UniProtKB - Q8BGM7 (AAKG3_MOUSE)
Protein
5'-AMP-activated protein kinase subunit gamma-3
Gene
Prkag3
Organism
Mus musculus (Mouse)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 225 | AMP, ADP or ATP 2By similarity | 1 | |
Binding sitei | 285 | AMP, ADP or ATP 1; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 306 | AMP 3By similarity | 1 | |
Binding sitei | 325 | AMP, ADP or ATP 2By similarity | 1 | |
Binding sitei | 355 | AMP 3By similarity | 1 | |
Binding sitei | 360 | AMP 3; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 424 | AMP, ADP or ATP 2By similarity | 1 | |
Binding sitei | 432 | AMP, ADP or ATP 2; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 453 | AMP 3By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 242 – 245 | AMP, ADP or ATP 1By similarity | 4 | |
Nucleotide bindingi | 306 – 307 | AMP, ADP or ATP 1By similarity | 2 | |
Nucleotide bindingi | 381 – 382 | AMP 3By similarity | 2 | |
Nucleotide bindingi | 397 – 400 | AMP, ADP or ATP 2By similarity | 4 | |
Nucleotide bindingi | 453 – 454 | AMP, ADP or ATP 2By similarity | 2 | |
Nucleotide bindingi | 469 – 472 | AMP 3By similarity | 4 |
GO - Molecular functioni
- AMP-activated protein kinase activity Source: Ensembl
- AMP binding Source: GO_Central
- ATP binding Source: UniProtKB-KW
- protein kinase binding Source: MGI
- protein kinase regulator activity Source: GO_Central
GO - Biological processi
- cellular response to glucose starvation Source: GO_Central
- fatty acid biosynthetic process Source: UniProtKB-KW
- glycogen biosynthetic process Source: MGI
- glycolytic process Source: MGI
- protein phosphorylation Source: GO_Central
- regulation of catalytic activity Source: GO_Central
- regulation of protein serine/threonine kinase activity Source: InterPro
- response to muscle activity involved in regulation of muscle adaptation Source: MGI
Keywordsi
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-1632852, Macroautophagy 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-3Short name: AMPK gamma3 Short name: AMPK subunit gamma-3 |
Gene namesi | Name:Prkag3 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1891343, Prkag3 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
- nucleotide-activated protein kinase complex Source: MGI
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000204385 | 1 – 489 | 5'-AMP-activated protein kinase subunit gamma-3Add BLAST | 489 |
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
PhosphoproteinProteomic databases
PaxDbi | Q8BGM7 |
PRIDEi | Q8BGM7 |
PTM databases
iPTMneti | Q8BGM7 |
PhosphoSitePlusi | Q8BGM7 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000006542, Expressed in quadriceps femoris and 99 other tissues |
Genevisiblei | Q8BGM7, 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 similarityGO - Molecular functioni
- protein kinase binding Source: MGI
Protein-protein interaction databases
ComplexPortali | CPX-5854, AMPK complex, alpha2-beta2-gamma3 variant CPX-5855, AMPK complex, alpha1-beta2-gamma3 variant CPX-5856, AMPK complex, alpha1-beta1-gamma3 variant CPX-5857, AMPK complex, alpha2-beta1-gamma3 variant |
STRINGi | 10090.ENSMUSP00000139909 |
Miscellaneous databases
RNActi | Q8BGM7, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 197 – 258 | CBS 1PROSITE-ProRule annotationAdd BLAST | 62 | |
Domaini | 280 – 340 | CBS 2PROSITE-ProRule annotationAdd BLAST | 61 | |
Domaini | 355 – 415 | CBS 3PROSITE-ProRule annotationAdd BLAST | 61 | |
Domaini | 427 – 486 | CBS 4PROSITE-ProRule annotationAdd BLAST | 60 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 293 – 314 | AMPK pseudosubstrateAdd BLAST | 22 |
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
Belongs to the 5'-AMP-activated protein kinase gamma subunit family.Curated
Keywords - Domaini
CBS domain, RepeatPhylogenomic databases
eggNOGi | KOG1764, Eukaryota |
GeneTreei | ENSGT00950000183019 |
HOGENOMi | CLU_021740_6_0_1 |
InParanoidi | Q8BGM7 |
OrthoDBi | 631088at2759 |
PhylomeDBi | Q8BGM7 |
TreeFami | TF313247 |
Family and domain databases
InterProi | View protein in InterPro IPR039168, AMPKG-3 IPR000644, CBS_dom |
PANTHERi | PTHR13780:SF31, PTHR13780:SF31, 1 hit |
Pfami | View protein in Pfam PF00571, CBS, 3 hits |
SMARTi | View protein in SMART SM00116, CBS, 4 hits |
PROSITEi | View protein in PROSITE PS51371, CBS, 4 hits |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8BGM7-1) [UniParc]FASTAAdd to basket
Also known as: Long
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE0CXJ7 | E0CXJ7_MOUSE | 5'-AMP-activated protein kinase sub... | Prkag3 | 268 | Annotation score: | ||
E0CX18 | E0CX18_MOUSE | 5'-AMP-activated protein kinase sub... | Prkag3 | 49 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 390 | G → GS in AAP22981 (PubMed:14970697).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015588 | 1 – 25 | Missing in isoform 2. 2 PublicationsAdd BLAST | 25 |
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 |
CCDSi | CCDS15055.1 [Q8BGM7-1] |
RefSeqi | NP_714966.1, NM_153744.3 [Q8BGM7-1] XP_006496051.1, XM_006495988.3 [Q8BGM7-1] XP_006496052.1, XM_006495989.3 [Q8BGM7-1] |
Genome annotation databases
Ensembli | ENSMUST00000081636; ENSMUSP00000080342; ENSMUSG00000006542 [Q8BGM7-1] ENSMUST00000113672; ENSMUSP00000109302; ENSMUSG00000006542 [Q8BGM7-2] ENSMUST00000160732; ENSMUSP00000125344; ENSMUSG00000006542 [Q8BGM7-1] ENSMUST00000188073; ENSMUSP00000139909; ENSMUSG00000006542 [Q8BGM7-1] |
GeneIDi | 241113 |
KEGGi | mmu:241113 |
UCSCi | uc007bnb.2, mouse [Q8BGM7-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS15055.1 [Q8BGM7-1] |
RefSeqi | NP_714966.1, NM_153744.3 [Q8BGM7-1] XP_006496051.1, XM_006495988.3 [Q8BGM7-1] XP_006496052.1, XM_006495989.3 [Q8BGM7-1] |
3D structure databases
SMRi | Q8BGM7 |
ModBasei | Search... |
Protein-protein interaction databases
ComplexPortali | CPX-5854, AMPK complex, alpha2-beta2-gamma3 variant CPX-5855, AMPK complex, alpha1-beta2-gamma3 variant CPX-5856, AMPK complex, alpha1-beta1-gamma3 variant CPX-5857, AMPK complex, alpha2-beta1-gamma3 variant |
STRINGi | 10090.ENSMUSP00000139909 |
PTM databases
iPTMneti | Q8BGM7 |
PhosphoSitePlusi | Q8BGM7 |
Proteomic databases
PaxDbi | Q8BGM7 |
PRIDEi | Q8BGM7 |
Protocols and materials databases
Antibodypediai | 1331, 251 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000081636; ENSMUSP00000080342; ENSMUSG00000006542 [Q8BGM7-1] ENSMUST00000113672; ENSMUSP00000109302; ENSMUSG00000006542 [Q8BGM7-2] ENSMUST00000160732; ENSMUSP00000125344; ENSMUSG00000006542 [Q8BGM7-1] ENSMUST00000188073; ENSMUSP00000139909; ENSMUSG00000006542 [Q8BGM7-1] |
GeneIDi | 241113 |
KEGGi | mmu:241113 |
UCSCi | uc007bnb.2, mouse [Q8BGM7-1] |
Organism-specific databases
CTDi | 53632 |
MGIi | MGI:1891343, Prkag3 |
Phylogenomic databases
eggNOGi | KOG1764, Eukaryota |
GeneTreei | ENSGT00950000183019 |
HOGENOMi | CLU_021740_6_0_1 |
InParanoidi | Q8BGM7 |
OrthoDBi | 631088at2759 |
PhylomeDBi | Q8BGM7 |
TreeFami | TF313247 |
Enzyme and pathway databases
Reactomei | R-MMU-1632852, Macroautophagy 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
BioGRID-ORCSi | 241113, 0 hits in 15 CRISPR screens |
PROi | PR:Q8BGM7 |
RNActi | Q8BGM7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000006542, Expressed in quadriceps femoris and 99 other tissues |
Genevisiblei | Q8BGM7, MM |
Family and domain databases
InterProi | View protein in InterPro IPR039168, AMPKG-3 IPR000644, CBS_dom |
PANTHERi | PTHR13780:SF31, PTHR13780:SF31, 1 hit |
Pfami | View protein in Pfam PF00571, CBS, 3 hits |
SMARTi | View protein in SMART SM00116, CBS, 4 hits |
PROSITEi | View protein in PROSITE PS51371, CBS, 4 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | AAKG3_MOUSE | |
Accessioni | Q8BGM7Primary (citable) accession number: Q8BGM7 Secondary accession number(s): Q0VG42, Q80WK8, Q8CJ41 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 13, 2005 |
Last sequence update: | March 1, 2003 | |
Last modified: | December 2, 2020 | |
This is version 122 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families