Reviewed, UniProtKB/Swiss-Prot Q09137 (AAPK2_RAT)

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
Synonyms:	Ampk, Ampk2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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 Ref.5
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. Ref.3 Ref.5
Subunit structure	Heterotrimer of a catalytic subunit, a beta and a gamma non-catalytic subunits.
Tissue specificity	Skeletal muscle, lower levels in liver, heart and kidney.
Induction	By AMP. Ref.3 Ref.5
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
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
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 direct assay. Source: RGD protein heterooligomerization Ref.3 Inferred from direct assay. Source: RGD regulation of lipid metabolic process Inferred from direct assay. Source: RGD response to stress Inferred from direct assay. Source: RGD
Cellular component	AMP-activated protein kinase complex Inferred from direct assay. Source: RGD nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	AMP-activated protein kinase activity Ref.3 Inferred from direct assay. Source: RGD ATP binding Inferred from direct assay. Source: RGD magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding, bridging Inferred from direct assay. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q09137-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: Q09137-2)

The sequence of this isoform differs from the canonical sequence as follows:
     32-388: Missing.
     392-552: Missing.

Note: Lacks the sequence parts essential for kinase activity and is therefore inactive.

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_0000085597
Regions
	Domain	16 – 268	253	Protein kinase
	Nucleotide binding	22 – 30	9	ATP By similarity
Sites
	Active site	139	1	Proton acceptor By similarity
	Binding site	45	1	ATP By similarity
Amino acid modifications
	Modified residue	69	1	N6-acetyllysine By similarity
	Modified residue	172	1	Phosphothreonine; by STK11 By similarity
	Modified residue	173	1	Phosphoserine By similarity
	Modified residue	176	1	Phosphoserine By similarity
	Modified residue	258	1	Phosphothreonine Ref.4
	Modified residue	377	1	Phosphoserine By similarity
	Modified residue	491	1	Phosphoserine Ref.4
	Modified residue	500	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	32 – 388	357	Missing in isoform Short.		VSP_004949
	Alternative sequence	392 – 552	161	Missing in isoform Short.		VSP_004950
Experimental info
	Sequence conflict	355	1	M → S in AAA85033. Ref.2
	Sequence conflict	462	1	N → D in AAA85033. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 2829E07F674D89B1	FASTA	552	62,258
	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 FYIPEYLNRS 250 260 270 280 290 300 IATLLMHMLQ VDPLKRATIK DIREHEWFKQ DLPSYLFPED PSYDANVIDD EAVKEVCEKF 310 320 330 340 350 360 ECTESEVMNS LYSGDPQDQL AVAYHLIIDN RRIMNQASEF YLASSPPTGS FMDDMAMHIP 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 SVDSSTAENH SLSGSLTGSL TGSTLSSASP RLGSHTMDFF 550 EMCASLITAL AR
	Isoform Short. Checksum: 4BF6E5CF5CF23F3B	FASTA	34	3,700
	10 20 30 MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KTTK

References

[1]	"Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism." Carling D., Aguan K., Woods A., Verhoeven A.J.M., Beri R.K., Brennan C.H., Sidebottom C., Davison M.D., Scott J. J. Biol. Chem. 269:11442-11448(1994) [PubMed: 7908907] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"Catalytic subunits of the porcine and rat 5'-AMP-activated protein kinase are members of the SNF1 protein kinase family." Gao G., Widmer J., Stapleton D., Teh T., Cox T., Kemp B.E., Witters L.A. Biochim. Biophys. Acta 1266:73-82(1995) [PubMed: 7718624] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Liver.
[3]	"Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade." Hawley S.A., Boudeau J., Reid J.L., Mustard K.J., Udd L., Makela T.P., Alessi D.R., Hardie D.G. J. Biol. 2:28.1-28.16(2003) [PubMed: 14511394] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[4]	"Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis." Woods A., Vertommen D., Neumann D., Turk R., Bayliss J., Schlattner U., Wallimann T., Carling D., Rider M.H. J. Biol. Chem. 278:28434-28442(2003) [PubMed: 12764152] [Abstract] Cited for: PHOSPHORYLATION AT THR-258 AND SER-491, MASS SPECTROMETRY.
[5]	"Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase." Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., Frenguelli B.G., Hardie D.G. Cell Metab. 2:9-19(2005) [PubMed: 16054095] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z29486 mRNA. Translation: CAA82620.1. U12149 mRNA. Translation: AAA85033.1.
IPI	IPI00201424. IPI00231190.
PIR	A53621.
RefSeq	NP_076481.1.
UniGene	Rn.64583
3D structure databases
SMR	Q09137. Positions 10-278, 353-551, 400-552.
ModBase	Search...
Protein-protein interaction databases
STRING	Q09137.
PTM databases
PhosphoSite	Q09137.
Proteomic databases
PRIDE	Q09137.
Genome annotation databases
Ensembl	ENSRNOT00000010680; ENSRNOP00000010680; ENSRNOG00000007706; Rattus norvegicus. [Genome view]
GeneID	78975.
KEGG	rno:78975.
UCSC	NM_023991. rat.
Organism-specific databases
CTD	78975.
RGD	620893. Prkaa2.
Phylogenomic databases
eggNOG	roNOG12508.
HOVERGEN	Q09137.
InParanoid	Q09137.
PhylomeDB	Q09137.
Enzyme and pathway databases
BRENDA	2.7.11.1. 248.
Gene expression databases
ArrayExpress	Q09137.
Genevestigator	Q09137.
GermOnline	ENSRNOG00000007706. Rattus norvegicus.
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	614450.

Entry information

Entry name

AAPK2_RAT

Accession

Primary (citable) accession number: Q09137

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	February 9, 2010
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)