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
//
