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Protein

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

Gene

PRKAG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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, ADP or ATP 22 Publications1
Binding sitei130AMP, ADP or ATP 1; via amide nitrogen and carbonyl oxygen2 Publications1
Binding sitei151AMP 33 Publications1
Binding sitei170AMP, ADP or ATP 22 Publications1
Binding sitei200AMP 33 Publications1
Binding sitei205AMP 3; via amide nitrogen and carbonyl oxygen3 Publications1
Binding sitei269AMP, ADP or ATP 22 Publications1
Binding sitei277AMP, ADP or ATP 2; via amide nitrogen and carbonyl oxygen2 Publications1
Binding sitei298AMP 33 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi87 – 90AMP, ADP or ATP 12 Publications4
Nucleotide bindingi151 – 152AMP, ADP or ATP 12 Publications2
Nucleotide bindingi226 – 227AMP 33 Publications2
Nucleotide bindingi242 – 245AMP, ADP or ATP 22 Publications4
Nucleotide bindingi298 – 299AMP, ADP or ATP 22 Publications2
Nucleotide bindingi314 – 317AMP 33 Publications4

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

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of SLC2A4 (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

EuPathDBiHostDB:ENSG00000181929.11
HGNCiHGNC:9385 PRKAG1
MIMi602742 gene
neXtProtiNX_P54619

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi56688

PTM databases

iPTMnetiP54619
PhosphoSitePlusiP54619

Expressioni

Gene expression databases

BgeeiENSG00000181929 Expressed in 223 organ(s), highest expression level in gastrocnemius
CleanExiHS_PRKAG1
ExpressionAtlasiP54619 baseline and differential
GenevisibleiP54619 HS

Organism-specific databases

HPAiHPA077805

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111558, 52 interactors
CORUMiP54619
DIPiDIP-39974N
IntActiP54619, 47 interactors
MINTiP54619
STRINGi9606.ENSP00000323867

Chemistry databases

BindingDBiP54619

Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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 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.3 Publications

Sequence similaritiesi

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiKOG1764 Eukaryota
COG0517 LUCA
GeneTreeiENSGT00390000009849
HOGENOMiHOG000176880
HOVERGENiHBG050431
KOiK07200
OMAiFPGVVIC
OrthoDBiEOG091G0CZV
PhylomeDBiP54619
TreeFamiTF313247

Family and domain databases

InterProiView protein in InterPro
IPR039166 AMPKG-1
IPR000644 CBS_dom
PANTHERiPTHR13780:SF38 PTHR13780:SF38, 1 hit
PfamiView protein in Pfam
PF00571 CBS, 3 hits
SMARTiView protein in SMART
SM00116 CBS, 4 hits
PROSITEiView protein in PROSITE
PS51371 CBS, 4 hits

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VYY9F8VYY9_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
280Annotation score:
H0YIC9H0YIC9_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
251Annotation score:
F8VPF5F8VPF5_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
145Annotation score:
F8VVA3F8VVA3_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
161Annotation score:
F8VSL2F8VSL2_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
125Annotation score:
F8VRY2F8VRY2_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
82Annotation score:
F8VSH3F8VSH3_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
69Annotation score:
F8VZX1F8VZX1_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
202Annotation score:
H0YHF8H0YHF8_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
93Annotation score:
F8W046F8W046_HUMAN
5'-AMP-activated protein kinase sub...
PRKAG1
82Annotation score:
There are more potential isoformsShow all

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03345389T → S. Corresponds to variant dbSNP:rs1126930Ensembl.1
Natural variantiVAR_033454329K → N. Corresponds to variant dbSNP:rs34210356Ensembl.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
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

Similar proteinsi

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
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[»]
5ISOX-ray2.63E/F1-331[»]
6B1UX-ray2.77E/F2-331[»]
6B2EX-ray3.80C2-331[»]
ProteinModelPortaliP54619
SMRiP54619
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111558, 52 interactors
CORUMiP54619
DIPiDIP-39974N
IntActiP54619, 47 interactors
MINTiP54619
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
ProteomicsDBi56688

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
EuPathDBiHostDB:ENSG00000181929.11
GeneCardsiPRKAG1
HGNCiHGNC:9385 PRKAG1
HPAiHPA077805
MIMi602742 gene
neXtProtiNX_P54619
OpenTargetsiENSG00000181929
PharmGKBiPA33751
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1764 Eukaryota
COG0517 LUCA
GeneTreeiENSGT00390000009849
HOGENOMiHOG000176880
HOVERGENiHBG050431
KOiK07200
OMAiFPGVVIC
OrthoDBiEOG091G0CZV
PhylomeDBiP54619
TreeFamiTF313247

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of SLC2A4 (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
PROiPR:P54619
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000181929 Expressed in 223 organ(s), highest expression level in gastrocnemius
CleanExiHS_PRKAG1
ExpressionAtlasiP54619 baseline and differential
GenevisibleiP54619 HS

Family and domain databases

InterProiView protein in InterPro
IPR039166 AMPKG-1
IPR000644 CBS_dom
PANTHERiPTHR13780:SF38 PTHR13780:SF38, 1 hit
PfamiView protein in Pfam
PF00571 CBS, 3 hits
SMARTiView protein in SMART
SM00116 CBS, 4 hits
PROSITEiView protein in PROSITE
PS51371 CBS, 4 hits
ProtoNetiSearch...

Entry informationi

Entry nameiAAKG1_HUMAN
AccessioniPrimary (citable) accession number: P54619
Secondary accession number(s): B4DDT7, Q8N7V9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: October 10, 2018
This is version 173 of the entry and version 1 of the sequence. See 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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