ID   DHTK1_MOUSE             Reviewed;         921 AA.
AC   A2ATU0; Q0VFY3; Q69ZE3; Q8BWT3;
DT   23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   20-FEB-2007, sequence version 1.
DT   27-MAR-2024, entry version 114.
DE   RecName: Full=2-oxoadipate dehydrogenase complex component E1;
DE            Short=E1a {ECO:0000250|UniProtKB:Q96HY7};
DE            Short=OADC-E1;
DE            Short=OADH-E1;
DE            EC=1.2.4.- {ECO:0000250|UniProtKB:Q96HY7};
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 330-587.
RC   TISSUE=Brain;
RX   PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA   Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA   Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT   The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT   identified by screening of terminal sequences of cDNA clones randomly
RT   sampled from size-fractionated libraries.";
RL   DNA Res. 11:205-218(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 525-921.
RC   STRAIN=C57BL/6J; TISSUE=Liver;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Kidney, Liver, Pancreas, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-184; LYS-189; LYS-801 AND
RP   LYS-819, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: 2-oxoadipate dehydrogenase (E1a) component of the 2-
CC       oxoadipate dehydrogenase complex (OADHC). Participates in the first
CC       step, rate limiting for the overall conversion of 2-oxoadipate (alpha-
CC       ketoadipate) to glutaryl-CoA and CO(2) catalyzed by the whole OADHC.
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). Can catalyze the decarboxylation
CC       of 2-oxoglutarate in vitro, but at a much lower rate than 2-oxoadipate.
CC       Responsible for the last step of L-lysine, L-hydroxylysine and L-
CC       tryptophan catabolism with the common product being 2-oxoadipate.
CC       {ECO:0000250|UniProtKB:Q96HY7}.
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:0000250|UniProtKB:Q96HY7};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69577;
CC         Evidence={ECO:0000250|UniProtKB:Q96HY7};
CC   -!- COFACTOR:
CC       Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC         Evidence={ECO:0000250|UniProtKB:Q96HY7};
CC   -!- PATHWAY: Amino-acid degradation. {ECO:0000250|UniProtKB:Q96HY7}.
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. {ECO:0000250|UniProtKB:Q96HY7}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q96HY7}.
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:0000250|UniProtKB:Q96HY7}.
CC   -!- SIMILARITY: Belongs to the alpha-ketoglutarate dehydrogenase family.
CC       {ECO:0000250|UniProtKB:Q96HY7}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAD32501.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR   EMBL; AL928924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC117994; AAI17995.1; -; mRNA.
DR   EMBL; AK173223; BAD32501.1; ALT_SEQ; mRNA.
DR   EMBL; AK050057; BAC34055.1; -; mRNA.
DR   CCDS; CCDS38040.1; -.
DR   RefSeq; NP_001074600.1; NM_001081131.2.
DR   AlphaFoldDB; A2ATU0; -.
DR   SMR; A2ATU0; -.
DR   BioGRID; 229102; 1.
DR   STRING; 10090.ENSMUSP00000092769; -.
DR   iPTMnet; A2ATU0; -.
DR   PhosphoSitePlus; A2ATU0; -.
DR   SwissPalm; A2ATU0; -.
DR   jPOST; A2ATU0; -.
DR   MaxQB; A2ATU0; -.
DR   PaxDb; 10090-ENSMUSP00000092769; -.
DR   PeptideAtlas; A2ATU0; -.
DR   ProteomicsDB; 277452; -.
DR   Pumba; A2ATU0; -.
DR   Antibodypedia; 24629; 156 antibodies from 23 providers.
DR   Ensembl; ENSMUST00000095147.9; ENSMUSP00000092769.3; ENSMUSG00000025815.15.
DR   GeneID; 209692; -.
DR   KEGG; mmu:209692; -.
DR   UCSC; uc008iga.1; mouse.
DR   AGR; MGI:2445096; -.
DR   CTD; 55526; -.
DR   MGI; MGI:2445096; Dhtkd1.
DR   VEuPathDB; HostDB:ENSMUSG00000025815; -.
DR   eggNOG; KOG0451; Eukaryota.
DR   GeneTree; ENSGT00950000183125; -.
DR   HOGENOM; CLU_004709_0_0_1; -.
DR   InParanoid; A2ATU0; -.
DR   OMA; TPAQYYH; -.
DR   OrthoDB; 3597773at2759; -.
DR   PhylomeDB; A2ATU0; -.
DR   TreeFam; TF314198; -.
DR   Reactome; R-MMU-389661; Glyoxylate metabolism and glycine degradation.
DR   BioGRID-ORCS; 209692; 1 hit in 76 CRISPR screens.
DR   ChiTaRS; Dhtkd1; mouse.
DR   PRO; PR:A2ATU0; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; A2ATU0; Protein.
DR   Bgee; ENSMUSG00000025815; Expressed in animal zygote and 171 other cell types or tissues.
DR   GO; GO:0005739; C:mitochondrion; ISS: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; ISS:UniProtKB.
DR   GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-KW.
DR   GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI.
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.
DR   Genevisible; A2ATU0; MM.
PE   1: Evidence at protein level;
KW   Glycolysis; Mitochondrion; Oxidoreductase; Reference proteome;
KW   Thiamine pyrophosphate; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..921
FT                   /note="2-oxoadipate dehydrogenase complex component E1"
FT                   /id="PRO_0000307937"
FT   REGION          300..319
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         184
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         189
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         801
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         819
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   CONFLICT        24
FT                   /note="G -> S (in Ref. 2; AAI17995)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        436
FT                   /note="H -> R (in Ref. 2; AAI17995)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   921 AA;  102793 MW;  E40170D7D26EED65 CRC64;
     MASAATVAAA GRALRRAVLL LRRGYQTERG VYGYRPRKAK SGEPRGDRAR PSVDHGLARL
     VTVYCEHGHK AAQINPLFPG QALLDTVPEI QALVRTLQGP FTTTGLLNLG KEAASLEEVL
     AYLNHIYCGP ISIETAQLQS QEERDWFARR FEELKKETFT TEERKYLSKL LLESQEFDHF
     LATKFATVKR YGGEGAESMM GFFHELLKLS AYGGITDIII GMPHRGRLNL LTGLLQLPPE
     LMFRKMRGLS EFPENVATIG DVLSHLTSSV DLDFGAHQPL HVTMLPNPSH LEAVNPVAVG
     KTRGRQQSRE DGDYSPNGSA QPGDKVICLQ VHGDASFCGQ GIVLETFTLS NLPHFRIGGS
     IHLIVNNQLG YTTPAERGRS SLYSSDIGKL VGCAIIHVNG DSPEEVVRAT RLAFEYQRQF
     RKDVIVDLLC YRQWGHNELD EPFFTNPVMY KIIRARKSIP DTYAEHLIAS GLMTQEEVSD
     IKTSYYTKLN DHLANVAHYS PPATNLQARW QGLVQPEACV TTWDTGVPLE LLRFIGVKSV
     EVPEELQVHS HLLKMYVQSR MEKVKNGSGL DWATAETLAL GSLLAQGFNV RLSGQDVGRG
     TFSQRHAMVV CQDTDDAYIP LNHMDPNQKG FLEVSNSPLS EEAVLGFEYG MSIESPTLLP
     LWEAQFGDFF NGAQIIFDTF ISGGEAKWLL QSGLVILLPH GYDGAGPEHS SCRIERFLQM
     CDSAEEGVDS DTVNMFVVHP TTPAQYFHLL RRQMIRNFRK PLIVASPKML LRYPAAVSTL
     EEMAPGTAFK PVIGDSSVDP KNVKTLIFCS GKHFYALLKQ RESLGTKKHD FAIIRLEELC
     PFPLDALQQE MSKYKHVRDV IWSQEEPQNM GPWSFVSPRF EKQLACRLRL VSRPPLPAPA
     VGIGTVHQQQ HEDILSKTFT Q
//