ID DHTK1_HUMAN Reviewed; 919 AA.
AC Q96HY7; Q68CU5; Q9BUM8; Q9HCE2;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 27-MAR-2024, entry version 161.
DE RecName: Full=2-oxoadipate dehydrogenase complex component E1;
DE Short=E1a {ECO:0000303|PubMed:29191460, ECO:0000303|PubMed:32695416};
DE Short=OADC-E1;
DE Short=OADH-E1;
DE EC=1.2.4.- {ECO:0000269|PubMed:29752936, ECO:0000269|PubMed:32633484, ECO:0000305|PubMed:29191460, ECO:0000305|PubMed:32695416};
DE AltName: Full=2-oxoadipate dehydrogenase, mitochondrial;
DE AltName: Full=Alpha-ketoadipate dehydrogenase;
DE Short=Alpha-KADH-E1;
DE AltName: Full=Dehydrogenase E1 and transketolase domain-containing protein 1;
DE AltName: Full=Probable 2-oxoglutarate dehydrogenase E1 component DHKTD1, mitochondrial;
DE Flags: Precursor;
GN Name=DHTKD1; Synonyms=KIAA1630;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-20; ASP-272;
RP LEU-308 AND MET-607.
RC TISSUE=Kidney, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-886, AND VARIANTS LEU-20;
RP ASP-272 AND MET-607.
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 380-919, AND VARIANT MET-607.
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP INVOLVEMENT IN CMT2Q, AND SUBCELLULAR LOCATION.
RX PubMed=23141294; DOI=10.1016/j.ajhg.2012.09.018;
RA Xu W.Y., Gu M.M., Sun L.H., Guo W.T., Zhu H.B., Ma J.F., Yuan W.T.,
RA Kuang Y., Ji B.J., Wu X.L., Chen Y., Zhang H.X., Sun F.T., Huang W.,
RA Huang L., Chen S.D., Wang Z.G.;
RT "A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in
RT a large Chinese pedigree.";
RL Am. J. Hum. Genet. 91:1088-1094(2012).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=29191460; DOI=10.1016/j.freeradbiomed.2017.11.018;
RA Nemeria N.S., Gerfen G., Nareddy P.R., Yang L., Zhang X., Szostak M.,
RA Jordan F.;
RT "The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes
RT share their E2 and E3 components for their function and both generate
RT reactive oxygen species.";
RL Free Radic. Biol. Med. 115:136-145(2018).
RN [7]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBUNIT.
RX PubMed=29752936; DOI=10.1016/j.bbabio.2018.05.001;
RA Nemeria N.S., Gerfen G., Yang L., Zhang X., Jordan F.;
RT "Evidence for functional and regulatory cross-talk between the
RT tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex and 2-
RT oxoadipate dehydrogenase on the l-lysine, l-hydroxylysine and l-tryptophan
RT degradation pathways from studies in vitro.";
RL Biochim. Biophys. Acta 1859:932-939(2018).
RN [8]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, VARIANTS AAKAD CYS-715
RP AND ARG-729, AND CHARACTERIZATION OF VARIANT AAKAD ARG-729.
RX PubMed=32303640; DOI=10.1074/jbc.ra120.012761;
RA Zhang X., Nemeria N.S., Leandro J., Houten S., Lazarus M., Gerfen G.,
RA Ozohanics O., Ambrus A., Nagy B., Brukh R., Jordan F.;
RT "Structure-function analyses of the G729R 2-oxoadipate dehydrogenase
RT genetic variant associated with a disorder of l-lysine metabolism.";
RL J. Biol. Chem. 295:8078-8095(2020).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=32633484; DOI=10.1021/acschembio.0c00114;
RA Leandro J., Khamrui S., Wang H., Suebsuwong C., Nemeria N.S., Huynh K.,
RA Moustakim M., Secor C., Wang M., Dodatko T., Stauffer B., Wilson C.G.,
RA Yu C., Arkin M.R., Jordan F., Sanchez R., DeVita R.J., Lazarus M.B.,
RA Houten S.M.;
RT "Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate
RT Complex.";
RL ACS Chem. Biol. 15:2041-2047(2020).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY,
RP COFACTOR, X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 45-919, INTERACTION WITH
RP DLST, AND CHARACTERIZATION OF VARIANTS AAKAD CYS-715 AND LEU-773.
RX PubMed=32695416; DOI=10.1107/s205225252000696x;
RA Bezerra G.A., Foster W.R., Bailey H.J., Hicks K.G., Sauer S.W.,
RA Dimitrov B., McCorvie T.J., Okun J.G., Rutter J., Koelker S., Yue W.W.;
RT "Crystal structure and interaction studies of human DHTKD1 provide insight
RT into a mitochondrial megacomplex in lysine catabolism.";
RL IUCrJ 7:693-706(2020).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP VARIANT AAKAD ARG-729.
RX PubMed=23141293; DOI=10.1016/j.ajhg.2012.10.006;
RA Danhauser K., Sauer S.W., Haack T.B., Wieland T., Staufner C., Graf E.,
RA Zschocke J., Strom T.M., Traub T., Okun J.G., Meitinger T., Hoffmann G.F.,
RA Prokisch H., Koelker S.;
RT "DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria.";
RL Am. J. Hum. Genet. 91:1082-1087(2012).
RN [14]
RP VARIANTS AAKAD GLY-234; 437-GLU--ALA-919 DEL; GLN-455; LEU-773 AND PRO-777.
RX PubMed=25860818; DOI=10.1007/s10545-015-9841-9;
RA Hagen J., te Brinke H., Wanders R.J., Knegt A.C., Oussoren E.,
RA Hoogeboom A.J., Ruijter G.J., Becker D., Schwab K.O., Franke I., Duran M.,
RA Waterham H.R., Sass J.O., Houten S.M.;
RT "Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria.";
RL J. Inherit. Metab. Dis. 38:873-879(2015).
RN [15]
RP VARIANTS AAKAD HIS-305; CYS-715 AND ARG-729.
RX PubMed=26141459; DOI=10.1007/8904_2015_462;
RA Stiles A.R., Venturoni L., Mucci G., Elbalalesy N., Woontner M.,
RA Goodman S., Abdenur J.E.;
RT "New Cases of DHTKD1 Mutations in Patients with 2-Ketoadipic Aciduria.";
RL JIMD Rep. 25:15-19(2016).
CC -!- FUNCTION: 2-oxoadipate dehydrogenase (E1a) component of the 2-
CC oxoadipate dehydrogenase complex (OADHC) (PubMed:29191460,
CC PubMed:29752936, PubMed:32303640, PubMed:32633484, PubMed:32695416).
CC Participates in the first step, rate limiting for the overall
CC conversion of 2-oxoadipate (alpha-ketoadipate) to glutaryl-CoA and
CC CO(2) catalyzed by the whole OADHC (PubMed:29191460, PubMed:32695416).
CC Catalyzes the irreversible decarboxylation of 2-oxoadipate via the
CC thiamine diphosphate (ThDP) cofactor and subsequent transfer of the
CC decarboxylated acyl intermediate on an oxidized dihydrolipoyl group
CC that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-
CC residue succinyltransferase or DLST) (Probable) (PubMed:29752936,
CC PubMed:32303640, PubMed:32633484). Can catalyze the decarboxylation of
CC 2-oxoglutarate in vitro, but at a much lower rate than 2-oxoadipate
CC (PubMed:29191460, PubMed:29752936, PubMed:32633484, PubMed:32695416).
CC Responsible for the last step of L-lysine, L-hydroxylysine and L-
CC tryptophan catabolism with the common product being 2-oxoadipate
CC (Probable). {ECO:0000269|PubMed:29191460, ECO:0000269|PubMed:29752936,
CC ECO:0000269|PubMed:32303640, ECO:0000269|PubMed:32633484,
CC ECO:0000269|PubMed:32695416, ECO:0000305|PubMed:29191460,
CC ECO:0000305|PubMed:29752936, ECO:0000305|PubMed:32303640,
CC ECO:0000305|PubMed:32633484, ECO:0000305|PubMed:32695416}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoadipate + H(+) + N(6)-[(R)-lipoyl]-L-lysyl-
CC [dihydrolipoyllysine-residue succinyltransferase] = CO2 + N(6)-[(R)-
CC S(8)-glutaryldihydrolipoyl]-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase]; Xref=Rhea:RHEA:69576, Rhea:RHEA-COMP:10483,
CC Rhea:RHEA-COMP:17726, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57499, ChEBI:CHEBI:83099, ChEBI:CHEBI:184385;
CC Evidence={ECO:0000269|PubMed:29752936, ECO:0000269|PubMed:32633484,
CC ECO:0000305|PubMed:29191460, ECO:0000305|PubMed:32695416};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69577;
CC Evidence={ECO:0000305|PubMed:29191460, ECO:0000305|PubMed:29752936,
CC ECO:0000305|PubMed:32633484, ECO:0000305|PubMed:32695416};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000269|PubMed:32695416};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.015 mM for 2-oxoadipate {ECO:0000269|PubMed:29191460,
CC ECO:0000269|PubMed:29752936};
CC KM=0.25 mM for 2-oxoglutarate {ECO:0000269|PubMed:29191460};
CC KM=0.2 mM for 2-oxoglutarate {ECO:0000269|PubMed:32695416};
CC KM=0.012 mM for 2-oxoadipate {ECO:0000269|PubMed:32303640};
CC Vmax=14.2 umol/min/mg enzyme using 2-oxoglutarate as substrate
CC {ECO:0000269|PubMed:32695416};
CC -!- PATHWAY: Amino-acid degradation. {ECO:0000305|PubMed:29191460,
CC ECO:0000305|PubMed:29752936, ECO:0000305|PubMed:32303640,
CC ECO:0000305|PubMed:32633484, ECO:0000305|PubMed:32695416}.
CC -!- SUBUNIT: The 2-oxoadipate dehydrogenase complex is composed of OADH (2-
CC oxoadipate dehydrogenase; E1a), DLST (dihydrolipoamide
CC succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3).
CC E1a functional unit is a dimer. Interacts with DLST (PubMed:32695416).
CC {ECO:0000269|PubMed:32695416, ECO:0000305|PubMed:29752936,
CC ECO:0000305|PubMed:32633484}.
CC -!- INTERACTION:
CC Q96HY7; O00327-8: BMAL1; NbExp=3; IntAct=EBI-11022401, EBI-11991546;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:23141294}.
CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2Q (CMT2Q) [MIM:615025]:
CC An axonal form of Charcot-Marie-Tooth disease, a disorder of the
CC peripheral nervous system, characterized by progressive weakness and
CC atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two
CC main groups on the basis of electrophysiologic properties and
CC histopathology: primary peripheral demyelinating neuropathies
CC (designated CMT1 when they are dominantly inherited) and primary
CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group
CC are characterized by signs of axonal degeneration in the absence of
CC obvious myelin alterations, normal or slightly reduced nerve conduction
CC velocities, and progressive distal muscle weakness and atrophy.
CC {ECO:0000269|PubMed:23141294}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Alpha-aminoadipic and alpha-ketoadipic aciduria (AAKAD)
CC [MIM:204750]: An autosomal recessive metabolic disorder characterized
CC by increased levels of 2-oxoadipate and 2-hydroxyadipate in the urine,
CC and elevated 2-aminoadipate in the plasma. Patients can have mild to
CC severe intellectual disability, muscular hypotonia, developmental
CC delay, ataxia, and epilepsy. Most cases are asymptomatic.
CC {ECO:0000269|PubMed:23141293, ECO:0000269|PubMed:25860818,
CC ECO:0000269|PubMed:26141459, ECO:0000269|PubMed:32303640,
CC ECO:0000269|PubMed:32695416}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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, respectively).
CC {ECO:0000303|PubMed:29752936, ECO:0000303|PubMed:32633484,
CC ECO:0000305|PubMed:32303640}.
CC -!- SIMILARITY: Belongs to the alpha-ketoglutarate dehydrogenase family.
CC {ECO:0000305|PubMed:29752936}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13456.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB13456.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. C-terminal exons are derived from the neighboring gene.; Evidence={ECO:0000305};
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DR EMBL; AC073160; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002477; AAH02477.1; -; mRNA.
DR EMBL; BC007955; AAH07955.1; -; mRNA.
DR EMBL; AB046850; BAB13456.1; ALT_SEQ; mRNA.
DR EMBL; CR749726; CAH18489.1; -; mRNA.
DR CCDS; CCDS7087.1; -.
DR PIR; T50617; T50617.
DR RefSeq; NP_061176.3; NM_018706.6.
DR PDB; 5RVW; X-ray; 1.61 A; A/B=45-919.
DR PDB; 5RVX; X-ray; 1.66 A; A/B=45-919.
DR PDB; 5RVY; X-ray; 1.61 A; A/B=45-919.
DR PDB; 5RVZ; X-ray; 1.98 A; A/B=45-919.
DR PDB; 5RW0; X-ray; 1.67 A; A/B=45-919.
DR PDB; 5RW1; X-ray; 1.52 A; A/B=45-919.
DR PDB; 6SY1; X-ray; 1.87 A; A/B=45-919.
DR PDB; 6U3J; X-ray; 2.25 A; A/B=25-919.
DR PDBsum; 5RVW; -.
DR PDBsum; 5RVX; -.
DR PDBsum; 5RVY; -.
DR PDBsum; 5RVZ; -.
DR PDBsum; 5RW0; -.
DR PDBsum; 5RW1; -.
DR PDBsum; 6SY1; -.
DR PDBsum; 6U3J; -.
DR AlphaFoldDB; Q96HY7; -.
DR SMR; Q96HY7; -.
DR BioGRID; 120698; 79.
DR IntAct; Q96HY7; 18.
DR MINT; Q96HY7; -.
DR STRING; 9606.ENSP00000263035; -.
DR iPTMnet; Q96HY7; -.
DR PhosphoSitePlus; Q96HY7; -.
DR SwissPalm; Q96HY7; -.
DR BioMuta; DHTKD1; -.
DR DMDM; 296434477; -.
DR EPD; Q96HY7; -.
DR jPOST; Q96HY7; -.
DR MassIVE; Q96HY7; -.
DR MaxQB; Q96HY7; -.
DR PaxDb; 9606-ENSP00000263035; -.
DR PeptideAtlas; Q96HY7; -.
DR ProteomicsDB; 76796; -.
DR Pumba; Q96HY7; -.
DR ABCD; Q96HY7; 1 sequenced antibody.
DR Antibodypedia; 24629; 156 antibodies from 23 providers.
DR DNASU; 55526; -.
DR Ensembl; ENST00000263035.9; ENSP00000263035.4; ENSG00000181192.12.
DR GeneID; 55526; -.
DR KEGG; hsa:55526; -.
DR MANE-Select; ENST00000263035.9; ENSP00000263035.4; NM_018706.7; NP_061176.4.
DR UCSC; uc001ild.6; human.
DR AGR; HGNC:23537; -.
DR CTD; 55526; -.
DR DisGeNET; 55526; -.
DR GeneCards; DHTKD1; -.
DR GeneReviews; DHTKD1; -.
DR HGNC; HGNC:23537; DHTKD1.
DR HPA; ENSG00000181192; Tissue enhanced (liver).
DR MalaCards; DHTKD1; -.
DR MIM; 204750; phenotype.
DR MIM; 614984; gene.
DR MIM; 615025; phenotype.
DR neXtProt; NX_Q96HY7; -.
DR OpenTargets; ENSG00000181192; -.
DR Orphanet; 79154; 2-aminoadipic 2-oxoadipic aciduria.
DR Orphanet; 329258; Autosomal dominant Charcot-Marie-Tooth disease type 2Q.
DR PharmGKB; PA134962952; -.
DR VEuPathDB; HostDB:ENSG00000181192; -.
DR eggNOG; KOG0451; Eukaryota.
DR GeneTree; ENSGT00950000183125; -.
DR HOGENOM; CLU_004709_0_0_1; -.
DR InParanoid; Q96HY7; -.
DR OMA; TPAQYYH; -.
DR OrthoDB; 3597773at2759; -.
DR PhylomeDB; Q96HY7; -.
DR TreeFam; TF314198; -.
DR BioCyc; MetaCyc:HS11585-MONOMER; -.
DR BRENDA; 1.2.1.105; 2681.
DR PathwayCommons; Q96HY7; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR SignaLink; Q96HY7; -.
DR BioGRID-ORCS; 55526; 9 hits in 1159 CRISPR screens.
DR ChiTaRS; DHTKD1; human.
DR GenomeRNAi; 55526; -.
DR Pharos; Q96HY7; Tbio.
DR PRO; PR:Q96HY7; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96HY7; Protein.
DR Bgee; ENSG00000181192; Expressed in liver and 195 other cell types or tissues.
DR ExpressionAtlas; Q96HY7; baseline and differential.
DR Genevisible; Q96HY7; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004591; F:oxoglutarate dehydrogenase (succinyl-transferring) activity; IEA:UniProtKB-EC.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IEA:InterPro.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; IMP:UniProtKB.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-KW.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
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; 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:SF4; 2-OXOADIPATE DEHYDROGENASE COMPLEX COMPONENT E1; 1.
DR PANTHER; PTHR23152; 2-OXOGLUTARATE DEHYDROGENASE; 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 3D-structure; Charcot-Marie-Tooth disease; Disease variant; Glycolysis;
KW Mitochondrion; Neurodegeneration; Neuropathy; Oxidoreductase;
KW Reference proteome; Thiamine pyrophosphate; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..919
FT /note="2-oxoadipate dehydrogenase complex component E1"
FT /id="PRO_0000307936"
FT REGION 299..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 183
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:A2ATU0"
FT MOD_RES 188
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:A2ATU0"
FT MOD_RES 800
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:A2ATU0"
FT MOD_RES 818
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:A2ATU0"
FT VARIANT 20
FT /note="F -> L (in dbSNP:rs1279138)"
FT /evidence="ECO:0000269|PubMed:10997877,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_036715"
FT VARIANT 234
FT /note="L -> G (in AAKAD; uncertain significance; requires 2
FT nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:25860818"
FT /id="VAR_085786"
FT VARIANT 272
FT /note="Y -> D (in dbSNP:rs3740015)"
FT /evidence="ECO:0000269|PubMed:10997877,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_036716"
FT VARIANT 305
FT /note="Q -> H (in AAKAD; uncertain significance;
FT dbSNP:rs200922071)"
FT /evidence="ECO:0000269|PubMed:26141459"
FT /id="VAR_085787"
FT VARIANT 308
FT /note="R -> L (in dbSNP:rs17849603)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036717"
FT VARIANT 350
FT /note="N -> D (in dbSNP:rs34716552)"
FT /id="VAR_036718"
FT VARIANT 437..919
FT /note="Missing (in AAKAD)"
FT /evidence="ECO:0000269|PubMed:25860818"
FT /id="VAR_085788"
FT VARIANT 455
FT /note="R -> Q (in AAKAD; uncertain significance;
FT dbSNP:rs142068634)"
FT /evidence="ECO:0000269|PubMed:25860818"
FT /id="VAR_085789"
FT VARIANT 607
FT /note="I -> M (in dbSNP:rs2062988)"
FT /evidence="ECO:0000269|PubMed:10997877,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_036719"
FT VARIANT 715
FT /note="R -> C (in AAKAD; decreased interaction with DLST;
FT dbSNP:rs200788729)"
FT /evidence="ECO:0000269|PubMed:26141459,
FT ECO:0000269|PubMed:32303640, ECO:0000269|PubMed:32695416"
FT /id="VAR_085790"
FT VARIANT 729
FT /note="G -> R (in AAKAD; affects the overall activity of
FT OADHC complex; affects assembly with DLST leading to
FT impaired channeling of reaction intermediates;
FT dbSNP:rs117225135)"
FT /evidence="ECO:0000269|PubMed:23141293,
FT ECO:0000269|PubMed:26141459, ECO:0000269|PubMed:32303640"
FT /id="VAR_069585"
FT VARIANT 773
FT /note="P -> L (in AAKAD; uncertain significance; thermally
FT more labile than wild-type protein; dbSNP:rs200355418)"
FT /evidence="ECO:0000269|PubMed:25860818"
FT /id="VAR_085791"
FT VARIANT 777
FT /note="S -> P (in AAKAD; uncertain significance;
FT dbSNP:rs1172299330)"
FT /evidence="ECO:0000269|PubMed:25860818"
FT /id="VAR_085792"
FT HELIX 54..66
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 67..70
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 115..126
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 140..155
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 160..183
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:5RVZ"
FT HELIX 198..212
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 226..232
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 238..245
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 268..283
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 293..307
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 323..332
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 333..338
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 341..348
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 352..354
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 359..365
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 383..390
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 393..398
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 402..419
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 423..428
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 446..454
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 458..468
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 474..493
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 494..496
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 528..537
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:5RVZ"
FT HELIX 549..553
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 555..565
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 567..569
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 571..584
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 588..593
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 594..598
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 606..609
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 611..613
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 619..622
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 631..635
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 641..653
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 657..662
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 666..672
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 673..678
FT /evidence="ECO:0007829|PDB:5RW1"
FT TURN 679..682
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 683..687
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 694..698
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 702..704
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 713..719
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 735..737
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 742..754
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 755..757
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 761..765
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 768..770
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 779..782
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 790..792
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 799..801
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 804..808
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 812..821
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 822..829
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 830..835
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 837..840
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 843..850
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 851..853
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 858..866
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 872..883
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 888..892
FT /evidence="ECO:0007829|PDB:5RW1"
FT STRAND 896..899
FT /evidence="ECO:0007829|PDB:5RW1"
FT HELIX 903..917
FT /evidence="ECO:0007829|PDB:5RW1"
SQ SEQUENCE 919 AA; 103077 MW; CD1E437F919324B6 CRC64;
MASATAAAAR RGLGRALPLF WRGYQTERGV YGYRPRKPES REPQGALERP PVDHGLARLV
TVYCEHGHKA AKINPLFTGQ ALLENVPEIQ ALVQTLQGPF HTAGLLNMGK EEASLEEVLV
YLNQIYCGQI SIETSQLQSQ DEKDWFAKRF EELQKETFTT EERKHLSKLM LESQEFDHFL
ATKFSTVKRY GGEGAESMMG FFHELLKMSA YSGITDVIIG MPHRGRLNLL TGLLQFPPEL
MFRKMRGLSE FPENFSATGD VLSHLTSSVD LYFGAHHPLH VTMLPNPSHL EAVNPVAVGK
TRGRQQSRQD GDYSPDNSAQ PGDRVICLQV HGDASFCGQG IVPETFTLSN LPHFRIGGSV
HLIVNNQLGY TTPAERGRSS LYCSDIGKLV GCAIIHVNGD SPEEVVRATR LAFEYQRQFR
KDVIIDLLCY RQWGHNELDE PFYTNPIMYK IIRARKSIPD TYAEHLIAGG LMTQEEVSEI
KSSYYAKLND HLNNMAHYRP PALNLQAHWQ GLAQPEAQIT TWSTGVPLDL LRFVGMKSVE
VPRELQMHSH LLKTHVQSRM EKMMDGIKLD WATAEALALG SLLAQGFNVR LSGQDVGRGT
FSQRHAIVVC QETDDTYIPL NHMDPNQKGF LEVSNSPLSE EAVLGFEYGM SIESPKLLPL
WEAQFGDFFN GAQIIFDTFI SGGEAKWLLQ SGIVILLPHG YDGAGPDHSS CRIERFLQMC
DSAEEGVDGD TVNMFVVHPT TPAQYFHLLR RQMVRNFRKP LIVASPKMLL RLPAAVSTLQ
EMAPGTTFNP VIGDSSVDPK KVKTLVFCSG KHFYSLVKQR ESLGAKKHDF AIIRVEELCP
FPLDSLQQEM SKYKHVKDHI WSQEEPQNMG PWSFVSPRFE KQLACKLRLV GRPPLPVPAV
GIGTVHLHQH EDILAKTFA
//
