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P35486

- ODPA_MOUSE

UniProt

P35486 - ODPA_MOUSE

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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

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

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
Complete GO annotation...

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.
REACT_253080. Pyruvate metabolism.

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. mitochondrion Source: MGI
  2. nucleus Source: Ensembl
  3. pyruvate dehydrogenase complex Source: UniProtKB
Complete GO annotation...

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

BgeeiP35486.
CleanExiMM_PDHA1.
ExpressionAtlasiP35486. baseline and differential.
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

« Hide

        10         20         30         40         50
MRKMLAAVSR VLAGSAQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP
60 70 80 90 100
PVTTVLTRED GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC
110 120 130 140 150
CVGLEAGINP TDHLITAYRA HGFTFTRGLP VRAILAELTG RRGGCAKGKG
160 170 180 190 200
GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA CKYNGKDEVC LTLYGDGAAN
210 220 230 240 250
QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST DYYKRGDFIP
260 270 280 290 300
GLRVDGMDIL CVREATKFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS
310 320 330 340 350
YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA
360 370 380 390
QFATADPEPP LEELGYHIYS SDPPFEVRGA NQWIKFKSVS
Length:390
Mass (Da):43,232
Last modified:June 1, 1994 - v1
Checksum:i40898944CE8E0A03
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.
REACT_253080. Pyruvate metabolism.

Miscellaneous databases

ChiTaRSi Pdha1. mouse.
NextBioi 294490.
PROi P35486.
SOURCEi Search...

Gene expression databases

Bgeei P35486.
CleanExi MM_PDHA1.
ExpressionAtlasi P35486. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 128 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