UniProtKB - Q2LL38 (AAKG3_BOVIN)
Protein
5'-AMP-activated protein kinase subunit gamma-3
Gene
PRKAG3
Organism
Bos taurus (Bovine)
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 | 232 | AMP, ADP or ATP 2By similarity | 1 | |
Binding sitei | 292 | AMP, ADP or ATP 1; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 313 | AMP 3By similarity | 1 | |
Binding sitei | 332 | AMP or ATP 2By similarity | 1 | |
Binding sitei | 363 | AMP 3By similarity | 1 | |
Binding sitei | 368 | AMP 3; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 432 | AMP, ADP or ATP 2By similarity | 1 | |
Binding sitei | 440 | AMP, ADP or ATP 2; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 461 | AMP 3By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 249 – 252 | AMP, ADP or ATP 1By similarity | 4 | |
Nucleotide bindingi | 313 – 314 | AMP, ADP or ATP 1By similarity | 2 | |
Nucleotide bindingi | 389 – 390 | AMP 3By similarity | 2 | |
Nucleotide bindingi | 405 – 408 | AMP, ADP or ATP 2By similarity | 4 | |
Nucleotide bindingi | 461 – 462 | AMP, ADP or ATP 2By similarity | 2 | |
Nucleotide bindingi | 477 – 480 | 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: GO_Central
- 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: Ensembl
- glycolytic process Source: Ensembl
- 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: Ensembl
Keywordsi
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-BTA-1632852, Macroautophagy R-BTA-380972, Energy dependent regulation of mTOR by LKB1-AMPK R-BTA-5628897, TP53 Regulates Metabolic Genes R-BTA-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 | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:33323, PRKAG3 |
Subcellular locationi
Nucleus
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
- nucleotide-activated protein kinase complex Source: GO_Central
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000240150 | 1 – 497 | 5'-AMP-activated protein kinase subunit gamma-3Add BLAST | 497 |
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.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q2LL38 |
PRIDEi | Q2LL38 |
Expressioni
Gene expression databases
Bgeei | ENSBTAG00000013492, Expressed in heart and 17 other tissues |
ExpressionAtlasi | Q2LL38, baseline |
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: GO_Central
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000017940 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 204 – 265 | CBS 1PROSITE-ProRule annotationAdd BLAST | 62 | |
Domaini | 287 – 345 | CBS 2PROSITE-ProRule annotationAdd BLAST | 59 | |
Domaini | 363 – 423 | CBS 3PROSITE-ProRule annotationAdd BLAST | 61 | |
Domaini | 435 – 494 | CBS 4PROSITE-ProRule annotationAdd BLAST | 60 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 300 – 321 | 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 | Q2LL38 |
OMAi | APFPKLG |
OrthoDBi | 631088at2759 |
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 (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q2LL38-1) [UniParc]FASTAAdd to basket
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
MEPAELEHAL CGSLFSTQTP SWSSFGGPEH QEMSFLEQGD STSWPSPAMT
60 70 80 90 100
TSAEISLGEQ RTKVSRWKSQ EDVEERELPG LEGGPQSRAA AESTGLEATF
110 120 130 140 150
PKATPLAQAT PLSAVGTPTT ERDSLPADCT ASASSSSTDD LDQGIEFSAP
160 170 180 190 200
AAWGDELGLV EERPAQCPSP QVPVLRLGWD DELRKPGAQV YMHFMQEHTC
210 220 230 240 250
YDAMATSSKL VIFDTMLQIK KAFFALVANG VRAAPLWDSK KQSFVGMLTI
260 270 280 290 300
TDFILVLHRY YRSPLVQIYE IEEHKIETWR EIYLQGCFKP LVSISPSDSL
310 320 330 340 350
FEAVYTLIKN RIHRLPVLDP VSGAVLHILT HKRLLKFLHI FQRTLLPRPS
360 370 380 390 400
FLYRTIQDLG IGTFRDLAVV LETAPILTAL DIFVDRRVSA LPVINEAGQV
410 420 430 440 450
VGLYSRFDVI HLAAQQTYNH LDISVGEALR RRTLCLEGVL SCQPHETLGE
460 470 480 490
VIDRIAREQV HRLVLVDETQ HLLGVVSLSD ILQALVLSPA GIDALGA
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A3Q1M611 | A0A3Q1M611_BOVIN | 5'-AMP-activated protein kinase sub... | PRKAG3 | 490 | Annotation score: | ||
A0A3Q1MEV1 | A0A3Q1MEV1_BOVIN | 5'-AMP-activated protein kinase sub... | PRKAG3 | 465 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 455 | I → F in AAZ31228 (PubMed:16416094).Curated | 1 | |
Sequence conflicti | 455 | I → F in AAZ31229 (PubMed:16416094).Curated | 1 | |
Sequence conflicti | 455 | I → F in AAZ31230 (PubMed:16416094).Curated | 1 | |
Sequence conflicti | 455 | I → F in AAZ31231 (PubMed:16416094).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 127 | A → S in strain: Charolais, Holstein and Limousin. 1 Publication | 1 | |
Natural varianti | 153 | W → S in strain: Charolais and Limousin. 1 Publication | 1 | |
Natural varianti | 262 | R → W in strain: Charolais, Holstein and Limousin. 1 Publication | 1 | |
Natural varianti | 358 | D → Y in strain: Charolais. 1 Publication | 1 | |
Natural varianti | 373 | T → M in strain: Limousin. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_019297 | 13 – 18 | Missing in isoform 2 and isoform 4. 1 Publication | 6 | |
Alternative sequenceiVSP_019298 | 342 | Missing in isoform 3 and isoform 4. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | DQ082732 mRNA Translation: AAZ31228.1 DQ082733 mRNA Translation: AAZ31229.1 DQ082734 mRNA Translation: AAZ31230.1 DQ082735 mRNA Translation: AAZ31231.1 DQ082736 Genomic DNA Translation: AAZ31232.1 DQ082736 Genomic DNA Translation: AAZ31233.1 DQ082736 Genomic DNA Translation: AAZ31234.1 DQ082736 Genomic DNA Translation: AAZ31235.1 |
RefSeqi | NP_001025473.2, NM_001030302.2 [Q2LL38-1] NP_001155891.1, NM_001162419.1 [Q2LL38-3] NP_001155892.1, NM_001162420.1 [Q2LL38-2] NP_001155893.1, NM_001162421.1 [Q2LL38-4] |
Genome annotation databases
Ensembli | ENSBTAT00000017940; ENSBTAP00000017940; ENSBTAG00000013492 [Q2LL38-1] |
GeneIDi | 511961 |
KEGGi | bta:511961 |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | DQ082732 mRNA Translation: AAZ31228.1 DQ082733 mRNA Translation: AAZ31229.1 DQ082734 mRNA Translation: AAZ31230.1 DQ082735 mRNA Translation: AAZ31231.1 DQ082736 Genomic DNA Translation: AAZ31232.1 DQ082736 Genomic DNA Translation: AAZ31233.1 DQ082736 Genomic DNA Translation: AAZ31234.1 DQ082736 Genomic DNA Translation: AAZ31235.1 |
RefSeqi | NP_001025473.2, NM_001030302.2 [Q2LL38-1] NP_001155891.1, NM_001162419.1 [Q2LL38-3] NP_001155892.1, NM_001162420.1 [Q2LL38-2] NP_001155893.1, NM_001162421.1 [Q2LL38-4] |
3D structure databases
SMRi | Q2LL38 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000017940 |
Proteomic databases
PaxDbi | Q2LL38 |
PRIDEi | Q2LL38 |
Genome annotation databases
Ensembli | ENSBTAT00000017940; ENSBTAP00000017940; ENSBTAG00000013492 [Q2LL38-1] |
GeneIDi | 511961 |
KEGGi | bta:511961 |
Organism-specific databases
CTDi | 53632 |
VGNCi | VGNC:33323, PRKAG3 |
Phylogenomic databases
eggNOGi | KOG1764, Eukaryota |
GeneTreei | ENSGT00950000183019 |
HOGENOMi | CLU_021740_6_0_1 |
InParanoidi | Q2LL38 |
OMAi | APFPKLG |
OrthoDBi | 631088at2759 |
TreeFami | TF313247 |
Enzyme and pathway databases
Reactomei | R-BTA-1632852, Macroautophagy R-BTA-380972, Energy dependent regulation of mTOR by LKB1-AMPK R-BTA-5628897, TP53 Regulates Metabolic Genes R-BTA-6804756, Regulation of TP53 Activity through Phosphorylation |
Gene expression databases
Bgeei | ENSBTAG00000013492, Expressed in heart and 17 other tissues |
ExpressionAtlasi | Q2LL38, baseline |
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_BOVIN | |
Accessioni | Q2LL38Primary (citable) accession number: Q2LL38 Secondary accession number(s): Q2LL34 Q2LL41 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 13, 2006 |
Last sequence update: | June 13, 2006 | |
Last modified: | December 2, 2020 | |
This is version 82 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families