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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

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

GO - Biological processi

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

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:97532. Pdha1.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: UniProtKB-SubCell
  • mitochondrion Source: MGI
  • myelin sheath Source: UniProtKB
  • nucleus Source: MGI
  • 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)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 residuei231PhosphothreonineBy similarity1
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.
MINTiMINT-4105793.
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.
OMAiWMYQKML.
OrthoDBiEOG091G0966.
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_008810.3.
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_008810.3.
UniGeneiMm.34775.

3D structure databases

ProteinModelPortaliP35486.
SMRiP35486.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202090. 1 interactor.
IntActiP35486. 6 interactors.
MINTiMINT-4105793.
STRINGi10090.ENSMUSP00000033662.

PTM databases

iPTMnetiP35486.
PhosphoSitePlusiP35486.
SwissPalmiP35486.

2D gel databases

REPRODUCTION-2DPAGEP35486.

Proteomic databases

EPDiP35486.
PaxDbiP35486.
PeptideAtlasiP35486.
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

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

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.

Miscellaneous databases

ChiTaRSiPdha1. mouse.
PROiP35486.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031299.
CleanExiMM_PDHA1.
ExpressionAtlasiP35486. baseline and differential.
GenevisibleiP35486. MM.

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...

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 2, 2016
This is version 146 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

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 one 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.