ODO1_HUMAN
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 03-AUG-2022, entry version 216.
DE RecName: Full=2-oxoglutarate dehydrogenase complex component E1;
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 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).
RN [16]
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).
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=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase] + 2-oxoglutarate + H(+) = (R)-N(6)-(S(8)-
CC succinyldihydrolipoyl)-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase] + CO2; Xref=Rhea:RHEA:12188, Rhea:RHEA-
CC COMP:10483, Rhea:RHEA-COMP:10484, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:83099,
CC ChEBI:CHEBI:83120; EC=1.2.4.2; Evidence={ECO:0000269|PubMed:24495017,
CC ECO:0000269|PubMed:25210035, ECO:0000269|PubMed:28435050,
CC 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) and DLD (dihydrolipoamide dehydrogenase; E3).
CC It contains multiple copies of the three enzymatic components (E1, E2
CC and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex
CC associates with KAT2A (PubMed:29211711). {ECO:0000269|PubMed:29211711}.
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";
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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 PDBsum; 3ERY; -.
DR AlphaFoldDB; Q02218; -.
DR SMR; Q02218; -.
DR BioGRID; 111017; 211.
DR CORUM; Q02218; -.
DR DIP; DIP-39353N; -.
DR IntAct; Q02218; 36.
DR MINT; Q02218; -.
DR STRING; 9606.ENSP00000222673; -.
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; Q02218; -.
DR PeptideAtlas; Q02218; -.
DR PRIDE; Q02218; -.
DR ProteomicsDB; 58058; -. [Q02218-1]
DR ProteomicsDB; 58059; -. [Q02218-2]
DR ProteomicsDB; 58060; -. [Q02218-3]
DR Antibodypedia; 13451; 241 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 CTD; 4967; -.
DR DisGeNET; 4967; -.
DR GeneCards; OGDH; -.
DR HGNC; HGNC:8124; OGDH.
DR HPA; ENSG00000105953; Tissue enhanced (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 PhylomeDB; Q02218; -.
DR TreeFam; TF300695; -.
DR BioCyc; MetaCyc:HS02832-MON; -.
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; 369 hits in 1080 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 184 other tissues.
DR ExpressionAtlas; Q02218; baseline and differential.
DR Genevisible; Q02218; HS.
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:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045252; C:oxoglutarate dehydrogenase complex; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IEA:Ensembl.
DR GO; GO:0031072; F:heat shock protein binding; IEA:Ensembl.
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:0006734; P:NADH metabolic process; IEA:Ensembl.
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 Gene3D; 3.40.50.11610; -; 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 PANTHER; PTHR23152; PTHR23152; 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; SSF52518; 2.
DR TIGRFAMs; TIGR00239; 2oxo_dh_E1; 1.
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"
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
