DLAT dihydrolipoamide S-acetyltransferase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: DLATprovided by HGNC
Official Full Name: dihydrolipoamide S-acetyltransferaseprovided by HGNC
Primary source: HGNC:2896
See related: Ensembl:ENSG00000150768; HPRD:10578; MIM:608770; Vega:OTTHUMG00000133751
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: DLTA; PDCE2; PDC-E2
Summary: This gene encodes component E2 of the multi-enzyme pyruvate dehydrogenase complex (PDC). PDC resides in the inner mitochondrial membrane and catalyzes the conversion of pyruvate to acetyl coenzyme A. The protein product of this gene, dihydrolipoamide acetyltransferase, accepts acetyl groups formed by the oxidative decarboxylation of pyruvate and transfers them to coenzyme A. Dihydrolipoamide acetyltransferase is the 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 enventually leads to cirrhosis and liver failure. Mutations in this gene are also a cause of pyruvate dehydrogenase E2 deficiency which causes primary lactic acidosis in infancy and early childhood.[provided by RefSeq, Oct 2009]

Genomic context

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Location :: 11q23.1

Sequence :: Chromosome: 11; NC_000011.9 (111895538..111935002)

See DLAT in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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

Solution structure and characterisation of the human pyruvate dehydrogenase complex core assembly
Title: Solution structure and characterisation of the human pyruvate dehydrogenase complex core assembly.
Data suggest that the catalytic site of pyruvate dehydrogenase complex E2 rather than the previously reported lipoyl binding peptide may contain immunodominant epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.
Title: Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.
tissue specificity of the autoimmune injury in primary biliary cirrhosis is a consequence of the unique characteristics of HIBECs during apoptosis and can be explained by exposure to immune system of intact immunoreactive PDC-E2 within apoptotic blebs.
Title: Apotopes and the biliary specificity of primary biliary cirrhosis.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Species specificity in the interaction between hE1beta and hE2 in pyruvate dehydrogenase complex.
Title: Binding of pyruvate dehydrogenase to the core of the human pyruvate dehydrogenase complex.
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.
This study report two unrelated patients with pyruvate dehydrogenase deficiency caused by defects in the E2 subunit.
Title: Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency.
Having found that there is an excellent and almost unique match between the PDC-E2 autoepitope and a sequence in mycobacterial hsp65s, we tested the corresponding peptides for cross-reactivity using sera from 90 Spanish and British PBC patients.
Title: Disease-specific cross-reactivity between mimicking peptides of heat shock protein of Mycobacterium gordonae and dominant epitope of E2 subunit of pyruvate dehydrogenase is common in Spanish but not British patients with primary biliary cirrhosis.
a novel HLA-A*0201-restricted epitope PDC-E2 165 to 174 was defined in patients with primary biliary cirrhosis.
Title: Comprehensive mapping of HLA-A0201-restricted CD8 T-cell epitopes on PDC-E2 in primary biliary cirrhosis.
study of facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferase
Title: Facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferase.

Submit: New GeneRIF Correction See all (11)

Phenotypes

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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 E2 deficiency

MIM: 245348

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P10515	P08559	PDHA1	HPRD	PubMed
P10515	O00330	PDHX	HPRD	PubMed
P10515	Q15118	PDK1	HPRD	PubMed
P10515	Q15119	PDK2	HPRD	PubMed
P10515	Q15120	PDK3	HPRD	PubMed
P10515	Q16654	PDK4	HPRD	PubMed
BioGRID:108081	BioGRID:118799	ACAD9	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:116183	COPS5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108081	BioGRID:107722	COX5B	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:114032	CUL1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108081	BioGRID:108082	DLD	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:109537	HSPA1L	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:115114	KIAA0101	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108081	BioGRID:125021	MMGT1	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:122371	MRPL1	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:110803	NDUFS4	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:111017	OGDH	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:111186	PDHA1	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:111187	PDHA2	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:111188	PDHB	BioGRID	PubMed	Reconstituted Complex
BioGRID:108081	BioGRID:113737	PDHX	BioGRID	PubMed	Co-fractionation; Reconstituted Complex; Two-hybrid
BioGRID:108081	BioGRID:111189	PDK1	BioGRID	PubMed	Reconstituted Complex
BioGRID:108081	BioGRID:111190	PDK2	BioGRID	PubMed	Reconstituted Complex
BioGRID:108081	BioGRID:111191	PDK3	BioGRID	PubMed	Reconstituted Complex
BioGRID:108081	BioGRID:117199	PRKD3	BioGRID	PubMed	Two-hybrid
BioGRID:108081	BioGRID:111657	PSMA3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108081	BioGRID:119602	SIRT7	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108081	BioGRID:115755	SYNCRIP	BioGRID	PubMed	Co-fractionation
BioGRID:108081	BioGRID:113102	TSG101	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108081	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Citrate cycle (TCA cycle), organism-specific biosystem (from KEGG)
Citrate cycle (TCA cycle), organism-specific biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Citrate cycle (TCA cycle), conserved biosystem (from KEGG)
Citrate cycle (TCA cycle), conserved biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Glycolysis / Gluconeogenesis, organism-specific biosystem (from KEGG)
Glycolysis / Gluconeogenesis, organism-specific biosystemGlycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabol...
Glycolysis / Gluconeogenesis, conserved biosystem (from KEGG)
Glycolysis / Gluconeogenesis, conserved biosystemGlycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabol...
Glycolysis and Gluconeogenesis, organism-specific biosystem (from WikiPathways)
Glycolysis and Gluconeogenesis, organism-specific biosystem
Glycolysis and Gluconeogenesis
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Pyruvate metabolism, organism-specific biosystem (from REACTOME)
Pyruvate metabolism, organism-specific biosystemPyruvate sits at an intersection of key pathways of energy metabolism. It is the end product of glycolysis and the starting point for gluconeogenesis, and can be generated by transamination of alanin...
Pyruvate metabolism, organism-specific biosystem (from KEGG)
Pyruvate metabolism, organism-specific biosystem
Pyruvate metabolism
Pyruvate metabolism, conserved biosystem (from KEGG)
Pyruvate metabolism, conserved biosystem
Pyruvate metabolism
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystem (from REACTOME)
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystemPyruvate metabolism and the citric acid (TCA) cycle together link the processes of energy metabolism in a human cell with one another and with key biosynthetic reactions. Pyruvate, derived from the r...
Pyruvate oxidation, pyruvate => acetyl-CoA, organism-specific biosystem (from KEGG)
Pyruvate oxidation, pyruvate => acetyl-CoA, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Pyruvate oxidation, pyruvate => acetyl-CoA, conserved biosystem (from KEGG)
Pyruvate oxidation, pyruvate => acetyl-CoA, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Regulation of pyruvate dehydrogenase (PDH) complex, organism-specific biosystem (from REACTOME)
Regulation of pyruvate dehydrogenase (PDH) complex, organism-specific biosystemThe mitochondrial pyruvate dehydrogenase (PDH) complex catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. PDH inactivati...
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystem (from REACTOME)
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystemThe metabolism of pyruvate provides one source of acetyl-CoA which enters the citric acid (TCA, tricarboxylic acid) cycle to generate energy and the reducing equivalent NADH. These reducing equivalen...
pyruvate decarboxylation to acetyl CoA, organism-specific biosystem (from BIOCYC)
pyruvate decarboxylation to acetyl CoA, organism-specific biosystem2-oxo acid dehydrogenase complexes convert 2-oxo acids to the corresponding acyl-CoA derivatives and produce NADH and : CARBON-DIOXIDE in an irreversible reaction. Five members of this family are kno...
pyruvate decarboxylation to acetyl CoA, conserved biosystem (from BIOCYC)
pyruvate decarboxylation to acetyl CoA, conserved biosystemGeneral Background 2-oxo acid dehydrogenase complexes convert 2-oxo acids to the corresponding acyl-CoA derivatives and produce NADH and |FRAME: CARBON-DIOXIDE| in an irreversible reaction. Five mem...

General gene information

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Markers

WI-14848 (e-PCR)
- UniSTS:41612

D11S3980 (e-PCR)
- UniSTS:66452

STS-Y00978 (e-PCR)
- UniSTS:31898

SHGC-30253 (e-PCR)
- UniSTS:21403

STS-AA025365 (e-PCR)
- UniSTS:54431

DLAT_8300 (e-PCR)
- UniSTS:467649

Genotypes

See DLAT SNP Geneview Report
See DLAT SNP Genotype Report
See DLAT SNP Variation Viewer Report

Homology

Homologs of the DLAT gene: The DLAT gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
dihydrolipoyllysine-residue acetyltransferase activity	NAS Non-traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acetyl-CoA biosynthetic process	NAS Non-traceable Author Statement more info
glucose 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
tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrial pyruvate dehydrogenase complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial

Names: dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial; PBC; M2 antigen complex 70 kDa subunit; pyruvate dehydrogenase complex component E2; E2 component of pyruvate dehydrogenase complex; 70 kDa mitochondrial autoantigen of primary biliary cirrhosis; dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex; dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex mitochondrial

NP_001922.2

EC 2.3.1.12

NCBI Reference Sequences (RefSeq)

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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_013342.1 RefSeqGene

Range

5001..44456

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001931.4 → NP_001922.2 dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial precursor

Status: REVIEWED

Source sequence(s)

AK057299, AW188637, BC039084

Consensus CDS

CCDS8354.1

UniProtKB/Swiss-Prot

P10515

UniProtKB/TrEMBL

Q86YI5

Related

ENSP00000280346, OTTHUMP00000165200, ENST00000280346, OTTHUMT00000258167

Conserved Domains (4) summary

cd06849
Location:219 – 293
Blast Score: 241

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 ...

pfam00198
Location:436 – 647
Blast Score: 723

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

pfam02817
Location:353 – 391
Blast Score: 175

E3_binding; e3 binding domain

TIGR01349
Location:221 – 647
Blast Score: 1500

PDHac_trf_mito; pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase, long form

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 PATCHES

Genomic

NW_003871080.1 Reference GRCh37.p10 PATCHES

Range

276805..316269

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p10 Primary Assembly

Range

111895538..111935002

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

107819561..107858905

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018922.1 Alternate CHM1_1.0

Range

111759007..111798564

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01039806.1 (8006..22875)	None
genomic	ABBA01039807.1	None
genomic	ABBA01039808.1	None
genomic	ABBA01039809.1	None
genomic	AMYH01004033.1 (58339..92136)	None
genomic	AMYH01004034.1	None
genomic	AP000907.6 (127063..165481)	None
genomic	CH471065.1	EAW67174.1
		EAW67175.1
genomic	EF444972.1	ACA05975.1
mRNA	AF317200.1	AAG31658.1
mRNA	AK057299.1	BAG51900.1
mRNA	AK223596.1	BAD97316.1
mRNA	AK296274.1	BAG58983.1
mRNA	AK297103.1	BAG59614.1
mRNA	AK299562.1	BAG61505.1
mRNA	AK303930.1	BAG64858.1
mRNA	AL832703.1	None
mRNA	AW188637.1	None
mRNA	BC039084.1	AAH39084.1
mRNA	DB551427.1	None
mRNA	X13822.1	CAA32052.1
mRNA	Y00978.1	CAA68787.1
other-genetic	DQ892447.2	ABM83373.1
other-genetic	DQ895658.2	ABM86584.1