AAKG2_HUMAN
ID AAKG2_HUMAN Reviewed; 569 AA.
AC Q9UGJ0; Q53Y07; Q6NUI0; Q75MP4; Q9NUZ9; Q9UDN8; Q9ULX8;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=5'-AMP-activated protein kinase subunit gamma-2;
DE Short=AMPK gamma2;
DE Short=AMPK subunit gamma-2;
DE AltName: Full=H91620p;
GN Name=PRKAG2;
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 B).
RA Hattori A., Seki N., Hayashi A., Kozuma S., Muramatsu M., Saito T.;
RT "Human homolog of AMPK gamma-1 chain.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX PubMed=10698692; DOI=10.1042/bj3460659;
RA Cheung P.C.F., Salt I.P., Davies S.P., Hardie D.G., Carling D.;
RT "Characterization of AMP-activated protein kinase gamma-subunit isoforms
RT and their role in AMP binding.";
RL Biochem. J. 346:659-669(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RX PubMed=11112354; DOI=10.1006/geno.2000.6376;
RA Lang T.M., Yu L., Qiang T., Jiang J.M., Chen Z., Xin Y.R., Liu G.Y.,
RA Zhao S.;
RT "Molecular cloning, genomic organization, and mapping of PRKAG2, a heart
RT abundant gamma-2 subunit of 5'-AMP-activated protein kinase, to human
RT chromosome 7q36.";
RL Genomics 70:258-263(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Placenta;
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] (ISOFORM B).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS B AND C).
RC TISSUE=Brain, and Liver;
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 [8]
RP DOMAIN CBS, AMP-BINDING, ATP-BINDING, CHARACTERIZATION OF VARIANTS WPWS
RP GLN-302; ARG-383 AND ASN-400, CHARACTERIZATION OF VARIANT WPWS GLY-531, AND
RP FUNCTION.
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 [9]
RP DOMAIN AMPK PSEUDOSUBSTRATE, AND MUTAGENESIS OF VAL-387.
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 [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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
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 [13]
RP PHOSPHORYLATION BY ULK1.
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 [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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP 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 VARIANT WPWS GLY-531.
RX PubMed=11748095; DOI=10.1161/hc5001.102111;
RA Gollob M.H., Seger J.J., Gollob T.N., Tapscott T., Gonzales O.,
RA Bachinski L., Roberts R.;
RT "Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular
RT preexcitation and conduction system disease with childhood onset and
RT absence of cardiac hypertrophy.";
RL Circulation 104:3030-3033(2001).
RN [18]
RP VARIANTS CMH6 LEU-350 INS AND ARG-383.
RX PubMed=11371514; DOI=10.1093/hmg/10.11.1215;
RA Blair E., Redwood C., Ashrafian H., Oliveira M., Broxholme J., Kerr B.,
RA Salmon A., Oestman-Smith I., Watkins H.;
RT "Mutations in the gamma(2) subunit of AMP-activated protein kinase cause
RT familial hypertrophic cardiomyopathy: evidence for the central role of
RT energy compromise in disease pathogenesis.";
RL Hum. Mol. Genet. 10:1215-1220(2001).
RN [19]
RP VARIANT WPWS GLN-302.
RX PubMed=11407343; DOI=10.1056/nejm200106143442403;
RA Gollob M.H., Green M.S., Tang A.S.-L., Gollob T., Karibe A.,
RA Al Sayegh A.H., Ahmad F., Lozado R., Shah G., Fananapazir L.,
RA Bachinski L.L., Roberts R.;
RT "Identification of a gene responsible for familial Wolff-Parkinson-White
RT syndrome.";
RL N. Engl. J. Med. 344:1823-1831(2001).
RN [20]
RP ERRATUM OF PUBMED:11407343.
RA Gollob M.H., Green M.S., Tang A.S.-L., Gollob T., Karibe A.,
RA Al Sayegh A.H., Ahmad F., Lozado R., Shah G., Fananapazir L.,
RA Bachinski L.L., Roberts R.;
RL N. Engl. J. Med. 345:552-552(2001).
RN [21]
RP ERRATUM OF PUBMED:11407343.
RA Gollob M.H., Green M.S., Tang A.S.-L., Gollob T., Karibe A.,
RA Al Sayegh A.H., Ahmad F., Lozado R., Shah G., Fananapazir L.,
RA Bachinski L.L., Roberts R.;
RL N. Engl. J. Med. 346:300-300(2002).
RN [22]
RP VARIANTS CMH6 GLN-302; ASN-400 AND ILE-488.
RX PubMed=11827995; DOI=10.1172/jci14571;
RA Arad M., Benson D.W., Perez-Atayde A.R., McKenna W.J., Sparks E.A.,
RA Kanter R.J., McGarry K., Seidman J.G., Seidman C.E.;
RT "Constitutively active AMP kinase mutations cause glycogen storage disease
RT mimicking hypertrophic cardiomyopathy.";
RL J. Clin. Invest. 109:357-362(2002).
RN [23]
RP VARIANT GSDH GLN-531, AND CHARACTERIZATION OF VARIANT GSDH GLN-531.
RX PubMed=15877279; DOI=10.1086/430840;
RA Burwinkel B., Scott J.W., Buehrer C., van Landeghem F.K.H., Cox G.F.,
RA Wilson C.J., Grahame Hardie D., Kilimann M.W.;
RT "Fatal congenital heart glycogenosis caused by a recurrent activating R531Q
RT mutation in the gamma 2-subunit of AMP-activated protein kinase (PRKAG2),
RT not by phosphorylase kinase deficiency.";
RL Am. J. Hum. Genet. 76:1034-1049(2005).
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:14722619}.
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 -!- INTERACTION:
CC Q9UGJ0; Q8NE08: COL25A1; NbExp=3; IntAct=EBI-2959705, EBI-25836642;
CC Q9UGJ0; I6L9F6: NEFL; NbExp=3; IntAct=EBI-2959705, EBI-10178578;
CC Q9UGJ0; Q13501: SQSTM1; NbExp=3; IntAct=EBI-2959705, EBI-307104;
CC Q9UGJ0-3; P05067: APP; NbExp=3; IntAct=EBI-25939641, EBI-77613;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=Q9UGJ0-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9UGJ0-2; Sequence=VSP_000261;
CC Name=C;
CC IsoId=Q9UGJ0-3; Sequence=VSP_015589;
CC -!- TISSUE SPECIFICITY: Isoform B is ubiquitously expressed except in liver
CC and thymus. The highest level is detected in heart with abundant
CC expression in placenta and testis.
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:0000250|UniProtKB:P80385}.
CC -!- PTM: Phosphorylated by ULK1; leading to negatively regulate AMPK
CC activity and suggesting the existence of a regulatory feedback loop
CC between ULK1 and AMPK. {ECO:0000269|PubMed:21460634}.
CC -!- DISEASE: Wolff-Parkinson-White syndrome (WPWS) [MIM:194200]: A
CC supernormal conduction disorder characterized by the presence of one or
CC several accessory atrioventricular connections, which can lead to
CC episodes of sporadic tachycardia. {ECO:0000269|PubMed:11407343,
CC ECO:0000269|PubMed:11748095, ECO:0000269|PubMed:14722619}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 6 (CMH6) [MIM:600858]: A
CC hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. CMH6 patients present Wolff-Parkinson-White ventricular
CC preexcitation, enlarged myocytes without myofiber disarray, and
CC glycogen-containing cytosolic vacuoles within cardiomyocytes.
CC {ECO:0000269|PubMed:11371514, ECO:0000269|PubMed:11827995}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Glycogen storage disease of heart lethal congenital (GSDH)
CC [MIM:261740]: Rare disease which leads to death within a few weeks to a
CC few months after birth, through heart failure and respiratory
CC compromise. {ECO:0000269|PubMed:15877279}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma
CC subunit family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH20540.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAS02032.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA84695.1; Type=Frameshift; Note=Frameshifts are upstream of the initiating Met of isoform B.; Evidence={ECO:0000305};
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DR EMBL; AB025580; BAA84695.1; ALT_FRAME; mRNA.
DR EMBL; AJ249976; CAB65116.1; -; mRNA.
DR EMBL; AF087875; AAK00413.1; -; mRNA.
DR EMBL; AK001887; BAA91962.1; -; mRNA.
DR EMBL; BT007127; AAP35791.1; -; mRNA.
DR EMBL; AC006358; AAS02032.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC006966; AAF03528.2; -; Genomic_DNA.
DR EMBL; AC093583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020540; AAH20540.2; ALT_INIT; mRNA.
DR EMBL; BC068598; AAH68598.1; -; mRNA.
DR CCDS; CCDS43683.1; -. [Q9UGJ0-3]
DR CCDS; CCDS47752.1; -. [Q9UGJ0-2]
DR CCDS; CCDS5928.1; -. [Q9UGJ0-1]
DR RefSeq; NP_001035723.1; NM_001040633.1. [Q9UGJ0-3]
DR RefSeq; NP_001291456.1; NM_001304527.1.
DR RefSeq; NP_001291460.1; NM_001304531.1. [Q9UGJ0-2]
DR RefSeq; NP_057287.2; NM_016203.3. [Q9UGJ0-1]
DR RefSeq; NP_077747.1; NM_024429.1. [Q9UGJ0-2]
DR RefSeq; XP_016867759.1; XM_017012270.1. [Q9UGJ0-3]
DR AlphaFoldDB; Q9UGJ0; -.
DR SMR; Q9UGJ0; -.
DR BioGRID; 119531; 48.
DR ComplexPortal; CPX-5786; AMPK complex, alpha1-beta1-gamma2 variant.
DR ComplexPortal; CPX-5844; AMPK complex, alpha2-beta1-gamma2 variant.
DR ComplexPortal; CPX-5845; AMPK complex, alpha2-beta2-gamma2 variant.
DR ComplexPortal; CPX-5846; AMPK complex, alpha1-beta2-gamma2 variant.
DR IntAct; Q9UGJ0; 43.
DR STRING; 9606.ENSP00000287878; -.
DR BindingDB; Q9UGJ0; -.
DR ChEMBL; CHEMBL2453; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB00131; Adenosine phosphate.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00273; Topiramate.
DR GlyGen; Q9UGJ0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UGJ0; -.
DR PhosphoSitePlus; Q9UGJ0; -.
DR BioMuta; PRKAG2; -.
DR DMDM; 14285344; -.
DR EPD; Q9UGJ0; -.
DR jPOST; Q9UGJ0; -.
DR MassIVE; Q9UGJ0; -.
DR MaxQB; Q9UGJ0; -.
DR PaxDb; Q9UGJ0; -.
DR PeptideAtlas; Q9UGJ0; -.
DR PRIDE; Q9UGJ0; -.
DR ProteomicsDB; 84222; -. [Q9UGJ0-1]
DR ProteomicsDB; 84223; -. [Q9UGJ0-2]
DR ProteomicsDB; 84224; -. [Q9UGJ0-3]
DR Antibodypedia; 1327; 162 antibodies from 30 providers.
DR DNASU; 51422; -.
DR Ensembl; ENST00000287878.9; ENSP00000287878.3; ENSG00000106617.15. [Q9UGJ0-1]
DR Ensembl; ENST00000392801.6; ENSP00000376549.2; ENSG00000106617.15. [Q9UGJ0-3]
DR Ensembl; ENST00000418337.6; ENSP00000387386.2; ENSG00000106617.15. [Q9UGJ0-2]
DR Ensembl; ENST00000476632.2; ENSP00000419493.2; ENSG00000106617.15. [Q9UGJ0-2]
DR Ensembl; ENST00000651378.1; ENSP00000499103.1; ENSG00000106617.15. [Q9UGJ0-2]
DR Ensembl; ENST00000651764.1; ENSP00000498796.1; ENSG00000106617.15. [Q9UGJ0-3]
DR Ensembl; ENST00000652159.1; ENSP00000499025.1; ENSG00000106617.15. [Q9UGJ0-3]
DR GeneID; 51422; -.
DR KEGG; hsa:51422; -.
DR MANE-Select; ENST00000287878.9; ENSP00000287878.3; NM_016203.4; NP_057287.2.
DR UCSC; uc003wki.4; human. [Q9UGJ0-1]
DR CTD; 51422; -.
DR DisGeNET; 51422; -.
DR GeneCards; PRKAG2; -.
DR GeneReviews; PRKAG2; -.
DR HGNC; HGNC:9386; PRKAG2.
DR HPA; ENSG00000106617; Tissue enhanced (heart).
DR MalaCards; PRKAG2; -.
DR MIM; 194200; phenotype.
DR MIM; 261740; phenotype.
DR MIM; 600858; phenotype.
DR MIM; 602743; gene.
DR neXtProt; NX_Q9UGJ0; -.
DR OpenTargets; ENSG00000106617; -.
DR Orphanet; 439854; Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR Orphanet; 907; NON RARE IN EUROPE: Wolff-Parkinson-White syndrome.
DR PharmGKB; PA33752; -.
DR VEuPathDB; HostDB:ENSG00000106617; -.
DR eggNOG; KOG1764; Eukaryota.
DR GeneTree; ENSGT00950000183019; -.
DR HOGENOM; CLU_021740_3_0_1; -.
DR OMA; XVQIYEL; -.
DR OrthoDB; 631088at2759; -.
DR PhylomeDB; Q9UGJ0; -.
DR TreeFam; TF313247; -.
DR PathwayCommons; Q9UGJ0; -.
DR Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-163680; AMPK inhibits chREBP transcriptional activation activity.
DR Reactome; R-HSA-200425; Carnitine metabolism.
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; Q9UGJ0; -.
DR SIGNOR; Q9UGJ0; -.
DR BioGRID-ORCS; 51422; 17 hits in 1083 CRISPR screens.
DR ChiTaRS; PRKAG2; human.
DR GeneWiki; PRKAG2; -.
DR GenomeRNAi; 51422; -.
DR Pharos; Q9UGJ0; Tchem.
DR PRO; PR:Q9UGJ0; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UGJ0; protein.
DR Bgee; ENSG00000106617; Expressed in right atrium auricular region and 172 other tissues.
DR ExpressionAtlas; Q9UGJ0; baseline and differential.
DR Genevisible; Q9UGJ0; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043531; F:ADP binding; IDA:BHF-UCL.
DR GO; GO:0016208; F:AMP binding; IBA:GO_Central.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; IMP:BHF-UCL.
DR GO; GO:0008607; F:phosphorylase kinase regulator activity; IMP:BHF-UCL.
DR GO; GO:0030295; F:protein kinase activator activity; IMP:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IDA:BHF-UCL.
DR GO; GO:0019887; F:protein kinase regulator activity; IBA:GO_Central.
DR GO; GO:0006754; P:ATP biosynthetic process; TAS:BHF-UCL.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0005977; P:glycogen metabolic process; IMP:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:BHF-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0050790; P:regulation of catalytic activity; IBA:GO_Central.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IMP:BHF-UCL.
DR GO; GO:0046320; P:regulation of fatty acid oxidation; TAS:BHF-UCL.
DR GO; GO:0046324; P:regulation of glucose import; TAS:BHF-UCL.
DR GO; GO:0006110; P:regulation of glycolytic process; IMP:BHF-UCL.
DR GO; GO:0016126; P:sterol biosynthetic process; TAS:BHF-UCL.
DR Gene3D; 3.10.580.10; -; 2.
DR InterPro; IPR039170; AMPKG-2.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR PANTHER; PTHR13780:SF122; PTHR13780:SF122; 1.
DR Pfam; PF00571; CBS; 3.
DR SMART; SM00116; CBS; 4.
DR SUPFAM; SSF54631; SSF54631; 2.
DR PROSITE; PS51371; CBS; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cardiomyopathy; CBS domain;
KW Disease variant; Fatty acid biosynthesis; Fatty acid metabolism;
KW Glycogen storage disease; Lipid biosynthesis; Lipid metabolism;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..569
FT /note="5'-AMP-activated protein kinase subunit gamma-2"
FT /id="PRO_0000204381"
FT DOMAIN 275..335
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 357..415
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 430..492
FT /note="CBS 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 504..562
FT /note="CBS 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 370..391
FT /note="AMPK pseudosubstrate"
FT COMPBIAS 1..17
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 102..175
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..217
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 302
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 302
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 302
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 302
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 317..322
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 317..322
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 317..322
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 362
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 362
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 362
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 383..384
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 383..384
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 383..384
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 383
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 384
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 402
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 402
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 402
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 432
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 437
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 458..459
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 474..477
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 474..477
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 474..477
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 501
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 501
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 501
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 530..531
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 530..531
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 530..531
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 530
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 546..549
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 165
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT VAR_SEQ 1..241
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:11112354,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|Ref.1, ECO:0000303|Ref.5"
FT /id="VSP_000261"
FT VAR_SEQ 1..44
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015589"
FT VARIANT 6
FT /note="M -> L (in dbSNP:rs3207363)"
FT /id="VAR_048250"
FT VARIANT 302
FT /note="R -> Q (in WPWS and CMH6; impaired AMP- and ATP-
FT binding; dbSNP:rs121908987)"
FT /evidence="ECO:0000269|PubMed:11407343,
FT ECO:0000269|PubMed:11827995, ECO:0000269|PubMed:14722619"
FT /id="VAR_013264"
FT VARIANT 350
FT /note="R -> RL (in CMH6; severe)"
FT /evidence="ECO:0000269|PubMed:11371514"
FT /id="VAR_013265"
FT VARIANT 383
FT /note="H -> R (in CMH6; severe; impaired AMP- and ATP-
FT binding; dbSNP:rs121908988)"
FT /evidence="ECO:0000269|PubMed:11371514,
FT ECO:0000269|PubMed:14722619"
FT /id="VAR_013266"
FT VARIANT 400
FT /note="T -> N (in CMH6; severe; impaired AMP- and ATP-
FT binding; dbSNP:rs28938173)"
FT /evidence="ECO:0000269|PubMed:11827995,
FT ECO:0000269|PubMed:14722619"
FT /id="VAR_013267"
FT VARIANT 488
FT /note="N -> I (in CMH6; severe; dbSNP:rs121908989)"
FT /evidence="ECO:0000269|PubMed:11827995"
FT /id="VAR_013268"
FT VARIANT 531
FT /note="R -> G (in WPWS; absence of cardiac hypertrophy;
FT onset in childhood; impaired AMP- and ATP-binding;
FT dbSNP:rs121908990)"
FT /evidence="ECO:0000269|PubMed:11748095,
FT ECO:0000269|PubMed:14722619"
FT /id="VAR_032909"
FT VARIANT 531
FT /note="R -> Q (in GSDH; reduction of binding affinities for
FT AMP and ATP; loss of cooperative binding; enhanced basal
FT activity; increased phosphorylation of the alpha-subunit;
FT dbSNP:rs121908991)"
FT /evidence="ECO:0000269|PubMed:15877279"
FT /id="VAR_013269"
FT MUTAGEN 387
FT /note="V->S: Induces phosphorylation by AMPK."
FT /evidence="ECO:0000269|PubMed:17255938"
SQ SEQUENCE 569 AA; 63066 MW; F51C30668C294089 CRC64;
MGSAVMDTKK KKDVSSPGGS GGKKNASQKR RSLRVHIPDL SSFAMPLLDG DLEGSGKHSS
RKVDSPFGPG SPSKGFFSRG PQPRPSSPMS APVRPKTSPG SPKTVFPFSY QESPPRSPRR
MSFSGIFRSS SKESSPNSNP ATSPGGIRFF SRSRKTSGLS SSPSTPTQVT KQHTFPLESY
KHEPERLENR IYASSSPPDT GQRFCPSSFQ SPTRPPLASP THYAPSKAAA LAAALGPAEA
GMLEKLEFED EAVEDSESGV YMRFMRSHKC YDIVPTSSKL VVFDTTLQVK KAFFALVANG
VRAAPLWESK KQSFVGMLTI TDFINILHRY YKSPMVQIYE LEEHKIETWR ELYLQETFKP
LVNISPDASL FDAVYSLIKN KIHRLPVIDP ISGNALYILT HKRILKFLQL FMSDMPKPAF
MKQNLDELGI GTYHNIAFIH PDTPIIKALN IFVERRISAL PVVDESGKVV DIYSKFDVIN
LAAEKTYNNL DITVTQALQH RSQYFEGVVK CNKLEILETI VDRIVRAEVH RLVVVNEADS
IVGIISLSDI LQALILTPAG AKQKETETE
