Q91WG5 (AAKG2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5'-AMP-activated protein kinase subunit gamma-2
Short name=AMPK gamma2
Short name=AMPK subunit gamma-2

Gene names

Name:

Prkag2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	566 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive By similarity.
Subunit structure	AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 By similarity.
Domain	The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1 By similarity. The CBS domains mediate binding to AMP, ADP and ATP. 2 sites bind either AMP or ATP, whereas a third site contains a tightly bound AMP that does not exchange. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP By similarity.
Post-translational modification	Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Ref.6
Sequence similarities	Belongs to the 5'-AMP-activated protein kinase gamma subunit family. Contains 4 CBS domains.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism
Coding sequence diversity	Alternative splicing
Domain	CBS domain Repeat
Ligand	ATP-binding Nucleotide-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW glycogen metabolic process Inferred from electronic annotation. Source: Compara intracellular protein kinase cascade Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-threonine phosphorylation Inferred from electronic annotation. Source: Compara regulation of fatty acid metabolic process Inferred from electronic annotation. Source: Compara regulation of glycolysis Inferred from electronic annotation. Source: Compara response to stress Traceable author statement PubMed 10098881. Source: MGI
Cellular_component	AMP-activated protein kinase complex Inferred from electronic annotation. Source: Compara
Molecular_function	ADP binding Inferred from electronic annotation. Source: Compara AMP-activated protein kinase activity Traceable author statement PubMed 10098881. Source: MGI ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cAMP-dependent protein kinase inhibitor activity Inferred from electronic annotation. Source: Compara cAMP-dependent protein kinase regulator activity Inferred from electronic annotation. Source: Compara phosphorylase kinase regulator activity Inferred from electronic annotation. Source: Compara protein kinase activator activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

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

Isoform A (identifier: Q91WG5-1)

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 B (identifier: Q91WG5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-240: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 566	566	5'-AMP-activated protein kinase subunit gamma-2		PRO_0000204382
Regions
	Domain	272 – 332	61	CBS 1
	Domain	354 – 412	59	CBS 2
	Domain	427 – 489	63	CBS 3
	Domain	501 – 559	59	CBS 4
	Motif	367 – 388	22	AMPK pseudosubstrate
Sites
	Binding site	299	1	AMP 1 By similarity
	Binding site	299	1	ATP 1 By similarity
	Binding site	380	1	AMP 2 By similarity
	Binding site	380	1	AMP 3 By similarity
	Binding site	380	1	ATP 2 By similarity
	Binding site	381	1	ATP 1 By similarity
	Binding site	381	1	ATP 2 By similarity
	Binding site	399	1	AMP 1 By similarity
	Binding site	399	1	ATP 1 By similarity
	Binding site	527	1	AMP 3 By similarity
	Binding site	528	1	AMP 1 By similarity
	Binding site	528	1	ATP 1 By similarity
Amino acid modifications
	Modified residue	65	1	Phosphoserine Ref.5
	Modified residue	71	1	Phosphoserine Ref.5
	Modified residue	73	1	Phosphoserine Ref.5
	Modified residue	90	1	Phosphoserine Ref.5
	Modified residue	138	1	Phosphoserine Ref.5
	Modified residue	158	1	Phosphoserine Ref.5
	Modified residue	161	1	Phosphoserine Ref.5
	Modified residue	162	1	Phosphoserine Ref.5
	Modified residue	196	1	Phosphoserine Ref.4
Natural variations
	Alternative sequence	1 – 240	240	Missing in isoform B.		VSP_015586
Experimental info
	Sequence conflict	257	1	V → F in AAH15283. Ref.3
	Sequence conflict	516	1	T → N in AAQ55224. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified July 27, 2011. Version 2. Checksum: D112BFD69D1C5ACB	FASTA	566	62,949
	10 20 30 40 50 60 MGSAAMDTKK KKEVSSPGGS SGKKNPSLKR RSLRVHIPDL SSFAMPLLDG DVENSEKHSS 70 80 90 100 110 120 RKVDSPFSSG SPSRGLFSRG PQPRPSSPVS APVRPKTSPG SPKTVFPFSY QESPPRSPRR 130 140 150 160 170 180 MSFSGIFRSS SKESSPNSNP STSPGGIRFF SRSRKTSSVS SSPSTPTQVT KQHPFPLESY 190 200 210 220 230 240 KQEPERPESR IYASSSPPDT GQRFCLAFQS PARPPLASPT YHAPLRTAVL AAAPGPAEAG 250 260 270 280 290 300 MLEKLEFQEE EDSESGVYMR FMRSHKCYDI VPTSSKLVVF DTTLQVKKAF FALVANGVRA 310 320 330 340 350 360 APLWESKKQS FVGMLTITDF INILHRYYKS PMVQIYELEE HKIETWRELY LQETFKPLVN 370 380 390 400 410 420 ISPDASLFDA VYSLIKNKIH RLPVIDPISG NALYILTHKR ILKFLQLFMS DMPKPAFMKQ 430 440 450 460 470 480 NLDELGIGTY HNIAFIHPDT PIIKALNIFV ERRISALPVV DESGKVVDIY SKFDVINLAA 490 500 510 520 530 540 EKTYNNLDIT VTQALQHRSQ YFEGVVKCSK LETLETIVDR IVRAEVHRLV VVNEADSIVG 550 560 IISLSDILQA LILTPAGAKQ KETETE
	Isoform B [UniParc]. Checksum: FEA2EEAB9550999A	FASTA	326	37,312
	10 20 30 40 50 60 MLEKLEFQEE EDSESGVYMR FMRSHKCYDI VPTSSKLVVF DTTLQVKKAF FALVANGVRA 70 80 90 100 110 120 APLWESKKQS FVGMLTITDF INILHRYYKS PMVQIYELEE HKIETWRELY LQETFKPLVN 130 140 150 160 170 180 ISPDASLFDA VYSLIKNKIH RLPVIDPISG NALYILTHKR ILKFLQLFMS DMPKPAFMKQ 190 200 210 220 230 240 NLDELGIGTY HNIAFIHPDT PIIKALNIFV ERRISALPVV DESGKVVDIY SKFDVINLAA 250 260 270 280 290 300 EKTYNNLDIT VTQALQHRSQ YFEGVVKCSK LETLETIVDR IVRAEVHRLV VVNEADSIVG 310 320 IISLSDILQA LILTPAGAKQ KETETE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of mouse protein kinase, AMP-activated, gamma 2 non-catalytic subunit." Zhou G., Jiang D., Zhang Y. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). Strain: C57BL/6J.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: FVB/N. Tissue: Kidney.
[4]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-196, MASS SPECTROMETRY. Tissue: Brain cortex.
[5]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-71; SER-73; SER-90; SER-138; SER-158; SER-161 AND SER-162, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop." Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B. Autophagy 7:696-706(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY ULK1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY348864 mRNA. Translation: AAQ55224.1. AC116151 Genomic DNA. No translation available. AC125270 Genomic DNA. No translation available. BC015283 mRNA. Translation: AAH15283.1.
IPI	IPI00128126. IPI00649331.
RefSeq	NP_001164027.1. NM_001170556.1. NP_663376.2. NM_145401.2.
UniGene	Mm.33649.
3D structure databases
ProteinModelPortal	Q91WG5.
SMR	Q91WG5. Positions 253-554.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q91WG5. 1 interaction.
PTM databases
PhosphoSite	Q91WG5.
Proteomic databases
PaxDb	Q91WG5.
PRIDE	Q91WG5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000030784; ENSMUSP00000030784; ENSMUSG00000028944. ENSMUST00000114975; ENSMUSP00000110626; ENSMUSG00000028944.
GeneID	108099.
KEGG	mmu:108099.
Organism-specific databases
CTD	51422.
MGI	MGI:1336153. Prkag2.
Phylogenomic databases
eggNOG	COG0517.
GeneTree	ENSGT00390000009849.
HOGENOM	HOG000176880.
HOVERGEN	HBG050431.
InParanoid	Q91WG5.
KO	K07200.
OMA	FSRGPQH.
OrthoDB	EOG45DWPQ.
Enzyme and pathway databases
Reactome	REACT_147847. Translocation of Glut4 to the Plasma Membrane. REACT_88307. Membrane Trafficking.
Gene expression databases
ArrayExpress	Q91WG5.
Bgee	Q91WG5.
Genevestigator	Q91WG5.
GermOnline	ENSMUSG00000028944. Mus musculus.
Family and domain databases
InterPro	IPR000644. Cysta_beta_synth_core. [Graphical view]
Pfam	PF00571. CBS. 3 hits. [Graphical view]
SMART	SM00116. CBS. 4 hits. [Graphical view]
PROSITE	PS51371. CBS. 4 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PRKAG2. mouse.
NextBio	360062.
SOURCE	Search...

Entry information

Entry name

AAKG2_MOUSE

Accession

Primary (citable) accession number: Q91WG5
Secondary accession number(s): E9QK80, Q6V7V5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program