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P54646 (AAPK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5'-AMP-activated protein kinase catalytic subunit alpha-2

Short name=AMPK subunit alpha-2
EC=2.7.11.1
Alternative name(s):
Acetyl-CoA carboxylase kinase
Short name=ACACA kinase
EC=2.7.11.27
Hydroxymethylglutaryl-CoA reductase kinase
Short name=HMGCR kinase
EC=2.7.11.31
Gene names
Name:PRKAA2
Synonyms:AMPK, AMPK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length552 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.18 Ref.19 Ref.22

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate.

ATP + [acetyl-CoA carboxylase] = ADP + [acetyl-CoA carboxylase] phosphate.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by phosphorylation on Thr-172. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172. ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-172, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (Ref.7). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation. Ref.7 Ref.10 Ref.25 Ref.28

Subunit structure

AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.

Subcellular location

Cytoplasm By similarity. Nucleus. Note: In response to stress, recruited by p53/TP53 to specific promoters. Ref.11

Domain

The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.

Post-translational modification

Ubiquitinated By similarity.

Phosphorylated at Thr-172 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-172 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by STK11/LKB1). Ref.10 Ref.20 Ref.26

Sequence similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAutophagy
Biological rhythms
Cholesterol biosynthesis
Cholesterol metabolism
Fatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
Transcription
Transcription regulation
Wnt signaling pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

carnitine shuttle

Traceable author statement. Source: Reactome

cell cycle arrest

Traceable author statement. Source: Reactome

cellular lipid metabolic process

Traceable author statement. Source: Reactome

cellular response to glucose starvation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to nutrient levels

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

energy reserve metabolic process

Traceable author statement. Source: Reactome

fatty acid biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

lipid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

membrane organization

Traceable author statement. Source: Reactome

negative regulation of TOR signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glycolytic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

regulation of circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of energy homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of fatty acid biosynthetic process

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to stress

Inferred from sequence or structural similarity. Source: UniProtKB

rhythmic process

Inferred from electronic annotation. Source: UniProtKB-KW

signal transduction

Traceable author statement Ref.1. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionAMP-activated protein kinase activity

Inferred from direct assay PubMed 18439900. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

[acetyl-CoA carboxylase] kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

chromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone serine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 18439900PubMed 20801214. Source: UniProtKB

protein kinase activity

Traceable author statement Ref.1. Source: ProtInc

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

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
Region291 – 37686AIS By similarity

Sites

Active site1391Proton acceptor By similarity
Binding site451ATP By similarity

Amino acid modifications

Modified residue1721Phosphothreonine; by LKB1 and CaMKK2 Ref.10 Ref.26
Modified residue2581Phosphothreonine By similarity
Modified residue3771Phosphoserine Ref.15 Ref.17
Modified residue4911Phosphoserine By similarity

Natural variations

Natural variant3711P → T in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.29 Ref.30
VAR_035623
Natural variant4071R → Q in a gastric adenocarcinoma sample; somatic mutation. Ref.30
VAR_040355
Natural variant5231S → G in a breast cancer sample; somatic mutation. Ref.29
VAR_035624

Experimental info

Mutagenesis1721T → D: Phosphomimetic mutant.
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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line."
Imamura K., Ogura T., Kishimoto A., Kaminishi M., Esumi H.
Biochem. Biophys. Res. Commun. 287:562-567(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Regulation of transcription by AMP-activated protein kinase: phosphorylation of p300 blocks its interaction with nuclear receptors."
Yang W., Hong Y.H., Shen X.Q., Frankowski C., Camp H.S., Leff T.
J. Biol. Chem. 276:38341-38344(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF EP300.
[7]"Role of AMP-activated protein kinase in mechanism of metformin action."
Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., Goodyear L.J., Moller D.E.
J. Clin. Invest. 108:1167-1174(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[8]"Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells."
Hallows K.R., Kobinger G.P., Wilson J.M., Witters L.A., Foskett J.K.
Am. J. Physiol. 284:C1297-C1308(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CFTR.
[9]"TSC2 mediates cellular energy response to control cell growth and survival."
Inoki K., Zhu T., Guan K.L.
Cell 115:577-590(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TSC2.
[10]"The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases."
Hurley R.L., Anderson K.A., Franzone J.M., Kemp B.E., Means A.R., Witters L.A.
J. Biol. Chem. 280:29060-29066(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-172, ENZYME REGULATION.
[11]"AMP-activated protein kinase induces a p53-dependent metabolic checkpoint."
Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., Birnbaum M.J., Thompson C.B.
Mol. Cell 18:283-293(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]"The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor."
Greer E.L., Oskoui P.R., Banko M.R., Maniar J.M., Gygi M.P., Gygi S.P., Brunet A.
J. Biol. Chem. 282:30107-30119(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF FOXO3.
[13]"Energy-dependent regulation of cell structure by AMP-activated protein kinase."
Lee J.H., Koh H., Kim M., Kim Y., Lee S.Y., Karess R.E., Lee S.H., Shong M., Kim J.M., Kim J., Chung J.
Nature 447:1017-1020(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL POLARITY.
[14]"AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5."
McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., Schertzer J.D., Kemp B.E., Hargreaves M.
Diabetes 57:860-867(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC5.
[15]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Cell-wide analysis of secretory granule dynamics in three dimensions in living pancreatic beta-cells: evidence against a role for AMPK-dependent phosphorylation of KLC1 at Ser517/Ser520 in glucose-stimulated insulin granule movement."
McDonald A., Fogarty S., Leclerc I., Hill E.V., Hardie D.G., Rutter G.A.
Biochem. Soc. Trans. 38:205-208(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF KLC1.
[19]"ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS."
Alexander A., Cai S.L., Kim J., Nanez A., Sahin M., MacLean K.H., Inoki K., Guan K.L., Shen J., Person M.D., Kusewitt D., Mills G.B., Kastan M.B., Walker C.L.
Proc. Natl. Acad. Sci. U.S.A. 107:4153-4158(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop."
Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.
Autophagy 7:696-706(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY ULK1.
[21]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy."
Egan D.F., Shackelford D.B., Mihaylova M.M., Gelino S., Kohnz R.A., Mair W., Vasquez D.S., Joshi A., Gwinn D.M., Taylor R., Asara J.M., Fitzpatrick J., Dillin A., Viollet B., Kundu M., Hansen M., Shaw R.J.
Science 331:456-461(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ULK1.
[23]"AMP-activated protein kinase in metabolic control and insulin signaling."
Towler M.C., Hardie D.G.
Circ. Res. 100:328-341(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[24]"AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy."
Hardie D.G.
Nat. Rev. Mol. Cell Biol. 8:774-785(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[25]"The ancient drug salicylate directly activates AMP-activated protein kinase."
Hawley S.A., Fullerton M.D., Ross F.A., Schertzer J.D., Chevtzoff C., Walker K.J., Peggie M.W., Zibrova D., Green K.A., Mustard K.J., Kemp B.E., Sakamoto K., Steinberg G.R., Hardie D.G.
Science 336:918-922(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION BY SALICYLATE.
[26]"N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells."
Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., Takano-Yamamoto T., Tamura S., Kobayashi T.
Biochem. J. 449:741-749(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: DEPHOSPHORYLATION AT THR-172.
[27]"A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation."
Littler D.R., Walker J.R., Davis T., Wybenga-Groot L.E., Finerty P.J. Jr., Newman E., Mackenzie F., Dhe-Paganon S.
Acta Crystallogr. F 66:143-151(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 6-279.
[28]"Structural basis for compound C inhibition of the human AMP-activated protein kinase alpha2 subunit kinase domain."
Handa N., Takagi T., Saijo S., Kishishita S., Takaya D., Toyama M., Terada T., Shirouzu M., Suzuki A., Lee S., Yamauchi T., Okada-Iwabu M., Iwabu M., Kadowaki T., Minokoshi Y., Yokoyama S.
Acta Crystallogr. D 67:480-487(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 6-279 OF MUTANT THR-172 IN COMPLEX WITH COMPOUND C, ENZYME REGULATION.
[29]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLY-523.
[30]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLN-407.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS605.1.
PIRS51025.
RefSeqNP_006243.2. NM_006252.3.
UniGeneHs.437039.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2H6DX-ray1.85A6-279[»]
2LTUNMR-A282-339[»]
2YZAX-ray3.02A6-279[»]
3AQVX-ray2.08A6-279[»]
4CFEX-ray3.02A/C1-552[»]
4CFFX-ray3.92A/C1-552[»]
ProteinModelPortalP54646.
SMRP54646. Positions 7-551.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111550. 45 interactions.
IntActP54646. 34 interactions.
MINTMINT-2804161.
STRING9606.ENSP00000360290.

Chemistry

BindingDBP54646.
ChEMBLCHEMBL3038455.
GuidetoPHARMACOLOGY1542.

PTM databases

PhosphoSiteP54646.

Polymorphism databases

DMDM20178276.

Proteomic databases

MaxQBP54646.
PaxDbP54646.
PRIDEP54646.

Protocols and materials databases

DNASU5563.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000371244; ENSP00000360290; ENSG00000162409.
GeneID5563.
KEGGhsa:5563.
UCSCuc001cyk.4. human.

Organism-specific databases

CTD5563.
GeneCardsGC01P057027.
HGNCHGNC:9377. PRKAA2.
HPACAB013043.
MIM600497. gene.
neXtProtNX_P54646.
PharmGKBPA33745.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233016.
HOVERGENHBG050432.
InParanoidP54646.
KOK07198.
OMATMHIPPG.
OrthoDBEOG7RRF6K.
PhylomeDBP54646.
TreeFamTF314032.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_11123. Membrane Trafficking.
REACT_200751. Organelle biogenesis and maintenance.
SignaLinkP54646.

Gene expression databases

BgeeP54646.
CleanExHS_PRKAA2.
GenevestigatorP54646.

Family and domain databases

InterProIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028783. PRKAA2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24343:SF82. PTHR24343:SF82. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP54646.
GeneWikiPRKAA2.
GenomeRNAi5563.
NextBio21552.
PROP54646.
SOURCESearch...

Entry information

Entry nameAAPK2_HUMAN
AccessionPrimary (citable) accession number: P54646
Secondary accession number(s): Q9H1E8, Q9UD43
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 16, 2002
Last modified: July 9, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM