Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P35486 (ODPA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

EC=1.2.4.1
Alternative name(s):
PDHE1-A type I
Gene names
Name:Pdha1
Synonyms:Pdha-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length390 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.12

Catalytic activity

Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2. Ref.4 Ref.12

Cofactor

Thiamine pyrophosphate.

Enzyme regulation

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

Subunit structure

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.

Subcellular location

Mitochondrion matrix Ref.10.

Tissue specificity

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

Post-translational modification

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.

Acetylation alters the phosphorylation pattern. Deacetylated by SIRT3. Ref.13

Disruption phenotype

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. Ref.4 Ref.5 Ref.7 Ref.12

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2929Mitochondrion By similarity
Chain30 – 390361Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
PRO_0000020442

Amino acid modifications

Modified residue631N6-acetyllysine; alternate Ref.15
Modified residue631N6-succinyllysine; alternate Ref.14
Modified residue2321Phosphoserine; by PDK1 Ref.6 Ref.10
Modified residue2441N6-acetyllysine; alternate Ref.15
Modified residue2441N6-succinyllysine; alternate Ref.14
Modified residue2671N6-acetyllysine Ref.15
Modified residue2771N6-succinyllysine Ref.14
Modified residue2931Phosphoserine; by PDK1, PDK2, PDK3 and PDK4 Ref.6 Ref.10 Ref.11
Modified residue2951Phosphoserine Ref.6
Modified residue3001Phosphoserine; by PDK1, PDK2, PDK3 and PDK4 Ref.6 Ref.10
Modified residue3011Phosphotyrosine Ref.8
Modified residue3131N6-acetyllysine; alternate Ref.14
Modified residue3131N6-succinyllysine; alternate Ref.14
Modified residue3211N6-acetyllysine Ref.15
Modified residue3361N6-acetyllysine Ref.13
Modified residue3851N6-succinyllysine Ref.14

Experimental info

Mutagenesis3361K → Q or R: Decreases phosphorylation at S-232 and S-300 but does not affect activity or substrate metabolism. Ref.13

Sequences

Sequence LengthMass (Da)Tools
P35486 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 40898944CE8E0A03

FASTA39043,232
        10         20         30         40         50         60 
MRKMLAAVSR VLAGSAQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED 

        70         80         90        100        110        120 
GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA 

       130        140        150        160        170        180 
HGFTFTRGLP VRAILAELTG RRGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA 

       190        200        210        220        230        240 
CKYNGKDEVC LTLYGDGAAN QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST 

       250        260        270        280        290        300 
DYYKRGDFIP GLRVDGMDIL CVREATKFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS 

       310        320        330        340        350        360 
YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP 

       370        380        390 
LEELGYHIYS SDPPFEVRGA NQWIKFKSVS 

« Hide

References

« Hide 'large scale' references
[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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M76727 mRNA. Translation: AAA53046.1.
BC007142 mRNA. Translation: AAH07142.1.
PIRS23506.
RefSeqNP_032836.1. NM_008810.2.
UniGeneMm.34775.

3D structure databases

ProteinModelPortalP35486.
SMRP35486. Positions 29-390.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP35486. 6 interactions.
MINTMINT-4105793.
STRING10090.ENSMUSP00000033662.

PTM databases

PhosphoSiteP35486.

2D gel databases

REPRODUCTION-2DPAGEP35486.

Proteomic databases

PaxDbP35486.
PRIDEP35486.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033662; ENSMUSP00000033662; ENSMUSG00000031299.
GeneID18597.
KEGGmmu:18597.
UCSCuc009utc.1. mouse.

Organism-specific databases

CTD5160.
MGIMGI:97532. Pdha1.

Phylogenomic databases

eggNOGCOG1071.
HOGENOMHOG000281336.
HOVERGENHBG001863.
InParanoidP35486.
KOK00161.
OMAEVKHYRE.
OrthoDBEOG73JKVQ.
PhylomeDBP35486.
TreeFamTF300742.

Gene expression databases

ArrayExpressP35486.
BgeeP35486.
CleanExMM_PDHA1.
GenevestigatorP35486.

Family and domain databases

InterProIPR001017. DH_E1.
IPR017597. Pyrv_DH_E1_asu_subgrp-y.
[Graphical view]
PfamPF00676. E1_dh. 1 hit.
[Graphical view]
TIGRFAMsTIGR03182. PDH_E1_alph_y. 1 hit.
ProtoNetSearch...

Other

ChiTaRSPDHA1. mouse.
NextBio294490.
PROP35486.
SOURCESearch...

Entry information

Entry nameODPA_MOUSE
AccessionPrimary (citable) accession number: P35486
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

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