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   03-AUG-2022, entry version 76.
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; 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=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue
CC         succinyltransferase] + 2-oxoglutarate + H(+) = (R)-N(6)-(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   -!- 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   -!- 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.XP_005549729.1; -.
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: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   Gene3D; 3.40.50.11610; -; 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   PANTHER; PTHR23152; PTHR23152; 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; SSF52518; 2.
DR   TIGRFAMs; TIGR00239; 2oxo_dh_E1; 1.
PE   2: Evidence at transcript 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_0000020433"
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;  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