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Protein

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

Gene

PRKAG1

Organism
Homo sapiens (Human)
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei70AMP 1By similarity1
Binding sitei70ATP 1By similarity1
Binding sitei151AMP 2By similarity1
Binding sitei151AMP 3By similarity1
Binding sitei151ATP 2By similarity1
Binding sitei152ATP 1By similarity1
Binding sitei152ATP 2By similarity1
Binding sitei170AMP 1By similarity1
Binding sitei170ATP 1By similarity1
Binding sitei298AMP 3By similarity1
Binding sitei299AMP 1By similarity1
Binding sitei299ATP 1By similarity1

GO - Molecular functioni

  • ADP binding Source: UniProtKB
  • AMP binding Source: UniProtKB
  • ATP binding Source: UniProtKB
  • cAMP-dependent protein kinase activity Source: ProtInc
  • cAMP-dependent protein kinase regulator activity Source: BHF-UCL
  • protein kinase activity Source: UniProtKB
  • protein kinase binding Source: BHF-UCL

GO - Biological processi

  • cell cycle arrest Source: Reactome
  • fatty acid biosynthetic process Source: UniProtKB-KW
  • macroautophagy Source: Reactome
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of protein kinase activity Source: BHF-UCL
  • protein phosphorylation Source: UniProtKB
  • regulation of glycolytic process Source: BHF-UCL
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • signal transduction Source: ProtInc
  • spermatogenesis Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000181929-MONOMER.
ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-1632852. Macroautophagy.
R-HSA-2151209. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiP54619.
SIGNORiP54619.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:9385. PRKAG1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleotide-activated protein kinase complex Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi90D → A: Reduced AMP-activation of phosphorylation of PRKAA1 or PRKAA2. Reduced ADP activation of phosphorylation of PRKAA1 or PRKAA2. 1 Publication1
Mutagenesisi245D → A: Reduced AMP-activation of phosphorylation of PRKAA1 or PRKAA2. Reduced ADP activation of phosphorylation of PRKAA1 or PRKAA2. 1 Publication1
Mutagenesisi317D → A: Reduced AMP-activation of phosphorylation of PRKAA1 or PRKAA2. Does not affect ADP activation of phosphorylation of PRKAA1 or PRKAA2. 1 Publication1

Organism-specific databases

DisGeNETi5571.
OpenTargetsiENSG00000181929.
PharmGKBiPA33751.

Chemistry databases

ChEMBLiCHEMBL2393.
DrugBankiDB00945. Acetylsalicylic acid.

Polymorphism and mutation databases

BioMutaiPRKAG1.
DMDMi1703037.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002043771 – 3315'-AMP-activated protein kinase subunit gamma-1Add BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei261Phosphoserine; by ULK1By similarity1
Modified residuei263Phosphothreonine; by ULK1By similarity1
Modified residuei270Phosphoserine; by ULK1By similarity1

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.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP54619.
MaxQBiP54619.
PaxDbiP54619.
PeptideAtlasiP54619.
PRIDEiP54619.

PTM databases

iPTMnetiP54619.
PhosphoSitePlusiP54619.

Expressioni

Gene expression databases

BgeeiENSG00000181929.
CleanExiHS_PRKAG1.
ExpressionAtlasiP54619. baseline and differential.
GenevisibleiP54619. HS.

Organism-specific databases

HPAiCAB006254.

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 FNIP2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
C1orf94Q6P1W53EBI-1181439,EBI-946029
CBSP355203EBI-1181439,EBI-740135
KEAP1Q141455EBI-1181439,EBI-751001
KRTAP4-2Q9BYR53EBI-1181439,EBI-10172511
PRKAA1Q1313110EBI-1181439,EBI-1181405
PRKAA2P546469EBI-1181439,EBI-1383852
PRKAB1Q9Y4786EBI-1181439,EBI-719769
PRKAB2O437418EBI-1181439,EBI-1053424
TEKT1Q969V43EBI-1181439,EBI-10180409

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi111558. 47 interactors.
DIPiDIP-39974N.
IntActiP54619. 30 interactors.
MINTiMINT-4649712.
STRINGi9606.ENSP00000323867.

Chemistry databases

BindingDBiP54619.

Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 35Combined sources7
Helixi38 – 40Combined sources3
Beta strandi44 – 52Combined sources9
Helixi57 – 67Combined sources11
Beta strandi72 – 76Combined sources5
Turni77 – 80Combined sources4
Beta strandi81 – 86Combined sources6
Helixi88 – 98Combined sources11
Beta strandi102 – 104Combined sources3
Helixi107 – 111Combined sources5
Helixi114 – 122Combined sources9
Helixi138 – 147Combined sources10
Beta strandi151 – 156Combined sources6
Turni158 – 160Combined sources3
Beta strandi163 – 168Combined sources6
Helixi169 – 177Combined sources9
Turni178 – 182Combined sources5
Helixi186 – 189Combined sources4
Helixi193 – 196Combined sources4
Helixi213 – 223Combined sources11
Beta strandi226 – 231Combined sources6
Beta strandi235 – 242Combined sources8
Helixi243 – 251Combined sources9
Beta strandi259 – 261Combined sources3
Helixi262 – 267Combined sources6
Helixi271 – 274Combined sources4
Beta strandi277 – 279Combined sources3
Helixi285 – 295Combined sources11
Beta strandi298 – 303Combined sources6
Beta strandi307 – 314Combined sources8
Helixi315 – 322Combined sources8
Turni323 – 325Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2UV4X-ray1.33A182-325[»]
2UV5X-ray1.69A182-325[»]
2UV6X-ray2.00A182-325[»]
2UV7X-ray2.00A182-325[»]
4CFEX-ray3.02E/F1-331[»]
4CFFX-ray3.92E/F1-331[»]
4RERX-ray4.05G24-327[»]
4REWX-ray4.58G24-327[»]
4ZHXX-ray2.99E/F2-331[»]
5EZVX-ray2.99E/F2-331[»]
ProteinModelPortaliP54619.
SMRiP54619.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54619.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 103CBS 1PROSITE-ProRule annotationAdd BLAST61
Domaini125 – 187CBS 2PROSITE-ProRule annotationAdd BLAST63
Domaini198 – 260CBS 3PROSITE-ProRule annotationAdd BLAST63
Domaini272 – 329CBS 4PROSITE-ProRule annotationAdd BLAST58

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi138 – 159AMPK 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.
The CBS domains mediate binding to AMP, ADP and ATP. 2 sites bind either AMP or ATP, whereas a third site contains a tightly bound AMP that does not exchange. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP.

Sequence similaritiesi

Contains 4 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiKOG1764. Eukaryota.
COG0517. LUCA.
GeneTreeiENSGT00390000009849.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
KOiK07200.
OMAiDVIHLMV.
OrthoDBiEOG091G0CZV.
PhylomeDBiP54619.
TreeFamiTF313247.

Family and domain databases

InterProiIPR000644. CBS_dom.
[Graphical view]
PfamiPF00571. CBS. 3 hits.
[Graphical view]
SMARTiSM00116. CBS. 4 hits.
[Graphical view]
PROSITEiPS51371. CBS. 4 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P54619-1) [UniParc]FASTAAdd to basket

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
METVISSDSS PAVENEHPQE TPESNNSVYT SFMKSHRCYD LIPTSSKLVV
60 70 80 90 100
FDTSLQVKKA FFALVTNGVR AAPLWDSKKQ SFVGMLTITD FINILHRYYK
110 120 130 140 150
SALVQIYELE EHKIETWREV YLQDSFKPLV CISPNASLFD AVSSLIRNKI
160 170 180 190 200
HRLPVIDPES GNTLYILTHK RILKFLKLFI TEFPKPEFMS KSLEELQIGT
210 220 230 240 250
YANIAMVRTT TPVYVALGIF VQHRVSALPV VDEKGRVVDI YSKFDVINLA
260 270 280 290 300
AEKTYNNLDV SVTKALQHRS HYFEGVLKCY LHETLETIIN RLVEAEVHRL
310 320 330
VVVDENDVVK GIVSLSDILQ ALVLTGGEKK P
Length:331
Mass (Da):37,579
Last modified:October 1, 1996 - v1
Checksum:i0F22B9CA1DBD87AE
GO
Isoform 2 (identifier: P54619-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: Missing.

Note: No experimental confirmation available.
Show »
Length:299
Mass (Da):34,084
Checksum:iA9BA11BA1205419E
GO
Isoform 3 (identifier: P54619-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-83: V → VVLRALSCPL

Note: No experimental confirmation available. May be due to competing acceptor splice site.
Show »
Length:340
Mass (Da):38,533
Checksum:iBCDF1B75723C4321
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03345389T → S.Corresponds to variant rs1126930dbSNPEnsembl.1
Natural variantiVAR_033454329K → N.Corresponds to variant rs34210356dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0467111 – 32Missing in isoform 2. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_04671283V → VVLRALSCPL in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U42412 mRNA. Translation: AAC50495.1.
BT007345 mRNA. Translation: AAP36009.1.
AK097606 mRNA. Translation: BAC05117.1.
AK293332 mRNA. Translation: BAG56848.1.
AC011603 Genomic DNA. No translation available.
BC000358 mRNA. Translation: AAH00358.1.
CCDSiCCDS55824.1. [P54619-2]
CCDS55825.1. [P54619-3]
CCDS8777.1. [P54619-1]
RefSeqiNP_001193638.1. NM_001206709.1. [P54619-3]
NP_001193639.1. NM_001206710.1. [P54619-2]
NP_002724.1. NM_002733.4. [P54619-1]
XP_006719562.1. XM_006719499.2. [P54619-2]
XP_011536864.1. XM_011538562.2. [P54619-2]
UniGeneiHs.530862.

Genome annotation databases

EnsembliENST00000316299; ENSP00000323867; ENSG00000181929. [P54619-3]
ENST00000548065; ENSP00000447433; ENSG00000181929. [P54619-1]
ENST00000552212; ENSP00000448972; ENSG00000181929. [P54619-2]
GeneIDi5571.
KEGGihsa:5571.
UCSCiuc001rsy.4. human. [P54619-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U42412 mRNA. Translation: AAC50495.1.
BT007345 mRNA. Translation: AAP36009.1.
AK097606 mRNA. Translation: BAC05117.1.
AK293332 mRNA. Translation: BAG56848.1.
AC011603 Genomic DNA. No translation available.
BC000358 mRNA. Translation: AAH00358.1.
CCDSiCCDS55824.1. [P54619-2]
CCDS55825.1. [P54619-3]
CCDS8777.1. [P54619-1]
RefSeqiNP_001193638.1. NM_001206709.1. [P54619-3]
NP_001193639.1. NM_001206710.1. [P54619-2]
NP_002724.1. NM_002733.4. [P54619-1]
XP_006719562.1. XM_006719499.2. [P54619-2]
XP_011536864.1. XM_011538562.2. [P54619-2]
UniGeneiHs.530862.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2UV4X-ray1.33A182-325[»]
2UV5X-ray1.69A182-325[»]
2UV6X-ray2.00A182-325[»]
2UV7X-ray2.00A182-325[»]
4CFEX-ray3.02E/F1-331[»]
4CFFX-ray3.92E/F1-331[»]
4RERX-ray4.05G24-327[»]
4REWX-ray4.58G24-327[»]
4ZHXX-ray2.99E/F2-331[»]
5EZVX-ray2.99E/F2-331[»]
ProteinModelPortaliP54619.
SMRiP54619.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111558. 47 interactors.
DIPiDIP-39974N.
IntActiP54619. 30 interactors.
MINTiMINT-4649712.
STRINGi9606.ENSP00000323867.

Chemistry databases

BindingDBiP54619.
ChEMBLiCHEMBL2393.
DrugBankiDB00945. Acetylsalicylic acid.

PTM databases

iPTMnetiP54619.
PhosphoSitePlusiP54619.

Polymorphism and mutation databases

BioMutaiPRKAG1.
DMDMi1703037.

Proteomic databases

EPDiP54619.
MaxQBiP54619.
PaxDbiP54619.
PeptideAtlasiP54619.
PRIDEiP54619.

Protocols and materials databases

DNASUi5571.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316299; ENSP00000323867; ENSG00000181929. [P54619-3]
ENST00000548065; ENSP00000447433; ENSG00000181929. [P54619-1]
ENST00000552212; ENSP00000448972; ENSG00000181929. [P54619-2]
GeneIDi5571.
KEGGihsa:5571.
UCSCiuc001rsy.4. human. [P54619-1]

Organism-specific databases

CTDi5571.
DisGeNETi5571.
GeneCardsiPRKAG1.
HGNCiHGNC:9385. PRKAG1.
HPAiCAB006254.
MIMi602742. gene.
neXtProtiNX_P54619.
OpenTargetsiENSG00000181929.
PharmGKBiPA33751.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1764. Eukaryota.
COG0517. LUCA.
GeneTreeiENSGT00390000009849.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
KOiK07200.
OMAiDVIHLMV.
OrthoDBiEOG091G0CZV.
PhylomeDBiP54619.
TreeFamiTF313247.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000181929-MONOMER.
ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-1632852. Macroautophagy.
R-HSA-2151209. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiP54619.
SIGNORiP54619.

Miscellaneous databases

ChiTaRSiPRKAG1. human.
EvolutionaryTraceiP54619.
GeneWikiiPRKAG1.
GenomeRNAii5571.
PROiP54619.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000181929.
CleanExiHS_PRKAG1.
ExpressionAtlasiP54619. baseline and differential.
GenevisibleiP54619. HS.

Family and domain databases

InterProiIPR000644. CBS_dom.
[Graphical view]
PfamiPF00571. CBS. 3 hits.
[Graphical view]
SMARTiSM00116. CBS. 4 hits.
[Graphical view]
PROSITEiPS51371. CBS. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAAKG1_HUMAN
AccessioniPrimary (citable) accession number: P54619
Secondary accession number(s): B4DDT7, Q8N7V9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.