ID ODO1_MACFA Reviewed; 1023 AA.
AC Q60HE2;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 27-NOV-2024, entry version 84.
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}; ORFNames=QccE-15394;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
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=N(6)-[(R)-lipoyl]-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase] + 2-oxoglutarate + H(+) = N(6)-[(R)-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;
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 Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
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: Homodimer (By similarity). The 2-oxoglutarate dehydrogenase
CC complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST
CC (dihydrolipoamide succinyltransferase; E2), DLD (dihydrolipoamide
CC dehydrogenase; E3) and the assembly factor KGD4 (By similarity). It
CC contains multiple copies of the three enzymatic components (E1, E2 and
CC E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex
CC associates with KAT2A. Interacts with ABHD11; this interaction
CC maintains the functional lipoylation of the 2-oxoglutarate
CC dehydrogenase complex (By similarity). {ECO:0000250|UniProtKB:Q02218,
CC ECO:0000250|UniProtKB:Q148N0}.
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; AB125185; BAD51973.1; -; mRNA.
DR AlphaFoldDB; Q60HE2; -.
DR SMR; Q60HE2; -.
DR STRING; 9541.ENSMFAP00000029899; -.
DR eggNOG; KOG0450; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProt.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
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:0006091; P:generation of precursor metabolites and energy; ISS:UniProtKB.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-KW.
DR GO; GO:0006104; P:succinyl-CoA metabolic process; ISS:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:TreeGrafter.
DR CDD; cd02016; TPP_E1_OGDC_like; 1.
DR FunFam; 3.40.50.12470:FF:000007; 2-oxoglutarate dehydrogenase e1 mitochondrial; 1.
DR FunFam; 3.40.50.970:FF:000002; 2-oxoglutarate dehydrogenase, E1 component; 1.
DR FunFam; 1.10.287.1150:FF:000001; 2-oxoglutarate dehydrogenase, mitochondrial isoform X1; 1.
DR FunFam; 3.40.50.11610:FF:000008; 2-oxoglutarate dehydrogenase, mitochondrial isoform X4; 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; IPR042179; KGD_C_sf.
DR InterPro; IPR031717; ODO-1/KGD_C.
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 Acetylation; Calcium; Glycolysis; Isopeptide bond; Magnesium;
KW Metal-binding; Mitochondrion; Nucleus; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Thiamine pyrophosphate; Transit peptide;
KW 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_0000020433"
FT BINDING 143
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 156
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 158
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 312
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 411
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 411
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 444
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 444
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 446
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 446
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250|UniProtKB:Q02218"
FT BINDING 676
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
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; 115909 MW; E134B1513A3F4B69 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 QLHDCNWVVV NCSTPGNFFH
VLRRQILLPF RKPLIIFTPK SLLRHPEARS SFDEMLPGTH FQRVIPEDGP AAQNPENVKR
LLFCTGKVYY DLTRERKARD MVGQVAITRI EQLSPFPFDL LLKEVQKYPN AELAWCQEEH
KNQGYYDYVK PRLRTTISRA KPVWYAGRDP AAAPATGNKK THLTELQRLL DTAFDLDVFK
NFS
//
