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UniProtKB/Swiss-Prot entry P54646


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

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Entry information
Entry name AAPK2_HUMAN
Primary accession number P54646
Secondary accession numbers Q9H1E8 Q9UD43
Integrated into Swiss-Prot on October 1, 1996
Sequence was last modified on April 16, 2002 (Sequence version 2)
Annotations were last modified on    September 2, 2008 (Entry version 82)
Name and origin of the protein
Protein name 5'-AMP-activated protein kinase catalytic subunit alpha-2
Synonyms AMPK alpha-2 chain
EC 2.7.11.1
Gene name
Name: PRKAA2
Synonyms: AMPK, AMPK2
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], AND FUNCTION.
TISSUE=Heart;
DOI=10.1016/0378-1119(94)90174-0; PubMed=7959015 [NCBI, ExPASy, EBI, Israel, Japan]
Aguan K., Scott J., See C.G., Sarkar N.H.;
"Characterization and chromosomal localization of the human homologue of a rat AMP-activated protein kinase-encoding gene: a major regulator of lipid metabolism in mammals.";
Gene 149:345-350(1994).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Skeletal muscle;
DOI=10.1016/0014-5793(94)01247-4; PubMed=7988703 [NCBI, ExPASy, EBI, Israel, Japan]
Beri R.K., Marley A.E., See C.G., Sopwith W.F., Aguan K., Carling D., Scott J., Carey F.;
"Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase.";
FEBS Lett. 356:117-121(1994).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-173 AND SER-176, 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).
[6]
VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLY-523.
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).
[7]
VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLN-407.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
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-172 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 (By similarity).
  • SUBUNIT: Heterotrimer of a catalytic subunit, a beta and a gamma non-catalytic subunits.
  • SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
  • SIMILARITY: Contains 1 protein kinase domain.
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
U06454; AAA64745.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL035705; CAC17574.2; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC069680; AAH69680.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC069740; AAH69740.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC069823; AAH69823.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR S51025; S51025.
RefSeq NP_006243.2; -.
UniGene Hs.437039
3D structure databases
PDB
2H6D; X-ray; 1.85 A; A=6-279.[ExPASy / RCSB / EBI]
2YZA; X-ray; 3.02 A; A=6-279.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 2H6D; -.
2YZA; -.
ModBase P54646.
Protein-protein interaction databases
IntAct P54646; -.
PTM databases
PhosphoSite P54646; -.
Enzyme and pathway databases
Reactome REACT_1505; Integration of energy metabolism.
Organism-specific databases
H-InvDB HIX0028788; -.
HGNC HGNC:9377; PRKAA2.
GenAtlas PRKAA2.
HPA CAB013043; -.
MIM 600497; gene. [NCBI / EBI]
PharmGKB PA33745; -.
GeneCards P54646.
Gene expression databases
ArrayExpress P54646; -.
CleanEx HS_PRKAA2; -.
GermOnline ENSG00000162409; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005654; Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0004672; Molecular function: protein kinase activity (traceable author statement from ProtInc).
GO:0006468; Biological process: protein amino acid phosphorylation (traceable author statement from ProtInc).
GO:0046320; Biological process: regulation of fatty acid oxidation (inferred from experiment from Reactome).
GO:0007165; Biological process: signal transduction (traceable author statement from ProtInc).
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 P54646.
Genome annotation databases
Ensembl ENSG00000162409; Homo sapiens. [Contig view]
GeneID 5563; -.
KEGG hsa:5563; -.
Phylogenomic databases
HOGENOM P54646; -.
HOVERGEN P54646; -.
Other
SOURCE PRKAA2; Homo sapiens.
ProtoNet P54646.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; 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   552  552     5'-AMP-activated protein kinase catalytic subunit alpha-2. PRO_0000085594
DOMAIN   16   268  253     Protein kinase. 
NP_BIND   22    30  9     ATP (By similarity). 
ACT_SITE   139   139        Proton acceptor (By similarity). 
BINDING   45    45        ATP (By similarity). 
MOD_RES   172   172        Phosphothreonine; by STK11 (By similarity). 
MOD_RES   173   173        Phosphoserine. 
MOD_RES   176   176        Phosphoserine. 
MOD_RES   258   258        Phosphothreonine (By similarity). 
MOD_RES   491   491        Phosphoserine (By similarity). 
MOD_RES   500   500        Phosphoserine (By similarity). 
VARIANT   371   371  1     P -> T (in breast cancer samples; infiltrating ductal carcinoma; somatic mutation). VAR_035623 
VARIANT   407   407  1     R -> Q (in a gastric adenocarcinoma sample; somatic mutation). VAR_040355 
VARIANT   523   523  1     S -> G (in a breast cancer sample; somatic mutation). VAR_035624 
CONFLICT   180   180        A -> T (in Ref. 1; AAA64745). 
CONFLICT   271   271        D -> G (in Ref. 1; AAA64745). 
CONFLICT   403   404        HL -> RQ (in Ref. 1; AAA64745). 
STRAND   16    24  9      
STRAND   26    35  10      
TURN   36    38  3      
STRAND   41    48  8      
HELIX   49    54  6      
HELIX   58    69  12      
STRAND   79    84  6      
STRAND   86    94  9      
HELIX   101   108  8      
HELIX   113   133  21      
HELIX   142   144  3      
STRAND   145   147  3      
STRAND   153   155  3      
HELIX   160   162  3      
HELIX   183   185  3      
HELIX   192   209  18      
HELIX   219   228  10      
HELIX   239   248  10      
HELIX   253   255  3      
HELIX   259   264  6      
HELIX   266   269  4      
HELIX   274   276  3      
Sequence information
Length: 552 AA [This is the length of the unprocessed precursor] Molecular weight: 62320 Da [This is the MW of the unprocessed precursor] CRC64: C46AAFC1D5104975 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KIGEHQLTGH KVAVKILNRQ KIRSLDVVGK 

        70         80         90        100        110        120 
IKREIQNLKL FRHPHIIKLY QVISTPTDFF MVMEYVSGGE LFDYICKHGR VEEMEARRLF 

       130        140        150        160        170        180 
QQILSAVDYC HRHMVVHRDL KPENVLLDAH MNAKIADFGL SNMMSDGEFL RTSCGSPNYA 

       190        200        210        220        230        240 
APEVISGRLY AGPEVDIWSC GVILYALLCG TLPFDDEHVP TLFKKIRGGV FYIPEYLNRS 

       250        260        270        280        290        300 
VATLLMHMLQ VDPLKRATIK DIREHEWFKQ DLPSYLFPED PSYDANVIDD EAVKEVCEKF 

       310        320        330        340        350        360 
ECTESEVMNS LYSGDPQDQL AVAYHLIIDN RRIMNQASEF YLASSPPSGS FMDDSAMHIP 

       370        380        390        400        410        420 
PGLKPHPERM PPLIADSPKA RCPLDALNTT KPKSLAVKKA KWHLGIRSQS KPYDIMAEVY 

       430        440        450        460        470        480 
RAMKQLDFEW KVVNAYHLRV RRKNPVTGNY VKMSLQLYLV DNRSYLLDFK SIDDEVVEQR 

       490        500        510        520        530        540 
SGSSTPQRSC SAAGLHRPRS SFDSTTAESH SLSGSLTGSL TGSTLSSVSP RLGSHTMDFF 

       550 
EMCASLITTL AR 

P54646 in FASTA format

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