ID   ODPX_HUMAN              Reviewed;         501 AA.
AC   O00330; B4DW62; D3DR11; E9PB14; E9PBP7; O60221; Q96FV8; Q99783;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2001, sequence version 3.
DT   27-MAR-2024, entry version 219.
DE   RecName: Full=Pyruvate dehydrogenase protein X component, mitochondrial;
DE   AltName: Full=Dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex;
DE   AltName: Full=E3-binding protein;
DE            Short=E3BP;
DE   AltName: Full=Lipoyl-containing pyruvate dehydrogenase complex component X;
DE   AltName: Full=proX;
DE   Flags: Precursor;
GN   Name=PDHX; Synonyms=PDX1;
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 [MRNA] (ISOFORM 1), AND VARIANT CYS-23.
RX   PubMed=9242632; DOI=10.1074/jbc.272.32.19746;
RA   Harris R.A., Bowker-Kinley M.M., Wu P., Jeng J., Popov K.M.;
RT   "Dihydrolipoamide dehydrogenase-binding protein of the human pyruvate
RT   dehydrogenase complex. DNA-derived amino acid sequence, expression, and
RT   reconstitution of the pyruvate dehydrogenase complex.";
RL   J. Biol. Chem. 272:19746-19751(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INVOLVEMENT IN PDHXD.
RC   TISSUE=Liver;
RX   PubMed=9399911; DOI=10.1086/301653;
RA   Aral B., Benelli C., Ait-Ghezala G., Amessou M., Fouque F., Maunoury C.,
RA   Creau N., Kamoun P., Marsac C.;
RT   "Mutations in PDX1, the human lipoyl-containing component X of the pyruvate
RT   dehydrogenase-complex gene on chromosome 11p1, in congenital lactic
RT   acidosis.";
RL   Am. J. Hum. Genet. 61:1318-1326(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9467010; DOI=10.1093/hmg/7.3.501;
RA   Ling M., McEachern G., Seyda A., Mackay N., Scherer S.W., Bratinova S.,
RA   Beatty B., Giovannucci-Uzielli M.L., Robinson B.H.;
RT   "Detection of a homozygous four base pair deletion in the protein X gene in
RT   a case of pyruvate dehydrogenase complex deficiency.";
RL   Hum. Mol. Genet. 7:501-505(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Aral B., Dey R., Marsac C.;
RT   "Human gene sequence for PDX1, the human lipoyl-containing component X of
RT   the pyruvate dehydrogenase complex.";
RL   Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Synovium;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-370.
RC   TISSUE=Brain;
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   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-501 (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=9110174; DOI=10.1101/gr.7.4.353;
RA   Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA   Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT   "Large-scale concatenation cDNA sequencing.";
RL   Genome Res. 7:353-358(1997).
RN   [10]
RP   SUBUNIT.
RX   PubMed=14638692; DOI=10.1074/jbc.m308172200;
RA   Hiromasa Y., Fujisawa T., Aso Y., Roche T.E.;
RT   "Organization of the cores of the mammalian pyruvate dehydrogenase complex
RT   formed by E2 and E2 plus the E3-binding protein and their capacities to
RT   bind the E1 and E3 components.";
RL   J. Biol. Chem. 279:6921-6933(2004).
RN   [11]
RP   INTERACTION WITH DLD, AND MUTAGENESIS OF ASN-190; ARG-208 AND ILE-210.
RX   PubMed=20160912; DOI=10.1016/j.molcatb.2009.05.001;
RA   Patel M.S., Korotchkina L.G., Sidhu S.;
RT   "Interaction of E1 and E3 components with the core proteins of the human
RT   pyruvate dehydrogenase complex.";
RL   J. Mol. Catal., B Enzym. 61:2-6(2009).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-194, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [13]
RP   INTERACTION WITH DLD.
RX   PubMed=20385101; DOI=10.1016/j.bbrc.2010.04.038;
RA   Park Y.H., Patel M.S.;
RT   "Characterization of interactions of dihydrolipoamide dehydrogenase with
RT   its binding protein in the human pyruvate dehydrogenase complex.";
RL   Biochem. Biophys. Res. Commun. 395:416-419(2010).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [15]
RP   INTERACTION WITH SIRT4, LIPOYLATION AT LYS-97, AND DELIPOYLATION AT LYS-97.
RX   PubMed=25525879; DOI=10.1016/j.cell.2014.11.046;
RA   Mathias R.A., Greco T.M., Oberstein A., Budayeva H.G., Chakrabarti R.,
RA   Rowland E.A., Kang Y., Shenk T., Cristea I.M.;
RT   "Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex
RT   activity.";
RL   Cell 159:1615-1625(2014).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-196, AND IDENTIFICATION BY
RP   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   [17]
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   [18]
RP   X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 54-274 IN COMPLEX WITH DLD.
RX   PubMed=16263718; DOI=10.1074/jbc.m507850200;
RA   Ciszak E.M., Makal A., Hong Y.S., Vettaikkorumakankauv A.K.,
RA   Korotchkina L.G., Patel M.S.;
RT   "How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide
RT   dehydrogenase in the human pyruvate dehydrogenase complex.";
RL   J. Biol. Chem. 281:648-655(2006).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 174-230 IN COMPLEX WITH DLD, AND
RP   MUTAGENESIS OF ARG-183; SER-185; PRO-186; ALA-187; ARG-189; ASN-190;
RP   GLU-193; ARG-208; ILE-210; LYS-213 AND GLU-214.
RX   PubMed=16442803; DOI=10.1016/j.str.2006.01.001;
RA   Brautigam C.A., Wynn R.M., Chuang J.L., Machius M., Tomchick D.R.,
RA   Chuang D.T.;
RT   "Structural insight into interactions between dihydrolipoamide
RT   dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase
RT   complex.";
RL   Structure 14:611-621(2006).
RN   [20]
RP   STRUCTURE BY NMR OF 57-141.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of RSGI RUH-054, a lipoyl domain from human 2-oxoacid
RT   dehydrogenase.";
RL   Submitted (OCT-2006) to the PDB data bank.
RN   [21]
RP   STRUCTURE BY ELECTRON MICROSCOPY (18.3 ANGSTROMS) OF INNER CORE OF THE
RP   COMPLEX, AND SUBUNIT.
RX   PubMed=20361979; DOI=10.1016/j.jmb.2010.03.043;
RA   Vijayakrishnan S., Kelly S.M., Gilbert R.J., Callow P., Bhella D.,
RA   Forsyth T., Lindsay J.G., Byron O.;
RT   "Solution structure and characterisation of the human pyruvate
RT   dehydrogenase complex core assembly.";
RL   J. Mol. Biol. 399:71-93(2010).
CC   -!- FUNCTION: Required for anchoring dihydrolipoamide dehydrogenase (E3) to
CC       the dihydrolipoamide transacetylase (E2) core of the pyruvate
CC       dehydrogenase complexes of eukaryotes. This specific binding is
CC       essential for a functional PDH complex.
CC   -!- SUBUNIT: Part of the inner core of the multimeric pyruvate
CC       dehydrogenase complex that is composed of about 48 DLAT and 12 PDHX
CC       molecules (PubMed:14638692, PubMed:20361979). This core binds multiple
CC       copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1),
CC       dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide
CC       dehydrogenase (DLD, E3) (PubMed:14638692). Interacts with SIRT4
CC       (PubMed:25525879). Interacts with DLD (PubMed:20385101,
CC       PubMed:16263718, PubMed:16442803, PubMed:20160912, PubMed:20361979).
CC       {ECO:0000269|PubMed:14638692, ECO:0000269|PubMed:16263718,
CC       ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:20160912,
CC       ECO:0000269|PubMed:20361979, ECO:0000269|PubMed:20385101,
CC       ECO:0000269|PubMed:25525879}.
CC   -!- INTERACTION:
CC       O00330; Q6RW13: AGTRAP; NbExp=5; IntAct=EBI-751566, EBI-741181;
CC       O00330; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-751566, EBI-7062247;
CC       O00330; P09622: DLD; NbExp=7; IntAct=EBI-751566, EBI-353366;
CC       O00330; Q9Y6E7: SIRT4; NbExp=4; IntAct=EBI-751566, EBI-2606540;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O00330-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O00330-2; Sequence=VSP_045271;
CC       Name=3;
CC         IsoId=O00330-3; Sequence=VSP_053817;
CC   -!- PTM: Delipoylated at Lys-97 by SIRT4, delipoylation decreases the PHD
CC       complex activity. {ECO:0000269|PubMed:25525879}.
CC   -!- DISEASE: Pyruvate dehydrogenase E3-binding protein deficiency (PDHXD)
CC       [MIM:245349]: A metabolic disorder characterized by decreased activity
CC       of the pyruvate dehydrogenase complex without observable reduction in
CC       the activities of enzymes E1, E2, or E3. Clinical features include
CC       hypotonia and psychomotor retardation. {ECO:0000269|PubMed:9399911}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; AF001437; AAB66315.1; -; mRNA.
DR   EMBL; Y13145; CAA73606.1; -; mRNA.
DR   EMBL; U82328; AAC39661.1; -; mRNA.
DR   EMBL; AJ298105; CAC18649.1; -; Genomic_DNA.
DR   EMBL; AK301384; BAG62924.1; -; mRNA.
DR   EMBL; AC107928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL138810; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL356215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471064; EAW68158.1; -; Genomic_DNA.
DR   EMBL; CH471064; EAW68160.1; -; Genomic_DNA.
DR   EMBL; BC010389; AAH10389.1; -; mRNA.
DR   EMBL; U79296; AAB50223.1; -; mRNA.
DR   CCDS; CCDS53616.1; -. [O00330-2]
DR   CCDS; CCDS7896.1; -. [O00330-1]
DR   RefSeq; NP_001128496.1; NM_001135024.1.
DR   RefSeq; NP_001159630.1; NM_001166158.1. [O00330-2]
DR   RefSeq; NP_003468.2; NM_003477.2. [O00330-1]
DR   PDB; 1ZY8; X-ray; 2.59 A; K/L/M/N/O=54-274.
DR   PDB; 2DNC; NMR; -; A=57-141.
DR   PDB; 2F5Z; X-ray; 2.18 A; K/L/M/N/O=173-228.
DR   PDB; 2F60; X-ray; 1.55 A; K=173-228.
DR   PDB; 6H60; EM; 6.00 A; A=1-501.
DR   PDBsum; 1ZY8; -.
DR   PDBsum; 2DNC; -.
DR   PDBsum; 2F5Z; -.
DR   PDBsum; 2F60; -.
DR   PDBsum; 6H60; -.
DR   AlphaFoldDB; O00330; -.
DR   SMR; O00330; -.
DR   BioGRID; 113737; 107.
DR   ComplexPortal; CPX-6233; Mitochondrial pyruvate dehydrogenase complex, somatic variant.
DR   ComplexPortal; CPX-6242; Mitochondrial pyruvate dehydrogenase complex, testis-specific variant.
DR   DIP; DIP-29026N; -.
DR   IntAct; O00330; 32.
DR   MINT; O00330; -.
DR   STRING; 9606.ENSP00000227868; -.
DR   GlyGen; O00330; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O00330; -.
DR   PhosphoSitePlus; O00330; -.
DR   SwissPalm; O00330; -.
DR   BioMuta; PDHX; -.
DR   EPD; O00330; -.
DR   jPOST; O00330; -.
DR   MassIVE; O00330; -.
DR   MaxQB; O00330; -.
DR   PaxDb; 9606-ENSP00000227868; -.
DR   PeptideAtlas; O00330; -.
DR   ProteomicsDB; 19121; -.
DR   ProteomicsDB; 19268; -.
DR   ProteomicsDB; 47851; -. [O00330-1]
DR   Pumba; O00330; -.
DR   Antibodypedia; 25893; 324 antibodies from 35 providers.
DR   DNASU; 8050; -.
DR   Ensembl; ENST00000227868.9; ENSP00000227868.4; ENSG00000110435.13. [O00330-1]
DR   Ensembl; ENST00000430469.6; ENSP00000415695.2; ENSG00000110435.13. [O00330-2]
DR   GeneID; 8050; -.
DR   KEGG; hsa:8050; -.
DR   MANE-Select; ENST00000227868.9; ENSP00000227868.4; NM_003477.3; NP_003468.2.
DR   UCSC; uc001mvt.4; human. [O00330-1]
DR   AGR; HGNC:21350; -.
DR   CTD; 8050; -.
DR   DisGeNET; 8050; -.
DR   GeneCards; PDHX; -.
DR   GeneReviews; PDHX; -.
DR   HGNC; HGNC:21350; PDHX.
DR   HPA; ENSG00000110435; Tissue enhanced (skeletal muscle, tongue).
DR   MalaCards; PDHX; -.
DR   MIM; 245349; phenotype.
DR   MIM; 608769; gene.
DR   neXtProt; NX_O00330; -.
DR   OpenTargets; ENSG00000110435; -.
DR   Orphanet; 255182; Pyruvate dehydrogenase E3-binding protein deficiency.
DR   PharmGKB; PA134976445; -.
DR   VEuPathDB; HostDB:ENSG00000110435; -.
DR   eggNOG; KOG0557; Eukaryota.
DR   GeneTree; ENSGT00940000156046; -.
DR   HOGENOM; CLU_016733_10_2_1; -.
DR   InParanoid; O00330; -.
DR   OMA; TIKQKPW; -.
DR   OrthoDB; 5483022at2759; -.
DR   PhylomeDB; O00330; -.
DR   TreeFam; TF332256; -.
DR   BioCyc; MetaCyc:ENSG00000110435-MONOMER; -.
DR   BRENDA; 1.2.1.104; 2681.
DR   PathwayCommons; O00330; -.
DR   Reactome; R-HSA-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR   Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR   Reactome; R-HSA-5362517; Signaling by Retinoic Acid.
DR   Reactome; R-HSA-70268; Pyruvate metabolism.
DR   SignaLink; O00330; -.
DR   SIGNOR; O00330; -.
DR   BioGRID-ORCS; 8050; 13 hits in 1164 CRISPR screens.
DR   ChiTaRS; PDHX; human.
DR   EvolutionaryTrace; O00330; -.
DR   GeneWiki; E3_binding_protein; -.
DR   GenomeRNAi; 8050; -.
DR   Pharos; O00330; Tbio.
DR   PRO; PR:O00330; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; O00330; Protein.
DR   Bgee; ENSG00000110435; Expressed in biceps brachii and 208 other cell types or tissues.
DR   ExpressionAtlas; O00330; baseline and differential.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; IPI:ComplexPortal.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0045254; C:pyruvate dehydrogenase complex; IDA:UniProtKB.
DR   GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR   GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IDA:ComplexPortal.
DR   CDD; cd06849; lipoyl_domain; 1.
DR   Gene3D; 2.40.50.100; -; 1.
DR   Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR   Gene3D; 4.10.320.10; E3-binding domain; 1.
DR   InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR   InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
DR   InterPro; IPR000089; Biotin_lipoyl.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR045257; E2/Pdx1.
DR   InterPro; IPR036625; E3-bd_dom_sf.
DR   InterPro; IPR004167; PSBD.
DR   InterPro; IPR011053; Single_hybrid_motif.
DR   PANTHER; PTHR23151; DIHYDROLIPOAMIDE ACETYL/SUCCINYL-TRANSFERASE-RELATED; 1.
DR   PANTHER; PTHR23151:SF9; PYRUVATE DEHYDROGENASE PROTEIN X COMPONENT, MITOCHONDRIAL; 1.
DR   Pfam; PF00198; 2-oxoacid_dh; 1.
DR   Pfam; PF00364; Biotin_lipoyl; 1.
DR   Pfam; PF02817; E3_binding; 1.
DR   SUPFAM; SSF52777; CoA-dependent acyltransferases; 1.
DR   SUPFAM; SSF47005; Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex; 1.
DR   SUPFAM; SSF51230; Single hybrid motif; 1.
DR   PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR   PROSITE; PS00189; LIPOYL; 1.
DR   PROSITE; PS51826; PSBD; 1.
DR   Genevisible; O00330; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Lipoyl; Mitochondrion;
KW   Phosphoprotein; Reference proteome; Transit peptide.
FT   TRANSIT         1..53
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           54..501
FT                   /note="Pyruvate dehydrogenase protein X component,
FT                   mitochondrial"
FT                   /id="PRO_0000020484"
FT   DOMAIN          56..132
FT                   /note="Lipoyl-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   DOMAIN          183..220
FT                   /note="Peripheral subunit-binding (PSBD)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT   REGION          142..175
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          225..268
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        145..166
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         97
FT                   /note="N6-lipoyllysine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT                   ECO:0000269|PubMed:25525879"
FT   MOD_RES         194
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         196
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         394
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BKZ9"
FT   VAR_SEQ         2..53
FT                   /note="AASWRLGCDPRLLRYLVGFPGRRSVGLVKGALGWSVSRGANWRWFHSTQWLR
FT                   -> QSGGAEGSPGAGRTGRGPGSGKAPPAEISSGAPDFPG (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_053817"
FT   VAR_SEQ         115..341
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_045271"
FT   VARIANT         23
FT                   /note="R -> C (in dbSNP:rs1049306)"
FT                   /evidence="ECO:0000269|PubMed:9242632"
FT                   /id="VAR_046619"
FT   VARIANT         101
FT                   /note="T -> A (in dbSNP:rs11539202)"
FT                   /id="VAR_046620"
FT   VARIANT         370
FT                   /note="D -> V (in dbSNP:rs17850649)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_046621"
FT   MUTAGEN         183
FT                   /note="R->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         185
FT                   /note="S->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         186
FT                   /note="P->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         187
FT                   /note="A->M: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         189
FT                   /note="R->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         190
FT                   /note="N->A: Decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803,
FT                   ECO:0000269|PubMed:20160912"
FT   MUTAGEN         190
FT                   /note="N->K: Moderately decreased interaction with DLD."
FT                   /evidence="ECO:0000269|PubMed:20160912"
FT   MUTAGEN         193
FT                   /note="E->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         208
FT                   /note="R->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         208
FT                   /note="R->D: Decreased interaction with DLD."
FT                   /evidence="ECO:0000269|PubMed:20160912"
FT   MUTAGEN         210
FT                   /note="I->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         210
FT                   /note="I->R: Decreased interaction with DLD."
FT                   /evidence="ECO:0000269|PubMed:20160912"
FT   MUTAGEN         210
FT                   /note="I->S: Decreased interaction with DLD."
FT                   /evidence="ECO:0000269|PubMed:20160912"
FT   MUTAGEN         213
FT                   /note="K->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   MUTAGEN         214
FT                   /note="E->A: Strongly decreased DLD binding."
FT                   /evidence="ECO:0000269|PubMed:16442803"
FT   CONFLICT        41
FT                   /note="A -> R (in Ref. 3; AAC39661)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        251
FT                   /note="A -> S (in Ref. 1; AAB66315 and 2; CAA73606)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="P -> S (in Ref. 5; BAG62924)"
FT                   /evidence="ECO:0000305"
FT   STRAND          57..60
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   STRAND          69..71
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   STRAND          73..78
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   STRAND          88..94
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   STRAND          99..103
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   STRAND          108..112
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   STRAND          122..125
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   STRAND          127..132
FT                   /evidence="ECO:0007829|PDB:2DNC"
FT   HELIX           180..183
FT                   /evidence="ECO:0007829|PDB:2F60"
FT   HELIX           186..194
FT                   /evidence="ECO:0007829|PDB:2F60"
FT   HELIX           199..201
FT                   /evidence="ECO:0007829|PDB:2F60"
FT   HELIX           207..209
FT                   /evidence="ECO:0007829|PDB:2F60"
FT   HELIX           213..230
FT                   /evidence="ECO:0007829|PDB:2F60"
SQ   SEQUENCE   501 AA;  54122 MW;  9CF0C1DAE9E12EF9 CRC64;
     MAASWRLGCD PRLLRYLVGF PGRRSVGLVK GALGWSVSRG ANWRWFHSTQ WLRGDPIKIL
     MPSLSPTMEE GNIVKWLKKE GEAVSAGDAL CEIETDKAVV TLDASDDGIL AKIVVEEGSK
     NIRLGSLIGL IVEEGEDWKH VEIPKDVGPP PPVSKPSEPR PSPEPQISIP VKKEHIPGTL
     RFRLSPAARN ILEKHSLDAS QGTATGPRGI FTKEDALKLV QLKQTGKITE SRPTPAPTAT
     PTAPSPLQAT AGPSYPRPVI PPVSTPGQPN AVGTFTEIPA SNIRRVIAKR LTESKSTVPH
     AYATADCDLG AVLKVRQDLV KDDIKVSVND FIIKAAAVTL KQMPDVNVSW DGEGPKQLPF
     IDISVAVATD KGLLTPIIKD AAAKGIQEIA DSVKALSKKA RDGKLLPEEY QGGSFSISNL
     GMFGIDEFTA VINPPQACIL AVGRFRPVLK LTEDEEGNAK LQQRQLITVT MSSDSRVVDD
     ELATRFLKSF KANLENPIRL A
//