ODPA_HUMAN
ID ODPA_HUMAN Reviewed; 390 AA.
AC P08559; A5YVE9; B2R5P7; B7Z3T7; B7Z3X5; Q53H41; Q5JPT8; Q9NP12; Q9UBJ8;
AC Q9UBU0; Q9UNG4; Q9UNG5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 3.
DT 03-AUG-2022, entry version 249.
DE RecName: Full=Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial;
DE EC=1.2.4.1;
DE AltName: Full=PDHE1-A type I;
DE Flags: Precursor;
GN Name=PDHA1; Synonyms=PHE1A;
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 [GENOMIC DNA].
RC TISSUE=Leukocyte;
RX PubMed=2227443; DOI=10.1016/0378-1119(90)90241-i;
RA Koike K., Urata Y., Matsuo S., Koike M.;
RT "Characterization and nucleotide sequence of the gene encoding the human
RT pyruvate dehydrogenase alpha-subunit.";
RL Gene 93:307-311(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 30-50, AND
RP TRANSIT PEPTIDE.
RX PubMed=2748588; DOI=10.1073/pnas.86.14.5330;
RA Ho L., Wexler I.D., Liu T.C., Thekkumkara T.J., Patel M.S.;
RT "Characterization of cDNAs encoding human pyruvate dehydrogenase alpha
RT subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5330-5334(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Liver;
RA Huh T.L., Chi Y.T., Casazza J.P., Veech R.L., Song B.J.;
RL Submitted (APR-1990) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3034892; DOI=10.1016/s0021-9258(18)48250-6;
RA Dahl H.-H.M., Hunt S.M., Hutchison W.M., Brown G.K.;
RT "The human pyruvate dehydrogenase complex. Isolation of cDNA clones for the
RT E1 alpha subunit, sequence analysis, and characterization of the mRNA.";
RL J. Biol. Chem. 262:7398-7403(1987).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=2745444; DOI=10.1016/s0021-9258(18)63857-8;
RA Maragos C., Hutchinson W.M., Hayasaki K., Brown G.K., Dahl H.-H.M.;
RT "Structural organization of the gene for the E1 alpha subunit of the human
RT pyruvate dehydrogenase complex.";
RL J. Biol. Chem. 264:12294-12298(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2828359; DOI=10.1016/s0021-9258(19)77975-7;
RA de Meirleir L., MacKay N., Wah A.M.L.H., Robinson B.H.;
RT "Isolation of a full-length complementary DNA coding for human E1 alpha
RT subunit of the pyruvate dehydrogenase complex.";
RL J. Biol. Chem. 263:1991-1995(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3422424; DOI=10.1073/pnas.85.1.41;
RA Koike K., Ohta S., Urata Y., Kagawa Y., Koike M.;
RT "Cloning and sequencing of cDNAs encoding alpha and beta subunits of human
RT pyruvate dehydrogenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:41-45(1988).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Okajima K.;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC TISSUE=Thalamus;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-282.
RC TISSUE=Dermoid cancer;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [12]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [14]
RP PROTEIN SEQUENCE OF 31-37.
RX PubMed=23146587; DOI=10.1016/j.ab.2012.10.040;
RA Candat A., Poupart P., Andrieu J.P., Chevrollier A., Reynier P.,
RA Rogniaux H., Avelange-Macherel M.H., Macherel D.;
RT "Experimental determination of organelle targeting-peptide cleavage sites
RT using transient expression of green fluorescent protein translational
RT fusions.";
RL Anal. Biochem. 434:44-51(2013).
RN [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 202-336, AND VARIANT LEU-282.
RX PubMed=10077682; DOI=10.1073/pnas.96.6.3320;
RA Harris E.E., Hey J.;
RT "X chromosome evidence for ancient human histories.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3320-3324(1999).
RN [16]
RP INVOLVEMENT IN PDHAD.
RX PubMed=1338114; DOI=10.1007/bf01800220;
RA Ito M., Huq A.H., Naito E., Saijo T., Takeda E., Kuroda Y.;
RT "Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase
RT deficiency due to rapid degradation of E1 protein.";
RL J. Inherit. Metab. Dis. 15:848-856(1992).
RN [17]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP SER-232; SER-293 AND SER-300.
RX PubMed=7782287; DOI=10.1074/jbc.270.24.14297;
RA Korotchkina L.G., Patel M.S.;
RT "Mutagenesis studies of the phosphorylation sites of recombinant human
RT pyruvate dehydrogenase. Site-specific regulation.";
RL J. Biol. Chem. 270:14297-14304(1995).
RN [18]
RP PHOSPHORYLATION AT SER-232; SER-293 AND SER-300.
RX PubMed=11486000; DOI=10.1074/jbc.m103069200;
RA Korotchkina L.G., Patel M.S.;
RT "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward
RT the three phosphorylation sites of human pyruvate dehydrogenase.";
RL J. Biol. Chem. 276:37223-37229(2001).
RN [19]
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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-321, 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [27]
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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [30]
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 [31]
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 [32]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH THIAMINE
RP PYROPHOSPHATE, AND COFACTOR.
RX PubMed=12651851; DOI=10.1074/jbc.m300339200;
RA Ciszak E.M., Korotchkina L.G., Dominiak P.M., Sidhu S., Patel M.S.;
RT "Structural basis for flip-flop action of thiamin pyrophosphate-dependent
RT enzymes revealed by human pyruvate dehydrogenase.";
RL J. Biol. Chem. 278:21240-21246(2003).
RN [33]
RP REVIEW ON VARIANTS.
RX PubMed=1301207; DOI=10.1002/humu.1380010203;
RA Dahl H.-H.M., Brown G.K., Brown R.M., Hansen L.L., Kerr D.S., Wexler I.D.,
RA Patel M.S., de Meirleir L., Lissens W., Chun K., McKay N., Robinson B.H.;
RT "Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene.";
RL Hum. Mutat. 1:97-102(1992).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 30-390, ACTIVITY REGULATION,
RP CATALYTIC ACTIVITY, MUTAGENESIS OF SER-293, AND PHOSPHORYLATION AT SER-293.
RX PubMed=17474719; DOI=10.1021/bi700083z;
RA Seifert F., Ciszak E., Korotchkina L., Golbik R., Spinka M., Dominiak P.,
RA Sidhu S., Brauer J., Patel M.S., Tittmann K.;
RT "Phosphorylation of serine 264 impedes active site accessibility in the E1
RT component of the human pyruvate dehydrogenase multienzyme complex.";
RL Biochemistry 46:6277-6287(2007).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 30-390 IN COMPLEX WITH PDHB,
RP SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP PHOSPHORYLATION AT SER-293 AND SER-300 BY PDK4.
RX PubMed=19081061; DOI=10.1016/j.str.2008.10.010;
RA Kato M., Wynn R.M., Chuang J.L., Tso S.C., Machius M., Li J., Chuang D.T.;
RT "Structural basis for inactivation of the human pyruvate dehydrogenase
RT complex by phosphorylation: role of disordered phosphorylation loops.";
RL Structure 16:1849-1859(2008).
RN [36]
RP VARIANTS PDHAD LYS-313 DEL AND HIS-378.
RX PubMed=1909401; DOI=10.1007/bf01800586;
RA Hansen L.L., Brown G.K., Kirby D.M., Dahl H.-H.M.;
RT "Characterization of the mutations in three patients with pyruvate
RT dehydrogenase E1 alpha deficiency.";
RL J. Inherit. Metab. Dis. 14:140-151(1991).
RN [37]
RP VARIANT PDHAD ASP-SER-TYR-ARG-THR-ARG-GLU-305 INS.
RX PubMed=1551669; DOI=10.1007/bf02265291;
RA De Meirleir L., Lissens W., Vamos E., Liebaers I.;
RT "Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion
RT mutation in the E1 alpha subunit.";
RL Hum. Genet. 88:649-652(1992).
RN [38]
RP VARIANT PDHAD CYS-302.
RX PubMed=1293379; DOI=10.1007/bf01800219;
RA Dahl H.-H.M., Hansen L.L., Brown R.M., Danks D.M., Rogers J.G., Brown G.K.;
RT "X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in
RT heterozygous females: variable manifestation of the same mutation.";
RL J. Inherit. Metab. Dis. 15:835-847(1992).
RN [39]
RP VARIANT PDHAD ALA-258.
RX PubMed=8498846; DOI=10.1002/ana.410330616;
RA Matthews P.M., Marchington D.R., Squier M., Land J., Brown R.M.,
RA Brown G.K.;
RT "Molecular genetic characterization of an X-linked form of Leigh's
RT syndrome.";
RL Ann. Neurol. 33:652-655(1993).
RN [40]
RP VARIANTS PDHAD MET-167; THR-199; ALA-231; GLY-263 AND LEU-292.
RX PubMed=8504306; DOI=10.1093/hmg/2.4.449;
RA Chun K., McKay N., Petrova-Benedict R., Robinson B.H.;
RT "Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase
RT leading to deficiency of the pyruvate dehydrogenase complex.";
RL Hum. Mol. Genet. 2:449-454(1993).
RN [41]
RP VARIANTS PDHAD ASN-243; ASN-315 AND HIS-378, AND VARIANT LEU-282.
RX PubMed=8032855; DOI=10.1093/brain/117.3.435;
RA Matthews P.M., Brown R.M., Otero L.J., Marchington D.R., LeGris M.,
RA Howes R., Meadows L.S., Shevell M., Scriver C.R., Brown G.K.;
RT "Pyruvate dehydrogenase deficiency. Clinical presentation and molecular
RT genetic characterization of five new patients.";
RL Brain 117:435-443(1994).
RN [42]
RP VARIANT PDHAD PRO-PRO-HIS-SER-TYR-ARG-THR-ARG-GLU-GLU-ILE-307 INS.
RX PubMed=7545958; DOI=10.1093/hmg/3.6.1021;
RA Hansen L.L., Horn N., Dahl H.-H.M., Kruse T.A.;
RT "Pyruvate dehydrogenase deficiency caused by a 33 base pair duplication in
RT the PDH E1 alpha subunit.";
RL Hum. Mol. Genet. 3:1021-1022(1994).
RN [43]
RP VARIANT PDHAD LEU-205.
RX PubMed=8199595; DOI=10.1002/humu.1380030210;
RA Dahl H.-H.M., Brown G.K.;
RT "Pyruvate dehydrogenase deficiency in a male caused by a point mutation
RT (F205L) in the E1 alpha subunit.";
RL Hum. Mutat. 3:152-155(1994).
RN [44]
RP VARIANT PDHAD GLN-263.
RX PubMed=7967473; DOI=10.1007/bf00711616;
RA Awata H., Endo F., Tanoue A., Kitano A., Matsuda I.;
RT "Characterization of a point mutation in the pyruvate dehydrogenase E1
RT alpha gene from two boys with primary lactic acidaemia.";
RL J. Inherit. Metab. Dis. 17:189-195(1994).
RN [45]
RP VARIANTS PDHAD CYS-72; LEU-205; GLY-263; ARG-311 DEL AND HIS-378.
RX PubMed=7887409;
RA Chun K., MacKay N., Petrova-Benedict R., Federico A., Fois A., Cole D.E.C.,
RA Robertson E., Robinson B.H.;
RT "Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon
RT skipping, insertion of duplicate sequence, and missense mutations leading
RT to the deficiency of the pyruvate dehydrogenase complex.";
RL Am. J. Hum. Genet. 56:558-569(1995).
RN [46]
RP VARIANT PDHAD PRO-10.
RX PubMed=7573035;
RA Takakubo F., Cartwright P., Hoogenraad N., Thorburn D.R., Collins F.,
RA Lithgow T., Dahl H.-H.M.;
RT "An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene,
RT affecting mitochondrial import of the precursor protein.";
RL Am. J. Hum. Genet. 57:772-780(1995).
RN [47]
RP VARIANT PDHAD LEU-217.
RX PubMed=7757088; DOI=10.1093/hmg/4.2.315;
RA Hemalatha S.G., Kerr D.S., Wexler I.D., Lusk M.M., Kaung M., Du Y.,
RA Kolli M., Schelper R.L., Patel M.S.;
RT "Pyruvate dehydrogenase complex deficiency due to a point mutation (P188L)
RT within the thiamine pyrophosphate binding loop of the E1 alpha subunit.";
RL Hum. Mol. Genet. 4:315-318(1995).
RN [48]
RP VARIANTS PDHAD CYS-72; ASP-113; ARG-162; GLY-263; HIS-288 AND CYS-302.
RX PubMed=8664900;
RX DOI=10.1002/(sici)1098-1004(1996)7:1<46::aid-humu6>3.0.co;2-n;
RA Lissens W., de Meirleir L., Seneca S., Benelli C., Marsac C.,
RA Poll-The B.T., Briones P., Ruitenbeek W., van Diggelen O., Chaigne D.,
RA Ramaekers V., Liebaers I.;
RT "Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight
RT patients with a pyruvate dehydrogenase complex deficiency.";
RL Hum. Mutat. 7:46-51(1996).
RN [49]
RP VARIANTS PDHAD VAL-210 AND ARG-311 DEL.
RX PubMed=8844217;
RX DOI=10.1002/(sici)1098-1004(1996)8:2<180::aid-humu11>3.0.co;2-z;
RA Tripatara A., Kerr D.S., Lusk M.M., Kolli M., Tan J., Patel M.S.;
RT "Three new mutations of the pyruvate dehydrogenase alpha subunit: a point
RT mutation (M181V), 3 bp deletion (-R282), and 16 bp insertion/frameshift
RT (K358SVS-->TVDQS).";
RL Hum. Mutat. 8:180-182(1996).
RN [50]
RP VARIANT PDHAD GLY-263.
RX PubMed=9266390; DOI=10.1023/a:1005305614374;
RA Naito E., Ito M., Yokota I., Saijo T., Matsuda J., Osaka H., Kimura S.,
RA Kuroda Y.;
RT "Biochemical and molecular analysis of an X-linked case of Leigh syndrome
RT associated with thiamin-responsive pyruvate dehydrogenase deficiency.";
RL J. Inherit. Metab. Dis. 20:539-548(1997).
RN [51]
RP VARIANTS PDHAD CYS-302 AND HIS-302.
RX PubMed=9671272;
RX DOI=10.1002/(sici)1098-1004(1998)12:2<114::aid-humu6>3.0.co;2-#;
RA Otero L.J., Brown R.M., Brown G.K.;
RT "Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene:
RT identification of further patients and in vitro demonstration of
RT pathogenicity.";
RL Hum. Mutat. 12:114-121(1998).
RN [52]
RP VARIANT THR-136.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [53]
RP VARIANT PDHAD CYS-302.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
CC -!- FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall
CC conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the
CC glycolytic pathway to the tricarboxylic cycle.
CC {ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue
CC acetyltransferase] + H(+) + pyruvate = (R)-N(6)-(S(8)-
CC acetyldihydrolipoyl)-L-lysyl-[dihydrolipoyllysine-residue
CC acetyltransferase] + CO2; Xref=Rhea:RHEA:19189, Rhea:RHEA-COMP:10480,
CC Rhea:RHEA-COMP:10481, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:83099, ChEBI:CHEBI:83111; EC=1.2.4.1;
CC Evidence={ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061,
CC ECO:0000269|PubMed:7782287};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000269|PubMed:12651851, ECO:0000269|PubMed:19081061};
CC -!- ACTIVITY REGULATION: Pyruvate dehydrogenase activity is inhibited by
CC phosphorylation of PDHA1; it is reactivated by dephosphorylation.
CC {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061,
CC ECO:0000269|PubMed:7782287}.
CC -!- SUBUNIT: Heterotetramer of two PDHA1 and two PDHB subunits. The
CC heterotetramer interacts with DLAT, and is part of the multimeric
CC pyruvate dehydrogenase complex that contains multiple copies of
CC pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT,
CC E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to
CC an inner core composed of about 48 DLAT and 12 PDHX molecules.
CC {ECO:0000269|PubMed:12651851, ECO:0000269|PubMed:14638692,
CC ECO:0000269|PubMed:19081061}.
CC -!- INTERACTION:
CC P08559; Q16891: IMMT; NbExp=4; IntAct=EBI-715747, EBI-473801;
CC P08559; P11177: PDHB; NbExp=4; IntAct=EBI-715747, EBI-1035872;
CC P08559; Q15118: PDK1; NbExp=2; IntAct=EBI-715747, EBI-7016221;
CC P08559-1; P11177-1: PDHB; NbExp=4; IntAct=EBI-25766512, EBI-25766519;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P08559-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08559-2; Sequence=VSP_042569;
CC Name=3;
CC IsoId=P08559-3; Sequence=VSP_042570;
CC Name=4;
CC IsoId=P08559-4; Sequence=VSP_043363;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family
CC kinases inactivates the enzyme; for this phosphorylation at a single
CC site is sufficient. Dephosphorylation at all three sites, i.e. at Ser-
CC 232, Ser-293 and Ser-300, is required for reactivation.
CC {ECO:0000269|PubMed:11486000, ECO:0000269|PubMed:17474719,
CC ECO:0000269|PubMed:19081061}.
CC -!- PTM: Acetylation alters the phosphorylation pattern. Deacetylated by
CC SIRT3 (By similarity). {ECO:0000250}.
CC -!- DISEASE: Pyruvate dehydrogenase E1-alpha deficiency (PDHAD)
CC [MIM:312170]: An enzymatic defect causing primary lactic acidosis in
CC children. It is associated with a broad clinical spectrum ranging from
CC fatal lactic acidosis in the newborn to chronic neurologic dysfunction
CC with structural abnormalities in the central nervous system without
CC systemic acidosis. {ECO:0000269|PubMed:1293379,
CC ECO:0000269|PubMed:1338114, ECO:0000269|PubMed:1551669,
CC ECO:0000269|PubMed:1909401, ECO:0000269|PubMed:27864847,
CC ECO:0000269|PubMed:7545958, ECO:0000269|PubMed:7573035,
CC ECO:0000269|PubMed:7757088, ECO:0000269|PubMed:7887409,
CC ECO:0000269|PubMed:7967473, ECO:0000269|PubMed:8032855,
CC ECO:0000269|PubMed:8199595, ECO:0000269|PubMed:8498846,
CC ECO:0000269|PubMed:8504306, ECO:0000269|PubMed:8664900,
CC ECO:0000269|PubMed:8844217, ECO:0000269|PubMed:9266390,
CC ECO:0000269|PubMed:9671272}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60055.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB59581.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D90084; BAA14121.1; -; Genomic_DNA.
DR EMBL; M24848; AAA36533.1; -; mRNA.
DR EMBL; X52709; CAA36933.1; -; mRNA.
DR EMBL; X52710; CAA36934.1; -; mRNA.
DR EMBL; M27257; AAA60051.1; -; Genomic_DNA.
DR EMBL; M29155; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29156; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29157; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29158; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29159; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29160; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29161; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29162; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29163; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; M29164; AAA60051.1; JOINED; Genomic_DNA.
DR EMBL; L13318; AAA60227.1; -; mRNA.
DR EMBL; J03503; AAA60055.1; ALT_INIT; mRNA.
DR EMBL; J03575; AAA60050.1; -; mRNA.
DR EMBL; L48690; AAB59581.1; ALT_FRAME; mRNA.
DR EMBL; EF590117; ABQ59099.1; -; mRNA.
DR EMBL; AK293250; BAH11476.1; -; mRNA.
DR EMBL; AK296457; BAH12361.1; -; mRNA.
DR EMBL; AK312263; BAG35194.1; -; mRNA.
DR EMBL; AK296341; BAH12323.1; -; mRNA.
DR EMBL; AK222740; BAD96460.1; -; mRNA.
DR EMBL; AL732326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471074; EAW98960.1; -; Genomic_DNA.
DR EMBL; BC002406; AAH02406.1; -; mRNA.
DR EMBL; AF125053; AAD23841.1; -; Genomic_DNA.
DR EMBL; AF125054; AAD23842.1; -; Genomic_DNA.
DR EMBL; AF125055; AAD23843.1; -; Genomic_DNA.
DR EMBL; AF125056; AAD23844.1; -; Genomic_DNA.
DR EMBL; AF125057; AAD23845.1; -; Genomic_DNA.
DR EMBL; AF125058; AAD23846.1; -; Genomic_DNA.
DR EMBL; AF125059; AAD23847.1; -; Genomic_DNA.
DR EMBL; AF125060; AAD23848.1; -; Genomic_DNA.
DR EMBL; AF125061; AAD23849.1; -; Genomic_DNA.
DR EMBL; AF125062; AAD23850.1; -; Genomic_DNA.
DR EMBL; AF125063; AAD23851.1; -; Genomic_DNA.
DR EMBL; AF125064; AAD23852.1; -; Genomic_DNA.
DR EMBL; AF125065; AAD23853.1; -; Genomic_DNA.
DR EMBL; AF125066; AAD23854.1; -; Genomic_DNA.
DR EMBL; AF125067; AAD23855.1; -; Genomic_DNA.
DR EMBL; AF125068; AAD23856.1; -; Genomic_DNA.
DR EMBL; AF125069; AAD23857.1; -; Genomic_DNA.
DR EMBL; AF125070; AAD23858.1; -; Genomic_DNA.
DR EMBL; AF125071; AAD23859.1; -; Genomic_DNA.
DR EMBL; AF125072; AAD23860.1; -; Genomic_DNA.
DR EMBL; AF125073; AAD23861.1; -; Genomic_DNA.
DR EMBL; AF125074; AAD23862.1; -; Genomic_DNA.
DR EMBL; AF125075; AAD23863.1; -; Genomic_DNA.
DR EMBL; AF125076; AAD23864.1; -; Genomic_DNA.
DR EMBL; AF125078; AAD23866.1; -; Genomic_DNA.
DR EMBL; AF125079; AAD23867.1; -; Genomic_DNA.
DR EMBL; AF125080; AAD23868.1; -; Genomic_DNA.
DR EMBL; AF125081; AAD23869.1; -; Genomic_DNA.
DR EMBL; AF125082; AAD23870.1; -; Genomic_DNA.
DR EMBL; AF125083; AAD23871.1; -; Genomic_DNA.
DR EMBL; AF125084; AAD23872.1; -; Genomic_DNA.
DR EMBL; AF125085; AAD23873.1; -; Genomic_DNA.
DR EMBL; AF125086; AAD23874.1; -; Genomic_DNA.
DR EMBL; AF125087; AAD23875.1; -; Genomic_DNA.
DR EMBL; AF125088; AAD23876.1; -; Genomic_DNA.
DR CCDS; CCDS14192.1; -. [P08559-1]
DR CCDS; CCDS55380.1; -. [P08559-4]
DR CCDS; CCDS55381.1; -. [P08559-2]
DR CCDS; CCDS55382.1; -. [P08559-3]
DR PIR; JQ0770; DEHUPA.
DR RefSeq; NP_000275.1; NM_000284.3. [P08559-1]
DR RefSeq; NP_001166925.1; NM_001173454.1. [P08559-4]
DR RefSeq; NP_001166926.1; NM_001173455.1. [P08559-2]
DR RefSeq; NP_001166927.1; NM_001173456.1. [P08559-3]
DR PDB; 1NI4; X-ray; 1.95 A; A/C=30-390.
DR PDB; 2OZL; X-ray; 1.90 A; A/C=30-390.
DR PDB; 3EXE; X-ray; 1.98 A; A/C/E/G=30-390.
DR PDB; 3EXF; X-ray; 3.00 A; A/C/E/G=30-390.
DR PDB; 3EXG; X-ray; 3.01 A; 1/3/5/A/C/E/G/I/K/M/O/Q/S/U/W/Y=30-390.
DR PDB; 3EXH; X-ray; 2.44 A; A/C/E/G=30-390.
DR PDB; 3EXI; X-ray; 2.20 A; A=30-390.
DR PDB; 6CER; X-ray; 2.69 A; A/C/E/G=30-390.
DR PDB; 6CFO; X-ray; 2.70 A; A/C=30-390.
DR PDBsum; 1NI4; -.
DR PDBsum; 2OZL; -.
DR PDBsum; 3EXE; -.
DR PDBsum; 3EXF; -.
DR PDBsum; 3EXG; -.
DR PDBsum; 3EXH; -.
DR PDBsum; 3EXI; -.
DR PDBsum; 6CER; -.
DR PDBsum; 6CFO; -.
DR AlphaFoldDB; P08559; -.
DR SMR; P08559; -.
DR BioGRID; 111186; 708.
DR ComplexPortal; CPX-376; Pyruvate dehydrogenase E1 heterotetramer.
DR ComplexPortal; CPX-6233; Mitochondrial pyruvate dehydrogenase complex, somatic variant.
DR DIP; DIP-37652N; -.
DR IntAct; P08559; 266.
DR MINT; P08559; -.
DR STRING; 9606.ENSP00000369134; -.
DR DrugBank; DB00157; NADH.
DR GlyGen; P08559; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P08559; -.
DR MetOSite; P08559; -.
DR PhosphoSitePlus; P08559; -.
DR SwissPalm; P08559; -.
DR BioMuta; PDHA1; -.
DR DMDM; 129063; -.
DR REPRODUCTION-2DPAGE; IPI00306301; -.
DR UCD-2DPAGE; P08559; -.
DR EPD; P08559; -.
DR jPOST; P08559; -.
DR MassIVE; P08559; -.
DR MaxQB; P08559; -.
DR PeptideAtlas; P08559; -.
DR PRIDE; P08559; -.
DR ProteomicsDB; 52117; -. [P08559-1]
DR ProteomicsDB; 52118; -. [P08559-2]
DR ProteomicsDB; 52119; -. [P08559-3]
DR ProteomicsDB; 52120; -. [P08559-4]
DR TopDownProteomics; P08559-3; -. [P08559-3]
DR TopDownProteomics; P08559-4; -. [P08559-4]
DR Antibodypedia; 24225; 674 antibodies from 37 providers.
DR DNASU; 5160; -.
DR Ensembl; ENST00000379806.9; ENSP00000369134.5; ENSG00000131828.14. [P08559-4]
DR Ensembl; ENST00000422285.7; ENSP00000394382.2; ENSG00000131828.14. [P08559-1]
DR Ensembl; ENST00000540249.5; ENSP00000440761.1; ENSG00000131828.14. [P08559-3]
DR Ensembl; ENST00000545074.5; ENSP00000438550.1; ENSG00000131828.14. [P08559-2]
DR GeneID; 5160; -.
DR KEGG; hsa:5160; -.
DR MANE-Select; ENST00000422285.7; ENSP00000394382.2; NM_000284.4; NP_000275.1.
DR UCSC; uc004czg.5; human. [P08559-1]
DR CTD; 5160; -.
DR DisGeNET; 5160; -.
DR GeneCards; PDHA1; -.
DR GeneReviews; PDHA1; -.
DR HGNC; HGNC:8806; PDHA1.
DR HPA; ENSG00000131828; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; PDHA1; -.
DR MIM; 300502; gene.
DR MIM; 312170; phenotype.
DR neXtProt; NX_P08559; -.
DR OpenTargets; ENSG00000131828; -.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR Orphanet; 79243; Pyruvate dehydrogenase E1-alpha deficiency.
DR PharmGKB; PA33150; -.
DR VEuPathDB; HostDB:ENSG00000131828; -.
DR eggNOG; KOG0225; Eukaryota.
DR GeneTree; ENSGT00530000063174; -.
DR HOGENOM; CLU_029393_5_2_1; -.
DR InParanoid; P08559; -.
DR OMA; LGYEMPC; -.
DR OrthoDB; 871160at2759; -.
DR PhylomeDB; P08559; -.
DR TreeFam; TF300742; -.
DR BioCyc; MetaCyc:HS05573-MON; -.
DR BRENDA; 1.2.1.104; 2681.
DR BRENDA; 1.2.4.1; 2681.
DR PathwayCommons; P08559; -.
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 SABIO-RK; P08559; -.
DR SignaLink; P08559; -.
DR SIGNOR; P08559; -.
DR BioGRID-ORCS; 5160; 40 hits in 714 CRISPR screens.
DR ChiTaRS; PDHA1; human.
DR EvolutionaryTrace; P08559; -.
DR GeneWiki; Pyruvate_dehydrogenase_(lipoamide)_alpha_1; -.
DR GenomeRNAi; 5160; -.
DR Pharos; P08559; Tbio.
DR PRO; PR:P08559; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P08559; protein.
DR Bgee; ENSG00000131828; Expressed in apex of heart and 204 other tissues.
DR ExpressionAtlas; P08559; baseline and differential.
DR Genevisible; P08559; HS.
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; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0045254; C:pyruvate dehydrogenase complex; IDA:UniProtKB.
DR GO; GO:0004739; F:pyruvate dehydrogenase (acetyl-transferring) activity; IDA:GO_Central.
DR GO; GO:0034604; F:pyruvate dehydrogenase (NAD+) activity; IEA:Ensembl.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IDA:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0061732; P:mitochondrial acetyl-CoA biosynthetic process from pyruvate; IEA:Ensembl.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR InterPro; IPR001017; DH_E1.
DR InterPro; IPR017597; Pyrv_DH_E1_asu_subgrp-y.
DR InterPro; IPR029061; THDP-binding.
DR Pfam; PF00676; E1_dh; 1.
DR SUPFAM; SSF52518; SSF52518; 1.
DR TIGRFAMs; TIGR03182; PDH_E1_alph_y; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Carbohydrate metabolism;
KW Direct protein sequencing; Disease variant; Glucose metabolism;
KW Leigh syndrome; Mitochondrion; Oxidoreductase; Phosphoprotein;
KW Primary mitochondrial disease; Pyruvate; Reference proteome;
KW Thiamine pyrophosphate; Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2748588"
FT CHAIN 30..390
FT /note="Pyruvate dehydrogenase E1 component subunit alpha,
FT somatic form, mitochondrial"
FT /id="PRO_0000020440"
FT MOD_RES 63
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 63
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 232
FT /note="Phosphoserine; by PDK1"
FT /evidence="ECO:0000269|PubMed:11486000,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 244
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 244
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 277
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 293
FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4"
FT /evidence="ECO:0000269|PubMed:11486000,
FT ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 300
FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4"
FT /evidence="ECO:0000269|PubMed:11486000,
FT ECO:0000269|PubMed:19081061"
FT MOD_RES 301
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 313
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 313
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 321
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 336
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 385
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT VAR_SEQ 19
FT /note="P -> PRHGLATLPSLVSISRLKQSSHLGLPKCWDYSHSLKTRQ (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.8"
FT /id="VSP_043363"
FT VAR_SEQ 96
FT /note="G -> GQFLLPLT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042569"
FT VAR_SEQ 170..200
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042570"
FT VARIANT 10
FT /note="R -> P (in PDHAD; affects mitochondrial import of
FT precursor protein; dbSNP:rs137853257)"
FT /evidence="ECO:0000269|PubMed:7573035"
FT /id="VAR_010238"
FT VARIANT 72
FT /note="R -> C (in PDHAD; dbSNP:rs863224148)"
FT /evidence="ECO:0000269|PubMed:7887409,
FT ECO:0000269|PubMed:8664900"
FT /id="VAR_004949"
FT VARIANT 113
FT /note="H -> D (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:8664900"
FT /id="VAR_004950"
FT VARIANT 136
FT /note="A -> T (probable disease-associated variant found in
FT a patient with moderate developmental delay, mild
FT dysmorphism and mildly elevated serum lactate;
FT dbSNP:rs138727886)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069381"
FT VARIANT 162
FT /note="G -> R (in PDHAD; dbSNP:rs866868610)"
FT /evidence="ECO:0000269|PubMed:8664900"
FT /id="VAR_004951"
FT VARIANT 167
FT /note="V -> M (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:8504306"
FT /id="VAR_004952"
FT VARIANT 199
FT /note="A -> T (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:8504306"
FT /id="VAR_004953"
FT VARIANT 205
FT /note="F -> L (in PDHAD; dbSNP:rs137853254)"
FT /evidence="ECO:0000269|PubMed:7887409,
FT ECO:0000269|PubMed:8199595"
FT /id="VAR_004954"
FT VARIANT 210
FT /note="M -> V (in PDHAD; dbSNP:rs794727843)"
FT /evidence="ECO:0000269|PubMed:8844217"
FT /id="VAR_004955"
FT VARIANT 217
FT /note="P -> L (in PDHAD; dbSNP:rs1131691792)"
FT /evidence="ECO:0000269|PubMed:7757088"
FT /id="VAR_004956"
FT VARIANT 231
FT /note="T -> A (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:8504306"
FT /id="VAR_004957"
FT VARIANT 243
FT /note="Y -> N (in PDHAD; dbSNP:rs137853255)"
FT /evidence="ECO:0000269|PubMed:8032855"
FT /id="VAR_021053"
FT VARIANT 258
FT /note="D -> A (in PDHAD; dbSNP:rs137853253)"
FT /evidence="ECO:0000269|PubMed:8498846"
FT /id="VAR_004958"
FT VARIANT 263
FT /note="R -> G (in PDHAD; dbSNP:rs137853259)"
FT /evidence="ECO:0000269|PubMed:7887409,
FT ECO:0000269|PubMed:8504306, ECO:0000269|PubMed:8664900,
FT ECO:0000269|PubMed:9266390"
FT /id="VAR_004959"
FT VARIANT 263
FT /note="R -> Q (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:7967473"
FT /id="VAR_004960"
FT VARIANT 282
FT /note="M -> L (in dbSNP:rs2229137)"
FT /evidence="ECO:0000269|PubMed:10077682,
FT ECO:0000269|PubMed:8032855, ECO:0000269|Ref.10"
FT /id="VAR_021054"
FT VARIANT 288
FT /note="R -> H (in PDHAD; dbSNP:rs137853258)"
FT /evidence="ECO:0000269|PubMed:8664900"
FT /id="VAR_021055"
FT VARIANT 292
FT /note="H -> L (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:8504306"
FT /id="VAR_004961"
FT VARIANT 302
FT /note="R -> C (in PDHAD; loss of activity; common mutation;
FT dbSNP:rs137853252)"
FT /evidence="ECO:0000269|PubMed:1293379,
FT ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:8664900,
FT ECO:0000269|PubMed:9671272"
FT /id="VAR_004962"
FT VARIANT 302
FT /note="R -> H (in PDHAD; dbSNP:rs1064794149)"
FT /evidence="ECO:0000269|PubMed:9671272"
FT /id="VAR_004963"
FT VARIANT 305
FT /note="E -> EDSYRTRE (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:1551669"
FT /id="VAR_020908"
FT VARIANT 307
FT /note="I -> IPPHSYRTREEI (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:7545958"
FT /id="VAR_020909"
FT VARIANT 311
FT /note="Missing (in PDHAD)"
FT /evidence="ECO:0000269|PubMed:7887409,
FT ECO:0000269|PubMed:8844217"
FT /id="VAR_004964"
FT VARIANT 313
FT /note="Missing (in PDHAD; dbSNP:rs137853251)"
FT /evidence="ECO:0000269|PubMed:1909401"
FT /id="VAR_004965"
FT VARIANT 315
FT /note="D -> N (in PDHAD; dbSNP:rs137853256)"
FT /evidence="ECO:0000269|PubMed:8032855"
FT /id="VAR_021056"
FT VARIANT 333
FT /note="E -> D (in dbSNP:rs2228067)"
FT /id="VAR_050436"
FT VARIANT 378
FT /note="R -> H (in PDHAD; dbSNP:rs137853250)"
FT /evidence="ECO:0000269|PubMed:1909401,
FT ECO:0000269|PubMed:7887409, ECO:0000269|PubMed:8032855"
FT /id="VAR_004966"
FT MUTAGEN 232
FT /note="S->A: Abolishes inactivation by phosphorylation;
FT when associated with A-293 and A-300."
FT /evidence="ECO:0000269|PubMed:7782287"
FT MUTAGEN 293
FT /note="S->A: Reduces enzyme activity. Abolishes
FT inactivation by phosphorylation; when associated with A-232
FT and A-300."
FT /evidence="ECO:0000269|PubMed:17474719,
FT ECO:0000269|PubMed:7782287"
FT MUTAGEN 293
FT /note="S->E: Interferes with substrate binding."
FT /evidence="ECO:0000269|PubMed:17474719,
FT ECO:0000269|PubMed:7782287"
FT MUTAGEN 300
FT /note="S->A: Abolishes inactivation by phosphorylation;
FT when associated with A-232 and A-293."
FT /evidence="ECO:0000269|PubMed:7782287"
FT CONFLICT 278
FT /note="G -> E (in Ref. 9; BAG35194)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="Y -> S (in Ref. 15; AAD23857)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="E -> D (in Ref. 15; AAD23857)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="A -> P (in Ref. 6; AAA60055)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="T -> A (in Ref. 6; AAA60055)"
FT /evidence="ECO:0000305"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 58..83
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:3EXF"
FT HELIX 98..106
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 121..126
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 131..138
FT /evidence="ECO:0007829|PDB:2OZL"
FT TURN 145..148
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:3EXE"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 170..184
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 202..213
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 218..224
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:2OZL"
FT TURN 245..248
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 259..274
FT /evidence="ECO:0007829|PDB:2OZL"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:3EXG"
FT STRAND 280..285
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 304..314
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 316..326
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 332..355
FT /evidence="ECO:0007829|PDB:2OZL"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 367..371
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:2OZL"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:2OZL"
SQ SEQUENCE 390 AA; 43296 MW; 4D685BBE44A92D4B CRC64;
MRKMLAAVSR VLSGASQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED
GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA
HGFTFTRGLS VREILAELTG RKGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA
CKYNGKDEVC LTLYGDGAAN QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST
DYYKRGDFIP GLRVDGMDIL CVREATRFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS
YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP
LEELGYHIYS SDPPFEVRGA NQWIKFKSVS
