ID   ODO1_XENLA              Reviewed;        1021 AA.
AC   Q6P6Z8; Q6GP46;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 87.
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: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;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo, and Spleen;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   TISSUE SPECIFICITY.
RX   PubMed=16901643; DOI=10.1016/j.neulet.2006.07.008;
RA   Sadakata T., Furuichi T.;
RT   "Identification and mRNA expression of Ogdh, QP-C, and two predicted genes
RT   in the postnatal mouse brain.";
RL   Neurosci. Lett. 405:217-222(2006).
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) 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. {ECO:0000250|UniProtKB:Q02218}.
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   -!- TISSUE SPECIFICITY: Expressed in the brain.
CC       {ECO:0000269|PubMed:16901643}.
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; BC061938; AAH61938.1; -; mRNA.
DR   EMBL; BC073298; AAH73298.1; -; mRNA.
DR   RefSeq; NP_001083614.1; NM_001090145.1.
DR   RefSeq; XP_018109665.1; XM_018254176.1.
DR   RefSeq; XP_018109666.1; XM_018254177.1.
DR   AlphaFoldDB; Q6P6Z8; -.
DR   SMR; Q6P6Z8; -.
DR   DNASU; 399021; -.
DR   GeneID; 399021; -.
DR   KEGG; xla:399021; -.
DR   AGR; Xenbase:XB-GENE-1010765; -.
DR   CTD; 399021; -.
DR   Xenbase; XB-GENE-1010765; ogdh.S.
DR   OrthoDB; 3597773at2759; -.
DR   SABIO-RK; Q6P6Z8; -.
DR   Proteomes; UP000186698; Chromosome 3S.
DR   Bgee; 399021; Expressed in egg cell and 19 other cell types or tissues.
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: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:0006096; P:glycolytic process; IEA:UniProtKB-KW.
DR   GO; GO:0106077; P:histone succinylation; ISS:UniProtKB.
DR   GO; GO:0006104; P:succinyl-CoA metabolic process; ISS:UniProtKB.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:InterPro.
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   2: Evidence at transcript level;
KW   Calcium; Glycolysis; Isopeptide bond; Metal-binding; Mitochondrion;
KW   Nucleus; Oxidoreductase; Reference proteome; Thiamine pyrophosphate;
KW   Transit peptide; Ubl conjugation.
FT   TRANSIT         1..40
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           41..1021
FT                   /note="2-oxoglutarate dehydrogenase complex component E1"
FT                   /id="PRO_0000310982"
FT   BINDING         153
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q02218"
FT   BINDING         155
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q02218"
FT   BINDING         157
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q02218"
FT   BINDING         178
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q02218"
FT   BINDING         180
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q02218"
FT   BINDING         182
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q02218"
FT   CROSSLNK        533
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        115
FT                   /note="S -> A (in Ref. 1; AAH73298)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1021 AA;  115633 MW;  1ED25C4DD47277DB CRC64;
     MFNLRTCASK LRPLTASQTI RSLKHNRPAA PRTFQQFRCL STPVAAEPFL SGTNSNYVEE
     MYYAWLENPK SVHKSWDIFF RNANAGASPG AAYQSPPSLG SSLSTLTQAQ SLLHSQPNVD
     KLVEDHLAVQ SLIRAYQIRG HHVAQLDPLG ILDADLDSCV PADIVTSSDK LGFYGLQESD
     LDKVFHLPTT TFIGGNEMAL PLREIIRRLE NAYCQHIGVE FMFINDLEQC QWIRQKFEAP
     GIMQFNNEEK RTLLARLVRS TRFEEFLHRK WSSEKRFGLE GCEVLIPALK TIIDKSSGNG
     VDYVIMGMPH RGRLNVLANV IRKELEQIFC QFDSKLEATD EGSGDVKYHL GMYHRRINRV
     TDRNITLSLV ANPSHLEAAD PVVQGKTKAE QFYCGDTEGK KVMAILLHGD AAFAGQGIVY
     ETFHLSDLPS HTTHGTVHVV VNNQIGFTTD PRMARSSPYP TDVARVVNAP IFHVNADDPE
     AVMYVCNVAA EWRSTFHKDV VVDLVCYRRN GHNEMDEPMF TQPLMYKQIR KQKAVLQKYA
     ETLISQGVVN QLEYEEEISK YDKICEEAFA RSKDEKILHI KHWLDSPWPG FFTLDGQPRS
     MTCPSTGLTE EDLTHIGNVA SSVPVEDFMI HGGLSRILKG RGEMVKNRTV DWALAEYMAL
     GSLLKEGIHI RLSGQDVERG TFSHRHHVLH DQNVDKRTCI PMNHLWPNQA PYTVCNSSLS
     EYGVLGFELG FAMASPNALV LWEAQFGDFH NTAQCIIDQF VCPGQAKWVR QNGIVLLLPH
     GMEGMGPEHS SARPERFLQM CNDDPDVWPK ASEDFAVGQL YDCNWIVVNC STPANFFHVI
     RRQILLPFRK PLIVFTPKSL LRHPEARSSF DDMLPSTHFQ RIIPEAGPAS QNPEGVKRLI
     FCTGKVYYEL TKERSGRDME GDVAIARVEQ LSPFPFDLVE KEVQKYPNAD LVWCQEEHKN
     QGYYDYVKPR LRTTIHRTKP VWYAGRDPAA APATGNKKTH LTELRRFLDT AFNLDAFKGH
     F
//