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Protein

5'-AMP-activated protein kinase subunit gamma-3

Gene

Prkag3

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)DescriptionActionsGraphical viewLength
Binding sitei225AMP, ADP or ATP 2By similarity1
Binding sitei285AMP, ADP or ATP 1; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei306AMP 3By similarity1
Binding sitei325AMP, ADP or ATP 2By similarity1
Binding sitei355AMP 3By similarity1
Binding sitei360AMP 3; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei424AMP, ADP or ATP 2By similarity1
Binding sitei432AMP, ADP or ATP 2; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei453AMP 3By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi242 – 245AMP, ADP or ATP 1By similarity4
Nucleotide bindingi306 – 307AMP, ADP or ATP 1By similarity2
Nucleotide bindingi381 – 382AMP 3By similarity2
Nucleotide bindingi397 – 400AMP, ADP or ATP 2By similarity4
Nucleotide bindingi453 – 454AMP, ADP or ATP 2By similarity2
Nucleotide bindingi469 – 472AMP 3By similarity4

GO - Molecular functioni

GO - Biological processi

  • fatty acid biosynthetic process Source: UniProtKB-KW
  • glucose transport Source: MGI
  • glycogen biosynthetic process Source: MGI
  • membrane organization Source: Reactome
  • mitochondrion organization Source: Reactome

Keywordsi

Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1445148. Translocation of GLUT4 to the plasma membrane.
R-MMU-1632852. Macroautophagy.
R-MMU-2151209. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
R-MMU-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-MMU-5628897. TP53 Regulates Metabolic Genes.
R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-AMP-activated protein kinase subunit gamma-3
Short name:
AMPK gamma3
Short name:
AMPK subunit gamma-3
Gene namesi
Name:Prkag3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1891343. Prkag3.

Subcellular locationi

GO - Cellular componenti

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002043851 – 4895'-AMP-activated protein kinase subunit gamma-3Add BLAST489

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

PaxDbiQ8BGM7.
PRIDEiQ8BGM7.

PTM databases

iPTMnetiQ8BGM7.
PhosphoSitePlusiQ8BGM7.

Expressioni

Gene expression databases

BgeeiENSMUSG00000006542.
ExpressionAtlasiQ8BGM7. baseline and differential.
GenevisibleiQ8BGM7. MM.

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000080342.

Structurei

3D structure databases

ProteinModelPortaliQ8BGM7.
SMRiQ8BGM7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini197 – 258CBS 1PROSITE-ProRule annotationAdd BLAST62
Domaini280 – 340CBS 2PROSITE-ProRule annotationAdd BLAST61
Domaini355 – 415CBS 3PROSITE-ProRule annotationAdd BLAST61
Domaini427 – 486CBS 4PROSITE-ProRule annotationAdd BLAST60

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi293 – 314AMPK pseudosubstrateAdd BLAST22

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 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.By similarity

Sequence similaritiesi

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiKOG1764. Eukaryota.
COG0517. LUCA.
GeneTreeiENSGT00390000009849.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
InParanoidiQ8BGM7.
KOiK07200.
OMAiAKASRWT.
OrthoDBiEOG091G0CZV.
PhylomeDBiQ8BGM7.
TreeFamiTF313247.

Family and domain databases

InterProiView protein in InterPro
IPR000644. CBS_dom.
PfamiView protein in Pfam
PF00571. CBS. 3 hits.
SMARTiView protein in SMART
SM00116. CBS. 4 hits.
PROSITEiView protein in PROSITE
PS51371. CBS. 4 hits.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8BGM7-1) [UniParc]FASTAAdd to basket
Also known as: Long

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
MEPELEHTLP GTLTWSHSGG PESQEMDFLE QGENSWPSPA VATSSERTCA
60 70 80 90 100
IRGVKASRWT RQEAVEEAEP PGLGEGAQSR PAAESTRQEA TFPKATPLAQ
110 120 130 140 150
AVPLAEAETS PTGWDLLLPD CAASAGGSST GDLELTIEFP APEAWDCELE
160 170 180 190 200
GLGKDRPRPG PSPQAPLLGL SWDDELQKPG AQVYMHFMQE HTCYDAMATS
210 220 230 240 250
SKLVIFDTTL EIKKAFFAMV ANGVRAAPLW DSKKQSFVGM LTITDFILVL
260 270 280 290 300
HRYYRSPLVQ IYEIEEHKIE TWREIYLQGC FKPLVSISPN DSLFEAVYAL
310 320 330 340 350
IKNRIHRLPV LDPVSGTVLY ILTHKRLLKF LHIFGALLPR PSFLCRTIQD
360 370 380 390 400
LGIGTFRDLA VVLETAPVLT ALDIFVDRRV SALPVVNESG QVVGLYSRFD
410 420 430 440 450
VIHLAAQQTY NHLDMSVGEA LRQRTLCLEG VLSCQPHESL GEVIDRIARE
460 470 480
QVHRLVLVDE TQHLLGVVSL SDILQALVLS PAGIDALSA
Length:489
Mass (Da):53,849
Last modified:March 1, 2003 - v1
Checksum:i85C9F71D8BDBDA5D
GO
Isoform 2 (identifier: Q8BGM7-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Show »
Length:464
Mass (Da):51,117
Checksum:iCEC324A5855C3F2E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti390G → GS in AAP22981 (PubMed:14970697).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0155881 – 25Missing in isoform 2. 2 PublicationsAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF525500 mRNA. Translation: AAN47137.1.
AF525501 mRNA. Translation: AAN47138.1.
AY263402 Genomic DNA. Translation: AAP22981.1.
AK036585 mRNA. Translation: BAC29492.1.
BC116749 mRNA. Translation: AAI16750.1.
BC116777 mRNA. Translation: AAI16778.1.
CCDSiCCDS15055.1. [Q8BGM7-1]
RefSeqiNP_714966.1. NM_153744.3. [Q8BGM7-1]
XP_006496051.1. XM_006495988.3. [Q8BGM7-1]
XP_006496052.1. XM_006495989.3. [Q8BGM7-1]
UniGeneiMm.166501.
Mm.453463.

Genome annotation databases

EnsembliENSMUST00000081636; ENSMUSP00000080342; ENSMUSG00000006542. [Q8BGM7-1]
ENSMUST00000113672; ENSMUSP00000109302; ENSMUSG00000006542. [Q8BGM7-2]
ENSMUST00000160732; ENSMUSP00000125344; ENSMUSG00000006542. [Q8BGM7-1]
ENSMUST00000188073; ENSMUSP00000139909; ENSMUSG00000006542. [Q8BGM7-1]
GeneIDi241113.
KEGGimmu:241113.
UCSCiuc007bnb.2. mouse. [Q8BGM7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF525500 mRNA. Translation: AAN47137.1.
AF525501 mRNA. Translation: AAN47138.1.
AY263402 Genomic DNA. Translation: AAP22981.1.
AK036585 mRNA. Translation: BAC29492.1.
BC116749 mRNA. Translation: AAI16750.1.
BC116777 mRNA. Translation: AAI16778.1.
CCDSiCCDS15055.1. [Q8BGM7-1]
RefSeqiNP_714966.1. NM_153744.3. [Q8BGM7-1]
XP_006496051.1. XM_006495988.3. [Q8BGM7-1]
XP_006496052.1. XM_006495989.3. [Q8BGM7-1]
UniGeneiMm.166501.
Mm.453463.

3D structure databases

ProteinModelPortaliQ8BGM7.
SMRiQ8BGM7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000080342.

PTM databases

iPTMnetiQ8BGM7.
PhosphoSitePlusiQ8BGM7.

Proteomic databases

PaxDbiQ8BGM7.
PRIDEiQ8BGM7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000081636; ENSMUSP00000080342; ENSMUSG00000006542. [Q8BGM7-1]
ENSMUST00000113672; ENSMUSP00000109302; ENSMUSG00000006542. [Q8BGM7-2]
ENSMUST00000160732; ENSMUSP00000125344; ENSMUSG00000006542. [Q8BGM7-1]
ENSMUST00000188073; ENSMUSP00000139909; ENSMUSG00000006542. [Q8BGM7-1]
GeneIDi241113.
KEGGimmu:241113.
UCSCiuc007bnb.2. mouse. [Q8BGM7-1]

Organism-specific databases

CTDi53632.
MGIiMGI:1891343. Prkag3.

Phylogenomic databases

eggNOGiKOG1764. Eukaryota.
COG0517. LUCA.
GeneTreeiENSGT00390000009849.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
InParanoidiQ8BGM7.
KOiK07200.
OMAiAKASRWT.
OrthoDBiEOG091G0CZV.
PhylomeDBiQ8BGM7.
TreeFamiTF313247.

Enzyme and pathway databases

ReactomeiR-MMU-1445148. Translocation of GLUT4 to the plasma membrane.
R-MMU-1632852. Macroautophagy.
R-MMU-2151209. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
R-MMU-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-MMU-5628897. TP53 Regulates Metabolic Genes.
R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.

Miscellaneous databases

PROiPR:Q8BGM7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000006542.
ExpressionAtlasiQ8BGM7. baseline and differential.
GenevisibleiQ8BGM7. MM.

Family and domain databases

InterProiView protein in InterPro
IPR000644. CBS_dom.
PfamiView protein in Pfam
PF00571. CBS. 3 hits.
SMARTiView protein in SMART
SM00116. CBS. 4 hits.
PROSITEiView protein in PROSITE
PS51371. CBS. 4 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiAAKG3_MOUSE
AccessioniPrimary (citable) accession number: Q8BGM7
Secondary accession number(s): Q0VG42, Q80WK8, Q8CJ41
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: March 1, 2003
Last modified: May 10, 2017
This is version 102 of the entry and version 1 of the sequence. See 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

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 one 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.