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Protein

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

Gene

Pdha1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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_278177. Regulation of pyruvate dehydrogenase (PDH) complex.
REACT_293106. Pyruvate metabolism.
REACT_306383. Signaling by Retinoic Acid.

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 Componenti: 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. myelin sheath Source: UniProtKB
  4. nucleus Source: MGI
  5. 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 SIRT3.2 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.
CCDSiCCDS41195.1.
PIRiS23506.
RefSeqiNP_032836.1. NM_008810.2.
UniGeneiMm.34775.

3D structure databases

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiP35486.

2D gel databases

REPRODUCTION-2DPAGEP35486.

Proteomic databases

MaxQBiP35486.
PaxDbiP35486.
PRIDEiP35486.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5160.
MGIiMGI:97532. Pdha1.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiREACT_278177. Regulation of pyruvate dehydrogenase (PDH) complex.
REACT_293106. Pyruvate metabolism.
REACT_306383. Signaling by Retinoic Acid.

Miscellaneous databases

ChiTaRSiPdha1. mouse.
NextBioi294490.
PROiP35486.
SOURCEiSearch...

Gene expression databases

BgeeiP35486.
CleanExiMM_PDHA1.
ExpressionAtlasiP35486. baseline and differential.
GenevestigatoriP35486.

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.
ProtoNetiSearch...

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(1991) [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(2003) [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 (MAR-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(2000) [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(2006) [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(2007) [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(2007) [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(2007) [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(2008) [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(2008) [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(2009) [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(2012) [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(2012) [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(2012) [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: April 1, 2015
This is version 132 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.