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Reviewed, UniProtKB/Swiss-Prot P54646 (AAPK2_HUMAN)

Last modified November 25, 2008. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    5'-AMP-activated protein kinase catalytic subunit alpha-2
      Short name=AMPK alpha-2 chain
    EC=2.7.11.1
Gene names
Name: PRKAA2
Synonyms: AMPK, AMPK2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length552 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (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 structure

Heterotrimer of a catalytic subunit, a beta and a gamma non-catalytic subunits.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PpardP353961EBI-1383852,EBI-1809541From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5525525'-AMP-activated protein kinase catalytic subunit alpha-2
PRO_0000085594

Regions

Domain16 – 268253Protein kinase
Nucleotide binding22 – 309ATP By similarity

Sites

Active site1391Proton acceptor By similarity
Binding site451ATP By similarity

Amino acid modifications

Modified residue1721Phosphothreonine; by STK11 By similarity
Modified residue1731Phosphoserine
Modified residue1761Phosphoserine
Modified residue2581Phosphothreonine By similarity
Modified residue3771Phosphoserine
Modified residue4911Phosphoserine By similarity
Modified residue5001Phosphoserine By similarity

Natural variations

Natural variant3711P → T in breast cancer samples; infiltrating ductal carcinoma; somatic mutation.
VAR_035623
Natural variant4071R → Q in a gastric adenocarcinoma sample; somatic mutation.
VAR_040355
Natural variant5231S → G in a breast cancer sample; somatic mutation.
VAR_035624

Experimental info

Sequence conflict1801A → T in AAA64745. Ref.1
Sequence conflict2711D → G in AAA64745. Ref.1
Sequence conflict403 – 4042HL → RQ in AAA64745. Ref.1

Secondary structure

.......................................... 552
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P54646-1 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: C46AAFC1D5104975

FASTA55262,320
        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 

« Hide

References

« Hide 'large scale' references
[1]"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."
Aguan K., Scott J., See C.G., Sarkar N.H.
Gene 149:345-350(1994) [PubMed: 7959015] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Heart.
[2]"Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase."
Beri R.K., Marley A.E., See C.G., Sopwith W.F., Aguan K., Carling D., Scott J., Carey F.
FEBS Lett. 356:117-121(1994) [PubMed: 7988703] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[3]"The DNA sequence and biological annotation of human chromosome 1."
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. expand/collapse author list , 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.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-173 AND SER-176, MASS SPECTROMETRY.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, MASS SPECTROMETRY.
[7]"The consensus coding sequences of human breast and colorectal cancers."
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. expand/collapse author list , 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.
Science 314:268-274(2006) [PubMed: 16959974] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLY-523.
[8]"Patterns of somatic mutation in human cancer genomes."
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. expand/collapse author list , 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.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLN-407.
+Additional computationally mapped references.

Cross-references

Sequence databases

U06454 mRNA. Translation: AAA64745.1.
AL035705 Genomic DNA. Translation: CAC17574.2.
BC069680 mRNA. Translation: AAH69680.1.
BC069740 mRNA. Translation: AAH69740.1.
BC069823 mRNA. Translation: AAH69823.1.
PIRS51025.
RefSeqNP_006243.2.
UniGeneHs.437039

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2H6DX-ray1.85A6-279[»]
2YZAX-ray3.02A6-279[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP54646.

PTM databases

PhosphoSiteP54646.

Genome annotation databases

EnsemblENSG00000162409. Homo sapiens. [Contig view]
GeneID5563.
KEGGhsa:5563.

Organism-specific databases

H-InvDBHIX0028788.
HGNCHGNC:9377. PRKAA2.
HPACAB013043.
MIM600497. gene.
PharmGKBPA33745.
GenAtlasSearch...