ID   ODO1_BOVIN              Reviewed;        1023 AA.
AC   Q148N0;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   22-AUG-2006, sequence version 1.
DT   27-MAR-2024, entry version 119.
DE   RecName: Full=2-oxoglutarate dehydrogenase complex component E1 {ECO:0000250|UniProtKB:Q02218};
DE            Short=E1o;
DE            Short=OGDC-E1;
DE            Short=OGDH-E1;
DE            EC=1.2.4.2 {ECO:0000250|UniProtKB:Q02218};
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:0000250|UniProtKB:Q02218};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Uterus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   SUBCELLULAR LOCATION, AND SUBUNIT.
RX   PubMed=36854377; DOI=10.1098/rsob.220363;
RA   Hevler J.F., Albanese P., Cabrera-Orefice A., Potter A., Jankevics A.,
RA   Misic J., Scheltema R.A., Brandt U., Arnold S., Heck A.J.R.;
RT   "MRPS36 provides a structural link in the eukaryotic 2-oxoglutarate
RT   dehydrogenase complex.";
RL   Open Biol. 13:220363-220363(2023).
CC   -!- FUNCTION: 2-oxoglutarate dehydrogenase (E1o) component of the 2-
CC       oxoglutarate dehydrogenase complex (OGDHC). Participates in the first
CC       step, rate limiting for the overall conversion of 2-oxoglutarate to
CC       succinyl-CoA and CO(2) catalyzed by the whole OGDHC. Catalyzes the
CC       irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate)
CC       via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of
CC       the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group
CC       that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-
CC       residue succinyltransferase or DLST). 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. Can
CC       catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much
CC       lower rate than 2-oxoglutarate. Mainly active in the mitochondrion. A
CC       fraction of the 2-oxoglutarate dehydrogenase complex also localizes in
CC       the nucleus and is required for lysine succinylation of histones:
CC       associates with KAT2A on chromatin and provides succinyl-CoA to histone
CC       succinyltransferase KAT2A. {ECO:0000250|UniProtKB:Q02218}.
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:0000250|UniProtKB:Q02218};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12189;
CC         Evidence={ECO:0000250|UniProtKB:Q02218};
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 (PubMed:36854377). 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:0000269|PubMed:36854377}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q5XI78}.
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   -!- 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}.
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DR   EMBL; BC118106; AAI18107.1; -; mRNA.
DR   RefSeq; NP_001069498.1; NM_001076030.1.
DR   RefSeq; XP_005205655.1; XM_005205598.3.
DR   AlphaFoldDB; Q148N0; -.
DR   SMR; Q148N0; -.
DR   IntAct; Q148N0; 1.
DR   STRING; 9913.ENSBTAP00000072974; -.
DR   PaxDb; 9913-ENSBTAP00000007922; -.
DR   PeptideAtlas; Q148N0; -.
DR   Ensembl; ENSBTAT00000007922.4; ENSBTAP00000007922.3; ENSBTAG00000006029.4.
DR   GeneID; 534599; -.
DR   KEGG; bta:534599; -.
DR   CTD; 4967; -.
DR   VEuPathDB; HostDB:ENSBTAG00000006029; -.
DR   VGNC; VGNC:32406; OGDH.
DR   eggNOG; KOG0450; Eukaryota.
DR   GeneTree; ENSGT00950000183125; -.
DR   HOGENOM; CLU_004709_1_1_1; -.
DR   InParanoid; Q148N0; -.
DR   OrthoDB; 3597773at2759; -.
DR   TreeFam; TF300695; -.
DR   Reactome; R-BTA-389661; Glyoxylate metabolism and glycine degradation.
DR   Reactome; R-BTA-71064; Lysine catabolism.
DR   Reactome; R-BTA-71403; Citric acid cycle (TCA cycle).
DR   Proteomes; UP000009136; Chromosome 4.
DR   Bgee; ENSBTAG00000006029; Expressed in corpus luteum and 105 other cell types or tissues.
DR   ExpressionAtlas; Q148N0; baseline and differential.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0045252; C:oxoglutarate dehydrogenase complex; ISS: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; ISS:UniProtKB.
DR   GO; GO:0030976; F:thiamine pyrophosphate binding; ISS:UniProtKB.
DR   GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR   GO; GO:0021695; P:cerebellar cortex development; IEA:Ensembl.
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; ISS: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; ISS: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.
PE   1: Evidence at protein level;
KW   Acetylation; Calcium; Glycolysis; Isopeptide bond; Metal-binding;
KW   Mitochondrion; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW   Thiamine pyrophosphate; 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_0000310981"
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;  115808 MW;  46C5D3161D41F551 CRC64;
     MFHLRTCAAK LRPLTASQTV KTFSQNRPAA ARTFGQIRCY TAPVAAEPFL SGTSSNYVEE
     MYYAWLENPK SVHKSWDIFF RNTNAGAPPG TAYQSPLPLS PGSLSAVARA GPLVEAQPNV
     DKLVEDHLAV QSLIRAYQIR GHHVAQLDPL GILDADLDSS VPADIISSTD KLGFYGLDES
     DLDKVFHLPT TTFIGGQESA LPLREIIRRL EMAYCQHIGV EFMFINDLEQ CQWIRQKFET
     PGVMQFTNEE 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
     SMTCPSTGLT EDILTHIGNV ASSVPVEDFT IHGGLSRILK TRGELVKNRT VDWALAEYMA
     FGSLLKEGIH IRLSGQDVER GTFSHRHHVL HDQNVDKRTC IPMNHLWPNQ APYTVCNSSL
     SEYGVLGFEL GFAMASPNAL VLWEAQFGDF HNTAQCIIDQ FICPGQAKWV RQNGIVLLLP
     HGMEGMGPEH SSARPERFLQ MCNDDPDVLP DLKEANFDIN QLYDCNWVVV NCSTPGNFFH
     VLRRQILLPF RKPLIIFTPK SLLRHPEARS NFDEMLPGTH FQRVIPEDGP AAQNPGNVKR
     LLFCTGKVYY DLTRERKARD MVEQVAITRI EQLSPFPFDL LLQEVQKYPS AELAWCQEEH
     KNQGYYDYVK PRLRTTISRA KPVWYAGRDP AAAPATGNKK THLTELQRLL DTAFDLDAFK
     NFS
//