Full text data of PRKAB1
PRKAB1
(AMPK)
[Confidence: low (only semi-automatic identification from reviews)]
5'-AMP-activated protein kinase subunit beta-1; AMPK subunit beta-1; AMPKb
Note: presumably soluble (membrane word is not in UniProt keywords or features)
5'-AMP-activated protein kinase subunit beta-1; AMPK subunit beta-1; AMPKb
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y478
ID AAKB1_HUMAN Reviewed; 270 AA.
AC Q9Y478; Q9UBV0; Q9UE20; Q9UEX2; Q9Y6V8;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=5'-AMP-activated protein kinase subunit beta-1;
DE Short=AMPK subunit beta-1;
DE Short=AMPKb;
GN Name=PRKAB1; Synonyms=AMPK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Carling D.;
RT "Non-catalytic beta and gamma subunits isoforms of the AMP-activated
RT protein kinase.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9224708; DOI=10.1016/S0014-5793(97)00569-3;
RA Stapleton D., Woollatt E., Mitchelhill K., Nicholl J.K.,
RA Fernandez C.S., Michell B.J., Witters L.A., Power D.A.,
RA Sutherland G.R., Kemp B.E.;
RT "AMP-activated protein kinase isoenzyme family: subunit structure and
RT chromosomal location.";
RL FEBS Lett. 409:452-456(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RA Yamagata K., Oda N., Furuta H., Vaxillaire M., Southam L., Boriraj V.,
RA Chen X., Oda Y., Takeda J., Yamada S., Nishigori H., Lebeau M.M.,
RA Lathrop M., Cox R.D., Bell G.I.;
RT "Transcription map of the 5cM region surrounding the hepatocyte
RT nuclear factor-1a/MODY3 gene on chromosome 12.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang X., Yu L., Tu Q.;
RT "Cloning and expression of the complete mRNA coding human AMP-
RT activated protein kinase.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH FNIP1.
RX PubMed=17028174; DOI=10.1073/pnas.0603781103;
RA Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L.,
RA Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III,
RA Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr.,
RA Linehan W.M., Schmidt L.S., Zbar B.;
RT "Folliculin encoded by the BHD gene interacts with a binding protein,
RT FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006).
RN [8]
RP INTERACTION WITH FNIP2.
RX PubMed=18403135; DOI=10.1016/j.gene.2008.02.022;
RA Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M.,
RA Valera V.A., Linehan W.M., Schmidt L.S.;
RT "Identification and characterization of a novel folliculin-interacting
RT protein FNIP2.";
RL Gene 415:60-67(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-4; SER-5; SER-6 AND
RP SER-108, AND MASS SPECTROMETRY.
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-40 AND SER-108,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, AND MASS
RP SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-40; SER-108 AND
RP THR-148, AND MASS SPECTROMETRY.
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 [LARGE SCALE ANALYSIS] AT SER-96 AND SER-108, AND MASS
RP SPECTROMETRY.
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40 AND SER-108, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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
RT regulatory feedback loop.";
RL Autophagy 7:696-706(2011).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP INTERACTION WITH PRKAA1 AND PRKAG1, MUTAGENESIS OF GLY-2, AND
RP MYRISTOYLATION AT GLY-2.
RX PubMed=21680840; DOI=10.1126/science.1200094;
RA Oakhill J.S., Steel R., Chen Z.P., Scott J.W., Ling N., Tam S.,
RA Kemp B.E.;
RT "AMPK is a direct adenylate charge-regulated protein kinase.";
RL Science 332:1433-1435(2011).
RN [19]
RP REVIEW ON FUNCTION.
RX PubMed=17307971; DOI=10.1161/01.RES.0000256090.42690.05;
RA Towler M.C., Hardie D.G.;
RT "AMP-activated protein kinase in metabolic control and insulin
RT signaling.";
RL Circ. Res. 100:328-341(2007).
RN [20]
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).
CC -!- FUNCTION: Non-catalytic subunit of AMP-activated protein kinase
CC (AMPK), an energy sensor protein kinase that plays a key role in
CC regulating cellular energy metabolism. In response to reduction of
CC intracellular ATP levels, AMPK activates energy-producing pathways
CC and inhibits energy-consuming processes: inhibits protein,
CC carbohydrate and lipid biosynthesis, as well as cell growth and
CC proliferation. AMPK acts via direct phosphorylation of metabolic
CC enzymes, and by longer-term effects via phosphorylation of
CC transcription regulators. Also acts as a regulator of cellular
CC polarity by remodeling the actin cytoskeleton; probably by
CC indirectly activating myosin. Beta non-catalytic subunit acts as a
CC scaffold on which the AMPK complex assembles, via its C-terminus
CC that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1,
CC PRKAG2 or PRKAG3).
CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit
CC (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-
CC catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with
CC FNIP1 and FNIP2.
CC -!- INTERACTION:
CC O70302:Cidea (xeno); NbExp=4; IntAct=EBI-719769, EBI-7927848;
CC P62993:GRB2; NbExp=2; IntAct=EBI-719769, EBI-401755;
CC Q13131:PRKAA1; NbExp=5; IntAct=EBI-719769, EBI-1181405;
CC P54619:PRKAG1; NbExp=4; IntAct=EBI-719769, EBI-1181439;
CC -!- DOMAIN: The glycogen-binding domain may target AMPK to glycogen so
CC that other factors like glycogen-bound debranching enzyme or
CC protein phosphatases can directly affect AMPK activity (By
CC similarity).
CC -!- PTM: Phosphorylated when associated with the catalytic subunit
CC (PRKAA1 or PRKAA2). Phosphorylated by ULK1; leading to negatively
CC regulate AMPK activity and suggesting the existence of a
CC regulatory feedback loop between ULK1 and AMPK.
CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase beta
CC subunit family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB71326.1; Type=Erroneous gene model prediction;
CC Sequence=AAC98897.1; Type=Frameshift; Positions=245;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRKAB1ID44100ch12q24.html";
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DR EMBL; AJ224515; CAA12024.1; -; mRNA.
DR EMBL; Y12556; CAA73146.1; -; mRNA.
DR EMBL; U83994; AAD09237.1; -; mRNA.
DR EMBL; U87276; AAD00625.1; -; Genomic_DNA.
DR EMBL; U87271; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87272; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87273; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87274; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87275; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; AF022116; AAC98897.1; ALT_FRAME; mRNA.
DR EMBL; AC002563; AAB71326.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC001007; AAH01007.1; -; mRNA.
DR EMBL; BC001056; AAH01056.1; -; mRNA.
DR EMBL; BC001823; AAH01823.1; -; mRNA.
DR EMBL; BC017671; AAH17671.1; -; mRNA.
DR PIR; T09514; T09514.
DR RefSeq; NP_006244.2; NM_006253.4.
DR RefSeq; XP_005253966.1; XM_005253909.1.
DR UniGene; Hs.741184; -.
DR ProteinModelPortal; Q9Y478; -.
DR SMR; Q9Y478; 77-270.
DR IntAct; Q9Y478; 16.
DR MINT; MINT-1400840; -.
DR STRING; 9606.ENSP00000229328; -.
DR BindingDB; Q9Y478; -.
DR ChEMBL; CHEMBL2096907; -.
DR DrugBank; DB00131; Adenosine monophosphate.
DR DrugBank; DB00331; Metformin.
DR CAZy; CBM48; Carbohydrate-Binding Module Family 48.
DR PhosphoSite; Q9Y478; -.
DR DMDM; 14194425; -.
DR PaxDb; Q9Y478; -.
DR PRIDE; Q9Y478; -.
DR Ensembl; ENST00000229328; ENSP00000229328; ENSG00000111725.
DR Ensembl; ENST00000541640; ENSP00000441369; ENSG00000111725.
DR GeneID; 5564; -.
DR KEGG; hsa:5564; -.
DR UCSC; uc001txg.3; human.
DR CTD; 5564; -.
DR GeneCards; GC12P120105; -.
DR HGNC; HGNC:9378; PRKAB1.
DR HPA; CAB005058; -.
DR HPA; HPA004247; -.
DR MIM; 602740; gene.
DR neXtProt; NX_Q9Y478; -.
DR PharmGKB; PA33746; -.
DR eggNOG; NOG238368; -.
DR HOGENOM; HOG000230597; -.
DR HOVERGEN; HBG050430; -.
DR InParanoid; Q9Y478; -.
DR KO; K07199; -.
DR OMA; DADIFHG; -.
DR OrthoDB; EOG7SXW3Z; -.
DR PhylomeDB; Q9Y478; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_11123; Membrane Trafficking.
DR SignaLink; Q9Y478; -.
DR GeneWiki; PRKAB1; -.
DR GenomeRNAi; 5564; -.
DR NextBio; 21556; -.
DR PRO; PR:Q9Y478; -.
DR ArrayExpress; Q9Y478; -.
DR Bgee; Q9Y478; -.
DR CleanEx; HS_PRKAB1; -.
DR Genevestigator; Q9Y478; -.
DR GO; GO:0031588; C:AMP-activated protein kinase complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
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:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
DR GO; GO:0050790; P:regulation of catalytic activity; IEA:Ensembl.
DR InterPro; IPR006828; AMP_prot_kin_bsu_interact-dom.
DR InterPro; IPR014756; Ig_E-set.
DR Pfam; PF04739; AMPKBI; 1.
DR SMART; SM01010; AMPKBI; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Lipoprotein; Myristate;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 270 5'-AMP-activated protein kinase subunit
FT beta-1.
FT /FTId=PRO_0000204363.
FT REGION 68 163 Glycogen-binding domain (By similarity).
FT MOD_RES 4 4 Phosphothreonine.
FT MOD_RES 5 5 Phosphoserine.
FT MOD_RES 6 6 Phosphoserine.
FT MOD_RES 19 19 Phosphothreonine.
FT MOD_RES 24 24 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 25 25 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 40 40 Phosphoserine.
FT MOD_RES 96 96 Phosphoserine.
FT MOD_RES 101 101 Phosphoserine (By similarity).
FT MOD_RES 108 108 Phosphoserine.
FT MOD_RES 148 148 Phosphothreonine.
FT MOD_RES 182 182 Phosphoserine (By similarity).
FT LIPID 2 2 N-myristoyl glycine.
FT MUTAGEN 2 2 G->A: Abolishes myristoylation and AMP-
FT enhanced phosphorylation of PRKAA1 or
FT PRKAA2.
FT CONFLICT 10 10 A -> G (in Ref. 2; CAA73146 and 4;
FT AAC98897).
FT CONFLICT 15 15 G -> A (in Ref. 1; CAA12024).
FT CONFLICT 20 20 P -> A (in Ref. 2; CAA73146 and 4;
FT AAC98897).
FT CONFLICT 22 22 R -> K (in Ref. 3; AAD09237/AAD00625).
FT CONFLICT 56 56 E -> Y (in Ref. 3; AAD09237/AAD00625).
SQ SEQUENCE 270 AA; 30382 MW; F0BCAA94D5BC15FC CRC64;
MGNTSSERAA LERHGGHKTP RRDSSGGTKD GDRPKILMDS PEDADLFHSE EIKAPEKEEF
LAWQHDLEVN DKAPAQARPT VFRWTGGGKE VYLSGSFNNW SKLPLTRSHN NFVAILDLPE
GEHQYKFFVD GQWTHDPSEP IVTSQLGTVN NIIQVKKTDF EVFDALMVDS QKCSDVSELS
SSPPGPYHQE PYVCKPEERF RAPPILPPHL LQVILNKDTG ISCDPALLPE PNHVMLNHLY
ALSIKDGVMV LSATHRYKKK YVTTLLYKPI
//
ID AAKB1_HUMAN Reviewed; 270 AA.
AC Q9Y478; Q9UBV0; Q9UE20; Q9UEX2; Q9Y6V8;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=5'-AMP-activated protein kinase subunit beta-1;
DE Short=AMPK subunit beta-1;
DE Short=AMPKb;
GN Name=PRKAB1; Synonyms=AMPK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Carling D.;
RT "Non-catalytic beta and gamma subunits isoforms of the AMP-activated
RT protein kinase.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9224708; DOI=10.1016/S0014-5793(97)00569-3;
RA Stapleton D., Woollatt E., Mitchelhill K., Nicholl J.K.,
RA Fernandez C.S., Michell B.J., Witters L.A., Power D.A.,
RA Sutherland G.R., Kemp B.E.;
RT "AMP-activated protein kinase isoenzyme family: subunit structure and
RT chromosomal location.";
RL FEBS Lett. 409:452-456(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RA Yamagata K., Oda N., Furuta H., Vaxillaire M., Southam L., Boriraj V.,
RA Chen X., Oda Y., Takeda J., Yamada S., Nishigori H., Lebeau M.M.,
RA Lathrop M., Cox R.D., Bell G.I.;
RT "Transcription map of the 5cM region surrounding the hepatocyte
RT nuclear factor-1a/MODY3 gene on chromosome 12.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang X., Yu L., Tu Q.;
RT "Cloning and expression of the complete mRNA coding human AMP-
RT activated protein kinase.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH FNIP1.
RX PubMed=17028174; DOI=10.1073/pnas.0603781103;
RA Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L.,
RA Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III,
RA Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr.,
RA Linehan W.M., Schmidt L.S., Zbar B.;
RT "Folliculin encoded by the BHD gene interacts with a binding protein,
RT FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006).
RN [8]
RP INTERACTION WITH FNIP2.
RX PubMed=18403135; DOI=10.1016/j.gene.2008.02.022;
RA Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M.,
RA Valera V.A., Linehan W.M., Schmidt L.S.;
RT "Identification and characterization of a novel folliculin-interacting
RT protein FNIP2.";
RL Gene 415:60-67(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-4; SER-5; SER-6 AND
RP SER-108, AND MASS SPECTROMETRY.
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-40 AND SER-108,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, AND MASS
RP SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-40; SER-108 AND
RP THR-148, AND MASS SPECTROMETRY.
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 [LARGE SCALE ANALYSIS] AT SER-96 AND SER-108, AND MASS
RP SPECTROMETRY.
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40 AND SER-108, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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
RT regulatory feedback loop.";
RL Autophagy 7:696-706(2011).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP INTERACTION WITH PRKAA1 AND PRKAG1, MUTAGENESIS OF GLY-2, AND
RP MYRISTOYLATION AT GLY-2.
RX PubMed=21680840; DOI=10.1126/science.1200094;
RA Oakhill J.S., Steel R., Chen Z.P., Scott J.W., Ling N., Tam S.,
RA Kemp B.E.;
RT "AMPK is a direct adenylate charge-regulated protein kinase.";
RL Science 332:1433-1435(2011).
RN [19]
RP REVIEW ON FUNCTION.
RX PubMed=17307971; DOI=10.1161/01.RES.0000256090.42690.05;
RA Towler M.C., Hardie D.G.;
RT "AMP-activated protein kinase in metabolic control and insulin
RT signaling.";
RL Circ. Res. 100:328-341(2007).
RN [20]
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).
CC -!- FUNCTION: Non-catalytic subunit of AMP-activated protein kinase
CC (AMPK), an energy sensor protein kinase that plays a key role in
CC regulating cellular energy metabolism. In response to reduction of
CC intracellular ATP levels, AMPK activates energy-producing pathways
CC and inhibits energy-consuming processes: inhibits protein,
CC carbohydrate and lipid biosynthesis, as well as cell growth and
CC proliferation. AMPK acts via direct phosphorylation of metabolic
CC enzymes, and by longer-term effects via phosphorylation of
CC transcription regulators. Also acts as a regulator of cellular
CC polarity by remodeling the actin cytoskeleton; probably by
CC indirectly activating myosin. Beta non-catalytic subunit acts as a
CC scaffold on which the AMPK complex assembles, via its C-terminus
CC that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1,
CC PRKAG2 or PRKAG3).
CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit
CC (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-
CC catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with
CC FNIP1 and FNIP2.
CC -!- INTERACTION:
CC O70302:Cidea (xeno); NbExp=4; IntAct=EBI-719769, EBI-7927848;
CC P62993:GRB2; NbExp=2; IntAct=EBI-719769, EBI-401755;
CC Q13131:PRKAA1; NbExp=5; IntAct=EBI-719769, EBI-1181405;
CC P54619:PRKAG1; NbExp=4; IntAct=EBI-719769, EBI-1181439;
CC -!- DOMAIN: The glycogen-binding domain may target AMPK to glycogen so
CC that other factors like glycogen-bound debranching enzyme or
CC protein phosphatases can directly affect AMPK activity (By
CC similarity).
CC -!- PTM: Phosphorylated when associated with the catalytic subunit
CC (PRKAA1 or PRKAA2). Phosphorylated by ULK1; leading to negatively
CC regulate AMPK activity and suggesting the existence of a
CC regulatory feedback loop between ULK1 and AMPK.
CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase beta
CC subunit family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB71326.1; Type=Erroneous gene model prediction;
CC Sequence=AAC98897.1; Type=Frameshift; Positions=245;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRKAB1ID44100ch12q24.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AJ224515; CAA12024.1; -; mRNA.
DR EMBL; Y12556; CAA73146.1; -; mRNA.
DR EMBL; U83994; AAD09237.1; -; mRNA.
DR EMBL; U87276; AAD00625.1; -; Genomic_DNA.
DR EMBL; U87271; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87272; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87273; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87274; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; U87275; AAD00625.1; JOINED; Genomic_DNA.
DR EMBL; AF022116; AAC98897.1; ALT_FRAME; mRNA.
DR EMBL; AC002563; AAB71326.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC001007; AAH01007.1; -; mRNA.
DR EMBL; BC001056; AAH01056.1; -; mRNA.
DR EMBL; BC001823; AAH01823.1; -; mRNA.
DR EMBL; BC017671; AAH17671.1; -; mRNA.
DR PIR; T09514; T09514.
DR RefSeq; NP_006244.2; NM_006253.4.
DR RefSeq; XP_005253966.1; XM_005253909.1.
DR UniGene; Hs.741184; -.
DR ProteinModelPortal; Q9Y478; -.
DR SMR; Q9Y478; 77-270.
DR IntAct; Q9Y478; 16.
DR MINT; MINT-1400840; -.
DR STRING; 9606.ENSP00000229328; -.
DR BindingDB; Q9Y478; -.
DR ChEMBL; CHEMBL2096907; -.
DR DrugBank; DB00131; Adenosine monophosphate.
DR DrugBank; DB00331; Metformin.
DR CAZy; CBM48; Carbohydrate-Binding Module Family 48.
DR PhosphoSite; Q9Y478; -.
DR DMDM; 14194425; -.
DR PaxDb; Q9Y478; -.
DR PRIDE; Q9Y478; -.
DR Ensembl; ENST00000229328; ENSP00000229328; ENSG00000111725.
DR Ensembl; ENST00000541640; ENSP00000441369; ENSG00000111725.
DR GeneID; 5564; -.
DR KEGG; hsa:5564; -.
DR UCSC; uc001txg.3; human.
DR CTD; 5564; -.
DR GeneCards; GC12P120105; -.
DR HGNC; HGNC:9378; PRKAB1.
DR HPA; CAB005058; -.
DR HPA; HPA004247; -.
DR MIM; 602740; gene.
DR neXtProt; NX_Q9Y478; -.
DR PharmGKB; PA33746; -.
DR eggNOG; NOG238368; -.
DR HOGENOM; HOG000230597; -.
DR HOVERGEN; HBG050430; -.
DR InParanoid; Q9Y478; -.
DR KO; K07199; -.
DR OMA; DADIFHG; -.
DR OrthoDB; EOG7SXW3Z; -.
DR PhylomeDB; Q9Y478; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_11123; Membrane Trafficking.
DR SignaLink; Q9Y478; -.
DR GeneWiki; PRKAB1; -.
DR GenomeRNAi; 5564; -.
DR NextBio; 21556; -.
DR PRO; PR:Q9Y478; -.
DR ArrayExpress; Q9Y478; -.
DR Bgee; Q9Y478; -.
DR CleanEx; HS_PRKAB1; -.
DR Genevestigator; Q9Y478; -.
DR GO; GO:0031588; C:AMP-activated protein kinase complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
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:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
DR GO; GO:0050790; P:regulation of catalytic activity; IEA:Ensembl.
DR InterPro; IPR006828; AMP_prot_kin_bsu_interact-dom.
DR InterPro; IPR014756; Ig_E-set.
DR Pfam; PF04739; AMPKBI; 1.
DR SMART; SM01010; AMPKBI; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Lipoprotein; Myristate;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 270 5'-AMP-activated protein kinase subunit
FT beta-1.
FT /FTId=PRO_0000204363.
FT REGION 68 163 Glycogen-binding domain (By similarity).
FT MOD_RES 4 4 Phosphothreonine.
FT MOD_RES 5 5 Phosphoserine.
FT MOD_RES 6 6 Phosphoserine.
FT MOD_RES 19 19 Phosphothreonine.
FT MOD_RES 24 24 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 25 25 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 40 40 Phosphoserine.
FT MOD_RES 96 96 Phosphoserine.
FT MOD_RES 101 101 Phosphoserine (By similarity).
FT MOD_RES 108 108 Phosphoserine.
FT MOD_RES 148 148 Phosphothreonine.
FT MOD_RES 182 182 Phosphoserine (By similarity).
FT LIPID 2 2 N-myristoyl glycine.
FT MUTAGEN 2 2 G->A: Abolishes myristoylation and AMP-
FT enhanced phosphorylation of PRKAA1 or
FT PRKAA2.
FT CONFLICT 10 10 A -> G (in Ref. 2; CAA73146 and 4;
FT AAC98897).
FT CONFLICT 15 15 G -> A (in Ref. 1; CAA12024).
FT CONFLICT 20 20 P -> A (in Ref. 2; CAA73146 and 4;
FT AAC98897).
FT CONFLICT 22 22 R -> K (in Ref. 3; AAD09237/AAD00625).
FT CONFLICT 56 56 E -> Y (in Ref. 3; AAD09237/AAD00625).
SQ SEQUENCE 270 AA; 30382 MW; F0BCAA94D5BC15FC CRC64;
MGNTSSERAA LERHGGHKTP RRDSSGGTKD GDRPKILMDS PEDADLFHSE EIKAPEKEEF
LAWQHDLEVN DKAPAQARPT VFRWTGGGKE VYLSGSFNNW SKLPLTRSHN NFVAILDLPE
GEHQYKFFVD GQWTHDPSEP IVTSQLGTVN NIIQVKKTDF EVFDALMVDS QKCSDVSELS
SSPPGPYHQE PYVCKPEERF RAPPILPPHL LQVILNKDTG ISCDPALLPE PNHVMLNHLY
ALSIKDGVMV LSATHRYKKK YVTTLLYKPI
//
MIM
602740
*RECORD*
*FIELD* NO
602740
*FIELD* TI
*602740 PROTEIN KINASE, AMP-ACTIVATED, NONCATALYTIC, BETA-1; PRKAB1
;;AMP-ACTIVATED PROTEIN KINASE, NONCATALYTIC, BETA-1;;
read moreAMPK-BETA-1
*FIELD* TX
The mammalian 5-prime-AMP-activated protein kinase (AMPK) appears to act
as a metabolic stress-sensing protein kinase. AMPK is a heterotrimeric
protein composed of a catalytic alpha subunit, a noncatalytic beta
subunit, and a noncatalytic gamma subunit. See PRKAA1 (602739) for
additional background.
CLONING
Using PCR with degenerate oligonucleotides based on the rat Ampk-beta-1
protein sequence, Woods et al. (1996) isolated rat liver cDNAs encoding
Ampk-beta-1. Both the Ampk-beta-1 mRNA and protein are widely expressed
in rat tissues. The predicted 270-amino acid protein has a calculated
mass of 30 kD, but Woods et al. (1996) reported that it migrates as a
38-kD protein by SDS-PAGE. Immunoprecipitation studies suggested that
Ampk-beta-1 mediates the association of the AMPK heterotrimeric complex
in vitro.
By searching the sequence databases with a rat Ampk-beta-1 cDNA,
Stapleton et al. (1997) identified an EST encoding human AMPK-beta-1.
The human and rat AMPK-beta-1 proteins have 95% amino acid sequence
identity. Thornton et al. (1998) reported that the predicted 271-amino
acid human AMPK-beta-1 protein shares 71% sequence identity with human
AMPK-beta-2 (PRKAB2; 602741). They found that both beta isoforms form
complexes with Ampk-alpha-1 (PRKAA1) and Ampk-alpha-2 (PRKAA2; 600497)
in rat liver and skeletal muscle. Coexpression of the alpha and
AMPK-gamma-1 (PRKAG1; 602742) subunits with either AMPK-beta-1 or
AMPK-beta-2 in mammalian cells did not reveal a significant difference
in AMPK activity between the 2 beta isoforms. Using Western blot
analysis and immunoprecipitation studies, Thornton et al. (1998)
determined that Ampk-beta-1 was expressed at higher levels than
Ampk-beta-2 in rat liver, while Ampk-beta-2 was more abundant in
skeletal muscle. They suggested that the marked difference in expression
patterns of Ampk-beta-1 and Ampk-beta-2 indicates tissue-specific roles
for these isoforms. By Northern blot analysis, Thornton et al. (1998)
found that AMPK-beta-1 was expressed as a 3-kb mRNA in all tissues
tested.
GENE FUNCTION
Minokoshi et al. (2004) investigated the potential role of AMP-activated
protein kinase (AMPK) in the hypothalamus in the regulation of food
intake. Minokoshi et al. (2004) reported that AMPK activity is inhibited
in arcuate and paraventricular hypothalamus by the anorexigenic hormone
leptin (164160), and in multiple hypothalamic regions by insulin
(176730), high glucose, and refeeding. A melanocortin receptor (see
155555) agonist, a potent anorexigen, decreased AMPK activity in
paraventricular hypothalamus, whereas agouti-related protein (602311),
an orexigen, increased AMPK activity. Melanocortin receptor signaling is
required for leptin and refeeding effects of AMPK in the paraventricular
hypothalamus. Dominant-negative AMPK expression in the hypothalamus was
sufficient to reduce food intake and body weight, whereas constitutively
active AMPK increased both. Alterations of hypothalamic AMPK activity
augmented changes in arcuate neuropeptide expression induced by fasting
and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary
for leptin's effects on food intake and body weight, as constitutively
active AMPK blocks these effects. Thus, Minokoshi et al. (2004)
concluded that hypothalamic AMPK plays a critical role in hormonal and
nutrient-derived anorexigenic and orexigenic signals and in energy
balance.
Baba et al. (2006) showed that FNIP1 (610594) interacted with the alpha,
beta, and gamma subunits of AMPK. FNIP1 was phosphorylated by AMPK, and
its phosphorylation was inhibited in a dose-dependent manner by an AMPK
inhibitor, resulting in reduced FNIP1 expression. FLCN (607273)
phosphorylation was diminished by rapamycin and amino acid starvation
and facilitated by FNIP1 overexpression, suggesting that FLCN
phosphorylation may be regulated by mTOR (FRAP1; 601231) and AMPK
signaling. Baba et al. (2006) concluded that FLCN and FNIP1 may be
involved in energy and/or nutrient sensing through the AMPK and mTOR
signaling pathways.
MAPPING
Stapleton et al. (1997) mapped the human AMPK-beta-1 gene to 12q24.1 by
fluorescence in situ hybridization.
BIOCHEMICAL FEATURES
- Crystal Structure
Xiao et al. (2007) reported the crystal structure of the regulatory
fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate
groups of AMP/ATP lie in a groove on the surface of the gamma domain,
which is lined with basic residues, many of which are associated with
disease-causing mutations. Structural and solution studies revealed that
2 sites on the gamma domain bind either AMP or magnesium ATP, whereas a
third site contains a tightly bound AMP that does not exchange. Xiao et
al. (2007) stated that their binding studies indicated that under
physiologic conditions AMPK mainly exists in its inactive form in
complex with magnesium ATP, which is much more abundant than AMP. Their
modeling studies suggested how changes in the concentration of AMP
enhance AMPK activity levels. The structure also suggested a mechanism
for propagating AMP/ATP signaling whereby a phosphorylated residue from
the alpha and/or beta subunits binds to the gamma subunit in the
presence of AMP but not when ATP is bound.
*FIELD* RF
1. Baba, M.; Hong, S.-B.; Sharma, N.; Warren, M. B.; Nickerson, M.
L.; Iwamatsu, A.; Esposito, D.; Gillette, W. K.; Hopkins, R. F., III;
Hartley, J. L.; Furihata, M.; Oishi, S.; Zhen, W.; Burke, T. R., Jr.;
Linehan, W. M.; Schmidt, L. S.; Zbar, B.: Folliculin encoded by the
BHD gene interacts with a binding protein, FNIP1, and AMPK, and is
involved in AMPK and mTOR signaling. Proc. Nat. Acad. Sci. 103:
15552-15557, 2006.
2. Minokoshi, Y.; Alquier, T.; Furukawa, N.; Kim, Y.-B.; Lee, A.;
Xue, B.; Mu, J.; Foufelle, F.; Ferre, P.; Birnbaum, M. J.; Stuck,
B. J.; Kahn, B. B.: AMP-kinase regulates food intake by responding
to hormonal and nutrient signals in the hypothalamus. Nature 428:
569-574, 2004.
3. Stapleton, D.; Woollatt, E.; Mitchelhill, K. I.; Nicholl, J. K.;
Fernandez, C. S.; Michell, B. J.; Witters, L. A.; Power, D. A.; Sutherland,
G. R.; Kemp, B. E.: AMP-activated protein kinase isoenzyme family:
subunit structure and chromosomal location. FEBS Lett. 409: 452-456,
1997.
4. Thornton, C.; Snowden, M. A.; Carling, D.: Identification of a
novel AMP-activated protein kinase beta subunit isoform that is highly
expressed in skeletal muscle. J. Biol. Chem. 273: 12443-12450, 1998.
5. Woods, A.; Cheung, P. C. F.; Smith, F. C.; Davison, M. D.; Scott,
J.; Beri, R. K.; Carling, D.: Characterization of AMP-activated protein
kinase beta and gamma subunits: assembly of the heterotrimeric complex
in vitro. J. Biol. Chem. 271: 10282-10290, 1996.
6. Xiao, B.; Heath, R.; Saiu, P.; Leiper, F. C.; Leone, P.; Jing,
C.; Walker, P. A.; Haire, L.; Eccleston, J. F.; Davis, C. T.; Martin,
S. R.; Carling, D.; Gamblin, S. J.: Structural basis for AMP binding
to mammalian AMP-activated protein kinase. Nature 449: 496-500,
2007.
*FIELD* CN
Ada Hamosh - updated: 10/11/2007
Dorothy S. Reilly - updated: 11/27/2006
Ada Hamosh - updated: 4/7/2004
*FIELD* CD
Rebekah S. Rasooly: 6/22/1998
*FIELD* ED
alopez: 10/16/2007
terry: 10/11/2007
wwang: 11/27/2006
alopez: 4/8/2004
terry: 4/7/2004
terry: 5/20/1999
psherman: 6/24/1998
*RECORD*
*FIELD* NO
602740
*FIELD* TI
*602740 PROTEIN KINASE, AMP-ACTIVATED, NONCATALYTIC, BETA-1; PRKAB1
;;AMP-ACTIVATED PROTEIN KINASE, NONCATALYTIC, BETA-1;;
read moreAMPK-BETA-1
*FIELD* TX
The mammalian 5-prime-AMP-activated protein kinase (AMPK) appears to act
as a metabolic stress-sensing protein kinase. AMPK is a heterotrimeric
protein composed of a catalytic alpha subunit, a noncatalytic beta
subunit, and a noncatalytic gamma subunit. See PRKAA1 (602739) for
additional background.
CLONING
Using PCR with degenerate oligonucleotides based on the rat Ampk-beta-1
protein sequence, Woods et al. (1996) isolated rat liver cDNAs encoding
Ampk-beta-1. Both the Ampk-beta-1 mRNA and protein are widely expressed
in rat tissues. The predicted 270-amino acid protein has a calculated
mass of 30 kD, but Woods et al. (1996) reported that it migrates as a
38-kD protein by SDS-PAGE. Immunoprecipitation studies suggested that
Ampk-beta-1 mediates the association of the AMPK heterotrimeric complex
in vitro.
By searching the sequence databases with a rat Ampk-beta-1 cDNA,
Stapleton et al. (1997) identified an EST encoding human AMPK-beta-1.
The human and rat AMPK-beta-1 proteins have 95% amino acid sequence
identity. Thornton et al. (1998) reported that the predicted 271-amino
acid human AMPK-beta-1 protein shares 71% sequence identity with human
AMPK-beta-2 (PRKAB2; 602741). They found that both beta isoforms form
complexes with Ampk-alpha-1 (PRKAA1) and Ampk-alpha-2 (PRKAA2; 600497)
in rat liver and skeletal muscle. Coexpression of the alpha and
AMPK-gamma-1 (PRKAG1; 602742) subunits with either AMPK-beta-1 or
AMPK-beta-2 in mammalian cells did not reveal a significant difference
in AMPK activity between the 2 beta isoforms. Using Western blot
analysis and immunoprecipitation studies, Thornton et al. (1998)
determined that Ampk-beta-1 was expressed at higher levels than
Ampk-beta-2 in rat liver, while Ampk-beta-2 was more abundant in
skeletal muscle. They suggested that the marked difference in expression
patterns of Ampk-beta-1 and Ampk-beta-2 indicates tissue-specific roles
for these isoforms. By Northern blot analysis, Thornton et al. (1998)
found that AMPK-beta-1 was expressed as a 3-kb mRNA in all tissues
tested.
GENE FUNCTION
Minokoshi et al. (2004) investigated the potential role of AMP-activated
protein kinase (AMPK) in the hypothalamus in the regulation of food
intake. Minokoshi et al. (2004) reported that AMPK activity is inhibited
in arcuate and paraventricular hypothalamus by the anorexigenic hormone
leptin (164160), and in multiple hypothalamic regions by insulin
(176730), high glucose, and refeeding. A melanocortin receptor (see
155555) agonist, a potent anorexigen, decreased AMPK activity in
paraventricular hypothalamus, whereas agouti-related protein (602311),
an orexigen, increased AMPK activity. Melanocortin receptor signaling is
required for leptin and refeeding effects of AMPK in the paraventricular
hypothalamus. Dominant-negative AMPK expression in the hypothalamus was
sufficient to reduce food intake and body weight, whereas constitutively
active AMPK increased both. Alterations of hypothalamic AMPK activity
augmented changes in arcuate neuropeptide expression induced by fasting
and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary
for leptin's effects on food intake and body weight, as constitutively
active AMPK blocks these effects. Thus, Minokoshi et al. (2004)
concluded that hypothalamic AMPK plays a critical role in hormonal and
nutrient-derived anorexigenic and orexigenic signals and in energy
balance.
Baba et al. (2006) showed that FNIP1 (610594) interacted with the alpha,
beta, and gamma subunits of AMPK. FNIP1 was phosphorylated by AMPK, and
its phosphorylation was inhibited in a dose-dependent manner by an AMPK
inhibitor, resulting in reduced FNIP1 expression. FLCN (607273)
phosphorylation was diminished by rapamycin and amino acid starvation
and facilitated by FNIP1 overexpression, suggesting that FLCN
phosphorylation may be regulated by mTOR (FRAP1; 601231) and AMPK
signaling. Baba et al. (2006) concluded that FLCN and FNIP1 may be
involved in energy and/or nutrient sensing through the AMPK and mTOR
signaling pathways.
MAPPING
Stapleton et al. (1997) mapped the human AMPK-beta-1 gene to 12q24.1 by
fluorescence in situ hybridization.
BIOCHEMICAL FEATURES
- Crystal Structure
Xiao et al. (2007) reported the crystal structure of the regulatory
fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate
groups of AMP/ATP lie in a groove on the surface of the gamma domain,
which is lined with basic residues, many of which are associated with
disease-causing mutations. Structural and solution studies revealed that
2 sites on the gamma domain bind either AMP or magnesium ATP, whereas a
third site contains a tightly bound AMP that does not exchange. Xiao et
al. (2007) stated that their binding studies indicated that under
physiologic conditions AMPK mainly exists in its inactive form in
complex with magnesium ATP, which is much more abundant than AMP. Their
modeling studies suggested how changes in the concentration of AMP
enhance AMPK activity levels. The structure also suggested a mechanism
for propagating AMP/ATP signaling whereby a phosphorylated residue from
the alpha and/or beta subunits binds to the gamma subunit in the
presence of AMP but not when ATP is bound.
*FIELD* RF
1. Baba, M.; Hong, S.-B.; Sharma, N.; Warren, M. B.; Nickerson, M.
L.; Iwamatsu, A.; Esposito, D.; Gillette, W. K.; Hopkins, R. F., III;
Hartley, J. L.; Furihata, M.; Oishi, S.; Zhen, W.; Burke, T. R., Jr.;
Linehan, W. M.; Schmidt, L. S.; Zbar, B.: Folliculin encoded by the
BHD gene interacts with a binding protein, FNIP1, and AMPK, and is
involved in AMPK and mTOR signaling. Proc. Nat. Acad. Sci. 103:
15552-15557, 2006.
2. Minokoshi, Y.; Alquier, T.; Furukawa, N.; Kim, Y.-B.; Lee, A.;
Xue, B.; Mu, J.; Foufelle, F.; Ferre, P.; Birnbaum, M. J.; Stuck,
B. J.; Kahn, B. B.: AMP-kinase regulates food intake by responding
to hormonal and nutrient signals in the hypothalamus. Nature 428:
569-574, 2004.
3. Stapleton, D.; Woollatt, E.; Mitchelhill, K. I.; Nicholl, J. K.;
Fernandez, C. S.; Michell, B. J.; Witters, L. A.; Power, D. A.; Sutherland,
G. R.; Kemp, B. E.: AMP-activated protein kinase isoenzyme family:
subunit structure and chromosomal location. FEBS Lett. 409: 452-456,
1997.
4. Thornton, C.; Snowden, M. A.; Carling, D.: Identification of a
novel AMP-activated protein kinase beta subunit isoform that is highly
expressed in skeletal muscle. J. Biol. Chem. 273: 12443-12450, 1998.
5. Woods, A.; Cheung, P. C. F.; Smith, F. C.; Davison, M. D.; Scott,
J.; Beri, R. K.; Carling, D.: Characterization of AMP-activated protein
kinase beta and gamma subunits: assembly of the heterotrimeric complex
in vitro. J. Biol. Chem. 271: 10282-10290, 1996.
6. Xiao, B.; Heath, R.; Saiu, P.; Leiper, F. C.; Leone, P.; Jing,
C.; Walker, P. A.; Haire, L.; Eccleston, J. F.; Davis, C. T.; Martin,
S. R.; Carling, D.; Gamblin, S. J.: Structural basis for AMP binding
to mammalian AMP-activated protein kinase. Nature 449: 496-500,
2007.
*FIELD* CN
Ada Hamosh - updated: 10/11/2007
Dorothy S. Reilly - updated: 11/27/2006
Ada Hamosh - updated: 4/7/2004
*FIELD* CD
Rebekah S. Rasooly: 6/22/1998
*FIELD* ED
alopez: 10/16/2007
terry: 10/11/2007
wwang: 11/27/2006
alopez: 4/8/2004
terry: 4/7/2004
terry: 5/20/1999
psherman: 6/24/1998