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Q91WG5 (AAKG2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5'-AMP-activated protein kinase subunit gamma-2

Short name=AMPK gamma2
Short name=AMPK subunit gamma-2
Gene names
Name:Prkag2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length566 AA.
Sequence statusComplete.
Protein existenceEvidence 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.5

Sequence similarities

Belongs to the 5'-AMP-activated protein kinase gamma subunit family.

Contains 4 CBS domains.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
   Coding sequence diversityAlternative splicing
   DomainCBS domain
Repeat
   LigandATP-binding
Nucleotide-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processfatty acid biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

glycogen metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Traceable author statement PubMed 10098881. Source: GOC

regulation of fatty acid metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of glycolysis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentAMP-activated protein kinase complex

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

   Molecular_functionADP binding

Inferred from electronic annotation. Source: Ensembl

AMP binding

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

cAMP-dependent protein kinase regulator activity

Inferred from electronic annotation. Source: Ensembl

phosphorylase kinase regulator activity

Inferred from electronic annotation. Source: Ensembl

protein kinase activator activity

Inferred from electronic annotation. Source: Ensembl

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5665665'-AMP-activated protein kinase subunit gamma-2
PRO_0000204382

Regions

Domain272 – 33261CBS 1
Domain354 – 41259CBS 2
Domain427 – 48963CBS 3
Domain501 – 55959CBS 4
Motif367 – 38822AMPK pseudosubstrate

Sites

Binding site2991AMP 1 By similarity
Binding site2991ATP 1 By similarity
Binding site3801AMP 2 By similarity
Binding site3801AMP 3 By similarity
Binding site3801ATP 2 By similarity
Binding site3811ATP 1 By similarity
Binding site3811ATP 2 By similarity
Binding site3991AMP 1 By similarity
Binding site3991ATP 1 By similarity
Binding site5271AMP 3 By similarity
Binding site5281AMP 1 By similarity
Binding site5281ATP 1 By similarity

Amino acid modifications

Modified residue651Phosphoserine Ref.4
Modified residue711Phosphoserine Ref.4
Modified residue731Phosphoserine Ref.4
Modified residue901Phosphoserine Ref.4
Modified residue1381Phosphoserine Ref.4
Modified residue1431Phosphoserine Ref.4
Modified residue1581Phosphoserine Ref.4
Modified residue1611Phosphoserine Ref.4
Modified residue1961Phosphoserine Ref.4

Natural variations

Alternative sequence1 – 240240Missing in isoform B.
VSP_015586

Experimental info

Sequence conflict2571V → F in AAH15283. Ref.3
Sequence conflict5161T → N in AAQ55224. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: D112BFD69D1C5ACB

FASTA56662,949
        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 

« Hide

Isoform B [UniParc].

Checksum: FEA2EEAB9550999A
Show »

FASTA32637,312

References

« Hide '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. expand/collapse author list , 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]"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-143; SER-158; SER-161 AND SER-196, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[5]"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.
RefSeqNP_001164027.1. NM_001170556.1.
NP_663376.2. NM_145401.2.
UniGeneMm.33649.

3D structure databases

ProteinModelPortalQ91WG5.
SMRQ91WG5. Positions 253-554.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid223832. 1 interaction.
IntActQ91WG5. 1 interaction.

PTM databases

PhosphoSiteQ91WG5.

Proteomic databases

PaxDbQ91WG5.
PRIDEQ91WG5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030784; ENSMUSP00000030784; ENSMUSG00000028944. [Q91WG5-1]
ENSMUST00000114975; ENSMUSP00000110626; ENSMUSG00000028944. [Q91WG5-2]
GeneID108099.
KEGGmmu:108099.
UCSCuc008wsk.2. mouse. [Q91WG5-1]

Organism-specific databases

CTD51422.
MGIMGI:1336153. Prkag2.

Phylogenomic databases

eggNOGCOG0517.
GeneTreeENSGT00390000009849.
HOGENOMHOG000176880.
HOVERGENHBG050431.
InParanoidQ91WG5.
KOK07200.
OMAXVQIYEL.
OrthoDBEOG74FF0W.
TreeFamTF313247.

Enzyme and pathway databases

ReactomeREACT_147847. Translocation of Glut4 to the Plasma Membrane.

Gene expression databases

ArrayExpressQ91WG5.
BgeeQ91WG5.
GenevestigatorQ91WG5.

Family and domain databases

InterProIPR000644. CBS_dom.
[Graphical view]
PfamPF00571. CBS. 3 hits.
[Graphical view]
SMARTSM00116. CBS. 4 hits.
[Graphical view]
PROSITEPS51371. CBS. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRKAG2. mouse.
NextBio360062.
PROQ91WG5.
SOURCESearch...

Entry information

Entry nameAAKG2_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot