PDHA1 pyruvate dehydrogenase (lipoamide) alpha 1 [Homo sapiens] - Gene

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Summary

Official Symbol: PDHA1provided by HGNC
Official Full Name: pyruvate dehydrogenase (lipoamide) alpha 1provided by HGNC
Primary source: HGNC:8806
Locus tag: RP11-723P2.1
See related: Ensembl:ENSG00000131828; HPRD:02420; MIM:300502; Vega:OTTHUMG00000021224
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PDHA; PHE1A; PDHCE1A
Summary: The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 alpha 1 subunit containing the E1 active site, and plays a key role in the function of the PDH complex. Mutations in this gene are associated with pyruvate dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

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Genomic context

Location :: Xp22.1

Sequence :: Chromosome: X; NC_000023.10 (19362011..19379825)

See PDHA1 in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

TNFalpha can inhibit pulmonary artery smooth muscle cells pyruvate dehydrogenase activity and induce a pulmonary arterial hypertension phenotype.
Title: Pyruvate dehydrogenase inhibition by the inflammatory cytokine TNFα contributes to the pathogenesis of pulmonary arterial hypertension.
We provide an efficient stepwise strategy for mutation screening in pyruvate dehydrogenase complex genes and expand the growing list of PDHA1 mutations analyzed at the structural level
Title: Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein.
Data show that overexpression of ErbB2 maintains PDH flux by suppressing PDK4 expression in an Erk-dependent manner.
Title: Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation.
4 affected female patients with PDHA1 mutations who had with severe cortical atrophy, dilated ventricles, and an incomplete corpus callosum.
Title: MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha deficiency.
We document the broad variability of clinical symptoms of pdha1 deficiency disease. We proved that normal PDHc activity may not exclude the disease.
Title: Two patients with clinically distinct manifestation of pyruvate dehydrogenase deficiency due to mutations in PDHA1 gene.
Novel nonsense mutation (R263X) of the E1alpha subunit in pyruvate dehydrogenase complex deficiency
Title: Novel mutation (R263X) of the E1α subunit in pyruvate dehydrogenase complex deficiency.
PDHA1 mutations were screened in 40 patients with biochemically demonstrated pyruvate dehydrogenase complex deficiency deficiency or strong clinical suspicion and changes with probable pathological significance were found in 20.
Title: Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency.
AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells.
Title: AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells.
Our results encourage the use of amino acid supplementation to overcome the metabolic/biochemical changes induced by PDHA1 gene specific mutations associated with mild pyruvate dehydrogenase complex phenotypes.
Title: Pyruvate dehydrogenase deficiency: identification of a novel mutation in the PDHA1 gene which responds to amino acid supplementation.
two synonymous mutations expand the spectrum of rare PDHA1 splicing mutations, all of which are located in non canonical splice sites.
Title: Two silent substitutions in the PDHA1 gene cause exon 5 skipping by disruption of a putative exonic splicing enhancer.

Submit: New GeneRIF Correction See all (17)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Pyruvate dehydrogenase E1-alpha deficiency

MIM: 312170

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000275.1	NP_005382.1	PDK3	BIND	PubMed	PDK3 interacts with and phosphorylates PDHA1 (E1p).
P08559	P10515	DLAT	HPRD	PubMed
P08559	P56537	EIF6	HPRD	PubMed
P08559	P08559	PDHA1	HPRD	PubMed
P08559	P11177	PDHB	HPRD	PubMed
P08559	Q15118	PDK1	HPRD	PubMed
P08559	Q15119	PDK2	HPRD	PubMed
P08559	Q15120	PDK3	HPRD	PubMed
P08559	Q16654	PDK4	HPRD	PubMed
P08559	Q9P0J1	PDP1	HPRD	PubMed
BioGRID:111186	BioGRID:118855	BABAM1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111186	BioGRID:121948	C12orf44	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111186	BioGRID:114096	DGKE	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111186	BioGRID:109898	EIF6	BioGRID	PubMed	Two-hybrid
BioGRID:111186	BioGRID:111188	PDHB	BioGRID	PubMed	Co-purification
BioGRID:111186	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111186	BioGRID:116078	USP19	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111186	BioGRID:124884	WDR20	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
oxidoreductase activity	IEA Inferred from Electronic Annotation more info
oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor	IEA Inferred from Electronic Annotation more info
pyruvate dehydrogenase (acetyl-transferring) activity	IEA Inferred from Electronic Annotation more info
pyruvate dehydrogenase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
glycolysis	IEA Inferred from Electronic Annotation more info
metabolic process	IEA Inferred from Electronic Annotation more info
pyruvate metabolic process	TAS Traceable Author Statement more info
regulation of acetyl-CoA biosynthetic process from pyruvate	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

Names: pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; PDHE1-A type I; pyruvate dehydrogenase complex, E1-alpha polypeptide 1

NP_000275.1

EC 1.2.4.1

NP_001166925.1

EC 1.2.4.1

NP_001166926.1

EC 1.2.4.1

NP_001166927.1

EC 1.2.4.1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016781.1 RefSeqGene

Range

5001..22815

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000284.3 → NP_000275.1 pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript and encodes isoform 1.

Source sequence(s)

AL732326, BU170389, DC361191, L13318, R49470

Consensus CDS

CCDS14192.1

UniProtKB/Swiss-Prot

P08559

Related

ENSP00000394382, OTTHUMP00000023015, ENST00000422285, OTTHUMT00000055977

Conserved Domains (2) summary

cd02000
Location:64 – 353
Blast Score: 951

TPP_E1_PDC_ADC_BCADC; Thiamine pyrophosphate (TPP) family, E1 of PDC_ADC_BCADC subfamily, TPP-binding module; composed of proteins similar to the E1 components of the human pyruvate dehydrogenase complex (PDC), the acetoin dehydrogenase complex (ADC) and the branched chain ...

TIGR03182
Location:58 – 370
Blast Score: 1327

PDH_E1_alph_y; pyruvate dehydrogenase E1 component, alpha subunit
NM_001173454.1 → NP_001166925.1 pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an additional in-frame coding exon compared to variant 1, resulting in a longer isoform (2) compared to isoform 1.

Source sequence(s)

AK293250, AL732326, BU170389, DC361191, R49470

Consensus CDS

CCDS55380.1

Related

ENSP00000369134, ENST00000379806

Conserved Domains (2) summary

cd02000
Location:102 – 391
Blast Score: 961

TPP_E1_PDC_ADC_BCADC; Thiamine pyrophosphate (TPP) family, E1 of PDC_ADC_BCADC subfamily, TPP-binding module; composed of proteins similar to the E1 components of the human pyruvate dehydrogenase complex (PDC), the acetoin dehydrogenase complex (ADC) and the branched chain ...

TIGR03182
Location:96 – 408
Blast Score: 1338

PDH_E1_alph_y; pyruvate dehydrogenase E1 component, alpha subunit
NM_001173455.1 → NP_001166926.1 pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternative acceptor splice site at one of the coding exons compared to variant 1, resulting in a longer isoform (3) compared to isoform 1.

Source sequence(s)

AK296341, AL732326, DC361191, R49470

Consensus CDS

CCDS55381.1

UniProtKB/Swiss-Prot

P08559

Related

ENSP00000438550, ENST00000545074

Conserved Domains (2) summary

cd02000
Location:64 – 360
Blast Score: 938

TPP_E1_PDC_ADC_BCADC; Thiamine pyrophosphate (TPP) family, E1 of PDC_ADC_BCADC subfamily, TPP-binding module; composed of proteins similar to the E1 components of the human pyruvate dehydrogenase complex (PDC), the acetoin dehydrogenase complex (ADC) and the branched chain ...

TIGR03182
Location:58 – 377
Blast Score: 1313

PDH_E1_alph_y; pyruvate dehydrogenase E1 component, alpha subunit
NM_001173456.1 → NP_001166927.1 pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) is missing an in-frame coding exon compared to variant 1, resulting in a shorter isoform (4) compared to isoform 1.

Source sequence(s)

AK296341, AK296457, AL732326, DC361191, R49470

Consensus CDS

CCDS55382.1

UniProtKB/Swiss-Prot

P08559

Related

ENSP00000440761, ENST00000540249

Conserved Domains (2) summary

cd02000
Location:64 – 322
Blast Score: 787

TPP_E1_PDC_ADC_BCADC; Thiamine pyrophosphate (TPP) family, E1 of PDC_ADC_BCADC subfamily, TPP-binding module; composed of proteins similar to the E1 components of the human pyruvate dehydrogenase complex (PDC), the acetoin dehydrogenase complex (ADC) and the branched chain ...

TIGR03182
Location:58 – 339
Blast Score: 1135

PDH_E1_alph_y; pyruvate dehydrogenase E1 component, alpha subunit

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p5 Primary Assembly

Range

19362011..19379825

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

17111170..17129001

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF085457.1	AAD16047.1
genomic	AF125053.1	AAD23841.1
genomic	AF125054.1	AAD23842.1
genomic	AF125055.1	AAD23843.1
genomic	AF125056.1	AAD23844.1
genomic	AF125057.1	AAD23845.1
genomic	AF125058.1	AAD23846.1
genomic	AF125059.1	AAD23847.1
genomic	AF125060.1	AAD23848.1
genomic	AF125061.1	AAD23849.1
genomic	AF125062.1	AAD23850.1
genomic	AF125063.1	AAD23851.1
genomic	AF125064.1	AAD23852.1
genomic	AF125065.1	AAD23853.1
genomic	AF125066.1	AAD23854.1
genomic	AF125067.1	AAD23855.1
genomic	AF125068.1	AAD23856.1
genomic	AF125069.1	AAD23857.1
genomic	AF125070.1	AAD23858.1
genomic	AF125071.1	AAD23859.1
genomic	AF125072.1	AAD23860.1
genomic	AF125073.1	AAD23861.1
genomic	AF125074.1	AAD23862.1
genomic	AF125075.1	AAD23863.1
genomic	AF125076.1	AAD23864.1
genomic	AF125078.1	AAD23866.1
genomic	AF125079.1	AAD23867.1
genomic	AF125080.1	AAD23868.1
genomic	AF125081.1	AAD23869.1
genomic	AF125082.1	AAD23870.1
genomic	AF125083.1	AAD23871.1
genomic	AF125084.1	AAD23872.1
genomic	AF125085.1	AAD23873.1
genomic	AF125086.1	AAD23874.1
genomic	AF125087.1	AAD23875.1
genomic	AF125088.1	AAD23876.1
genomic	AL732326.4	CAI41287.1
		CAI41288.1
		CAI41289.1
		CAI41290.1
		CAI41291.1
		CAI41292.1
genomic	CH471074.1	EAW98960.1
		EAW98961.1
genomic	D90084.1	BAA14121.1
genomic	M21447.1	AAA31853.2
genomic	M27257.1	AAA60051.1
genomic	U75933.1	AAB39723.1
genomic	U75934.1	AAB39724.1
genomic	U75935.1	AAB39725.1
genomic	U75936.1	AAB39726.1
genomic	U75937.1	AAB39727.1
genomic	U75938.1	AAB39728.1
genomic	U75939.1	AAB39729.1
genomic	U75940.1	AAB39730.1
mRNA	AK129887.1	None
mRNA	AK222740.1	BAD96460.1
mRNA	AK222988.1	BAD96708.1
mRNA	AK293250.1	BAH11476.1
mRNA	AK296341.1	BAH12323.1
mRNA	AK296457.1	BAH12361.1
mRNA	AK312263.1	BAG35194.1
mRNA	AW204705.1	None
mRNA	BC002406.1	AAH02406.1
mRNA	BU170389.1	None
mRNA	DA075402.1	None
mRNA	DC361191.1	None
mRNA	EF576990.1	ABQ58815.1
mRNA	EF590116.1	None
mRNA	EF590117.1	ABQ59099.1
mRNA	J03503.1	AAA60055.1
mRNA	J03575.1	AAA60050.1
mRNA	L13318.1	AAA60227.1
mRNA	L48690.1	AAB59581.1
mRNA	M24848.1	AAA36533.1
mRNA	R49470.1	None
mRNA	X52709.1	CAA36933.1
mRNA	X52710.1	CAA36934.1
other-genetic	DQ891865.2	ABM82791.1
other-genetic	DQ895054.2	ABM85980.1
other-genetic	DQ895057.2	ABM85983.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P08559.3	GenPept	UniProtKB/Swiss-Prot:P08559
P78557	GenPept	UniProtKB/TrEMBL:P78557
Q53GE3	GenPept	UniProtKB/TrEMBL:Q53GE3
Q5JPT9	GenPept	UniProtKB/TrEMBL:Q5JPT9
Q5JPU0	GenPept	UniProtKB/TrEMBL:Q5JPU0
Q5JPU1	GenPept	UniProtKB/TrEMBL:Q5JPU1
Q5JPU2	GenPept	UniProtKB/TrEMBL:Q5JPU2
Q5JPU3	GenPept	UniProtKB/TrEMBL:Q5JPU3
Q6LCA3	GenPept	UniProtKB/TrEMBL:Q6LCA3
Q99724	GenPept	UniProtKB/TrEMBL:Q99724
Q99725	GenPept	UniProtKB/TrEMBL:Q99725
Q9NP11	GenPept	UniProtKB/TrEMBL:Q9NP11
Q9UNV7	GenPept	UniProtKB/TrEMBL:Q9UNV7