidence="ECO:0007829|PDB:6C9J"
FT STRAND 408..413
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 417..430
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 434..439
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 442..448
FT /evidence="ECO:0007829|PDB:6C9H"
FT TURN 450..452
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 455..464
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:6C9H"
FT STRAND 470..476
FT /evidence="ECO:0007829|PDB:6C9H"
FT HELIX 542..557
FT /evidence="ECO:0007829|PDB:6C9H"
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
