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Q8BRK8 (AAPK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.21

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. UniProtKB Q13131

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

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

Cofactor

Magnesium By similarity. UniProtKB Q13131

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. 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.6 Ref.19 Ref.22

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 By similarity.

Subcellular location

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

Domain

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

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) By similarity. Ref.6 Ref.8 Ref.18

Disruption phenotype

Mice develop obesity when animals are fed a high-fat diet, as a result of an enhanced lipid accumulation in pre-existing adipocytes but not in other tissues. Ref.4

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
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete 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

cellular response to glucose starvation

Inferred from direct assay Ref.20. Source: UniProtKB

cellular response to nutrient levels

Inferred from direct assay Ref.20. Source: UniProtKB

cholesterol biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

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 mutant phenotype Ref.8. Source: UniProtKB

histone-serine phosphorylation

Inferred from direct assay Ref.16. Source: GOC

lipid biosynthetic process

Inferred from direct assay Ref.19. Source: UniProtKB

negative regulation of TOR signaling

Inferred from mutant phenotype Ref.13. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of autophagy

Inferred from mutant phenotype Ref.20. Source: UniProtKB

positive regulation of glycolytic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of circadian rhythm

Inferred from mutant phenotype Ref.14. Source: UniProtKB

regulation of energy homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to stress

Inferred from mutant phenotype Ref.16. Source: UniProtKB

rhythmic process

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 10098881. Source: MGI

   Molecular_functionAMP-activated protein kinase activity

Inferred from direct assay Ref.13Ref.14Ref.20Ref.19. 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 direct assay Ref.16. Source: UniProtKB

histone serine kinase activity

Inferred from direct assay Ref.16. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.14Ref.19. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

protein serine/threonine/tyrosine kinase activity

Inferred from sequence orthology PubMed 22797923. Source: MGI

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_0000262957

Regions

Domain16 – 268253Protein kinase
Nucleotide binding22 – 309ATP By similarity UniProtKB P28523
Region291 – 37686AIS By similarity

Sites

Active site1391Proton acceptor By similarity UniProtKB P28523
Binding site451ATP UniProtKB P28523

Amino acid modifications

Modified residue1721Phosphothreonine; by LKB1 and CaMKK2 Ref.6 Ref.8 UniProtKB Q13131
Modified residue2581Phosphothreonine By similarity
Modified residue3771Phosphoserine Ref.12
Modified residue4911Phosphoserine By similarity

Experimental info

Mutagenesis451K → A: Loss of kinase activity. Ref.17
Mutagenesis1571D → A: Loss of kinase activity. Ref.16
Sequence conflict151H → D in BAE22188. Ref.3
Sequence conflict2891D → V in BAC31746. Ref.3
Sequence conflict3801A → E in BAE22188. Ref.3
Sequence conflict5021F → Y in BAE22188. Ref.3
Sequence conflict5061T → K in BAE22188. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q8BRK8 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 020B11E2685BFE39

FASTA55262,022
        10         20         30         40         50         60 
MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KIGEHQLTGH KVAVKILNRQ KIRSLDVVGK 

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

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

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

       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 KACDIMAEVY 

       430        440        450        460        470        480 
RAMKQLGFEW KVVNAYHLRV RRKNPVTGNY VKMSLQLYLV DSRSYLLDFK SIDDEVVEQR 

       490        500        510        520        530        540 
SGSSTPQRSC SAAGLHRARS SFDSSTAENH SLSGSLTGSL TGSTLSSASP RLGSHTMDFF 

       550 
EMCASLITAL AR 

« Hide

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[2]"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].
Tissue: Brain.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-552.
Strain: C57BL/6J.
Tissue: Brain cortex and Medulla oblongata.
[4]"Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit."
Villena J.A., Viollet B., Andreelli F., Kahn A., Vaulont S., Sul H.S.
Diabetes 53:2242-2249(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[5]"The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading."
Jorgensen S.B., Nielsen J.N., Birk J.B., Olsen G.S., Viollet B., Andreelli F., Schjerling P., Vaulont S., Hardie D.G., Hansen B.F., Richter E.A., Wojtaszewski J.F.
Diabetes 53:3074-3081(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF GYS1.
[6]"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.
[7]"The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism."
Koo S.-H., Flechner L., Qi L., Zhang X., Screaton R.A., Jeffries S., Hedrick S., Xu W., Boussouar F., Brindle P., Takemori H., Montminy M.
Nature 437:1109-1111(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CRTC2.
[8]"The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin."
Shaw R.J., Lamia K.A., Vasquez D., Koo S.-H., Bardeesy N., Depinho R.A., Montminy M., Cantley L.C.
Science 310:1642-1646(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CRTC2, PHOSPHORYLATION AT THR-172.
[9]"AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits."
Treebak J.T., Glund S., Deshmukh A., Klein D.K., Long Y.C., Jensen T.E., Jorgensen S.B., Viollet B., Andersson L., Neumann D., Wallimann T., Richter E.A., Chibalin A.V., Zierath J.R., Wojtaszewski J.F.
Diabetes 55:2051-2058(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TBC1D4.
[10]"Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle."
Kramer H.F., Witczak C.A., Fujii N., Jessen N., Taylor E.B., Arnolds D.E., Sakamoto K., Hirshman M.F., Goodyear L.J.
Diabetes 55:2067-2076(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TBC1D4.
[11]"AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha."
Jager S., Handschin C., St-Pierre J., Spiegelman B.M.
Proc. Natl. Acad. Sci. U.S.A. 104:12017-12022(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PPARGC1A.
[12]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[13]"AMPK phosphorylation of raptor mediates a metabolic checkpoint."
Gwinn D.M., Shackelford D.B., Egan D.F., Mihaylova M.M., Mery A., Vasquez D.S., Turk B.E., Shaw R.J.
Mol. Cell 30:214-226(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RPTOR.
[14]"AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation."
Lamia K.A., Sachdeva U.M., DiTacchio L., Williams E.C., Alvarez J.G., Egan D.F., Vasquez D.S., Juguilon H., Panda S., Shaw R.J., Thompson C.B., Evans R.M.
Science 326:437-440(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CRY1.
[15]"AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of beta-catenin at Ser 552."
Zhao J., Yue W., Zhu M.J., Sreejayan N., Du M.
Biochem. Biophys. Res. Commun. 395:146-151(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CTNNB1.
[16]"Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation."
Bungard D., Fuerth B.J., Zeng P.Y., Faubert B., Maas N.L., Viollet B., Carling D., Thompson C.B., Jones R.G., Berger S.L.
Science 329:1201-1205(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF H2B, MUTAGENESIS OF ASP-157.
[17]"AMP-activated protein kinase regulates beta-catenin transcription via histone deacetylase 5."
Zhao J.X., Yue W.F., Zhu M.J., Du M.
J. Biol. Chem. 286:16426-16434(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC5, MUTAGENESIS OF LYS-45.
[18]"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.
[19]"AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice."
Li Y., Xu S., Mihaylova M.M., Zheng B., Hou X., Jiang B., Park O., Luo Z., Lefai E., Shyy J.Y., Gao B., Wierzbicki M., Verbeuren T.J., Shaw R.J., Cohen R.A., Zang M.
Cell Metab. 13:376-388(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF SREBF1 AND SREBF2, ENZYME REGULATION.
[20]"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1."
Kim J., Kundu M., Viollet B., Guan K.L.
Nat. Cell Biol. 13:132-141(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ULK1.
[21]"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.
[22]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL627307, AL929466 Genomic DNA. Translation: CAM18832.1.
AL929466, AL627307 Genomic DNA. Translation: CAM24127.1.
BC138565 mRNA. Translation: AAI38566.1.
BC138566 mRNA. Translation: AAI38567.1.
AK044030 mRNA. Translation: BAC31746.1.
AK134573 mRNA. Translation: BAE22188.1.
CCDSCCDS18416.1.
RefSeqNP_835279.2. NM_178143.2.
UniGeneMm.48638.

3D structure databases

ProteinModelPortalQ8BRK8.
SMRQ8BRK8. Positions 7-551.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid223817. 1 interaction.

Chemistry

ChEMBLCHEMBL1255154.

PTM databases

PhosphoSiteQ8BRK8.

Proteomic databases

MaxQBQ8BRK8.
PaxDbQ8BRK8.
PRIDEQ8BRK8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030243; ENSMUSP00000030243; ENSMUSG00000028518.
GeneID108079.
KEGGmmu:108079.
UCSCuc008tyd.2. mouse.

Organism-specific databases

CTD5563.
MGIMGI:1336173. Prkaa2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115114.
HOGENOMHOG000233016.
HOVERGENHBG050432.
InParanoidB1ASQ8.
KOK07198.
OMAXGVILYA.
OrthoDBEOG7RRF6K.
TreeFamTF314032.

Enzyme and pathway databases

ReactomeREACT_147847. Translocation of Glut4 to the Plasma Membrane.
REACT_209837. Membrane Trafficking.
REACT_224594. Organelle biogenesis and maintenance.

Gene expression databases

BgeeQ8BRK8.
GenevestigatorQ8BRK8.

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

ChiTaRSPRKAA2. mouse.
NextBio360016.
PROQ8BRK8.
SOURCESearch...

Entry information

Entry nameAAPK2_MOUSE
AccessionPrimary (citable) accession number: Q8BRK8
Secondary accession number(s): B1ASQ8, Q3UYM4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 104 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot