ID ODO1_HUMAN Reviewed; 1023 AA. AC Q02218; B4E2U9; D3DVL0; E9PBM1; Q96DD3; Q9UDX0; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 3. DT 27-MAR-2024, entry version 225. DE RecName: Full=2-oxoglutarate dehydrogenase complex component E1 {ECO:0000305}; DE Short=E1o; DE Short=OGDC-E1; DE Short=OGDH-E1; DE EC=1.2.4.2 {ECO:0000269|PubMed:24495017, ECO:0000269|PubMed:25210035, ECO:0000269|PubMed:28435050, ECO:0000269|PubMed:29211711}; DE AltName: Full=2-oxoglutarate dehydrogenase, mitochondrial; DE AltName: Full=Alpha-ketoglutarate dehydrogenase; DE Short=Alpha-KGDH-E1; DE AltName: Full=Thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase; DE Flags: Precursor; GN Name=OGDH {ECO:0000312|HGNC:HGNC:8124}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=1542694; DOI=10.1073/pnas.89.5.1963; RA Koike K., Urata Y., Goto S.; RT "Cloning and nucleotide sequence of the cDNA encoding human 2-oxoglutarate RT dehydrogenase (lipoamide)."; RL Proc. Natl. Acad. Sci. U.S.A. 89:1963-1967(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION. RX PubMed=7622061; DOI=10.1016/0378-1119(95)00086-l; RA Koike K.; RT "The gene encoding human 2-oxoglutarate dehydrogenase: structural RT organization and mapping to chromosome 7p13-p14."; RL Gene 159:261-266(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Bone marrow, and Muscle; 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 [7] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-534, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC TISSUE=Mammary cancer; RX PubMed=17370265; DOI=10.1002/pmic.200600410; RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.; RT "Tryptic digestion of ubiquitin standards reveals an improved strategy for RT identifying ubiquitinated proteins by mass spectrometry."; RL Proteomics 7:868-874(2007). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-970, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, CALCIUM-BINDING SITES, RP COFACTOR, AND MUTAGENESIS OF ASP-154. RX PubMed=24495017; DOI=10.1042/bj20131664; RA Armstrong C.T., Anderson J.L., Denton R.M.; RT "Studies on the regulation of the human E1 subunit of the 2-oxoglutarate RT dehydrogenase complex, including the identification of a novel calcium- RT binding site."; RL Biochem. J. 459:369-381(2014). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=25210035; DOI=10.1074/jbc.m114.591073; RA Nemeria N.S., Ambrus A., Patel H., Gerfen G., Adam-Vizi V., Tretter L., RA Zhou J., Wang J., Jordan F.; RT "Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin- RT derived radical by aerobic oxidation of the enamine intermediate."; RL J. Biol. Chem. 289:29859-29873(2014). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28435050; DOI=10.1016/j.freeradbiomed.2017.04.017; RA Nemeria N.S., Gerfen G., Guevara E., Nareddy P.R., Szostak M., Jordan F.; RT "The human Krebs cycle 2-oxoglutarate dehydrogenase complex creates an RT additional source of superoxide/hydrogen peroxide from 2-oxoadipate as RT alternative substrate."; RL Free Radic. Biol. Med. 108:644-654(2017). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT, AND RP MUTAGENESIS OF 459-PRO-TYR-460. RX PubMed=29211711; DOI=10.1038/nature25003; RA Wang Y., Guo Y.R., Liu K., Yin Z., Liu R., Xia Y., Tan L., Yang P., RA Lee J.H., Li X.J., Hawke D., Zheng Y., Qian X., Lyu J., He J., Xing D., RA Tao Y.J., Lu Z.; RT "KAT2A coupled with the alpha-KGDH complex acts as a histone H3 RT succinyltransferase."; RL Nature 552:273-277(2017). RN [16] RP INTERACTION WITH ABHD11. RX PubMed=32792488; DOI=10.1038/s41467-020-17862-6; RA Bailey P.S.J., Ortmann B.M., Martinelli A.W., Houghton J.W., Costa A.S.H., RA Burr S.P., Antrobus R., Frezza C., Nathan J.A.; RT "ABHD11 maintains 2-oxoglutarate metabolism by preserving functional RT lipoylation of the 2-oxoglutarate dehydrogenase complex."; RL Nat. Commun. 11:4046-4046(2020). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 932-940 IN COMPLEX WITH H-2 CLASS RP I HISTOCOMPATIBILITY COMPLEX. RX PubMed=18973345; DOI=10.1021/bi801349g; RA Jones L.L., Colf L.A., Bankovich A.J., Stone J.D., Gao Y.G., Chan C.M., RA Huang R.H., Garcia K.C., Kranz D.M.; RT "Different thermodynamic binding mechanisms and peptide fine specificities RT associated with a panel of structurally similar high-affinity T cell RT receptors."; RL Biochemistry 47:12398-12408(2008). CC -!- FUNCTION: 2-oxoglutarate dehydrogenase (E1o) component of the 2- CC oxoglutarate dehydrogenase complex (OGDHC) (PubMed:24495017, CC PubMed:25210035, PubMed:28435050). Participates in the first step, rate CC limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA CC and CO(2) catalyzed by the whole OGDHC (PubMed:24495017, CC PubMed:25210035, PubMed:28435050). Catalyzes the irreversible CC decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) via the CC thiamine diphosphate (ThDP) cofactor and subsequent transfer of the CC decarboxylated acyl intermediate on an oxidized dihydrolipoyl group CC that is covalently amidated to the E2 enzyme (dihydrolipoyllysine- CC residue succinyltransferase or DLST) (PubMed:24495017, PubMed:25210035, CC PubMed:28435050). Plays a key role in the Krebs (citric acid) cycle, CC which is a common pathway for oxidation of fuel molecules, including CC carbohydrates, fatty acids, and amino acids (PubMed:25210035). Can CC catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much CC lower rate than 2-oxoglutarate (PubMed:28435050). Mainly active in the CC mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate CC dehydrogenase complex also localizes in the nucleus and is required for CC lysine succinylation of histones: associates with KAT2A on chromatin CC and provides succinyl-CoA to histone succinyltransferase KAT2A CC (PubMed:29211711). {ECO:0000269|PubMed:24495017, CC ECO:0000269|PubMed:25210035, ECO:0000269|PubMed:28435050, CC ECO:0000269|PubMed:29211711, ECO:0000303|PubMed:25210035}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + H(+) + N(6)-[(R)-lipoyl]-L-lysyl- CC [dihydrolipoyllysine-residue succinyltransferase] = CO2 + N(6)-[(R)- CC S(8)-succinyldihydrolipoyl]-L-lysyl-[dihydrolipoyllysine-residue CC succinyltransferase]; Xref=Rhea:RHEA:12188, Rhea:RHEA-COMP:10483, CC Rhea:RHEA-COMP:10484, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:83099, ChEBI:CHEBI:83120; EC=1.2.4.2; CC Evidence={ECO:0000269|PubMed:24495017, ECO:0000269|PubMed:25210035, CC ECO:0000269|PubMed:28435050, ECO:0000269|PubMed:29211711}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12189; CC Evidence={ECO:0000305|PubMed:24495017, ECO:0000305|PubMed:25210035, CC ECO:0000305|PubMed:28435050, ECO:0000305|PubMed:29211711}; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000269|PubMed:24495017}; CC -!- ACTIVITY REGULATION: Calcium ions and ADP stimulate, whereas ATP and CC NADH reduce catalytic activity. {ECO:0000269|PubMed:24495017}. CC -!- SUBUNIT: The 2-oxoglutarate dehydrogenase complex is composed of OGDH CC (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide CC succinyltransferase; E2), DLD (dihydrolipoamide dehydrogenase; E3), and CC the assembly factor KGD4 (By similarity). It contains multiple copies CC of the three enzymatic components (E1, E2 and E3). In the nucleus, the CC 2-oxoglutarate dehydrogenase complex associates with KAT2A CC (PubMed:29211711). Interacts with ABHD11; this interaction maintains CC the functional lipoylation of the 2-oxoglutarate dehydrogenase complex CC (PubMed:32792488). {ECO:0000250|UniProtKB:Q148N0, CC ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:32792488}. CC -!- INTERACTION: CC Q02218; P54253: ATXN1; NbExp=3; IntAct=EBI-747213, EBI-930964; CC Q02218; P42858: HTT; NbExp=3; IntAct=EBI-747213, EBI-466029; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:29211711}. CC Nucleus {ECO:0000269|PubMed:29211711}. Note=Mainly localizes in the CC mitochondrion. A small fraction localizes to the nucleus, where the 2- CC oxoglutarate dehydrogenase complex is required for histone CC succinylation. {ECO:0000269|PubMed:29211711}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q02218-1; Sequence=Displayed; CC Name=2; CC IsoId=Q02218-2; Sequence=VSP_042313; CC Name=3; CC IsoId=Q02218-3; Sequence=VSP_043628, VSP_043629; CC -!- MISCELLANEOUS: [Isoform 2]: Probably insensitive to calcium. CC {ECO:0000305}. CC -!- MISCELLANEOUS: The mitochondrial 2-oxoglutarate and 2-oxoadipate CC dehydrogenase complexes (OGDHC and OADHC, respectively) share their E2 CC (DLST) and E3 (dihydrolipoyl dehydrogenase or DLD) components, but the CC E1 component is specific to each complex (E1o and E1a (DHTK1), CC respectively). {ECO:0000250|UniProtKB:Q96HY7}. CC -!- SIMILARITY: Belongs to the alpha-ketoglutarate dehydrogenase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA01393.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA06836.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-ketoglutarate dehydrogenase CC entry; CC URL="https://en.wikipedia.org/wiki/Alpha-ketoglutarate_dehydrogenase"; 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; D10523; BAA01393.1; ALT_FRAME; mRNA. DR EMBL; D32064; BAA06836.1; ALT_FRAME; Genomic_DNA. DR EMBL; AK304439; BAG65261.1; -; mRNA. DR EMBL; AC004859; AAQ96884.1; -; Genomic_DNA. DR EMBL; AC004859; AAQ96885.1; -; Genomic_DNA. DR EMBL; AC011894; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471128; EAW61086.1; -; Genomic_DNA. DR EMBL; CH471128; EAW61087.1; -; Genomic_DNA. DR EMBL; CH471128; EAW61089.1; -; Genomic_DNA. DR EMBL; BC004964; AAH04964.1; -; mRNA. DR EMBL; BC009580; AAH09580.1; -; mRNA. DR EMBL; BC014617; AAH14617.1; -; mRNA. DR CCDS; CCDS34627.1; -. [Q02218-1] DR CCDS; CCDS47580.1; -. [Q02218-3] DR CCDS; CCDS55107.1; -. [Q02218-2] DR PIR; A38234; A38234. DR RefSeq; NP_001003941.1; NM_001003941.2. [Q02218-3] DR RefSeq; NP_001158508.1; NM_001165036.1. [Q02218-2] DR RefSeq; NP_002532.2; NM_002541.3. [Q02218-1] DR PDB; 3ERY; X-ray; 1.95 A; P/Q=932-940. DR PDB; 7WGR; EM; 2.92 A; A/B=129-1023. DR PDBsum; 3ERY; -. DR PDBsum; 7WGR; -. DR AlphaFoldDB; Q02218; -. DR EMDB; EMD-32485; -. DR SMR; Q02218; -. DR BioGRID; 111017; 233. DR CORUM; Q02218; -. DR DIP; DIP-39353N; -. DR IntAct; Q02218; 42. DR MINT; Q02218; -. DR STRING; 9606.ENSP00000388183; -. DR ChEMBL; CHEMBL2816; -. DR DrugBank; DB00157; NADH. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB09092; Xanthinol. DR CarbonylDB; Q02218; -. DR GlyGen; Q02218; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q02218; -. DR MetOSite; Q02218; -. DR PhosphoSitePlus; Q02218; -. DR SwissPalm; Q02218; -. DR BioMuta; OGDH; -. DR DMDM; 160332299; -. DR REPRODUCTION-2DPAGE; IPI00098902; -. DR CPTAC; CPTAC-554; -. DR CPTAC; CPTAC-555; -. DR EPD; Q02218; -. DR jPOST; Q02218; -. DR MassIVE; Q02218; -. DR MaxQB; Q02218; -. DR PaxDb; 9606-ENSP00000222673; -. DR PeptideAtlas; Q02218; -. DR ProteomicsDB; 58058; -. [Q02218-1] DR ProteomicsDB; 58059; -. [Q02218-2] DR ProteomicsDB; 58060; -. [Q02218-3] DR Pumba; Q02218; -. DR Antibodypedia; 13451; 262 antibodies from 27 providers. DR DNASU; 4967; -. DR Ensembl; ENST00000222673.6; ENSP00000222673.5; ENSG00000105953.16. [Q02218-1] DR Ensembl; ENST00000443864.6; ENSP00000388084.2; ENSG00000105953.16. [Q02218-3] DR Ensembl; ENST00000449767.5; ENSP00000392878.1; ENSG00000105953.16. [Q02218-2] DR GeneID; 4967; -. DR KEGG; hsa:4967; -. DR MANE-Select; ENST00000222673.6; ENSP00000222673.5; NM_002541.4; NP_002532.2. DR UCSC; uc003tlm.4; human. [Q02218-1] DR AGR; HGNC:8124; -. DR CTD; 4967; -. DR DisGeNET; 4967; -. DR GeneCards; OGDH; -. DR HGNC; HGNC:8124; OGDH. DR HPA; ENSG00000105953; Tissue enhanced (heart muscle, skeletal muscle, tongue). DR MalaCards; OGDH; -. DR MIM; 613022; gene. DR neXtProt; NX_Q02218; -. DR OpenTargets; ENSG00000105953; -. DR Orphanet; 31; Oxoglutaric aciduria. DR PharmGKB; PA31910; -. DR VEuPathDB; HostDB:ENSG00000105953; -. DR eggNOG; KOG0450; Eukaryota. DR GeneTree; ENSGT00950000183125; -. DR HOGENOM; CLU_004709_2_3_1; -. DR InParanoid; Q02218; -. DR OMA; RDSYCRT; -. DR OrthoDB; 3597773at2759; -. DR PhylomeDB; Q02218; -. DR TreeFam; TF300695; -. DR BioCyc; MetaCyc:HS02832-MONOMER; -. DR BRENDA; 1.2.1.105; 2681. DR PathwayCommons; Q02218; -. DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation. DR Reactome; R-HSA-71064; Lysine catabolism. DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle). DR SABIO-RK; Q02218; -. DR SignaLink; Q02218; -. DR SIGNOR; Q02218; -. DR BioGRID-ORCS; 4967; 389 hits in 1161 CRISPR screens. DR ChiTaRS; OGDH; human. DR EvolutionaryTrace; Q02218; -. DR GeneWiki; OGDH; -. DR GenomeRNAi; 4967; -. DR Pharos; Q02218; Tbio. DR PRO; PR:Q02218; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q02218; Protein. DR Bgee; ENSG00000105953; Expressed in apex of heart and 186 other cell types or tissues. DR ExpressionAtlas; Q02218; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0045252; C:oxoglutarate dehydrogenase complex; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0034602; F:oxoglutarate dehydrogenase (NAD+) activity; IEA:Ensembl. DR GO; GO:0004591; F:oxoglutarate dehydrogenase (succinyl-transferring) activity; IDA:UniProtKB. DR GO; GO:0030976; F:thiamine pyrophosphate binding; IDA:UniProtKB. DR GO; GO:0006103; P:2-oxoglutarate metabolic process; IDA:UniProtKB. DR GO; GO:0021695; P:cerebellar cortex development; IEA:Ensembl. DR GO; GO:0006091; P:generation of precursor metabolites and energy; ISS:UniProtKB. DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-KW. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0106077; P:histone succinylation; IDA:UniProtKB. DR GO; GO:0061034; P:olfactory bulb mitral cell layer development; IEA:Ensembl. DR GO; GO:0021860; P:pyramidal neuron development; IEA:Ensembl. DR GO; GO:0021756; P:striatum development; IEA:Ensembl. DR GO; GO:0006104; P:succinyl-CoA metabolic process; IDA:UniProtKB. DR GO; GO:0022028; P:tangential migration from the subventricular zone to the olfactory bulb; IEA:Ensembl. DR GO; GO:0021794; P:thalamus development; IEA:Ensembl. DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central. DR CDD; cd02016; TPP_E1_OGDC_like; 1. DR Gene3D; 3.40.50.12470; -; 1. DR Gene3D; 3.40.50.970; -; 1. DR Gene3D; 3.40.50.11610; Multifunctional 2-oxoglutarate metabolism enzyme, C-terminal domain; 1. DR Gene3D; 1.10.287.1150; TPP helical domain; 1. DR InterPro; IPR032106; 2-oxogl_dehyd_N. DR InterPro; IPR011603; 2oxoglutarate_DH_E1. DR InterPro; IPR001017; DH_E1. DR InterPro; IPR031717; KGD_C. DR InterPro; IPR042179; KGD_C_sf. DR InterPro; IPR029061; THDP-binding. DR InterPro; IPR005475; Transketolase-like_Pyr-bd. DR NCBIfam; TIGR00239; 2oxo_dh_E1; 1. DR PANTHER; PTHR23152; 2-OXOGLUTARATE DEHYDROGENASE; 1. DR PANTHER; PTHR23152:SF7; 2-OXOGLUTARATE DEHYDROGENASE COMPLEX COMPONENT E1; 1. DR Pfam; PF16078; 2-oxogl_dehyd_N; 1. DR Pfam; PF00676; E1_dh; 1. DR Pfam; PF16870; OxoGdeHyase_C; 1. DR Pfam; PF02779; Transket_pyr; 1. DR PIRSF; PIRSF000157; Oxoglu_dh_E1; 1. DR SMART; SM00861; Transket_pyr; 1. DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 2. DR Genevisible; Q02218; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Calcium; Glycolysis; KW Isopeptide bond; Metal-binding; Mitochondrion; Nucleus; Oxidoreductase; KW Phosphoprotein; Reference proteome; Thiamine pyrophosphate; KW Transit peptide; Ubl conjugation. FT TRANSIT 1..40 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 41..1023 FT /note="2-oxoglutarate dehydrogenase complex component E1" FT /id="PRO_0000020432" FT BINDING 154 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:24495017" FT BINDING 156 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:24495017" FT BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305|PubMed:24495017" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:24495017" FT BINDING 181 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:24495017" FT BINDING 183 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:24495017" FT MOD_RES 74 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q60597" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60597" FT MOD_RES 401 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q60597" FT MOD_RES 564 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q60597" FT MOD_RES 970 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT CROSSLNK 534 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:17370265" FT VAR_SEQ 139..172 FT /note="IRGHHVAQLDPLGILDADLDSSVPADIISSTDKL -> VRGHHIAKLDPLGI FT SCVNFDDAPVTVSSNV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042313" FT VAR_SEQ 404..427 FT /note="MSILLHGDAAFAGQGIVYETFHLS -> RPRERRARQIVKAPCSSMEFRSPT FT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043628" FT VAR_SEQ 428..1023 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043629" FT VARIANT 1018 FT /note="V -> I (in dbSNP:rs2070607)" FT /id="VAR_050435" FT MUTAGEN 154 FT /note="D->A: Six-fold decrease in sensitivity for calcium." FT /evidence="ECO:0000269|PubMed:24495017" FT MUTAGEN 459..460 FT /note="PY->AA: Abolished enzyme activity and ability to FT promote histone succinylation." FT /evidence="ECO:0000269|PubMed:29211711" FT CONFLICT 730..733 FT /note="LGFA -> AGLR (in Ref. 1; BAA01393 and 2; BAA06836)" FT /evidence="ECO:0000305" FT CONFLICT 755 FT /note="Q -> L (in Ref. 3; BAG65261)" FT /evidence="ECO:0000305" FT CONFLICT 831 FT /note="N -> D (in Ref. 2; BAA06836)" FT /evidence="ECO:0000305" FT CONFLICT 989 FT /note="D -> N (in Ref. 1; BAA01393 and 2; BAA06836)" FT /evidence="ECO:0000305" FT HELIX 130..144 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 149..153 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 169..174 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 179..181 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 182..187 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 199..202 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 203..214 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 215..221 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 228..239 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 248..271 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 286..300 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 304..308 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 314..320 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 326..334 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 343..345 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 367..370 FT /evidence="ECO:0007829|PDB:7WGR" FT TURN 377..380 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 381..395 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 401..410 FT /evidence="ECO:0007829|PDB:7WGR" FT TURN 411..416 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 419..428 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 430..432 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 438..443 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 452..454 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 457..460 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 463..465 FT /evidence="ECO:0007829|PDB:7WGR" FT TURN 466..469 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 472..476 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 480..497 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 501..506 FT /evidence="ECO:0007829|PDB:7WGR" FT TURN 520..522 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 524..530 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 536..547 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 552..573 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 611..621 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 633..647 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 653..666 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 670..675 FT /evidence="ECO:0007829|PDB:7WGR" FT TURN 676..680 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 689..691 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 693..695 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 702..705 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 706..709 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 713..717 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 724..732 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 737..744 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 750..754 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 755..760 FT /evidence="ECO:0007829|PDB:7WGR" FT TURN 761..768 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 776..780 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 784..786 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 788..791 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 795..799 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 819..824 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 828..830 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 835..847 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 848..850 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 854..858 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 860..864 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 872..874 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 890..893 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 895..897 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 899..904 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 908..918 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 925..929 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 931..935 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 940..947 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 954..960 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 966..976 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 984..988 FT /evidence="ECO:0007829|PDB:7WGR" FT STRAND 992..995 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 999..1014 FT /evidence="ECO:0007829|PDB:7WGR" FT HELIX 1020..1022 FT /evidence="ECO:0007829|PDB:7WGR" SQ SEQUENCE 1023 AA; 115935 MW; F428DD342F232E7C CRC64; MFHLRTCAAK LRPLTASQTV KTFSQNRPAA ARTFQQIRCY SAPVAAEPFL SGTSSNYVEE MYCAWLENPK SVHKSWDIFF RNTNAGAPPG TAYQSPLPLS RGSLAAVAHA QSLVEAQPNV DKLVEDHLAV QSLIRAYQIR GHHVAQLDPL GILDADLDSS VPADIISSTD KLGFYGLDES DLDKVFHLPT TTFIGGQESA LPLREIIRRL EMAYCQHIGV EFMFINDLEQ CQWIRQKFET PGIMQFTNEE KRTLLARLVR STRFEEFLQR KWSSEKRFGL EGCEVLIPAL KTIIDKSSEN GVDYVIMGMP HRGRLNVLAN VIRKELEQIF CQFDSKLEAA DEGSGDVKYH LGMYHRRINR VTDRNITLSL VANPSHLEAA DPVVMGKTKA EQFYCGDTEG KKVMSILLHG DAAFAGQGIV YETFHLSDLP SYTTHGTVHV VVNNQIGFTT DPRMARSSPY PTDVARVVNA PIFHVNSDDP EAVMYVCKVA AEWRSTFHKD VVVDLVCYRR NGHNEMDEPM FTQPLMYKQI RKQKPVLQKY AELLVSQGVV NQPEYEEEIS KYDKICEEAF ARSKDEKILH IKHWLDSPWP GFFTLDGQPR SMSCPSTGLT EDILTHIGNV ASSVPVENFT IHGGLSRILK TRGEMVKNRT VDWALAEYMA FGSLLKEGIH IRLSGQDVER GTFSHRHHVL HDQNVDKRTC IPMNHLWPNQ APYTVCNSSL SEYGVLGFEL GFAMASPNAL VLWEAQFGDF HNTAQCIIDQ FICPGQAKWV RQNGIVLLLP HGMEGMGPEH SSARPERFLQ MCNDDPDVLP DLKEANFDIN QLYDCNWVVV NCSTPGNFFH VLRRQILLPF RKPLIIFTPK SLLRHPEARS SFDEMLPGTH FQRVIPEDGP AAQNPENVKR LLFCTGKVYY DLTRERKARD MVGQVAITRI EQLSPFPFDL LLKEVQKYPN AELAWCQEEH KNQGYYDYVK PRLRTTISRA KPVWYAGRDP AAAPATGNKK THLTELQRLL DTAFDLDVFK NFS //