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UniProtKB/Swiss-Prot entry Q13131


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name AAPK1_HUMAN
Primary accession number Q13131
Secondary accession numbers O00286 Q5D0E1 Q86VS1 Q9UNQ4
Integrated into Swiss-Prot on July 15, 1998
Sequence was last modified on September 13, 2005 (Sequence version 3)
Annotations were last modified on    November 4, 2008 (Entry version 92)
Name and origin of the protein
Protein name 5'-AMP-activated protein kinase catalytic subunit alpha-1
Synonyms AMPK alpha-1 chain
EC 2.7.11.1
Gene name
Name: PRKAA1
Synonyms: AMPK1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Mammary gland;
Yano K.;
"Nucleotide sequence of cDNA for human AMP-activated protein kinase alpha-1.";
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Umbilical cord blood;
DOI=10.1101/gr.140200; PubMed=11042152 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.";
Genome Res. 10:1546-1560(2000).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Brain, and Testis;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 27-200.
TISSUE=Intestine;
Taboada E.N., Hickey D.A.;
Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 294-550.
TISSUE=Liver;
DOI=10.1074/jbc.271.2.611; PubMed=8557660 [NCBI, ExPASy, EBI, Israel, Japan]
Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., Teh T., House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E.;
"Mammalian AMP-activated protein kinase subfamily.";
J. Biol. Chem. 271:611-614(1996).
[6]
FUNCTION, AND ENZYME REGULATION.
DOI=10.1038/sj.emboj.7600110; PubMed=14976552 [NCBI, ExPASy, EBI, Israel, Japan]
Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.;
"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.";
EMBO J. 23:833-843(2004).
[7]
FUNCTION, AND ENZYME REGULATION.
DOI=10.1016/j.cmet.2005.05.009; PubMed=16054095 [NCBI, ExPASy, EBI, Israel, Japan]
Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., Frenguelli B.G., Hardie D.G.;
"Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase.";
Cell Metab. 2:9-19(2005).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487, AND MASS SPECTROMETRY.
DOI=10.1021/pr050048h; PubMed=16083285 [NCBI, ExPASy, EBI, Israel, Japan]
Kim J.-E., Tannenbaum S.R., White F.M.;
"Global phosphoproteome of HT-29 human colon adenocarcinoma cells.";
J. Proteome Res. 4:1339-1346(2005).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-433, AND MASS SPECTROMETRY.
DOI=10.1016/j.cell.2007.11.025; PubMed=18083107 [NCBI, ExPASy, EBI, Israel, Japan]
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.";
Cell 131:1190-1203(2007).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487, AND MASS SPECTROMETRY.
TISSUE=Platelet;
DOI=10.1021/pr0704130; PubMed=18088087 [NCBI, ExPASy, EBI, Israel, Japan]
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-373, AND MASS SPECTROMETRY.
DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan]
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[12]
INTERACTION WITH FNIP1.
DOI=10.1073/pnas.0603781103; PubMed=17028174 [NCBI, ExPASy, EBI, Israel, Japan]
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. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006).
[13]
INTERACTION WITH FNIP2.
DOI=10.1016/j.gene.2008.02.022; PubMed=18403135 [NCBI, ExPASy, EBI, Israel, Japan]
Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., Valera V.A., Linehan W.M., Schmidt L.S.;
"Identification and characterization of a novel folliculin-interacting protein FNIP2.";
Gene 415:60-67(2008).
[14]
VARIANT [LARGE SCALE ANALYSIS] ARG-7.
DOI=10.1126/science.1133427; PubMed=16959974 [NCBI, ExPASy, EBI, Israel, Japan]
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal cancers.";
Science 314:268-274(2006).
Comments
  • FUNCTION: Responsible for the regulation of fatty acid synthesis by phosphorylation of acetyl-CoA carboxylase. It also regulates cholesterol synthesis via phosphorylation and inactivation of hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase. Appears to act as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-AMP rises in response to fuel limitation and/or hypoxia. This is a catalytic subunit.
  • CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
  • COFACTOR: Magnesium.
  • ENZYME REGULATION: Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-174 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Also activated by phosphorylation by CAMKK2 triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio.
  • SUBUNIT: Heterotrimer of an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2.
  • INTERACTION:
    P35396:Ppard (xeno); NbExp=1; IntAct=EBI-1181405, EBI-1809541;
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDQ13131-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDQ13131-2
    Features which should be applied to build the isoform sequence: VSP_035431.
  • SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
  • SIMILARITY: Contains 1 protein kinase domain.
  • SEQUENCE CAUTION:
    • Sequence=AAH48980.1; Type=Erroneous initiation; Note=Translation N-terminally shortened
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AB022017; BAA36547.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF100763; AAD43027.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC037303; AAH37303.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC048980; AAH48980.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U22456; AAA64850.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Y12856; CAA73361.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR G01743; G01743.
RefSeq NP_006242.5; -.
NP_996790.3; -.
UniGene Hs.43322
3D structure databases
HSSP Q63450; 1A06. [HSSP ENTRY / PDB]
SMR Q13131; 12-280.
ModBase Q13131.
Protein-protein interaction databases
IntAct Q13131; -.
PTM databases
PhosphoSite Q13131; -.
Organism-specific databases
H-InvDB HIX0004832; -.
HGNC HGNC:9376; PRKAA1.
GenAtlas PRKAA1.
HPA CAB005050; -.
MIM 602739; gene. [NCBI / EBI]
PharmGKB PA33744; -.
GeneCards Q13131.
Gene expression databases
ArrayExpress Q13131; -.
CleanEx HS_PRKAA1; -.
GermOnline ENSG00000132356; Homo sapiens.
Ontologies
GO
GO:0005622; Cellular component: intracellular (inferred by curator from UniProtKB).
GO:0004691; Molecular function: cAMP-dependent protein kinase activity (non-traceable author statement from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0000187; Biological process: activation of MAPK activity (non-traceable author statement from UniProtKB).
GO:0046318; Biological process: negative regulation of glucosylceramide biosynthetic process (non-traceable author statement from UniProtKB).
GO:0045768; Biological process: positive regulation of anti-apoptosis (non-traceable author statement from UniProtKB).
GO:0045542; Biological process: positive regulation of cholesterol biosynthetic process (non-traceable author statement from UniProtKB).
GO:0001666; Biological process: response to hypoxia (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR015741; AMPK.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.
PANTHER PTHR22982:SF61; AMPK; 1.
Pfam PF00069; Pkinase; 1.
Pfam graphical view of domain structure.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00220; S_TKc; 1.
SMART graphical view of domain structure.
PROSITE PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS Q13131.
ProtoNet Q13131.
Genome annotation databases
Ensembl ENSG00000132356; Homo sapiens. [Contig view]
GeneID 5562; -.
KEGG hsa:5562; -.
Phylogenomic databases
HOVERGEN Q13131; -.
Other
DrugBank DB00131; Adenosine monophosphate.
DB00171; Adenosine triphosphate.
DB00914; Phenformin.
SOURCE PRKAA1; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Alternative splicing; ATP-binding; Cholesterol biosynthesis; Fatty acid biosynthesis; Kinase; Lipid synthesis; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Serine/threonine-protein kinase; Steroid biosynthesis; Sterol biosynthesis; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   550  550     5'-AMP-activated protein kinase catalytic subunit alpha-1. PRO_0000085589
DOMAIN   18   270  253     Protein kinase. 
NP_BIND   24    32  9     ATP (By similarity). 
ACT_SITE   141   141        Proton acceptor (By similarity). 
BINDING   47    47        ATP (By similarity). 
MOD_RES   174   174        Phosphothreonine; by STK11 (By similarity). 
MOD_RES   175   175        Phosphoserine (By similarity). 
MOD_RES   260   260        Phosphothreonine (By similarity). 
MOD_RES   373   373        Phosphothreonine. 
MOD_RES   433   433        Phosphotyrosine. 
MOD_RES   487   487        Phosphoserine. 
MOD_RES   499   499        Phosphoserine (By similarity). 
VAR_SEQ   112   112        R -> RKSDVPGVVKTGSTKE (in isoform 2). VSP_035431
VARIANT   7     7  1     Q -> R (in a breast cancer sample; somatic mutation). VAR_035622 
CONFLICT   1     1        M -> L (in Ref. 3; AAH48980). 
CONFLICT   28    28        T -> A (in Ref. 4; AAA64850). 
CONFLICT   193   193        A -> V (in Ref. 4; AAA64850). 
CONFLICT   199   199        I -> L (in Ref. 4; AAA64850). 
CONFLICT   260   260        T -> S (in Ref. 1; BAA36547). 
Sequence information
Length: 550 AA [This is the length of the unprocessed precursor] Molecular weight: 62808 Da [This is the MW of the unprocessed precursor] CRC64: F878493C3158B1C2 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MATAEKQKHD GRVKIGHYIL GDTLGVGTFG KVKVGKHELT GHKVAVKILN RQKIRSLDVV 

        70         80         90        100        110        120 
GKIRREIQNL KLFRHPHIIK LYQVISTPSD IFMVMEYVSG GELFDYICKN GRLDEKESRR 

       130        140        150        160        170        180 
LFQQILSGVD YCHRHMVVHR DLKPENVLLD AHMNAKIADF GLSNMMSDGE FLRTSCGSPN 

       190        200        210        220        230        240 
YAAPEVISGR LYAGPEVDIW SSGVILYALL CGTLPFDDDH VPTLFKKICD GIFYTPQYLN 

       250        260        270        280        290        300 
PSVISLLKHM LQVDPMKRAT IKDIREHEWF KQDLPKYLFP EDPSYSSTMI DDEALKEVCE 

       310        320        330        340        350        360 
KFECSEEEVL SCLYNRNHQD PLAVAYHLII DNRRIMNEAK DFYLATSPPD SFLDDHHLTR 

       370        380        390        400        410        420 
PHPERVPFLV AETPRARHTL DELNPQKSKH QGVRKAKWHL GIRSQSRPND IMAEVCRAIK 

       430        440        450        460        470        480 
QLDYEWKVVN PYYLRVRRKN PVTSTYSKMS LQLYQVDSRT YLLDFRSIDD EITEAKSGTA 

       490        500        510        520        530        540 
TPQRSGSVSN YRSCQRSDSD AEAQGKSSEV SLTSSVTSLD SSPVDLTPRP GSHTIEFFEM 

       550 
CANLIKILAQ 

Q13131 in FASTA format

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