Reviewed, UniProtKB/Swiss-Prot Q8BRK8 (AAPK2_MOUSE)

Names and origin

Protein names

Recommended name:
    5'-AMP-activated protein kinase catalytic subunit alpha-2
      Short name=AMPK subunit alpha-2
    EC=2.7.11.1

Gene names

Name:

Prkaa2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	552 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.3 UniProtKB Q13131
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q13131
Cofactor	Magnesium By similarity. UniProtKB Q13131
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. UniProtKB Q13131
Subunit structure	Heterotrimer of a catalytic subunit, a beta and a gamma non-catalytic subunits By similarity. UniProtKB Q13131
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.3
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Fatty acid biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro response to stress Traceable author statement. Source: MGI
Cellular component	nucleus Inferred from direct assay. Source: MGI
Molecular function	AMP-activated protein kinase activity Traceable author statement. Source: MGI ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 552	552	5'-AMP-activated protein kinase catalytic subunit alpha-2		PRO_0000262957
Regions
	Domain	16 – 268	253	Protein kinase
	Nucleotide binding	22 – 30	9	ATP By similarity UniProtKB P28523
Sites
	Active site	139	1	Proton acceptor By similarity UniProtKB P28523
	Binding site	45	1	ATP By similarity UniProtKB P28523
Amino acid modifications
	Modified residue	69	1	N6-acetyllysine By similarity
	Modified residue	172	1	Phosphothreonine; by STK11 By similarity UniProtKB Q13131
	Modified residue	173	1	Phosphoserine Ref.4
	Modified residue	176	1	Phosphoserine By similarity
	Modified residue	377	1	Phosphoserine By similarity
	Modified residue	500	1	Phosphoserine Ref.4
Experimental info
	Sequence conflict	15	1	H → D in BAE22188. Ref.2
	Sequence conflict	289	1	V → D in BAE22188. Ref.2
	Sequence conflict	380	1	A → E in BAE22188. Ref.2
	Sequence conflict	502	1	F → Y in BAE22188. Ref.2
	Sequence conflict	506	1	T → K in BAE22188. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8BRK8-1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: 593911EAB3BBFE3F	FASTA	552	62,006
	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 PSYDANVIVD 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

References

	« Hide 'large scale' referencesShow '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. , 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: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[2]	"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. , 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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-552. Strain: C57BL/6J. Tissue: Brain cortex and Medulla oblongata.
[3]	"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: 15331533] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]	"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: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-173 AND SER-500, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL627307 Genomic DNA. No translation available. AK044030 mRNA. Translation: BAC31746.1. AK134573 mRNA. Translation: BAE22188.1.
IPI	IPI00123445.
UniGene	Mm.48638
3D structure databases
HSSP	HSSP built from PDB template 2EUE based on UniProtKB P06782.
SMR	Q8BRK8. Positions 10-278, 352-551, 400-552.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8BRK8.
PTM databases
PhosphoSite	Q8BRK8.
Proteomic databases
PRIDE	Q8BRK8.
Genome annotation databases
Ensembl	ENSMUST00000030243; ENSMUSP00000030243; ENSMUSG00000028518; Mus musculus. [Genome view]
UCSC	uc008tyd.1. mouse.
Organism-specific databases
MGI	MGI:1336173. Prkaa2.
Phylogenomic databases
eggNOG	roNOG12508.
HOGENOM	HBG755340.
HOVERGEN	Q8BRK8.
InParanoid	Q8BRK8.
PhylomeDB	Q8BRK8.
Enzyme and pathway databases
BRENDA	2.7.11.1. 244.
Gene expression databases
ArrayExpress	Q8BRK8.
Bgee	Q8BRK8.
Genevestigator	Q8BRK8.
GermOnline	ENSMUSG00000028518. Mus musculus.
Family and domain databases
InterPro	IPR020636. Ca/CaM-dep_prot_kinase-like. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR015741. Prot_kinase_Snf1-like_AMPK. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
PANTHER	PTHR22982:SF61. AMPK. 1 hit. PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	360016.
SOURCE	Search...

Entry information

Entry name

AAPK2_MOUSE

Accession

Primary (citable) accession number: Q8BRK8
Secondary accession number(s): Q3UYM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	November 28, 2006
Last modified:	February 9, 2010
This is version 60 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)