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P35486

- ODPA_MOUSE

UniProt

P35486 - ODPA_MOUSE

Protein

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

Gene

Pdha1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    Functioni

    The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and thereby links the glycolytic pathway to the tricarboxylic cycle.2 Publications

    Catalytic activityi

    Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2.2 Publications

    Cofactori

    Thiamine pyrophosphate.

    Enzyme regulationi

    Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA1; it is reactivated by dephosphorylation.

    GO - Molecular functioni

    1. pyruvate dehydrogenase (acetyl-transferring) activity Source: UniProtKB-EC
    2. pyruvate dehydrogenase activity Source: MGI

    GO - Biological processi

    1. acetyl-CoA biosynthetic process from pyruvate Source: UniProtKB
    2. glucose metabolic process Source: UniProtKB-KW
    3. glycolytic process Source: InterPro
    4. tricarboxylic acid cycle Source: UniProtKB

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Carbohydrate metabolism, Glucose metabolism, Tricarboxylic acid cycle

    Keywords - Ligandi

    Pyruvate, Thiamine pyrophosphate

    Enzyme and pathway databases

    ReactomeiREACT_226284. Regulation of pyruvate dehydrogenase (PDH) complex.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (EC:1.2.4.1)
    Alternative name(s):
    PDHE1-A type I
    Gene namesi
    Name:Pdha1
    Synonyms:Pdha-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:97532. Pdha1.

    Subcellular locationi

    Mitochondrion matrix 1 Publication

    GO - Cellular componenti

    1. mitochondrial matrix Source: UniProtKB-SubCell
    2. mitochondrion Source: MGI
    3. pyruvate dehydrogenase complex Source: UniProtKB

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Disruption phenotypei

    Complete embryonic lethality. Normal embryonic development ceases about 9.5 dpc. Conditional gene disruption in the heart causes death shortly after weaning in male mice fed normal chow, while mice on high fat diet survive, but develop left ventricular hypertrophy, due to impaired glucose and energy metabolism in the heart. Likewise, conditional gene disruption in pancreas islet beta cells disrupts normal insulin secretion in response to glucose stimuli, while conditional gene disruption in oocytes causes reduced ATP levels and thereby prevents normal meiosis during oocyte maturation.4 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi336 – 3361K → Q or R: Decreases phosphorylation at S-232 and S-300 but does not affect activity or substrate metabolism. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2929MitochondrionBy similarityAdd
    BLAST
    Chaini30 – 390361Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrialPRO_0000020442Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei63 – 631N6-acetyllysine; alternate1 Publication
    Modified residuei63 – 631N6-succinyllysine; alternate1 Publication
    Modified residuei232 – 2321Phosphoserine; by PDK12 Publications
    Modified residuei244 – 2441N6-acetyllysine; alternate1 Publication
    Modified residuei244 – 2441N6-succinyllysine; alternate1 Publication
    Modified residuei267 – 2671N6-acetyllysine1 Publication
    Modified residuei277 – 2771N6-succinyllysine1 Publication
    Modified residuei293 – 2931Phosphoserine; by PDK1, PDK2, PDK3 and PDK43 Publications
    Modified residuei295 – 2951Phosphoserine1 Publication
    Modified residuei300 – 3001Phosphoserine; by PDK1, PDK2, PDK3 and PDK42 Publications
    Modified residuei301 – 3011Phosphotyrosine1 Publication
    Modified residuei313 – 3131N6-acetyllysine; alternate1 Publication
    Modified residuei313 – 3131N6-succinyllysine; alternate1 Publication
    Modified residuei321 – 3211N6-acetyllysine1 Publication
    Modified residuei336 – 3361N6-acetyllysine1 Publication
    Modified residuei385 – 3851N6-succinyllysine1 Publication

    Post-translational modificationi

    Phosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family kinases inactivates the enzyme; for this phosphorylation at a single site is sufficient. Phosphorylation at Ser-293 interferes with access to active site, and thereby inactivates the enzyme. Dephosphorylation at all three sites, i.e. at Ser-232, Ser-293 and Ser-300, is required for reactivation By similarity.By similarity
    Acetylation alters the phosphorylation pattern. Deacetylated by SIRT3.7 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP35486.
    PaxDbiP35486.
    PRIDEiP35486.

    2D gel databases

    REPRODUCTION-2DPAGEP35486.

    PTM databases

    PhosphoSiteiP35486.

    Expressioni

    Tissue specificityi

    In all tissues, but in very low amount in testis.

    Gene expression databases

    ArrayExpressiP35486.
    BgeeiP35486.
    CleanExiMM_PDHA1.
    GenevestigatoriP35486.

    Interactioni

    Subunit structurei

    Heterotetramer of two PDHA1 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules By similarity.By similarity

    Protein-protein interaction databases

    IntActiP35486. 6 interactions.
    MINTiMINT-4105793.
    STRINGi10090.ENSMUSP00000033662.

    Structurei

    3D structure databases

    ProteinModelPortaliP35486.
    SMRiP35486. Positions 29-390.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG1071.
    HOGENOMiHOG000281336.
    HOVERGENiHBG001863.
    InParanoidiP35486.
    KOiK00161.
    OMAiRGPNQWI.
    OrthoDBiEOG73JKVQ.
    PhylomeDBiP35486.
    TreeFamiTF300742.

    Family and domain databases

    Gene3Di3.40.50.970. 1 hit.
    InterProiIPR001017. DH_E1.
    IPR017597. Pyrv_DH_E1_asu_subgrp-y.
    IPR029061. THDP-binding.
    [Graphical view]
    PfamiPF00676. E1_dh. 1 hit.
    [Graphical view]
    SUPFAMiSSF52518. SSF52518. 1 hit.
    TIGRFAMsiTIGR03182. PDH_E1_alph_y. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P35486-1 [UniParc]FASTAAdd to Basket

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    MRKMLAAVSR VLAGSAQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP    50
    PVTTVLTRED GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC 100
    CVGLEAGINP TDHLITAYRA HGFTFTRGLP VRAILAELTG RRGGCAKGKG 150
    GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA CKYNGKDEVC LTLYGDGAAN 200
    QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST DYYKRGDFIP 250
    GLRVDGMDIL CVREATKFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS 300
    YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA 350
    QFATADPEPP LEELGYHIYS SDPPFEVRGA NQWIKFKSVS 390
    Length:390
    Mass (Da):43,232
    Last modified:June 1, 1994 - v1
    Checksum:i40898944CE8E0A03
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M76727 mRNA. Translation: AAA53046.1.
    BC007142 mRNA. Translation: AAH07142.1.
    CCDSiCCDS41195.1.
    PIRiS23506.
    RefSeqiNP_032836.1. NM_008810.2.
    UniGeneiMm.34775.

    Genome annotation databases

    EnsembliENSMUST00000033662; ENSMUSP00000033662; ENSMUSG00000031299.
    GeneIDi18597.
    KEGGimmu:18597.
    UCSCiuc009utc.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M76727 mRNA. Translation: AAA53046.1 .
    BC007142 mRNA. Translation: AAH07142.1 .
    CCDSi CCDS41195.1.
    PIRi S23506.
    RefSeqi NP_032836.1. NM_008810.2.
    UniGenei Mm.34775.

    3D structure databases

    ProteinModelPortali P35486.
    SMRi P35486. Positions 29-390.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P35486. 6 interactions.
    MINTi MINT-4105793.
    STRINGi 10090.ENSMUSP00000033662.

    PTM databases

    PhosphoSitei P35486.

    2D gel databases

    REPRODUCTION-2DPAGE P35486.

    Proteomic databases

    MaxQBi P35486.
    PaxDbi P35486.
    PRIDEi P35486.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000033662 ; ENSMUSP00000033662 ; ENSMUSG00000031299 .
    GeneIDi 18597.
    KEGGi mmu:18597.
    UCSCi uc009utc.1. mouse.

    Organism-specific databases

    CTDi 5160.
    MGIi MGI:97532. Pdha1.

    Phylogenomic databases

    eggNOGi COG1071.
    HOGENOMi HOG000281336.
    HOVERGENi HBG001863.
    InParanoidi P35486.
    KOi K00161.
    OMAi RGPNQWI.
    OrthoDBi EOG73JKVQ.
    PhylomeDBi P35486.
    TreeFami TF300742.

    Enzyme and pathway databases

    Reactomei REACT_226284. Regulation of pyruvate dehydrogenase (PDH) complex.

    Miscellaneous databases

    ChiTaRSi PDHA1. mouse.
    NextBioi 294490.
    PROi P35486.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P35486.
    Bgeei P35486.
    CleanExi MM_PDHA1.
    Genevestigatori P35486.

    Family and domain databases

    Gene3Di 3.40.50.970. 1 hit.
    InterProi IPR001017. DH_E1.
    IPR017597. Pyrv_DH_E1_asu_subgrp-y.
    IPR029061. THDP-binding.
    [Graphical view ]
    Pfami PF00676. E1_dh. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52518. SSF52518. 1 hit.
    TIGRFAMsi TIGR03182. PDH_E1_alph_y. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Isolation and characterisation of the mouse pyruvate dehydrogenase E1 alpha genes."
      Fitzgerald G.F., Hutchison W.M., Dahl H.-H.M.
      Biochim. Biophys. Acta 1131:83-90(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Mammary gland.
    3. Lubec G., Klug S., Kang S.U.
      Submitted (APR-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 46-58; 120-127; 133-141; 159-182; 216-244; 246-263; 268-274; 278-321; 324-343 AND 379-385, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: C57BL/6.
      Tissue: Brain and Hippocampus.
    4. "Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development."
      Johnson M.T., Mahmood S., Hyatt S.L., Yang H.S., Soloway P.D., Hanson R.W., Patel M.S.
      Mol. Genet. Metab. 74:293-302(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, FUNCTION.
    5. "Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo."
      Johnson M.T., Freeman E.A., Gardner D.K., Hunt P.A.
      Biol. Reprod. 77:2-8(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-293; SER-295 AND SER-300, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    7. "Tissue-specific pyruvate dehydrogenase complex deficiency causes cardiac hypertrophy and sudden death of weaned male mice."
      Sidhu S., Gangasani A., Korotchkina L.G., Suzuki G., Fallavollita J.A., Canty J.M. Jr., Patel M.S.
      Am. J. Physiol. 295:H946-H952(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    8. "Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
      Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
      J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Brain.
    9. "Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis."
      Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.
      J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    10. "Monitoring phosphorylation of the pyruvate dehydrogenase complex."
      Rardin M.J., Wiley S.E., Naviaux R.K., Murphy A.N., Dixon J.E.
      Anal. Biochem. 389:157-164(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-232; SER-293 AND SER-300.
    11. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. "Beta-cell-specific pyruvate dehydrogenase deficiency impairs glucose-stimulated insulin secretion."
      Srinivasan M., Choi C.S., Ghoshal P., Pliss L., Pandya J.D., Hill D., Cline G., Patel M.S.
      Am. J. Physiol. 299:E910-E917(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, FUNCTION.
    13. "Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation."
      Jing E., O'Neill B.T., Rardin M.J., Kleinridders A., Ilkeyeva O.R., Ussar S., Bain J.R., Lee K.Y., Verdin E.M., Newgard C.B., Gibson B.W., Kahn C.R.
      Diabetes 62:3404-3417(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION AT LYS-336, MUTAGENESIS OF LYS-336.
    14. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-313, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-63; LYS-244; LYS-277; LYS-313 AND LYS-385, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast and Liver.
    15. "Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
      Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
      Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-63; LYS-244; LYS-267 AND LYS-321, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.

    Entry informationi

    Entry nameiODPA_MOUSE
    AccessioniPrimary (citable) accession number: P35486
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 126 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

    External Data

    Dasty 3