[1]	NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. TISSUE=Liver; PubMed=7908907 [NCBI, ExPASy, EBI, Israel, Japan] Carling D., Aguan K., Woods A., Verhoeven A.J.M., Beri R.K., Brennan C.H., Sidebottom C., Davison M.D., Scott J.; "Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism."; J. Biol. Chem. 269:11442-11448(1994).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=Sprague-Dawley; TISSUE=Liver; DOI=10.1016/0167-4889(94)00222-Z; PubMed=7718624 [NCBI, ExPASy, EBI, Israel, Japan] Gao G., Widmer J., Stapleton D., Teh T., Cox T., Kemp B.E., Witters L.A.; "Catalytic subunits of the porcine and rat 5'-AMP-activated protein kinase are members of the SNF1 protein kinase family."; Biochim. Biophys. Acta 1266:73-82(1995).
[3]	FUNCTION, AND ENZYME REGULATION. DOI=10.1186/1475-4924-2-28; PubMed=14511394 [NCBI, ExPASy, EBI, Israel, Japan] Hawley S.A., Boudeau J., Reid J.L., Mustard K.J., Udd L., Makela T.P., Alessi D.R., Hardie D.G.; "Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade."; J. Biol. 2:28.1-28.16(2003).
[4]	PHOSPHORYLATION AT THR-258 AND SER-491, AND MASS SPECTROMETRY. DOI=10.1074/jbc.M303946200; PubMed=12764152 [NCBI, ExPASy, EBI, Israel, Japan] Woods A., Vertommen D., Neumann D., Turk R., Bayliss J., Schlattner U., Wallimann T., Carling D., Rider M.H.; "Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis."; J. Biol. Chem. 278:28434-28442(2003).
[5]	FUNCTION, AND ENZYME REGULATION. DOI=10.1016/j.cmet.2005.05.009; PubMed=16054095 [NCBI, ExPASy, EBI, Israel, Japan] Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., Frenguelli B.G., Hardie D.G.; "Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase."; Cell Metab. 2:9-19(2005).

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

ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.

Name	Long
Isoform ID	Q09137-1
This is the isoform sequence displayed in this entry.

Name	Short
Isoform ID	Q09137-2
Note: Lacks the sequence parts essential for kinase activity and is therefore inactive.
Features which should be applied to build the isoform sequence: VSP_004949, VSP_004950.

TISSUE SPECIFICITY: Skeletal muscle, lower levels in liver, heart and kidney.
INDUCTION: By AMP.
SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
SIMILARITY: Contains 1 protein kinase domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

Z29486; CAA82620.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U12149; AAA85033.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A53621; A53621.

NP_076481.1; -.

3D structure databases

HSSP

Q63450; 1A06. [HSSP ENTRY / PDB]

Q09137; 10-278.

PTM databases

Q09137; -.

Organism-specific databases

RGD

620893; Prkaa2.

Gene expression databases

ArrayExpress

Q09137; -.

GermOnline

ENSRNOG00000007706; Rattus norvegicus.

Ontologies

GO:0005654;	Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0005524;	Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0000287;	Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004674;	Molecular function: protein serine/threonine kinase activity (inferred from electronic annotation from InterPro).
GO:0006695;	Biological process: cholesterol biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0006633;	Biological process: fatty acid biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0006468;	Biological process: protein amino acid phosphorylation (inferred from electronic annotation from InterPro).
QuickGo view.

Family and domain databases

InterPro

IPR015741; AMPK.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.

PANTHER

PTHR22982:SF61; AMPK; 1.

Pfam

PF00069; Pkinase; 1.
Pfam graphical view of domain structure.

ProDom

PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00220; S_TKc; 1.
SMART graphical view of domain structure.

PROSITE

PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSRNOG00000007706; Rattus norvegicus. [Contig view]

GeneID

78975; -.

KEGG

rno:78975; -.

Phylogenomic databases

HOVERGEN

Q09137; -.

Other

614450; -.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; ATP-binding; Cholesterol biosynthesis; Direct protein sequencing; Fatty acid biosynthesis; Kinase; Lipid synthesis; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; Serine/threonine-protein kinase; Steroid biosynthesis; Sterol biosynthesis; Transferase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 552`	`552`	`5'-AMP-activated protein kinase catalytic subunit alpha-2.`	`PRO_0000085597`
`DOMAIN`	`16 268`	`253`	`Protein kinase.`
`NP_BIND`	`22 30`	`9`	`ATP (By similarity).`
`ACT_SITE`	`139 139`		`Proton acceptor (By similarity).`
`BINDING`	`45 45`		`ATP (By similarity).`
`MOD_RES`	`172 172`		`Phosphothreonine; by STK11 (By similarity).`
`MOD_RES`	`173 173`		`Phosphoserine (By similarity).`
`MOD_RES`	`176 176`		`Phosphoserine (By similarity).`
`MOD_RES`	`258 258`		`Phosphothreonine.`
`MOD_RES`	`377 377`		`Phosphoserine (By similarity).`
`MOD_RES`	`491 491`		`Phosphoserine.`
`MOD_RES`	`500 500`		`Phosphoserine (By similarity).`
`VAR_SEQ`	`32 388`		`Missing (in isoform Short).`	`VSP_004949`
`VAR_SEQ`	`392 552`		`Missing (in isoform Short).`	`VSP_004950`
`CONFLICT`	`355 355`		`M -> S (in Ref. 2; AAA85033).`
`CONFLICT`	`462 462`		`N -> D (in Ref. 2; AAA85033).`

Sequence information

Length: 552 AA [This is the length of the unprocessed precursor]

Molecular weight: 62258 Da [This is the MW of the unprocessed precursor]

CRC64: 2829E07F674D89B1 [This is a checksum on the sequence]

        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

Q09137 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools