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Protein

5'-AMP-activated protein kinase subunit gamma-1

Gene

Prkag1

Organism
Rattus norvegicus (Rat)
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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei69AMP, ADP or ATP 21 Publication1
Binding sitei129AMP, ADP or ATP 1; via amide nitrogen and carbonyl oxygen1 Publication1
Binding sitei150AMP 31 Publication1
Binding sitei169AMP, ADP or ATP 21 Publication1
Binding sitei199AMP 31 Publication1
Binding sitei204AMP 3; via amide nitrogen and carbonyl oxygen1 Publication1
Binding sitei268AMP, ADP or ATP 21 Publication1
Binding sitei276AMP, ADP or ATP 2; via amide nitrogen and carbonyl oxygen1 Publication1
Binding sitei297AMP 31 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi86 – 89AMP, ADP or ATP 11 Publication4
Nucleotide bindingi150 – 151AMP, ADP or ATP 11 Publication2
Nucleotide bindingi225 – 226AMP 31 Publication2
Nucleotide bindingi241 – 244AMP, ADP or ATP 21 Publication4
Nucleotide bindingi297 – 298AMP, ADP or ATP 21 Publication2
Nucleotide bindingi313 – 316AMP 31 Publication4

GO - Molecular functioni

  • ADP binding Source: UniProtKB
  • AMP binding Source: UniProtKB
  • ATP binding Source: UniProtKB
  • protein kinase binding Source: RGD

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.11.31. 5301.
ReactomeiR-RNO-163680. AMPK inhibits chREBP transcriptional activation activity.
R-RNO-201722. Formation of the beta-catenin:TCF transactivating complex.
R-RNO-3769402. Deactivation of the beta-catenin transactivating complex.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-AMP-activated protein kinase subunit gamma-1
Short name:
AMPK gamma1
Short name:
AMPK subunit gamma-1
Short name:
AMPKg
Gene namesi
Name:Prkag1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi3388. Prkag1.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • nucleotide-activated protein kinase complex Source: UniProtKB
  • protein complex Source: RGD

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002043801 – 3305'-AMP-activated protein kinase subunit gamma-1Add BLAST330

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei260Phosphoserine; by ULK11 Publication1
Modified residuei262Phosphothreonine; by ULK11 Publication1
Modified residuei269Phosphoserine; by ULK11 Publication1

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

Phosphoprotein

Proteomic databases

PaxDbiP80385.
PRIDEiP80385.

PTM databases

iPTMnetiP80385.
PhosphoSitePlusiP80385.

Expressioni

Tissue specificityi

Highly expressed in heart and brain, also found in kidney, white adipose tissue, lung and spleen.

Gene expression databases

BgeeiENSRNOG00000061499.
GenevisibleiP80385. 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

DIPiDIP-37278N.
IntActiP80385. 1 interactor.
MINTiMINT-4566137.
STRINGi10116.ENSRNOP00000020093.

Structurei

Secondary structure

1330
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 26Combined sources3
Helixi27 – 34Combined sources8
Helixi37 – 40Combined sources4
Beta strandi43 – 51Combined sources9
Helixi56 – 66Combined sources11
Beta strandi69 – 75Combined sources7
Turni76 – 79Combined sources4
Beta strandi80 – 86Combined sources7
Helixi87 – 101Combined sources15
Turni102 – 104Combined sources3
Helixi108 – 110Combined sources3
Helixi113 – 120Combined sources8
Beta strandi121 – 124Combined sources4
Helixi137 – 147Combined sources11
Beta strandi152 – 155Combined sources4
Turni157 – 159Combined sources3
Beta strandi162 – 166Combined sources5
Helixi168 – 178Combined sources11
Beta strandi181 – 183Combined sources3
Helixi186 – 189Combined sources4
Helixi192 – 195Combined sources4
Beta strandi206 – 209Combined sources4
Helixi212 – 222Combined sources11
Beta strandi225 – 230Combined sources6
Beta strandi234 – 241Combined sources8
Helixi242 – 244Combined sources3
Helixi246 – 250Combined sources5
Beta strandi258 – 260Combined sources3
Helixi261 – 264Combined sources4
Helixi265 – 267Combined sources3
Beta strandi269 – 271Combined sources3
Beta strandi277 – 279Combined sources3
Beta strandi280 – 283Combined sources4
Helixi284 – 294Combined sources11
Beta strandi297 – 302Combined sources6
Beta strandi306 – 313Combined sources8
Helixi314 – 322Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V8QX-ray2.10E1-330[»]
2V92X-ray2.40E1-330[»]
2V9JX-ray2.53E1-330[»]
2Y8LX-ray2.50E1-330[»]
2Y8QX-ray2.80E1-330[»]
2YA3X-ray2.51E1-330[»]
4CFHX-ray3.24E1-330[»]
4EAGX-ray2.70C1-330[»]
4EAIX-ray2.28C1-330[»]
4EAJX-ray2.61C1-330[»]
4EAKX-ray2.50C1-330[»]
4EALX-ray2.51C1-330[»]
4QFGX-ray3.46C1-330[»]
4QFRX-ray3.34C1-330[»]
4QFSX-ray3.55C1-330[»]
5KQ5X-ray3.41C1-330[»]
5T5TX-ray3.46C1-330[»]
5UFUX-ray3.45C1-330[»]
ProteinModelPortaliP80385.
SMRiP80385.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP80385.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 102CBS 1PROSITE-ProRule annotationAdd BLAST61
Domaini124 – 186CBS 2PROSITE-ProRule annotationAdd BLAST63
Domaini197 – 259CBS 3PROSITE-ProRule annotationAdd BLAST63
Domaini271 – 328CBS 4PROSITE-ProRule annotationAdd BLAST58

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi137 – 158AMPK 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.4 Publications

Sequence similaritiesi

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiKOG1764. Eukaryota.
COG0517. LUCA.
GeneTreeiENSGT00760000119228.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
InParanoidiP80385.
KOiK07200.
PhylomeDBiP80385.
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.

Sequencei

Sequence statusi: Complete.

P80385-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:330
Mass (Da):37,386
Last modified:November 1, 1997 - v3
Checksum:i36031E526C1F1E97
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti114E → Q AA sequence (PubMed:7961907).Curated1
Sequence conflicti201A → P AA sequence (PubMed:7961907).Curated1

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.
PIRiT10759.
RefSeqiNP_037142.1. NM_013010.2.
UniGeneiRn.11089.

Genome annotation databases

EnsembliENSRNOT00000083354; ENSRNOP00000070458; ENSRNOG00000061499.
GeneIDi25520.
KEGGirno:25520.
UCSCiRGD:3388. rat.

Similar proteinsi

Entry informationi

Entry nameiAAKG1_RAT
AccessioniPrimary (citable) accession number: P80385
Secondary accession number(s): Q4QQW6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 1, 1997
Last modified: August 30, 2017
This is version 135 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families