[1]	NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 13-29; 79-104; 118-129; 139-149; 155-171; 225-246; 261-265; 275-294; 315-330; 339-356; 364-373; 396-415; 426-435; 447-464 AND 496-506. STRAIN=Sprague-Dawley; TISSUE=Hypothalamus, and Liver; DOI=10.1074/jbc.271.2.611; PubMed=8557660 [NCBI, ExPASy, EBI, Israel, Japan] Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., Teh T., House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E.; "Mammalian AMP-activated protein kinase subfamily."; J. Biol. Chem. 271:611-614(1996).
[2]	INTERACTION WITH SUBUNITS BETA AND GAMMA. STRAIN=Sprague-Dawley; TISSUE=Hypothalamus, and Liver; PubMed=7961907 [NCBI, ExPASy, EBI, Israel, Japan] Stapleton D., Gao G., Michell B.J., Widmer J., Mitchelhill K.I., Teh T., House C.M., Witters L.A., Kemp B.E.; "Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase."; J. Biol. Chem. 269:29343-29346(1994).
[3]	FUNCTION, ENZYME REGULATION, AND PHOSPHORYLATION AT THR-172. 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-485, MUTAGENESIS OF THR-172; THR-258 AND SER-485, 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 an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2 (By similarity).
TISSUE SPECIFICITY: Low expression in kidney, liver, lung, heart and brain.
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

U40819; AAC52355.1; -; mRNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_062015.1; -.

UniGene

Rn.87789

3D structure databases

PDB

2V8Q; X-ray; 2.10 A; A=396-548.	[ExPASy / RCSB / EBI]
2V92; X-ray; 2.40 A; A=396-548.	[ExPASy / RCSB / EBI]
2V9J; X-ray; 2.53 A; A=396-548.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

2V8Q; -.
2V92; -.
2V9J; -.

P54645; 10-278.

PTM databases

P54645; -.

Organism-specific databases

RGD

3387; Prkaa1.

Gene expression databases

ArrayExpress

P54645; -.

GermOnline

ENSRNOG00000012799; Rattus norvegicus.

Ontologies

GO:0042557;	Molecular function: eukaryotic elongation factor-2 kinase activator activity (non-traceable author statement from UniProtKB).
GO:0017148;	Biological process: negative regulation of translation (non-traceable author statement from UniProtKB).
GO:0046321;	Biological process: positive regulation of fatty acid oxidation (non-traceable author statement from UniProtKB).
GO:0045722;	Biological process: positive regulation of gluconeogenesis (non-traceable author statement from UniProtKB).
GO:0046326;	Biological process: positive regulation of glucose import (non-traceable author statement from UniProtKB).
GO:0006468;	Biological process: protein amino acid phosphorylation (non-traceable author statement from UniProtKB).
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

ENSRNOG00000012799; Rattus norvegicus. [Contig view]

GeneID

65248; -.

KEGG

rno:65248; -.

Phylogenomic databases

HOVERGEN

P54645; -.

Other

NextBio

614203; -.

UniRef

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

Keywords

3D-structure; 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`	`1 548`	`548`	`5'-AMP-activated protein kinase catalytic subunit alpha-1.`	`PRO_0000085593`
`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.`
`MOD_RES`	`173 173`		`Phosphoserine (By similarity).`
`MOD_RES`	`258 258`		`Phosphothreonine.`
`MOD_RES`	`371 371`		`Phosphothreonine (By similarity).`
`MOD_RES`	`431 431`		`Phosphotyrosine (By similarity).`
`MOD_RES`	`485 485`		`Phosphoserine.`
`MOD_RES`	`497 497`		`Phosphoserine (By similarity).`
`MUTAGEN`	`172 172`		`T->E: Hinders activation.`
`MUTAGEN`	`258 258`		`T->A: Hinders activation.`
`MUTAGEN`	`258 258`		`T->D: Retains activation ability.`
`MUTAGEN`	`485 485`		`S->A: Hinders activation.`
`MUTAGEN`	`485 485`		`S->D: Retains activation ability.`
`CONFLICT`	`462 462`		`D -> L (in Ref. 1; protein sequence).`
`STRAND`	`396 402`	`7`
`HELIX`	`406 419`	`14`
`STRAND`	`423 428`	`6`
`STRAND`	`431 437`	`7`
`TURN`	`439 441`	`3`
`STRAND`	`444 453`	`10`
`STRAND`	`455 457`	`3`
`STRAND`	`459 466`	`8`
`HELIX`	`531 544`	`14`

Sequence information

Length: 548 AA [This is the length of the unprocessed precursor]

Molecular weight: 62600 Da [This is the MW of the unprocessed precursor]

CRC64: 5CCA3281C195F867 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MAEKQKHDGR VKIGHYILGD TLGVGTFGKV KVGKHELTGH KVAVKILNRQ KIRSLDVVGK 

        70         80         90        100        110        120 
IRREIQNLKL FRHPHIIKLY QVISTPSDIF MVMEYVSGGE LFDYICKNGR LDEKESRRLF 

       130        140        150        160        170        180 
QQILSGVDYC HRHMVVHRDL KPENVLLDAH MNAKIADFGL SNMMSDGEFL RTSCGSPNYA 

       190        200        210        220        230        240 
APEVISGRLY AGPEVDIWSS GVILYALLCG TLPFDDDHVP TLFKKICDGI FYTPQYLNPS 

       250        260        270        280        290        300 
VISLLKHMLQ VDPMKRATIK DIREHEWFKQ DLPKYLFPED PSYSSTMIDD EALKEVCEKF 

       310        320        330        340        350        360 
ECSEEEVLSC LYNRNHQDPL AVAYHLIIDN RRIMNEAKDF YLATSPPDSF LDDHHLTRPH 

       370        380        390        400        410        420 
PERVPFLVAE TPRARHTLDE LNPQKSKHQG VRKAKWHLGI RSQSRPNDIM AEVCRAIKQL 

       430        440        450        460        470        480 
DYEWKVVNPY YLRVRRKNPV TSTFSKMSLQ LYQVDSRTYL LDFRSIDDEI TEAKSGTATP 

       490        500        510        520        530        540 
QRSGSISNYR SCQRSDSDAE AQGKPSEVSL TSSVTSLDSS PVDVAPRPGS HTIEFFEMCA 


NLIKILAQ

P54645 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