AAKG1_MOUSE
ID AAKG1_MOUSE Reviewed; 330 AA.
AC O54950; Q5PRE8;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=5'-AMP-activated protein kinase subunit gamma-1;
DE Short=AMPK gamma1;
DE Short=AMPK subunit gamma-1;
DE Short=AMPKg;
GN Name=Prkag1; Synonyms=Prkaac;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=11306812; DOI=10.1159/000056884;
RA Shamsadin R., Jantsan K., Adham I.M., Engel W.;
RT "Cloning, organisation, chromosomal localization and expression analysis of
RT the mouse Prkag1 gene.";
RL Cytogenet. Cell Genet. 92:134-138(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP PHOSPHORYLATION BY ULK1 AND ULK2.
RX PubMed=21460634; DOI=10.4161/auto.7.7.15451;
RA Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M.,
RA Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.;
RT "Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory
RT feedback loop.";
RL Autophagy 7:696-706(2011).
CC -!- FUNCTION: AMP/ATP-binding subunit of AMP-activated protein kinase
CC (AMPK), an energy sensor protein kinase that plays a key role in
CC regulating cellular energy metabolism. In response to reduction of
CC intracellular ATP levels, AMPK activates energy-producing pathways and
CC inhibits energy-consuming processes: inhibits protein, carbohydrate and
CC lipid biosynthesis, as well as cell growth and proliferation. AMPK acts
CC via direct phosphorylation of metabolic enzymes, and by longer-term
CC effects via phosphorylation of transcription regulators. Also acts as a
CC regulator of cellular polarity by remodeling the actin cytoskeleton;
CC probably by indirectly activating myosin. Gamma non-catalytic subunit
CC mediates binding to AMP, ADP and ATP, leading to activate or inhibit
CC AMPK: AMP-binding results in allosteric activation of alpha catalytic
CC subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and
CC preventing dephosphorylation of catalytic subunits. ADP also stimulates
CC phosphorylation, without stimulating already phosphorylated catalytic
CC subunit. ATP promotes dephosphorylation of catalytic subunit, rendering
CC the AMPK enzyme inactive (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1
CC or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic
CC subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The AMPK pseudosubstrate motif resembles the sequence around
CC sites phosphorylated on target proteins of AMPK, except the presence of
CC a non-phosphorylatable residue in place of Ser. In the absence of AMP
CC this pseudosubstrate sequence may bind to the active site groove on the
CC alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the
CC upstream activating kinase STK11/LKB1 (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The 4 CBS domains mediate binding to nucleotides. Of the 4
CC potential nucleotide-binding sites, 3 are occupied, designated as sites
CC 1, 3, and 4 based on the CBS modules that provide the acidic residue
CC for coordination with the 2'- and 3'-hydroxyl groups of the ribose of
CC AMP. Of these, site 4 appears to be a structural site that retains a
CC tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can
CC bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-
CC affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP,
CC ADP or ATP 2) is the weakest nucleotide-binding site on the gamma
CC subunit, yet it is exquisitely sensitive to changes in nucleotide
CC levels and this allows AMPK to respond rapidly to changes in cellular
CC energy status. Site 3 is likely to be responsible for protection of a
CC conserved threonine in the activation loop of the alpha catalytic
CC subunit through conformational changes induced by binding of AMP or
CC ADP. {ECO:0000250|UniProtKB:P80385}.
CC -!- PTM: Phosphorylated by ULK1 and ULK2; leading to negatively regulate
CC AMPK activity and suggesting the existence of a regulatory feedback
CC loop between ULK1, ULK2 and AMPK. {ECO:0000269|PubMed:21460634}.
CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma
CC subunit family. {ECO:0000305}.
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DR EMBL; AF036535; AAB95475.1; -; mRNA.
DR EMBL; BC086660; AAH86660.1; -; mRNA.
DR CCDS; CCDS49724.1; -.
DR RefSeq; NP_058061.2; NM_016781.2.
DR AlphaFoldDB; O54950; -.
DR SMR; O54950; -.
DR BioGRID; 202364; 5.
DR ComplexPortal; CPX-5698; AMPK complex, alpha1-beta1-gamma1 variant.
DR ComplexPortal; CPX-5851; AMPK complex, alpha2-beta2-gamma1 variant.
DR ComplexPortal; CPX-5852; AMPK complex, alpha2-beta1-gamma1 variant.
DR ComplexPortal; CPX-5853; AMPK complex, alpha1-beta2-gamma1 variant.
DR CORUM; O54950; -.
DR IntAct; O54950; 5.
DR MINT; O54950; -.
DR STRING; 10090.ENSMUSP00000132499; -.
DR BindingDB; O54950; -.
DR ChEMBL; CHEMBL4524004; -.
DR iPTMnet; O54950; -.
DR PhosphoSitePlus; O54950; -.
DR SwissPalm; O54950; -.
DR EPD; O54950; -.
DR jPOST; O54950; -.
DR PaxDb; O54950; -.
DR PeptideAtlas; O54950; -.
DR PRIDE; O54950; -.
DR ProteomicsDB; 296431; -.
DR Antibodypedia; 25778; 466 antibodies from 34 providers.
DR DNASU; 19082; -.
DR Ensembl; ENSMUST00000168846; ENSMUSP00000132499; ENSMUSG00000067713.
DR GeneID; 19082; -.
DR KEGG; mmu:19082; -.
DR UCSC; uc007xoa.1; mouse.
DR CTD; 5571; -.
DR MGI; MGI:108411; Prkag1.
DR VEuPathDB; HostDB:ENSMUSG00000067713; -.
DR eggNOG; KOG1764; Eukaryota.
DR GeneTree; ENSGT00950000183019; -.
DR HOGENOM; CLU_021740_3_0_1; -.
DR InParanoid; O54950; -.
DR OMA; ACVKMLE; -.
DR OrthoDB; 631088at2759; -.
DR PhylomeDB; O54950; -.
DR TreeFam; TF313247; -.
DR BioGRID-ORCS; 19082; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Prkag1; mouse.
DR PRO; PR:O54950; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O54950; protein.
DR Bgee; ENSMUSG00000067713; Expressed in saccule of membranous labyrinth and 253 other tissues.
DR ExpressionAtlas; O54950; baseline and differential.
DR Genevisible; O54950; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR GO; GO:0016208; F:AMP binding; ISS:UniProtKB.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019887; F:protein kinase regulator activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0031669; P:cellular response to nutrient levels; ISO:MGI.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0051170; P:import into nucleus; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0050790; P:regulation of catalytic activity; ISO:MGI.
DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; IEA:InterPro.
DR Gene3D; 3.10.580.10; -; 2.
DR InterPro; IPR039166; AMPKG-1.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR PANTHER; PTHR13780:SF38; PTHR13780:SF38; 1.
DR Pfam; PF00571; CBS; 3.
DR SMART; SM00116; CBS; 4.
DR SUPFAM; SSF54631; SSF54631; 2.
DR PROSITE; PS51371; CBS; 4.
PE 1: Evidence at protein level;
KW ATP-binding; CBS domain; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..330
FT /note="5'-AMP-activated protein kinase subunit gamma-1"
FT /id="PRO_0000204378"
FT DOMAIN 42..102
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 124..186
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 197..259
FT /note="CBS 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 271..328
FT /note="CBS 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 137..158
FT /note="AMPK pseudosubstrate"
FT BINDING 69
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 69
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 84..89
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 84..89
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 84..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 129
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 129
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 129
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 150..151
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 150..151
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 150..151
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 150
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 151
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 169
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 169
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 169
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 199
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 204
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 225..226
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 241..244
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 241..244
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 241..244
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 268
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 268
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 268
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 276
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 276
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 276
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 297..298
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 297..298
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 297..298
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 297
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 313..316
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 260
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 262
FT /note="Phosphothreonine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 269
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT CONFLICT 80
FT /note="S -> C (in Ref. 1; AAB95475)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="L -> S (in Ref. 1; AAB95475)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="T -> I (in Ref. 1; AAB95475)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="A -> D (in Ref. 1; AAB95475)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 330 AA; 37520 MW; 539F70EC8819C34D CRC64;
MESVAAESSP ALENEHFQET PESNNSVYTS FMKSHRCYDL IPTSSKLVVF DTSLQVKKAF
FALVTNGVRA APLWDSKKQS FVGMLTITDF INILHRYYKS ALVQIYELEE HKIETWREVY
LQDSFKPLVC ISPNASLFDA VSSLIRNKIH RLPVIDPESG NTLYILTHKR ILKFLKLFIT
EFPKPEFMSK SLQELQIGTY ANIAMVRTTT PVYVALGIFV QHRVSALPVV DEKGRVVDIY
SKFDVINLAA EKTYNNLDVS VTKALQHRSH YFEGVLKCYL HETLETIINR LVEAEVHRLV
VVDEHDVVKG IVSLSDILQA LVLTGGEKKP
