UniProtKB - P80385 (AAKG1_RAT)
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Protein
5'-AMP-activated protein kinase subunit gamma-1
Gene
Prkag1
Organism
Rattus norvegicus (Rat)
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.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 69 | AMP, ADP or ATP 21 Publication | 1 | |
Binding sitei | 129 | AMP, ADP or ATP 1; via amide nitrogen and carbonyl oxygen1 Publication | 1 | |
Binding sitei | 150 | AMP 31 Publication | 1 | |
Binding sitei | 169 | AMP, ADP or ATP 21 Publication | 1 | |
Binding sitei | 199 | AMP 31 Publication | 1 | |
Binding sitei | 204 | AMP 3; via amide nitrogen and carbonyl oxygen1 Publication | 1 | |
Binding sitei | 268 | AMP, ADP or ATP 21 Publication | 1 | |
Binding sitei | 276 | AMP, ADP or ATP 2; via amide nitrogen and carbonyl oxygen1 Publication | 1 | |
Binding sitei | 297 | AMP 31 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 86 – 89 | AMP, ADP or ATP 11 Publication | 4 | |
Nucleotide bindingi | 150 – 151 | AMP, ADP or ATP 11 Publication | 2 | |
Nucleotide bindingi | 225 – 226 | AMP 31 Publication | 2 | |
Nucleotide bindingi | 241 – 244 | AMP, ADP or ATP 21 Publication | 4 | |
Nucleotide bindingi | 297 – 298 | AMP, ADP or ATP 21 Publication | 2 | |
Nucleotide bindingi | 313 – 316 | AMP 31 Publication | 4 |
GO - Molecular functioni
- ADP binding Source: UniProtKB
- AMP binding Source: UniProtKB
- ATP binding Source: UniProtKB
- protein kinase activity Source: RGD
- protein kinase binding Source: RGD
GO - Biological processi
- fatty acid biosynthetic process Source: UniProtKB-KW
- nuclear import Source: RGD
- positive regulation of gene expression Source: RGD
- protein heterooligomerization Source: RGD
- protein phosphorylation Source: RGD
- regulation of catalytic activity Source: RGD
Keywordsi
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.31. 5301. |
Reactomei | R-RNO-201722. Formation of the beta-catenin:TCF transactivating complex. R-RNO-3214841. PKMTs methylate histone lysines. R-RNO-3769402. Deactivation of the beta-catenin transactivating complex. R-RNO-8936459. RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function. |
Names & Taxonomyi
Protein namesi | Recommended name: 5'-AMP-activated protein kinase subunit gamma-1Short name: AMPK gamma1 Short name: AMPK subunit gamma-1 Short name: AMPKg |
Gene namesi | Name:Prkag1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3388. Prkag1. |
Subcellular locationi
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000204380 | 1 – 330 | 5'-AMP-activated protein kinase subunit gamma-1Add BLAST | 330 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 260 | Phosphoserine; by ULK11 Publication | 1 | |
Modified residuei | 262 | Phosphothreonine; by ULK11 Publication | 1 | |
Modified residuei | 269 | Phosphoserine; by ULK11 Publication | 1 |
Post-translational modificationi
Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. There is some ambiguity for a phosphosite: Ser-260/Thr-262.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | P80385. |
PRIDEi | P80385. |
PTM databases
iPTMneti | P80385. |
PhosphoSitePlusi | P80385. |
Expressioni
Tissue specificityi
Highly expressed in heart and brain, also found in kidney, white adipose tissue, lung and spleen.
Gene expression databases
Bgeei | ENSRNOG00000061499. |
Genevisiblei | P80385. RN. |
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 FNIP2.2 Publications
GO - Molecular functioni
- protein kinase binding Source: RGD
Protein-protein interaction databases
DIPi | DIP-37278N. |
IntActi | P80385. 4 interactors. |
STRINGi | 10116.ENSRNOP00000020093. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 24 – 26 | Combined sources | 3 | |
Helixi | 27 – 34 | Combined sources | 8 | |
Helixi | 37 – 40 | Combined sources | 4 | |
Beta strandi | 43 – 51 | Combined sources | 9 | |
Helixi | 56 – 66 | Combined sources | 11 | |
Beta strandi | 69 – 75 | Combined sources | 7 | |
Turni | 76 – 79 | Combined sources | 4 | |
Beta strandi | 80 – 86 | Combined sources | 7 | |
Helixi | 87 – 101 | Combined sources | 15 | |
Turni | 102 – 104 | Combined sources | 3 | |
Helixi | 108 – 110 | Combined sources | 3 | |
Helixi | 113 – 120 | Combined sources | 8 | |
Beta strandi | 121 – 124 | Combined sources | 4 | |
Helixi | 137 – 147 | Combined sources | 11 | |
Beta strandi | 152 – 155 | Combined sources | 4 | |
Turni | 157 – 159 | Combined sources | 3 | |
Beta strandi | 162 – 166 | Combined sources | 5 | |
Helixi | 168 – 178 | Combined sources | 11 | |
Beta strandi | 181 – 183 | Combined sources | 3 | |
Helixi | 186 – 189 | Combined sources | 4 | |
Helixi | 192 – 195 | Combined sources | 4 | |
Beta strandi | 206 – 209 | Combined sources | 4 | |
Helixi | 212 – 222 | Combined sources | 11 | |
Beta strandi | 225 – 230 | Combined sources | 6 | |
Beta strandi | 234 – 241 | Combined sources | 8 | |
Helixi | 242 – 244 | Combined sources | 3 | |
Helixi | 246 – 250 | Combined sources | 5 | |
Beta strandi | 258 – 260 | Combined sources | 3 | |
Helixi | 261 – 264 | Combined sources | 4 | |
Helixi | 265 – 267 | Combined sources | 3 | |
Beta strandi | 269 – 271 | Combined sources | 3 | |
Beta strandi | 277 – 279 | Combined sources | 3 | |
Beta strandi | 280 – 283 | Combined sources | 4 | |
Helixi | 284 – 294 | Combined sources | 11 | |
Beta strandi | 297 – 302 | Combined sources | 6 | |
Beta strandi | 306 – 313 | Combined sources | 8 | |
Helixi | 314 – 322 | Combined sources | 9 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2V8Q | X-ray | 2.10 | E | 1-330 | [»] | |
2V92 | X-ray | 2.40 | E | 1-330 | [»] | |
2V9J | X-ray | 2.53 | E | 1-330 | [»] | |
2Y8L | X-ray | 2.50 | E | 1-330 | [»] | |
2Y8Q | X-ray | 2.80 | E | 1-330 | [»] | |
2YA3 | X-ray | 2.51 | E | 1-330 | [»] | |
4CFH | X-ray | 3.24 | E | 1-330 | [»] | |
4EAG | X-ray | 2.70 | C | 1-330 | [»] | |
4EAI | X-ray | 2.28 | C | 1-330 | [»] | |
4EAJ | X-ray | 2.61 | C | 1-330 | [»] | |
4EAK | X-ray | 2.50 | C | 1-330 | [»] | |
4EAL | X-ray | 2.51 | C | 1-330 | [»] | |
4QFG | X-ray | 3.46 | C | 1-330 | [»] | |
4QFR | X-ray | 3.34 | C | 1-330 | [»] | |
4QFS | X-ray | 3.55 | C | 1-330 | [»] | |
5KQ5 | X-ray | 3.41 | C | 1-330 | [»] | |
5T5T | X-ray | 3.46 | C | 1-330 | [»] | |
5UFU | X-ray | 3.45 | C | 1-330 | [»] | |
ProteinModelPortali | P80385. | |||||
SMRi | P80385. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P80385. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 42 – 102 | CBS 1PROSITE-ProRule annotationAdd BLAST | 61 | |
Domaini | 124 – 186 | CBS 2PROSITE-ProRule annotationAdd BLAST | 63 | |
Domaini | 197 – 259 | CBS 3PROSITE-ProRule annotationAdd BLAST | 63 | |
Domaini | 271 – 328 | CBS 4PROSITE-ProRule annotationAdd BLAST | 58 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 137 – 158 | 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.4 Publications
Sequence similaritiesi
Belongs to the 5'-AMP-activated protein kinase gamma subunit family.Curated
Keywords - Domaini
CBS domain, RepeatPhylogenomic databases
eggNOGi | KOG1764. Eukaryota. COG0517. LUCA. |
GeneTreei | ENSGT00760000119228. |
HOGENOMi | HOG000176880. |
HOVERGENi | HBG050431. |
InParanoidi | P80385. |
KOi | K07200. |
PhylomeDBi | P80385. |
TreeFami | TF313247. |
Family and domain databases
InterProi | View protein in InterPro IPR000644. CBS_dom. |
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. |
i Sequence
Sequence statusi: Complete.
P80385-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MESVAAESAP APENEHSQET PESNSSVYTT FMKSHRCYDL IPTSSKLVVF
60 70 80 90 100
DTSLQVKKAF FALVTNGVRA APLWDSKKQS FVGMLTITDF INILHRYYKS
110 120 130 140 150
ALVQIYELEE HKIETWREVY LQDSFKPLVC ISPNASLFDA VSSLIRNKIH
160 170 180 190 200
RLPVIDPESG NTLYILTHKR ILKFLKLFIT EFPKPEFMSK SLEELQIGTY
210 220 230 240 250
ANIAMVRTTT PVYVALGIFV QHRVSALPVV DEKGRVVDIY SKFDVINLAA
260 270 280 290 300
EKTYNNLDVS VTKALQHRSH YFEGVLKCYL HETLEAIINR LVEAEVHRLV
310 320 330
VVDEHDVVKG IVSLSDILQA LVLTGGEKKP
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 114 | E → Q AA sequence (PubMed:7961907).Curated | 1 | |
Sequence conflicti | 201 | A → P AA sequence (PubMed:7961907).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X95578 mRNA. Translation: CAA64831.1. BC097940 mRNA. Translation: AAH97940.1. U42413 mRNA. Translation: AAC52580.1. |
PIRi | T10759. |
RefSeqi | NP_037142.1. NM_013010.2. |
UniGenei | Rn.11089. |
Genome annotation databases
Ensembli | ENSRNOT00000083354; ENSRNOP00000070458; ENSRNOG00000061499. |
GeneIDi | 25520. |
KEGGi | rno:25520. |
UCSCi | RGD:3388. rat. |
Similar proteinsi
Entry informationi
Entry namei | AAKG1_RAT | |
Accessioni | P80385Primary (citable) accession number: P80385 Secondary accession number(s): Q4QQW6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | November 1, 1997 | |
Last modified: | February 28, 2018 | |
This is version 140 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |