ID IDHG1_MOUSE Reviewed; 393 AA. AC P70404; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 186. DE RecName: Full=Isocitrate dehydrogenase [NAD] subunit gamma 1, mitochondrial; DE AltName: Full=Isocitric dehydrogenase subunit gamma; DE AltName: Full=NAD(+)-specific ICDH subunit gamma; DE Flags: Precursor; GN Name=Idh3g; 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]. RX PubMed=9286695; DOI=10.1006/geno.1997.4822; RA Brenner V., Nyakatura G., Rosenthal A., Platzer M.; RT "Genomic organization of two novel genes on human Xq28: compact head to RT head arrangement of IDH gamma and TRAP delta is conserved in rat and RT mouse."; RL Genomics 44:8-14(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Platzer M., Brenner V., Reichwald K., Wiehe T., Oksche A., Rosenthal A.; RT "Comparative sequence analysis of the mouse L1cam locus and the RT corresponding region of human Xq28."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP PROTEIN SEQUENCE OF 70-108; 116-129; 137-190 AND 227-237, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus; RA Lubec G., Kang S.U., Sunyer B., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200; RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.; RT "Comprehensive identification of phosphorylation sites in postsynaptic RT density preparations."; RL Mol. Cell. Proteomics 5:914-922(2006). RN [5] 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 [6] RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-226, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-206, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=23576753; DOI=10.1073/pnas.1302961110; RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.; RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria RT identifies substrates of SIRT3 in metabolic pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013). CC -!- FUNCTION: Regulatory subunit which plays a role in the allosteric CC regulation of the enzyme catalyzing the decarboxylation of isocitrate CC (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha CC (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the CC alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal CC activity but the full activity of the heterotetramer (containing two CC subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly CC and cooperative function of both heterodimers. CC {ECO:0000250|UniProtKB:P51553}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P51553}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:P51553}; CC Note=Divalent metal cations; Mn(2+) or Mg(2+). Activity higher in CC presence of Mn(2+) than of Mg(2+). Binds 1 Mg(2+) or Mn(2+) ion per CC subunit. {ECO:0000250|UniProtKB:P51553}; CC -!- ACTIVITY REGULATION: The heterotetramer and the heterodimer composed of CC IDH3A and IDH3G subunits can be allosterically activated by citrate CC (CIT) or/and ADP, and the two activators can act independently or CC synergistically. The heterodimer composed of IDH3A and IDH3B subunits CC cannot be allosterically regulated and the allosteric regulation of the CC heterotetramer is through the IDH3G subunit and not the IDH3B subunit. CC The IDH3G subunit contains the allosteric site which consists of a CIT- CC binding site and an ADP-binding site, and the binding of CIT and ADP CC causes conformational changes at the allosteric site which are CC transmitted to the active site in the catalytic subunit (IDH3A) through CC a cascade of conformational changes at the heterodimer interface, CC leading to stabilization of the isocitrate-binding at the active site CC and thus activation of the enzyme. ATP can activate the heterotetramer CC and the heterodimer composed of IDH3A and IDH3G subunits at low CC concentrations but inhibits their activities at high concentrations, CC whereas ATP exhibits only inhibitory effect on the heterodimer composed CC of IDH3A and IDH3B subunits. {ECO:0000250|UniProtKB:P51553}. CC -!- SUBUNIT: Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and CC gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer CC containing one IDH3A and one IDH3B subunit and the heterodimer CC containing one IDH3A and one IDH3G subunit assemble into a CC heterotetramer (which contains two subunits of IDH3A, one of IDH3B and CC one of IDH3G) and further into the heterooctamer. CC {ECO:0000250|UniProtKB:P51553}. CC -!- SUBCELLULAR LOCATION: Mitochondrion. CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate CC dehydrogenases 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; U68564; AAC53340.1; -; mRNA. DR EMBL; AF133093; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS30212.1; -. DR RefSeq; NP_032349.1; NM_008323.1. DR AlphaFoldDB; P70404; -. DR SMR; P70404; -. DR BioGRID; 200511; 47. DR ComplexPortal; CPX-556; Mitochondrial isocitrate dehydrogenase complex (NAD+). DR IntAct; P70404; 7. DR MINT; P70404; -. DR STRING; 10090.ENSMUSP00000056502; -. DR GlyGen; P70404; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P70404; -. DR PhosphoSitePlus; P70404; -. DR SwissPalm; P70404; -. DR EPD; P70404; -. DR jPOST; P70404; -. DR PaxDb; 10090-ENSMUSP00000056502; -. DR PeptideAtlas; P70404; -. DR ProteomicsDB; 267191; -. DR Pumba; P70404; -. DR Antibodypedia; 408; 283 antibodies from 32 providers. DR DNASU; 15929; -. DR Ensembl; ENSMUST00000052761.9; ENSMUSP00000056502.9; ENSMUSG00000002010.18. DR GeneID; 15929; -. DR KEGG; mmu:15929; -. DR UCSC; uc009tmp.1; mouse. DR AGR; MGI:1099463; -. DR CTD; 3421; -. DR MGI; MGI:1099463; Idh3g. DR VEuPathDB; HostDB:ENSMUSG00000002010; -. DR eggNOG; KOG0784; Eukaryota. DR GeneTree; ENSGT00950000182989; -. DR HOGENOM; CLU_031953_0_0_1; -. DR InParanoid; P70404; -. DR OMA; PWSCDYY; -. DR OrthoDB; 143577at2759; -. DR PhylomeDB; P70404; -. DR TreeFam; TF315033; -. DR Reactome; R-MMU-71403; Citric acid cycle (TCA cycle). DR BioGRID-ORCS; 15929; 1 hit in 77 CRISPR screens. DR ChiTaRS; Idh3g; mouse. DR PRO; PR:P70404; -. DR Proteomes; UP000000589; Chromosome X. DR RNAct; P70404; Protein. DR Bgee; ENSMUSG00000002010; Expressed in cardiac muscle of left ventricle and 277 other cell types or tissues. DR ExpressionAtlas; P70404; baseline and differential. DR GO; GO:0005962; C:mitochondrial isocitrate dehydrogenase complex (NAD+); ISO:MGI. DR GO; GO:0005739; C:mitochondrion; HDA:MGI. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; ISS:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0006103; P:2-oxoglutarate metabolic process; ISO:MGI. DR GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB. DR GO; GO:0006734; P:NADH metabolic process; ISO:MGI. DR GO; GO:0045926; P:negative regulation of growth; ISO:MGI. DR GO; GO:0006099; P:tricarboxylic acid cycle; ISO:MGI. DR Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1. DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS. DR InterPro; IPR004434; Isocitrate_DH_NAD. DR InterPro; IPR024084; IsoPropMal-DH-like_dom. DR NCBIfam; TIGR00175; mito_nad_idh; 1. DR PANTHER; PTHR11835; DECARBOXYLATING DEHYDROGENASES-ISOCITRATE, ISOPROPYLMALATE, TARTRATE; 1. DR PANTHER; PTHR11835:SF58; ISOCITRATE DEHYDROGENASE [NAD] SUBUNIT GAMMA 1, MITOCHONDRIAL; 1. DR Pfam; PF00180; Iso_dh; 1. DR SMART; SM01329; Iso_dh; 1. DR SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1. DR PROSITE; PS00470; IDH_IMDH; 1. DR Genevisible; P70404; MM. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Direct protein sequencing; Magnesium; Manganese; KW Metal-binding; Mitochondrion; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Transit peptide; Tricarboxylic acid cycle. FT TRANSIT 1..39 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 40..393 FT /note="Isocitrate dehydrogenase [NAD] subunit gamma 1, FT mitochondrial" FT /id="PRO_0000014451" FT BINDING 120 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 133 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 136 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 167 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 254 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_note="ligand shared with catalytic subunit" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 254 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 312 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 313 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 324 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT MOD_RES 130 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P41565" FT MOD_RES 206 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 226 FT /note="N6-succinyllysine" FT /evidence="ECO:0007744|PubMed:23806337" SQ SEQUENCE 393 AA; 42785 MW; 4023560C44C1F4D3 CRC64; MALKVAIAAG GAAKAMLKPT LLCRPWEVLA AHVAPRRSIS SQQTIPPSAK YGGRHTVTMI PGDGIGPELM LHVKSVFRHA CVPVDFEEVH VSSNADEEDI RNAIMAIRRN RVALKGNIET NHNLPPSHKS RNNILRTSLD LYANVIHCKS LPGVVTRHKD IDILIVRENT EGEYSSLEHE SVAGVVESLK IITKAKSLRI AEYAFKLAQE SGRKKVTAVH KANIMKLGDG LFLQCCREVA AHYPQITFDS MIVDNTTMQL VSRPQQFDVM VMPNLYGNIV NNVCAGLVGG PGLVAGANYG HVYAVFETAT RNTGKSIANK NIANPTATLL ASCMMLDHLK LHSYATSIRK AVLASMDNEN MHTPDIGGQG TTSQAIQDII RHIRIINGRA VEA //