PDHX pyruvate dehydrogenase complex, component X [Homo sapiens] - Gene

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Summary

Official Symbol: PDHXprovided by HGNC
Official Full Name: pyruvate dehydrogenase complex, component Xprovided by HGNC
Primary source: HGNC:21350
See related: Ensembl:ENSG00000110435; HPRD:02002; MIM:608769; Vega:OTTHUMG00000166491
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: E3BP; OPDX; PDX1; proX; DLDBP
Summary: The pyruvate dehydrogenase (PDH) complex is located in the mitochondrial matrix and catalyzes the conversion of pyruvate to acetyl coenzyme A. The PDH complex thereby links glycolysis to Krebs cycle. The PDH complex contains three catalytic subunits, E1, E2, and E3, two regulatory subunits, E1 kinase and E1 phosphatase, and a non-catalytic subunit, E3 binding protein (E3BP). This gene encodes the E3 binding protein subunit; also known as component X of the pyruvate dehydrogenase complex. This protein tethers E3 dimers to the E2 core of the PDH complex. Defects in this gene are a cause of pyruvate dehydrogenase deficiency which results in neurological dysfunction and lactic acidosis in infancy and early childhood. This protein is also a minor antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC eventually leads to cirrhosis and liver failure. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]

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Genomic context

Location :: 11p13

Sequence :: Chromosome: 11; NC_000011.9 (34937677..35017675)

See PDHX in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 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?

genetic association with systemic lupus erythematosus to a haplotype between PDHX and CD44 was established.
Title: Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
PDHX-assisted photosensitization with rose Bengal induces structural and functional alteration of mitochondria in HeLa cells.
Title: Enzyme-assisted photosensitization with rose Bengal acetate induces structural and functional alteration of mitochondria in HeLa cells.
determination that PDH and complex III exist at a steady-state ratio of 1:100, 1:128 and 1:202 in HeLa cell extracts, fibroblast mitochondria and heart tissue mitochondria, respectively
Title: Quantitative proteomics: the copy number of pyruvate dehydrogenase is more than 10(2)-fold lower than that of complex III in human mitochondria.
model of the pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and binding of the E1 and E3 components
Title: Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components.
specificity of pairing for human E3BP with E3 from its subcomplex structure to be most likely due to conformational rigidity of the binding fragment of the E3-binding domain of E3BP and its exquisite amino acid match with the E3 target interface
Title: How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex.
These data provide an additional case of E3BP deficiency with a unique and previously unreported deletion in the PDHX gene.
Title: Leigh's disease due to a new mutation in the PDHX gene.
A cluster of disease-causing E3 mutations located near the center of the E3BD/E3 interface prevents the efficient recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction of the PDC catalytic machine.
Title: Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex.
Despite the presence of antibodies reactive with PDC-E3BP in the majority of primary biliary cirrhosis (PBC) patients this self-protein is not a dominant T-cell autoantigen in PBC.
Title: PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis.

Submit: New GeneRIF Correction

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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

Lacticacidemia due to PDX1 deficiency

MIM: 245349

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Products	Interactant	Other Gene	Source	Pubs	Description
O00330	P10515	DLAT	HPRD	PubMed
O00330	P09622	DLD	HPRD	PubMed
O00330	Q09472	EP300	HPRD	PubMed
O00330	Q01844	EWSR1	HPRD	PubMed
O00330	P11177	PDHB	HPRD	PubMed
O00330	Q15119	PDK2	HPRD	PubMed
BioGRID:113737	BioGRID:108081	DLAT	BioGRID	PubMed	Reconstituted Complex
BioGRID:113737	BioGRID:108431	EWSR1	BioGRID	PubMed	Two-hybrid
BioGRID:113737	BioGRID:111188	PDHB	BioGRID	PubMed	Co-purification
BioGRID:113737	BioGRID:111190	PDK2	BioGRID	PubMed	Reconstituted Complex
BioGRID:113737	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
transferase activity, transferring acyl groups	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
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 protein X component, mitochondrial

Names: pyruvate dehydrogenase protein X component, mitochondrial; pyruvate dehydrogenase complex, E3-binding protein subunit; lipoyl-containing pyruvate dehydrogenase complex component X; pyruvate dehydrogenase complex, lipoyl-containing component X; dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex

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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_013368.1 RefSeqGene

Range

5001..84999

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001135024.1 → NP_001128496.1 pyruvate dehydrogenase protein X component, mitochondrial isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a segment in the 5' region, resulting in upstream in-frame AUG start codon, as compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus, as compared to isoform 1.

Source sequence(s)

AA282215, BI915296, DA573433, U79296

Consensus CDS

CCDS44569.1

UniProtKB/TrEMBL

E9PB14

UniProtKB/Swiss-Prot

O00330

Related

ENSP00000389404, OTTHUMP00000233038, ENST00000448838, OTTHUMT00000390016

Conserved Domains (4) summary

cd06849
Location:42 – 116
Blast Score: 258

lipoyl_domain; Lipoyl domain of the dihydrolipoyl acyltransferase component (E2) of 2-oxo acid dehydrogenases. 2-oxo acid dehydrogenase multienzyme complexes, like pyruvate dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2-oxo acid ...

PRK11856
Location:41 – 485
Blast Score: 961

PRK11856; branched-chain alpha-keto acid dehydrogenase subunit E2; Reviewed

pfam02817
Location:166 – 203
Blast Score: 123

E3_binding; e3 binding domain

cl02008
Location:276 – 485
Blast Score: 647

2-oxoacid_dh; 2-oxoacid dehydrogenases acyltransferase (catalytic domain)
NM_001166158.1 → NP_001159630.1 pyruvate dehydrogenase protein X component, mitochondrial isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks multiple in-frame exons in the central coding region, compared to variant 1, resulting in a protein (isoform 3) that lacks 227 aa, compared to isoform 1.

Source sequence(s)

AA282215, AC107928, AF001437, BC010389

Consensus CDS

CCDS53616.1

UniProtKB/TrEMBL

E9PBP7

UniProtKB/Swiss-Prot

O00330

Related

ENSP00000415695, OTTHUMP00000233040, ENST00000430469, OTTHUMT00000390018

Conserved Domains (2) summary

cd06849
Location:57 – 114
Blast Score: 231

lipoyl_domain; Lipoyl domain of the dihydrolipoyl acyltransferase component (E2) of 2-oxo acid dehydrogenases. 2-oxo acid dehydrogenase multienzyme complexes, like pyruvate dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2-oxo acid ...

cl02008
Location:109 – 273
Blast Score: 508

2-oxoacid_dh; 2-oxoacid dehydrogenases acyltransferase (catalytic domain)
NM_003477.2 → NP_003468.2 pyruvate dehydrogenase protein X component, mitochondrial isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AA282215, AC107928, AF001437, BC010389

Consensus CDS

CCDS7896.1

UniProtKB/Swiss-Prot

O00330

Related

ENSP00000227868, OTTHUMP00000233039, ENST00000227868, OTTHUMT00000390017

Conserved Domains (4) summary

cd06849
Location:57 – 131
Blast Score: 264

lipoyl_domain; Lipoyl domain of the dihydrolipoyl acyltransferase component (E2) of 2-oxo acid dehydrogenases. 2-oxo acid dehydrogenase multienzyme complexes, like pyruvate dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2-oxo acid ...

PRK11856
Location:56 – 500
Blast Score: 980

PRK11856; branched-chain alpha-keto acid dehydrogenase subunit E2; Reviewed

pfam02817
Location:181 – 218
Blast Score: 124

E3_binding; e3 binding domain

cl02008
Location:291 – 500
Blast Score: 652

2-oxoacid_dh; 2-oxoacid dehydrogenases acyltransferase (catalytic domain)

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_000011.9 Reference GRCh37.p5 Primary Assembly

Range

34937677..35017675

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

34636155..34716134

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC107928.3 (147874..160763)	None
genomic	AJ298105.1	CAC18649.1
genomic	AL138810.10 (16036..82987)	None
genomic	CH471064.2	EAW68158.1
		EAW68159.1
		EAW68160.1
mRNA	AA282215.1	None
mRNA	AF001437.1	AAB66315.1
mRNA	AF052166.1	None
mRNA	AK301384.1	BAG62924.1
mRNA	AK312463.1	BAG35370.1
mRNA	BC010389.1	AAH10389.1
mRNA	BI915296.1	None
mRNA	BX648910.1	None
mRNA	DA573433.1	None
mRNA	U79296.1	AAB50223.1
mRNA	U82328.1	AAC39661.1
mRNA	Y13145.1	CAA73606.1
other-genetic	JF432191.1	ADZ15408.1