DHTK1_MOUSE
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 03-AUG-2022, entry version 106.
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=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase] + 2-oxoadipate + H(+) = (R)-N6-(S8-
CC glutaryldihydrolipoyl)-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase] + CO2; Xref=Rhea:RHEA:69576, Rhea:RHEA-
CC COMP:10483, Rhea:RHEA-COMP:17726, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57499, ChEBI:CHEBI:83099,
CC ChEBI:CHEBI:184385; 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; A2ATU0; -.
DR PeptideAtlas; A2ATU0; -.
DR PRIDE; A2ATU0; -.
DR ProteomicsDB; 277452; -.
DR Antibodypedia; 24629; 132 antibodies from 22 providers.
DR Ensembl; ENSMUST00000026924; ENSMUSP00000026924; ENSMUSG00000025815.
DR Ensembl; ENSMUST00000095147; ENSMUSP00000092769; ENSMUSG00000025815.
DR GeneID; 209692; -.
DR KEGG; mmu:209692; -.
DR UCSC; uc008iga.1; mouse.
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; GMAIDNP; -.
DR OrthoDB; 134699at2759; -.
DR PhylomeDB; A2ATU0; -.
DR TreeFam; TF314198; -.
DR Reactome; R-MMU-389661; Glyoxylate metabolism and glycine degradation.
DR BioGRID-ORCS; 209692; 1 hit in 71 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 168 other tissues.
DR Genevisible; A2ATU0; MM.
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 Gene3D; 3.40.50.11610; -; 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 PANTHER; PTHR23152; PTHR23152; 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 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
