Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial precursor

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P35486 (ODPA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 113. History...

Clusters with 100%, 90%, 50% identity |

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	390 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.13
Catalytic activity	Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO₂. Ref.4 Ref.13
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.12.
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.
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.6 Ref.7 Ref.13

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism Tricarboxylic acid cycle
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	Pyruvate Thiamine pyrophosphate
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	acetyl-CoA biosynthetic process from pyruvate Inferred from sequence or structural similarity. Source: UniProtKB glycolysis Inferred from electronic annotation. Source: InterPro tricarboxylic acid cycle Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 14651853 PubMed 18614015. Source: MGI pyruvate dehydrogenase complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	pyruvate dehydrogenase (acetyl-transferring) activity Inferred from electronic annotation. Source: EC pyruvate dehydrogenase activity Inferred from mutant phenotype Ref.4. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 29

Mitochondrion By similarity

Chain

30 – 390

361

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

PRO_0000020442

Amino acid modifications

Modified residue

232

Phosphoserine; by PDK1 Ref.9 Ref.10 Ref.12

Modified residue

289

Phosphotyrosine Ref.10

Modified residue

293

Phosphoserine; by PDK1, PDK2, PDK3 and PDK4 Ref.5 Ref.9 Ref.10 Ref.11 Ref.12

Modified residue

295

Phosphoserine By similarity

Modified residue

300

Phosphoserine; by PDK1, PDK2, PDK3 and PDK4 Ref.9 Ref.10 Ref.11 Ref.12

Modified residue

301

Phosphotyrosine Ref.8

Modified residue

321

N6-acetyllysine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

P35486 [UniParc].

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

390

43,232

        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' referencesShow '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, 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]	"Proteomic analysis of in vivo phosphorylated synaptic proteins." Collins M.O., Yu L., Coba M.P., Husi H., Campuzano I., Blackstock W.P., Choudhary J.S., Grant S.G. J. Biol. Chem. 280:5972-5982(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293, MASS SPECTROMETRY. Tissue: Forebrain.
[6]	"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.
[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, MASS SPECTROMETRY. Tissue: Brain.
[9]	"Mitochondrial phosphoproteome revealed by an improved IMAC method and MS/MS/MS." Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y. Mol. Cell. Proteomics 6:669-676(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-293 AND SER-300, MASS SPECTROMETRY. Tissue: Liver.
[10]	"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; TYR-289; SER-293 AND SER-300, MASS SPECTROMETRY. Tissue: Liver.
[11]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293 AND SER-300, MASS SPECTROMETRY. Tissue: Melanoma.
[12]	"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.
[13]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M76727 mRNA. Translation: AAA53046.1. BC007142 mRNA. Translation: AAH07142.1.
IPI	IPI00337893.
PIR	S23506.
RefSeq	NP_032836.1. NM_008810.2.
UniGene	Mm.34775.
3D structure databases
ProteinModelPortal	P35486.
SMR	P35486. Positions 29-390.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35486. 3 interactions.
STRING	10090.ENSMUSP00000033662.
PTM databases
PhosphoSite	P35486.
2D gel databases
REPRODUCTION-2DPAGE	P35486.
Proteomic databases
PaxDb	P35486.
PRIDE	P35486.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033662; ENSMUSP00000033662; ENSMUSG00000031299.
GeneID	18597.
KEGG	mmu:18597.
Organism-specific databases
CTD	5160.
MGI	MGI:97532. Pdha1.
Phylogenomic databases
eggNOG	COG1071.
HOGENOM	HOG000281336.
HOVERGEN	HBG001863.
InParanoid	P35486.
KO	K00161.
OrthoDB	EOG4W0XD6.
Gene expression databases
ArrayExpress	P35486.
Bgee	P35486.
CleanEx	MM_PDHA1.
Genevestigator	P35486.
GermOnline	ENSMUSG00000031299. Mus musculus.
Family and domain databases
InterPro	IPR001017. DH_E1. IPR017597. Pyrv_DH_E1_asu_subgrp-y. [Graphical view]
Pfam	PF00676. E1_dh. 1 hit. [Graphical view]
TIGRFAMs	TIGR03182. PDH_E1_alph_y. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	PDHA1. mouse.
NextBio	294490.
SOURCE	Search...

Entry information

Entry name

ODPA_MOUSE

Accession

Primary (citable) accession number: P35486

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	April 3, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents