ID ODO1_RAT Reviewed; 1023 AA. AC Q5XI78; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 1. DT 27-MAR-2024, entry version 133. DE RecName: Full=2-oxoglutarate dehydrogenase complex component E1 {ECO:0000305}; DE Short=E1o {ECO:0000303|PubMed:18783430}; DE Short=OGDC-E1; DE Short=OGDH-E1 {ECO:0000303|PubMed:18783430}; DE EC=1.2.4.2 {ECO:0000305|PubMed:18783430}; 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 {ECO:0000303|PubMed:18783430}; DE Flags: Precursor; GN Name=Ogdh {ECO:0000312|RGD:1561359}; Synonyms=Ogdhl; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; 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 [2] RP PROTEIN SEQUENCE OF 82-101; 123-135; 172-184 AND 583-600, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord; RA Lubec G., Afjehi-Sadat L.; RL Submitted (DEC-2006) to UniProtKB. RN [3] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=18783430; DOI=10.1111/j.1742-4658.2008.06632.x; RA Bunik V., Kaehne T., Degtyarev D., Shcherbakova T., Reiser G.; RT "Novel isoenzyme of 2-oxoglutarate dehydrogenase is identified in brain, RT but not in heart."; RL FEBS J. 275:4990-5006(2008). CC -!- FUNCTION: 2-oxoglutarate dehydrogenase (E1o) component of the 2- CC oxoglutarate dehydrogenase complex (OGDHC) (PubMed:18783430). CC Participates in the first step, rate limiting for the overall CC conversion of 2-oxoglutarate to succinyl-CoA and CO(2) catalyzed by the CC whole OGDHC (Probable). Catalyzes the irreversible decarboxylation of CC 2-oxoglutarate (alpha-ketoglutarate) via the thiamine diphosphate CC (ThDP) cofactor and subsequent transfer of the decarboxylated acyl CC intermediate on an oxidized dihydrolipoyl group that is covalently CC amidated to the E2 enzyme (dihydrolipoyllysine-residue CC succinyltransferase or DLST) (Probable). Plays a key role in the Krebs CC (citric acid) cycle, which is a common pathway for oxidation of fuel CC molecules, including carbohydrates, fatty acids, and amino acids (By CC similarity). Can catalyze the decarboxylation of 2-oxoadipate in vitro, CC but at a much lower rate than 2-oxoglutarate (By similarity). Mainly CC active in the mitochondrion. 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 (By CC similarity). {ECO:0000250|UniProtKB:Q02218, CC ECO:0000269|PubMed:18783430, ECO:0000305|PubMed:18783430}. 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:0000305|PubMed:18783430}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12189; CC Evidence={ECO:0000305|PubMed:18783430}; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000250|UniProtKB:Q02218}; CC -!- ACTIVITY REGULATION: Calcium ions and ADP stimulate, whereas ATP and CC NADH reduce catalytic activity. {ECO:0000250|UniProtKB:Q02218}. 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. Interacts CC with ABHD11; this interaction maintains the functional lipoylation of CC the 2-oxoglutarate dehydrogenase complex (By similarity). CC {ECO:0000250|UniProtKB:Q02218, ECO:0000250|UniProtKB:Q148N0}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:18783430}. CC Nucleus {ECO:0000250|UniProtKB:Q02218}. 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:0000250|UniProtKB:Q02218}. CC -!- TISSUE SPECIFICITY: The OGDH-containing OGDHC complex is present in the CC brain and in the heart. {ECO:0000269|PubMed:18783430}. 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 --------------------------------------------------------------------------- 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; BC083811; AAH83811.1; -; mRNA. DR RefSeq; NP_001017461.1; NM_001017461.1. DR RefSeq; XP_006251508.1; XM_006251446.3. DR RefSeq; XP_006251509.1; XM_006251447.2. DR RefSeq; XP_017460322.1; XM_017604833.1. DR RefSeq; XP_017460323.1; XM_017604834.1. DR AlphaFoldDB; Q5XI78; -. DR SMR; Q5XI78; -. DR BioGRID; 262341; 2. DR IntAct; Q5XI78; 1. DR STRING; 10116.ENSRNOP00000068674; -. DR GlyGen; Q5XI78; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q5XI78; -. DR PhosphoSitePlus; Q5XI78; -. DR jPOST; Q5XI78; -. DR PaxDb; 10116-ENSRNOP00000054026; -. DR Ensembl; ENSRNOT00000057199.5; ENSRNOP00000054026.2; ENSRNOG00000005130.8. DR GeneID; 360975; -. DR KEGG; rno:360975; -. DR AGR; RGD:1561359; -. DR CTD; 4967; -. DR RGD; 1561359; Ogdh. DR eggNOG; KOG0450; Eukaryota. DR GeneTree; ENSGT00950000183125; -. DR InParanoid; Q5XI78; -. DR OrthoDB; 3597773at2759; -. DR PhylomeDB; Q5XI78; -. DR Reactome; R-RNO-389661; Glyoxylate metabolism and glycine degradation. DR Reactome; R-RNO-71064; Lysine catabolism. DR Reactome; R-RNO-71403; Citric acid cycle (TCA cycle). DR SABIO-RK; Q5XI78; -. DR PRO; PR:Q5XI78; -. DR Proteomes; UP000002494; Chromosome 14. DR Bgee; ENSRNOG00000005130; Expressed in skeletal muscle tissue and 18 other cell types or tissues. DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0045252; C:oxoglutarate dehydrogenase complex; IDA:RGD. DR GO; GO:0031072; F:heat shock protein binding; IPI:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0034602; F:oxoglutarate dehydrogenase (NAD+) activity; ISO:RGD. DR GO; GO:0004591; F:oxoglutarate dehydrogenase (succinyl-transferring) activity; IDA:RGD. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:RGD. DR GO; GO:0030976; F:thiamine pyrophosphate binding; ISS:UniProtKB. DR GO; GO:0006103; P:2-oxoglutarate metabolic process; IDA:RGD. DR GO; GO:0021695; P:cerebellar cortex development; ISO:RGD. 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; ISO:RGD. DR GO; GO:0106077; P:histone succinylation; ISS:UniProtKB. DR GO; GO:0006734; P:NADH metabolic process; IDA:RGD. DR GO; GO:0061034; P:olfactory bulb mitral cell layer development; ISO:RGD. DR GO; GO:0021860; P:pyramidal neuron development; ISO:RGD. DR GO; GO:0021756; P:striatum development; ISO:RGD. DR GO; GO:0006104; P:succinyl-CoA metabolic process; IDA:RGD. DR GO; GO:0022028; P:tangential migration from the subventricular zone to the olfactory bulb; ISO:RGD. DR GO; GO:0021794; P:thalamus development; ISO:RGD. DR GO; GO:0006099; P:tricarboxylic acid cycle; IDA:RGD. 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 World-2DPAGE; 0004:Q5XI78; -. PE 1: Evidence at protein level; KW Acetylation; Calcium; Direct protein sequencing; 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_0000271367" FT BINDING 154 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q02218" FT BINDING 156 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q02218" FT BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q02218" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02218" FT BINDING 181 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02218" FT BINDING 183 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02218" 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:0000250|UniProtKB:Q02218" FT CROSSLNK 534 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q02218" SQ SEQUENCE 1023 AA; 116296 MW; B258886383FBD98C CRC64; MFHLRTCAAK LRPLTASQTV KTFSQNKPAA IRTFQQIRCY SAPVAAEPFL SGTSSNYVEE MYCAWLENPK SVHKSWDIFF RNTNAGAPPG TAYQSPLSLS RSSLATMAHA QSLVEAQPNV DKLVEDHLAV QSLIRAYQIR GHHVAQLDPL GILDADLDSS VPADIISSTD KLGFYGLHES DLDKVFHLPT TTFIGGQEPA LPLREIIRRL EMAYCQHIGV EFMFINDLEQ CQWIRQKFET PGIMQFTNEE KRTLLARLVR STRFEEFLQR KWSSEKRFGL EGCEVLIPAL KTIIDMSSAN GVDYVIMGMP HRGRLNVLAN VIRKELEQIF CQFDSKLEAA DEGSGDMKYH LGMYHRRINR VTDRNITLSL VANPSHLEAA DPVVMGKTKA EQFYCGDTEG KKVMSILLHG DAAFAGQGIV YETFHLSDLP SYTTHGTVHV VVNNQIGFTT DPRMARSSPY PTDVARVVNA PIFHVNSDDP EAVMYVCKVA AEWRNTFHKD VVVDLVCYRR NGHNEMDEPM FTQPLMYKQI RKQKPVLQKY AELLVSQGVV NQPEYEEEIS KYDKICEEAF TRSKDEKILH IKHWLDSPWP GFFTLDGQPR SMTCPSTGLE EDILTHIGNV ASSVPVENFT IHGGLSRILK TRRELVTNRT VDWALAEYMA FGSLLKEGIH VRLSGQDVER GTFSHRHHVL HDQNVDKRTC IPMNHLWPNQ APYTVCNSSL SEYGVLGFEL GFAMASPNAL VLWEAQFGDF NNMAQCIIDQ FICPGQAKWV RQNGIVLLLP HGMEGMGPEH SSARPERFLQ MCNDDPDVLP NLQEENFDIS QLYDCNWIVV NCSTPGNFFH VLRRQILLPF RKPLIVFTPK SLLRHPEART SFDEMLPGTH FQRVIPEDGP AAQNPDKVKR LLFCTGKVYY DLTRERKARD MAEEVAITRI EQLSPFPFDL LLKEAQKYPN AELAWCQEEH KNQGYYDYVK PRLRTTIDRA KPVWYAGRDP AAAPATGNKK THLTELQRFL DTAFDLDAFK KFS //