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Protein

5'-AMP-activated protein kinase subunit gamma-2

Gene

Prkag2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei299 – 2991AMP 1By similarity
Binding sitei299 – 2991ATP 1By similarity
Binding sitei380 – 3801AMP 2By similarity
Binding sitei380 – 3801AMP 3By similarity
Binding sitei380 – 3801ATP 2By similarity
Binding sitei381 – 3811ATP 1By similarity
Binding sitei381 – 3811ATP 2By similarity
Binding sitei399 – 3991AMP 1By similarity
Binding sitei399 – 3991ATP 1By similarity
Binding sitei527 – 5271AMP 3By similarity
Binding sitei528 – 5281AMP 1By similarity
Binding sitei528 – 5281ATP 1By similarity

GO - Molecular functioni

  1. ADP binding Source: MGI
  2. AMP-activated protein kinase activity Source: MGI
  3. AMP binding Source: Ensembl
  4. ATP binding Source: MGI
  5. cAMP-dependent protein kinase inhibitor activity Source: MGI
  6. cAMP-dependent protein kinase regulator activity Source: MGI
  7. phosphorylase kinase regulator activity Source: MGI
  8. protein kinase activator activity Source: MGI
  9. protein kinase binding Source: MGI

GO - Biological processi

  1. fatty acid biosynthetic process Source: UniProtKB-KW
  2. glycogen metabolic process Source: MGI
  3. intracellular signal transduction Source: MGI
  4. negative regulation of protein kinase activity Source: MGI
  5. negative regulation of protein serine/threonine kinase activity Source: MGI
  6. positive regulation of peptidyl-threonine phosphorylation Source: MGI
  7. positive regulation of protein kinase activity Source: MGI
  8. regulation of fatty acid metabolic process Source: MGI
  9. regulation of glycolytic process Source: MGI
Complete GO annotation...

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_273617. AMPK inhibits chREBP transcriptional activation activity.
REACT_288513. Regulation of AMPK activity via LKB1.
REACT_293784. Import of palmitoyl-CoA into the mitochondrial matrix.
REACT_302653. Translocation of GLUT4 to the plasma membrane.
REACT_307891. Regulation of Rheb GTPase activity by AMPK.
REACT_321345. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-AMP-activated protein kinase subunit gamma-2
Short name:
AMPK gamma2
Short name:
AMPK subunit gamma-2
Gene namesi
Name:Prkag2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1336153. Prkag2.

Subcellular locationi

GO - Cellular componenti

  1. AMP-activated protein kinase complex Source: MGI
  2. cytosol Source: Reactome
  3. extracellular space Source: MGI
  4. nucleoplasm Source: Reactome
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 5665665'-AMP-activated protein kinase subunit gamma-2PRO_0000204382Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei65 – 651Phosphoserine1 Publication
Modified residuei71 – 711Phosphoserine1 Publication
Modified residuei73 – 731Phosphoserine1 Publication
Modified residuei90 – 901Phosphoserine1 Publication
Modified residuei138 – 1381Phosphoserine1 Publication
Modified residuei143 – 1431Phosphoserine1 Publication
Modified residuei158 – 1581Phosphoserine1 Publication
Modified residuei161 – 1611Phosphoserine1 Publication
Modified residuei196 – 1961Phosphoserine1 Publication

Post-translational modificationi

Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ91WG5.
PaxDbiQ91WG5.
PRIDEiQ91WG5.

PTM databases

PhosphoSiteiQ91WG5.

Expressioni

Gene expression databases

BgeeiQ91WG5.
ExpressionAtlasiQ91WG5. baseline and differential.
GenevestigatoriQ91WG5.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi223832. 1 interaction.
IntActiQ91WG5. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ91WG5.
SMRiQ91WG5. Positions 257-554.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini272 – 33261CBS 1PROSITE-ProRule annotationAdd
BLAST
Domaini354 – 41259CBS 2PROSITE-ProRule annotationAdd
BLAST
Domaini427 – 48963CBS 3PROSITE-ProRule annotationAdd
BLAST
Domaini501 – 55959CBS 4PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi367 – 38822AMPK pseudosubstrateAdd
BLAST

Domaini

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).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).By similarity

Sequence similaritiesi

Contains 4 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiCOG0517.
GeneTreeiENSGT00390000009849.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
InParanoidiQ91WG5.
KOiK07200.
OMAiXVQIYEL.
OrthoDBiEOG74FF0W.
TreeFamiTF313247.

Family and domain databases

InterProiIPR000644. CBS_dom.
[Graphical view]
PfamiPF00571. CBS. 3 hits.
[Graphical view]
SMARTiSM00116. CBS. 4 hits.
[Graphical view]
PROSITEiPS51371. CBS. 4 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: Q91WG5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGSAAMDTKK KKEVSSPGGS SGKKNPSLKR RSLRVHIPDL SSFAMPLLDG
60 70 80 90 100
DVENSEKHSS RKVDSPFSSG SPSRGLFSRG PQPRPSSPVS APVRPKTSPG
110 120 130 140 150
SPKTVFPFSY QESPPRSPRR MSFSGIFRSS SKESSPNSNP STSPGGIRFF
160 170 180 190 200
SRSRKTSSVS SSPSTPTQVT KQHPFPLESY KQEPERPESR IYASSSPPDT
210 220 230 240 250
GQRFCLAFQS PARPPLASPT YHAPLRTAVL AAAPGPAEAG MLEKLEFQEE
260 270 280 290 300
EDSESGVYMR FMRSHKCYDI VPTSSKLVVF DTTLQVKKAF FALVANGVRA
310 320 330 340 350
APLWESKKQS FVGMLTITDF INILHRYYKS PMVQIYELEE HKIETWRELY
360 370 380 390 400
LQETFKPLVN ISPDASLFDA VYSLIKNKIH RLPVIDPISG NALYILTHKR
410 420 430 440 450
ILKFLQLFMS DMPKPAFMKQ NLDELGIGTY HNIAFIHPDT PIIKALNIFV
460 470 480 490 500
ERRISALPVV DESGKVVDIY SKFDVINLAA EKTYNNLDIT VTQALQHRSQ
510 520 530 540 550
YFEGVVKCSK LETLETIVDR IVRAEVHRLV VVNEADSIVG IISLSDILQA
560
LILTPAGAKQ KETETE
Length:566
Mass (Da):62,949
Last modified:July 27, 2011 - v2
Checksum:iD112BFD69D1C5ACB
GO
Isoform B (identifier: Q91WG5-2) [UniParc]FASTAAdd to basket

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

Show »
Length:326
Mass (Da):37,312
Checksum:iFEA2EEAB9550999A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti257 – 2571V → F in AAH15283 (PubMed:15489334).Curated
Sequence conflicti516 – 5161T → N in AAQ55224 (Ref. 1) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 240240Missing in isoform B. 1 PublicationVSP_015586Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY348864 mRNA. Translation: AAQ55224.1.
AC116151 Genomic DNA. No translation available.
AC125270 Genomic DNA. No translation available.
BC015283 mRNA. Translation: AAH15283.1.
CCDSiCCDS19130.1. [Q91WG5-1]
CCDS51437.1. [Q91WG5-2]
RefSeqiNP_001164027.1. NM_001170556.1. [Q91WG5-2]
NP_663376.2. NM_145401.2. [Q91WG5-1]
UniGeneiMm.33649.

Genome annotation databases

EnsembliENSMUST00000030784; ENSMUSP00000030784; ENSMUSG00000028944. [Q91WG5-1]
ENSMUST00000114975; ENSMUSP00000110626; ENSMUSG00000028944. [Q91WG5-2]
GeneIDi108099.
KEGGimmu:108099.
UCSCiuc008wsk.2. mouse. [Q91WG5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY348864 mRNA. Translation: AAQ55224.1.
AC116151 Genomic DNA. No translation available.
AC125270 Genomic DNA. No translation available.
BC015283 mRNA. Translation: AAH15283.1.
CCDSiCCDS19130.1. [Q91WG5-1]
CCDS51437.1. [Q91WG5-2]
RefSeqiNP_001164027.1. NM_001170556.1. [Q91WG5-2]
NP_663376.2. NM_145401.2. [Q91WG5-1]
UniGeneiMm.33649.

3D structure databases

ProteinModelPortaliQ91WG5.
SMRiQ91WG5. Positions 257-554.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223832. 1 interaction.
IntActiQ91WG5. 1 interaction.

PTM databases

PhosphoSiteiQ91WG5.

Proteomic databases

MaxQBiQ91WG5.
PaxDbiQ91WG5.
PRIDEiQ91WG5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030784; ENSMUSP00000030784; ENSMUSG00000028944. [Q91WG5-1]
ENSMUST00000114975; ENSMUSP00000110626; ENSMUSG00000028944. [Q91WG5-2]
GeneIDi108099.
KEGGimmu:108099.
UCSCiuc008wsk.2. mouse. [Q91WG5-1]

Organism-specific databases

CTDi51422.
MGIiMGI:1336153. Prkag2.

Phylogenomic databases

eggNOGiCOG0517.
GeneTreeiENSGT00390000009849.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
InParanoidiQ91WG5.
KOiK07200.
OMAiXVQIYEL.
OrthoDBiEOG74FF0W.
TreeFamiTF313247.

Enzyme and pathway databases

ReactomeiREACT_273617. AMPK inhibits chREBP transcriptional activation activity.
REACT_288513. Regulation of AMPK activity via LKB1.
REACT_293784. Import of palmitoyl-CoA into the mitochondrial matrix.
REACT_302653. Translocation of GLUT4 to the plasma membrane.
REACT_307891. Regulation of Rheb GTPase activity by AMPK.
REACT_321345. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.

Miscellaneous databases

ChiTaRSiPrkag2. mouse.
NextBioi360062.
PROiQ91WG5.
SOURCEiSearch...

Gene expression databases

BgeeiQ91WG5.
ExpressionAtlasiQ91WG5. baseline and differential.
GenevestigatoriQ91WG5.

Family and domain databases

InterProiIPR000644. CBS_dom.
[Graphical view]
PfamiPF00571. CBS. 3 hits.
[Graphical view]
SMARTiSM00116. CBS. 4 hits.
[Graphical view]
PROSITEiPS51371. CBS. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of mouse protein kinase, AMP-activated, gamma 2 non-catalytic subunit."
    Zhou G., Jiang D., Zhang Y.
    Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
    Strain: C57BL/6J.
  2. 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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
    Strain: FVB/N.
    Tissue: Kidney.
  4. 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(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY ULK1.

Entry informationi

Entry nameiAAKG2_MOUSE
AccessioniPrimary (citable) accession number: Q91WG5
Secondary accession number(s): E9QK80, Q6V7V5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: July 27, 2011
Last modified: April 1, 2015
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.