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 27-MAR-2024, entry version 171. 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, RC Pancreas, 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. {ECO:0000250|UniProtKB:P54619}. 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. CC {ECO:0000250|UniProtKB:P54619}. 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 -!- PTM: Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated CC protein kinase (AMPK) activity. {ECO:0000250|UniProtKB:P54619}. CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma CC subunit family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 6. 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 GlyGen; O54950; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O54950; -. DR PhosphoSitePlus; O54950; -. DR SwissPalm; O54950; -. DR EPD; O54950; -. DR jPOST; O54950; -. DR PaxDb; 10090-ENSMUSP00000132499; -. DR PeptideAtlas; O54950; -. DR ProteomicsDB; 296431; -. DR Pumba; O54950; -. DR Antibodypedia; 25778; 511 antibodies from 34 providers. DR DNASU; 19082; -. DR Ensembl; ENSMUST00000168846.3; ENSMUSP00000132499.2; ENSMUSG00000067713.8. DR GeneID; 19082; -. DR KEGG; mmu:19082; -. DR UCSC; uc007xoa.1; mouse. DR AGR; MGI:108411; -. 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; APLWNNQ; -. DR OrthoDB; 880743at2759; -. DR PhylomeDB; O54950; -. DR TreeFam; TF313247; -. DR Reactome; R-MMU-1632852; Macroautophagy. DR Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation. DR BioGRID-ORCS; 19082; 4 hits in 81 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 256 other cell types or tissues. DR ExpressionAtlas; O54950; baseline and differential. 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; TAS: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: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 CDD; cd04618; CBS_euAMPK_gamma-like_repeat1; 1. DR CDD; cd04641; CBS_euAMPK_gamma-like_repeat2; 1. DR Gene3D; 3.10.580.10; CBS-domain; 2. DR InterPro; IPR000644; CBS_dom. DR InterPro; IPR046342; CBS_dom_sf. DR PANTHER; PTHR13780:SF38; 5'-AMP-ACTIVATED PROTEIN KINASE SUBUNIT GAMMA-1; 1. DR PANTHER; PTHR13780; AMP-ACTIVATED PROTEIN KINASE, GAMMA REGULATORY SUBUNIT; 1. DR Pfam; PF00571; CBS; 4. DR SMART; SM00116; CBS; 4. DR SUPFAM; SSF54631; CBS-domain pair; 2. DR PROSITE; PS51371; CBS; 4. DR Genevisible; O54950; MM. PE 1: Evidence at protein level; KW ATP-binding; CBS domain; Fatty acid biosynthesis; Fatty acid metabolism; KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Nucleotide-binding; KW Phosphoprotein; 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 //