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Protein

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

Gene

Pdha1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

  • pyruvate dehydrogenase (acetyl-transferring) activity Source: UniProtKB-EC
  • pyruvate dehydrogenase (NAD+) activity Source: MGI
  • pyruvate dehydrogenase activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processCarbohydrate metabolism, Glucose metabolism, Tricarboxylic acid cycle
LigandPyruvate, Thiamine pyrophosphate

Enzyme and pathway databases

ReactomeiR-MMU-204174 Regulation of pyruvate dehydrogenase (PDH) complex
R-MMU-389661 Glyoxylate metabolism and glycine degradation
R-MMU-5362517 Signaling by Retinoic Acid
R-MMU-70268 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:97532 Pdha1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi336K → Q or R: Decreases phosphorylation at S-232 and S-300 but does not affect activity or substrate metabolism. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 29MitochondrionBy similarityAdd BLAST29
ChainiPRO_000002044230 – 390Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrialAdd BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei63N6-acetyllysine; alternateCombined sources1
Modified residuei63N6-succinyllysine; alternateCombined sources1
Modified residuei232Phosphoserine; by PDK1Combined sources1 Publication1
Modified residuei244N6-acetyllysine; alternateCombined sources1
Modified residuei244N6-succinyllysine; alternateCombined sources1
Modified residuei267N6-acetyllysineCombined sources1
Modified residuei277N6-succinyllysineCombined sources1
Modified residuei293Phosphoserine; by PDK1, PDK2, PDK3 and PDK4Combined sources1 Publication1
Modified residuei295PhosphoserineCombined sources1
Modified residuei300Phosphoserine; by PDK1, PDK2, PDK3 and PDK4Combined sources1 Publication1
Modified residuei301PhosphotyrosineCombined sources1
Modified residuei313N6-acetyllysine; alternateCombined sources1
Modified residuei313N6-succinyllysine; alternateCombined sources1
Modified residuei321N6-acetyllysineCombined sources1
Modified residuei336N6-acetyllysine1 Publication1
Modified residuei385N6-succinyllysineCombined sources1

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

EPDiP35486
PaxDbiP35486
PeptideAtlasiP35486
PRIDEiP35486

2D gel databases

REPRODUCTION-2DPAGEP35486

PTM databases

iPTMnetiP35486
PhosphoSitePlusiP35486
SwissPalmiP35486

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000031299
CleanExiMM_PDHA1
ExpressionAtlasiP35486 baseline and differential
GenevisibleiP35486 MM

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

BioGridi202090, 1 interactor
IntActiP35486, 6 interactors
MINTiP35486
STRINGi10090.ENSMUSP00000033662

Structurei

3D structure databases

ProteinModelPortaliP35486
SMRiP35486
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0225 Eukaryota
COG1071 LUCA
GeneTreeiENSGT00530000063174
HOGENOMiHOG000281336
HOVERGENiHBG001863
InParanoidiP35486
KOiK00161
OMAiRRFEDKC
OrthoDBiEOG091G0966
PhylomeDBiP35486
TreeFamiTF300742

Family and domain databases

InterProiView protein in InterPro
IPR001017 DH_E1
IPR017597 Pyrv_DH_E1_asu_subgrp-y
IPR029061 THDP-binding
PfamiView protein in Pfam
PF00676 E1_dh, 1 hit
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_008810.3
UniGeneiMm.34775

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiODPA_MOUSE
AccessioniPrimary (citable) accession number: P35486
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: May 23, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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