Reviewed, UniProtKB/Swiss-Prot Q5EG47 (AAPK1_MOUSE)

Names and origin

Protein names

Recommended name:
    5'-AMP-activated protein kinase catalytic subunit alpha-1
      Short name=AMPK alpha-1 chain
    EC=2.7.11.1

Gene names

Name:

Prkaa1

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	548 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 By similarity.
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 structure	Heterotrimer of an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2 By similarity.
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	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 fatty acid oxidation Inferred from mutant phenotype. Source: MGI glucose metabolic process Inferred from mutant phenotype. Source: MGI protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 548	548	5'-AMP-activated protein kinase catalytic subunit alpha-1		PRO_0000085590
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	172	1	Phosphothreonine; by STK11 By similarity
	Modified residue	173	1	Phosphoserine
	Modified residue	345	1	Phosphoserine By similarity
	Modified residue	371	1	Phosphothreonine By similarity
	Modified residue	431	1	Phosphotyrosine By similarity
	Modified residue	475	1	Phosphoserine By similarity
	Modified residue	479	1	Phosphothreonine By similarity
	Modified residue	485	1	Phosphoserine By similarity
	Modified residue	497	1	Phosphoserine

Sequences

	Sequence		Length	Mass (Da)
	Q5EG47-1 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: FCC0D4C20FFF44D1	FASTA	548	62,556
	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 VDPMKRAAIK 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 AQGKPSDVSL TSSVTSLDSS PVDVAPRPGS HTIEFFEMCA NLIKILAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Xie X., Chen Y. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6N. Tissue: Muscle.
[2]	"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: ENZYME REGULATION, PHOSPHORYLATION AT THR-172.
[3]	"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-497, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY885266 mRNA. Translation: AAW79567.1.
UniGene	Mm.207004
3D structure databases
SMR	Q5EG47. Positions 10-278.
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000050697. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:2145955. Prkaa1.
Phylogenomic databases
HOVERGEN	Q5EG47.
Gene expression databases
ArrayExpress	Q5EG47.
GermOnline	ENSMUSG00000050697. Mus musculus.
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]
PANTHER	PTHR22982:SF61. AMPK. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
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
SOURCE	Search...

Entry information

Entry name

AAPK1_MOUSE

Accession

Primary (citable) accession number: Q5EG47

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	March 15, 2005
Last modified:	November 25, 2008
This is version 38 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)