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Database: UniProt
Entry: P54619
LinkDB: P54619
Original site: P54619 
ID   AAKG1_HUMAN             Reviewed;         331 AA.
AC   P54619; B4DDT7; Q8N7V9;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   17-JUN-2020, entry version 188.
DE   RecName: Full=5'-AMP-activated protein kinase subunit gamma-1;
DE            Short=AMPK gamma1;
DE            Short=AMPK subunit gamma-1;
DE            Short=AMPKg;
GN   Name=PRKAG1;
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 [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Fetal liver;
RX   PubMed=8621499; DOI=10.1074/jbc.271.15.8675;
RA   Gao G., Fernandez C.S., Stapleton D., Auster A.S., Widmer J., Dyck J.R.B.,
RA   Kemp B.E., Witters L.A.;
RT   "Non-catalytic beta- and gamma-subunit isoforms of the 5'-AMP-activated
RT   protein kinase.";
RL   J. Biol. Chem. 271:8675-8681(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC   TISSUE=Glial tumor, and Testis;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Muscle;
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   [6]
RP   DOMAIN CBS, AMP-BINDING, AND ATP-BINDING.
RX   PubMed=14722619; DOI=10.1172/jci200419874;
RA   Scott J.W., Hawley S.A., Green K.A., Anis M., Stewart G., Scullion G.A.,
RA   Norman D.G., Hardie D.G.;
RT   "CBS domains form energy-sensing modules whose binding of adenosine ligands
RT   is disrupted by disease mutations.";
RL   J. Clin. Invest. 113:274-284(2004).
RN   [7]
RP   INTERACTION WITH FNIP1, AND IDENTIFICATION BY MASS SPECTROMETRY.
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   [8]
RP   DOMAIN AMPK PSEUDOSUBSTRATE.
RX   PubMed=17255938; DOI=10.1038/sj.emboj.7601542;
RA   Scott J.W., Ross F.A., Liu J.K., Hardie D.G.;
RT   "Regulation of AMP-activated protein kinase by a pseudosubstrate sequence
RT   on the gamma subunit.";
RL   EMBO J. 26:806-815(2007).
RN   [9]
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   [10]
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   [11]
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   [12]
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   [13]
RP   INTERACTION WITH PRKAA1 AND PRKAB1, DOMAIN CBS, ADP-BINDING, MUTAGENESIS OF
RP   ASP-90; ASP-245 AND ASP-317, AND FUNCTION.
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   [14]
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   [15]
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   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE 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., 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   [17]
RP   X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 182-325 IN COMPLEX WITH AMP.
RX   PubMed=17452784; DOI=10.1107/s0907444907009110;
RA   Day P., Sharff A., Parra L., Cleasby A., Williams M., Hoerer S., Nar H.,
RA   Redemann N., Tickle I., Yon J.;
RT   "Structure of a CBS-domain pair from the regulatory gamma1 subunit of human
RT   AMPK in complex with AMP and ZMP.";
RL   Acta Crystallogr. D 63:587-596(2007).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (3.02 ANGSTROMS) IN COMPLEX WITH AMP.
RX   PubMed=24352254; DOI=10.1038/ncomms4017;
RA   Xiao B., Sanders M.J., Carmena D., Bright N.J., Haire L.F., Underwood E.,
RA   Patel B.R., Heath R.B., Walker P.A., Hallen S., Giordanetto F.,
RA   Martin S.R., Carling D., Gamblin S.J.;
RT   "Structural basis of AMPK regulation by small molecule activators.";
RL   Nat. Commun. 4:3017-3017(2013).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (4.05 ANGSTROMS) OF 24-327 IN COMPLEX WITH AMP.
RX   PubMed=25412657; DOI=10.1038/cr.2014.150;
RA   Li X., Wang L., Zhou X.E., Ke J., de Waal P.W., Gu X., Tan M.H., Wang D.,
RA   Wu D., Xu H.E., Melcher K.;
RT   "Structural basis of AMPK regulation by adenine nucleotides and glycogen.";
RL   Cell Res. 25:50-66(2015).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS) OF 2-331.
RX   PubMed=26952388; DOI=10.1038/ncomms10912;
RA   Langendorf C.G., Ngoei K.R., Scott J.W., Ling N.X., Issa S.M., Gorman M.A.,
RA   Parker M.W., Sakamoto K., Oakhill J.S., Kemp B.E.;
RT   "Structural basis of allosteric and synergistic activation of AMPK by
RT   furan-2-phosphonic derivative C2 binding.";
RL   Nat. Commun. 7:10912-10912(2016).
CC   -!- FUNCTION: AMP/ATP-binding 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 and
CC       inhibits energy-consuming processes: inhibits protein, carbohydrate and
CC       lipid biosynthesis, as well as cell growth and proliferation. AMPK acts
CC       via direct phosphorylation of metabolic enzymes, and by longer-term
CC       effects via phosphorylation of transcription regulators. Also acts as a
CC       regulator of cellular polarity by remodeling the actin cytoskeleton;
CC       probably by indirectly activating myosin. Gamma non-catalytic subunit
CC       mediates binding to AMP, ADP and ATP, leading to activate or inhibit
CC       AMPK: AMP-binding results in allosteric activation of alpha catalytic
CC       subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and
CC       preventing dephosphorylation of catalytic subunits. ADP also stimulates
CC       phosphorylation, without stimulating already phosphorylated catalytic
CC       subunit. ATP promotes dephosphorylation of catalytic subunit, rendering
CC       the AMPK enzyme inactive. {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). Interacts with FNIP1 and FNIP2.
CC       {ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18403135,
CC       ECO:0000269|PubMed:21680840}.
CC   -!- INTERACTION:
CC       P54619; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-1181439, EBI-946029;
CC       P54619; P35520: CBS; NbExp=3; IntAct=EBI-1181439, EBI-740135;
CC       P54619; Q14145: KEAP1; NbExp=6; IntAct=EBI-1181439, EBI-751001;
CC       P54619; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-1181439, EBI-11959885;
CC       P54619; P60412: KRTAP10-11; NbExp=5; IntAct=EBI-1181439, EBI-10217483;
CC       P54619; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-1181439, EBI-10172150;
CC       P54619; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-1181439, EBI-739863;
CC       P54619; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-1181439, EBI-10172511;
CC       P54619; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-1181439, EBI-1044640;
CC       P54619; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-1181439, EBI-11958364;
CC       P54619; P50221: MEOX1; NbExp=3; IntAct=EBI-1181439, EBI-2864512;
CC       P54619; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1181439, EBI-16439278;
CC       P54619; P26367: PAX6; NbExp=3; IntAct=EBI-1181439, EBI-747278;
CC       P54619; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-1181439, EBI-742388;
CC       P54619; Q13131: PRKAA1; NbExp=13; IntAct=EBI-1181439, EBI-1181405;
CC       P54619; P54646: PRKAA2; NbExp=12; IntAct=EBI-1181439, EBI-1383852;
CC       P54619; Q9Y478: PRKAB1; NbExp=12; IntAct=EBI-1181439, EBI-719769;
CC       P54619; O43741: PRKAB2; NbExp=16; IntAct=EBI-1181439, EBI-1053424;
CC       P54619; Q969V4: TEKT1; NbExp=6; IntAct=EBI-1181439, EBI-10180409;
CC       P54619; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-1181439, EBI-2505861;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P54619-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P54619-2; Sequence=VSP_046711;
CC       Name=3;
CC         IsoId=P54619-3; Sequence=VSP_046712;
CC   -!- DOMAIN: The AMPK pseudosubstrate motif resembles the sequence around
CC       sites phosphorylated on target proteins of AMPK, except the presence of
CC       a non-phosphorylatable residue in place of Ser. In the absence of AMP
CC       this pseudosubstrate sequence may bind to the active site groove on the
CC       alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the
CC       upstream activating kinase STK11/LKB1.
CC   -!- DOMAIN: The 4 CBS domains mediate binding to nucleotides. Of the 4
CC       potential nucleotide-binding sites, 3 are occupied, designated as sites
CC       1, 3, and 4 based on the CBS modules that provide the acidic residue
CC       for coordination with the 2'- and 3'-hydroxyl groups of the ribose of
CC       AMP. Of these, site 4 appears to be a structural site that retains a
CC       tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can
CC       bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-
CC       affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP,
CC       ADP or ATP 2) is the weakest nucleotide-binding site on the gamma
CC       subunit, yet it is exquisitely sensitive to changes in nucleotide
CC       levels and this allows AMPK to respond rapidly to changes in cellular
CC       energy status. Site 3 is likely to be responsible for protection of a
CC       conserved threonine in the activation loop of the alpha catalytic
CC       subunit through conformational changes induced by binding of AMP or
CC       ADP. {ECO:0000269|PubMed:17452784, ECO:0000269|PubMed:24352254,
CC       ECO:0000269|PubMed:25412657}.
CC   -!- PTM: 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. {ECO:0000269|PubMed:21460634}.
CC   -!- MISCELLANEOUS: [Isoform 3]: May be due to competing acceptor splice
CC       site. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma
CC       subunit family. {ECO:0000305}.
DR   EMBL; U42412; AAC50495.1; -; mRNA.
DR   EMBL; BT007345; AAP36009.1; -; mRNA.
DR   EMBL; AK097606; BAC05117.1; -; mRNA.
DR   EMBL; AK293332; BAG56848.1; -; mRNA.
DR   EMBL; AC011603; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC000358; AAH00358.1; -; mRNA.
DR   CCDS; CCDS55824.1; -. [P54619-2]
DR   CCDS; CCDS55825.1; -. [P54619-3]
DR   CCDS; CCDS8777.1; -. [P54619-1]
DR   RefSeq; NP_001193638.1; NM_001206709.1. [P54619-3]
DR   RefSeq; NP_001193639.1; NM_001206710.1. [P54619-2]
DR   RefSeq; NP_002724.1; NM_002733.4. [P54619-1]
DR   RefSeq; XP_006719562.1; XM_006719499.2.
DR   RefSeq; XP_011536864.1; XM_011538562.2. [P54619-2]
DR   PDB; 2UV4; X-ray; 1.33 A; A=182-325.
DR   PDB; 2UV5; X-ray; 1.69 A; A=182-325.
DR   PDB; 2UV6; X-ray; 2.00 A; A=182-325.
DR   PDB; 2UV7; X-ray; 2.00 A; A=182-325.
DR   PDB; 4CFE; X-ray; 3.02 A; E/F=1-331.
DR   PDB; 4CFF; X-ray; 3.92 A; E/F=1-331.
DR   PDB; 4RER; X-ray; 4.05 A; G=24-327.
DR   PDB; 4REW; X-ray; 4.58 A; G=24-327.
DR   PDB; 4ZHX; X-ray; 2.99 A; E/F=2-331.
DR   PDB; 5EZV; X-ray; 2.99 A; E/F=2-331.
DR   PDB; 5ISO; X-ray; 2.63 A; E/F=1-331.
DR   PDB; 6B1U; X-ray; 2.77 A; E/F=2-331.
DR   PDB; 6B2E; X-ray; 3.80 A; C=2-331.
DR   PDB; 6C9F; X-ray; 2.92 A; C=1-331.
DR   PDB; 6C9G; X-ray; 2.70 A; C=1-331.
DR   PDB; 6C9H; X-ray; 2.65 A; C=1-331.
DR   PDB; 6C9J; X-ray; 3.05 A; C=1-325.
DR   PDBsum; 2UV4; -.
DR   PDBsum; 2UV5; -.
DR   PDBsum; 2UV6; -.
DR   PDBsum; 2UV7; -.
DR   PDBsum; 4CFE; -.
DR   PDBsum; 4CFF; -.
DR   PDBsum; 4RER; -.
DR   PDBsum; 4REW; -.
DR   PDBsum; 4ZHX; -.
DR   PDBsum; 5EZV; -.
DR   PDBsum; 5ISO; -.
DR   PDBsum; 6B1U; -.
DR   PDBsum; 6B2E; -.
DR   PDBsum; 6C9F; -.
DR   PDBsum; 6C9G; -.
DR   PDBsum; 6C9H; -.
DR   PDBsum; 6C9J; -.
DR   SMR; P54619; -.
DR   BioGRID; 111558; 61.
DR   CORUM; P54619; -.
DR   DIP; DIP-39974N; -.
DR   IntAct; P54619; 59.
DR   MINT; P54619; -.
DR   STRING; 9606.ENSP00000323867; -.
DR   BindingDB; P54619; -.
DR   ChEMBL; CHEMBL2393; -.
DR   DrugBank; DB00945; Acetylsalicylic acid.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugBank; DB00273; Topiramate.
DR   iPTMnet; P54619; -.
DR   PhosphoSitePlus; P54619; -.
DR   BioMuta; PRKAG1; -.
DR   DMDM; 1703037; -.
DR   EPD; P54619; -.
DR   jPOST; P54619; -.
DR   MassIVE; P54619; -.
DR   MaxQB; P54619; -.
DR   PaxDb; P54619; -.
DR   PeptideAtlas; P54619; -.
DR   PRIDE; P54619; -.
DR   ProteomicsDB; 3890; -.
DR   ProteomicsDB; 56688; -. [P54619-1]
DR   Antibodypedia; 25778; 434 antibodies.
DR   DNASU; 5571; -.
DR   Ensembl; ENST00000316299; ENSP00000323867; ENSG00000181929. [P54619-3]
DR   Ensembl; ENST00000548065; ENSP00000447433; ENSG00000181929. [P54619-1]
DR   Ensembl; ENST00000552212; ENSP00000448972; ENSG00000181929. [P54619-2]
DR   GeneID; 5571; -.
DR   KEGG; hsa:5571; -.
DR   UCSC; uc001rsy.4; human. [P54619-1]
DR   CTD; 5571; -.
DR   DisGeNET; 5571; -.
DR   EuPathDB; HostDB:ENSG00000181929.11; -.
DR   GeneCards; PRKAG1; -.
DR   HGNC; HGNC:9385; PRKAG1.
DR   HPA; ENSG00000181929; Low tissue specificity.
DR   MIM; 602742; gene.
DR   neXtProt; NX_P54619; -.
DR   OpenTargets; ENSG00000181929; -.
DR   PharmGKB; PA33751; -.
DR   eggNOG; KOG1764; Eukaryota.
DR   eggNOG; COG0517; LUCA.
DR   GeneTree; ENSGT00950000183019; -.
DR   HOGENOM; CLU_021740_3_0_1; -.
DR   KO; K07200; -.
DR   OMA; LNCKETK; -.
DR   OrthoDB; 631088at2759; -.
DR   PhylomeDB; P54619; -.
DR   TreeFam; TF313247; -.
DR   Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane.
DR   Reactome; R-HSA-1632852; Macroautophagy.
DR   Reactome; R-HSA-2151209; Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
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-9613354; Lipophagy.
DR   Reactome; R-HSA-9619483; Activation of AMPK downstream of NMDARs.
DR   SignaLink; P54619; -.
DR   SIGNOR; P54619; -.
DR   BioGRID-ORCS; 5571; 34 hits in 790 CRISPR screens.
DR   ChiTaRS; PRKAG1; human.
DR   EvolutionaryTrace; P54619; -.
DR   GeneWiki; PRKAG1; -.
DR   GenomeRNAi; 5571; -.
DR   Pharos; P54619; Tbio.
DR   PRO; PR:P54619; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P54619; protein.
DR   Bgee; ENSG00000181929; Expressed in gastrocnemius and 222 other tissues.
DR   ExpressionAtlas; P54619; baseline and differential.
DR   Genevisible; P54619; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0031588; C:nucleotide-activated protein kinase complex; ISS:UniProtKB.
DR   GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR   GO; GO:0016208; F:AMP binding; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR   GO; GO:0004691; F:cAMP-dependent protein kinase activity; TAS:ProtInc.
DR   GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; TAS:BHF-UCL.
DR   GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IDA:BHF-UCL.
DR   GO; GO:0019887; F:protein kinase regulator activity; ISS:GO_Central.
DR   GO; GO:0007050; P:cell cycle arrest; TAS:Reactome.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0051170; P:import into nucleus; IEA:Ensembl.
DR   GO; GO:0016236; P:macroautophagy; TAS:Reactome.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR   GO; GO:0045860; P:positive regulation of protein kinase activity; TAS:BHF-UCL.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0006110; P:regulation of glycolytic process; TAS:BHF-UCL.
DR   GO; GO:0016241; P:regulation of macroautophagy; TAS:Reactome.
DR   GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
DR   IDEAL; IID00660; -.
DR   InterPro; IPR039166; AMPKG-1.
DR   InterPro; IPR000644; CBS_dom.
DR   PANTHER; PTHR13780:SF38; PTHR13780:SF38; 1.
DR   Pfam; PF00571; CBS; 3.
DR   SMART; SM00116; CBS; 4.
DR   PROSITE; PS51371; CBS; 4.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; CBS domain;
KW   Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism;
KW   Lipid biosynthesis; Lipid metabolism; Nucleotide-binding; Phosphoprotein;
KW   Polymorphism; Reference proteome; Repeat.
FT   CHAIN           1..331
FT                   /note="5'-AMP-activated protein kinase subunit gamma-1"
FT                   /id="PRO_0000204377"
FT   DOMAIN          43..103
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   DOMAIN          125..187
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   DOMAIN          198..260
FT                   /note="CBS 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   DOMAIN          272..329
FT                   /note="CBS 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   NP_BIND         87..90
FT                   /note="AMP, ADP or ATP 1"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   NP_BIND         151..152
FT                   /note="AMP, ADP or ATP 1"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   NP_BIND         226..227
FT                   /note="AMP 3"
FT                   /evidence="ECO:0000269|PubMed:17452784,
FT                   ECO:0000269|PubMed:24352254, ECO:0000269|PubMed:25412657"
FT   NP_BIND         242..245
FT                   /note="AMP, ADP or ATP 2"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   NP_BIND         298..299
FT                   /note="AMP, ADP or ATP 2"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   NP_BIND         314..317
FT                   /note="AMP 3"
FT                   /evidence="ECO:0000269|PubMed:17452784,
FT                   ECO:0000269|PubMed:24352254, ECO:0000269|PubMed:25412657"
FT   MOTIF           138..159
FT                   /note="AMPK pseudosubstrate"
FT   BINDING         70
FT                   /note="AMP, ADP or ATP 2"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   BINDING         130
FT                   /note="AMP, ADP or ATP 1; via amide nitrogen and carbonyl
FT                   oxygen"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   BINDING         151
FT                   /note="AMP 3"
FT                   /evidence="ECO:0000269|PubMed:17452784,
FT                   ECO:0000269|PubMed:24352254, ECO:0000269|PubMed:25412657"
FT   BINDING         170
FT                   /note="AMP, ADP or ATP 2"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   BINDING         200
FT                   /note="AMP 3"
FT                   /evidence="ECO:0000269|PubMed:17452784,
FT                   ECO:0000269|PubMed:24352254, ECO:0000269|PubMed:25412657"
FT   BINDING         205
FT                   /note="AMP 3; via amide nitrogen and carbonyl oxygen"
FT                   /evidence="ECO:0000269|PubMed:17452784,
FT                   ECO:0000269|PubMed:24352254, ECO:0000269|PubMed:25412657"
FT   BINDING         269
FT                   /note="AMP, ADP or ATP 2"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   BINDING         277
FT                   /note="AMP, ADP or ATP 2; via amide nitrogen and carbonyl
FT                   oxygen"
FT                   /evidence="ECO:0000269|PubMed:24352254,
FT                   ECO:0000269|PubMed:25412657"
FT   BINDING         298
FT                   /note="AMP 3"
FT                   /evidence="ECO:0000269|PubMed:17452784,
FT                   ECO:0000269|PubMed:24352254, ECO:0000269|PubMed:25412657"
FT   MOD_RES         261
FT                   /note="Phosphoserine; by ULK1"
FT                   /evidence="ECO:0000250|UniProtKB:P80385"
FT   MOD_RES         263
FT                   /note="Phosphothreonine; by ULK1"
FT                   /evidence="ECO:0000250|UniProtKB:P80385"
FT   MOD_RES         270
FT                   /note="Phosphoserine; by ULK1"
FT                   /evidence="ECO:0000250|UniProtKB:P80385"
FT   VAR_SEQ         1..32
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_046711"
FT   VAR_SEQ         83
FT                   /note="V -> VVLRALSCPL (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_046712"
FT   VARIANT         89
FT                   /note="T -> S (in dbSNP:rs1126930)"
FT                   /id="VAR_033453"
FT   VARIANT         329
FT                   /note="K -> N (in dbSNP:rs34210356)"
FT                   /id="VAR_033454"
FT   MUTAGEN         90
FT                   /note="D->A: Reduced AMP-activation of phosphorylation of
FT                   PRKAA1 or PRKAA2. Reduced ADP activation of phosphorylation
FT                   of PRKAA1 or PRKAA2."
FT                   /evidence="ECO:0000269|PubMed:21680840"
FT   MUTAGEN         245
FT                   /note="D->A: Reduced AMP-activation of phosphorylation of
FT                   PRKAA1 or PRKAA2. Reduced ADP activation of phosphorylation
FT                   of PRKAA1 or PRKAA2."
FT                   /evidence="ECO:0000269|PubMed:21680840"
FT   MUTAGEN         317
FT                   /note="D->A: Reduced AMP-activation of phosphorylation of
FT                   PRKAA1 or PRKAA2. Does not affect ADP activation of
FT                   phosphorylation of PRKAA1 or PRKAA2."
FT                   /evidence="ECO:0000269|PubMed:21680840"
FT   HELIX           28..35
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   HELIX           38..41
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   STRAND          44..52
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   HELIX           57..67
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   STRAND          70..76
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   TURN            77..80
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   STRAND          81..87
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   HELIX           88..98
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   STRAND          102..104
FT                   /evidence="ECO:0000244|PDB:6B1U"
FT   HELIX           107..111
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   HELIX           114..122
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   TURN            123..125
FT                   /evidence="ECO:0000244|PDB:6C9F"
FT   STRAND          134..137
FT                   /evidence="ECO:0000244|PDB:6C9G"
FT   HELIX           138..148
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   STRAND          153..156
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   TURN            158..160
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   STRAND          163..167
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   HELIX           169..179
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   HELIX           180..182
FT                   /evidence="ECO:0000244|PDB:5ISO"
FT   HELIX           186..189
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          190..192
FT                   /evidence="ECO:0000244|PDB:6B1U"
FT   HELIX           193..196
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          207..210
FT                   /evidence="ECO:0000244|PDB:6C9F"
FT   HELIX           213..223
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          226..231
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          235..242
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   HELIX           243..251
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          259..261
FT                   /evidence="ECO:0000244|PDB:5EZV"
FT   HELIX           262..267
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   HELIX           271..274
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          277..279
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   HELIX           285..295
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          298..303
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   STRAND          307..314
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   HELIX           315..322
FT                   /evidence="ECO:0000244|PDB:2UV4"
FT   TURN            323..325
FT                   /evidence="ECO:0000244|PDB:5EZV"
SQ   SEQUENCE   331 AA;  37579 MW;  0F22B9CA1DBD87AE CRC64;
     METVISSDSS PAVENEHPQE TPESNNSVYT SFMKSHRCYD LIPTSSKLVV FDTSLQVKKA
     FFALVTNGVR AAPLWDSKKQ SFVGMLTITD FINILHRYYK SALVQIYELE EHKIETWREV
     YLQDSFKPLV CISPNASLFD AVSSLIRNKI HRLPVIDPES GNTLYILTHK RILKFLKLFI
     TEFPKPEFMS KSLEELQIGT YANIAMVRTT TPVYVALGIF VQHRVSALPV VDEKGRVVDI
     YSKFDVINLA AEKTYNNLDV SVTKALQHRS HYFEGVLKCY LHETLETIIN RLVEAEVHRL
     VVVDENDVVK GIVSLSDILQ ALVLTGGEKK P
//
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