DLAT

Protein identityUniProt · HPA

UniProt accession

P10515

Gene

DLAT

Ensembl

ENSG00000150768

Chromosome

11

Canonical length

647 aa

Protein class

Citric acid cycle related proteins, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria,Connecting piece

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

647 residues, UniProt reviewed canonical sequence.

>P10515|DLAT
     1  MWRVCARRAQ NVAPWAGLEA RWTALQEVPG TPRVTSRSGP APARRNSVTT GYGGVRALCG
    61  WTPSSGATPR NRLLLQLLGS PGRRYYSLPP HQKVPLPSLS PTMQAGTIAR WEKKEGDKIN
   121  EGDLIAEVET DKATVGFESL EECYMAKILV AEGTRDVPIG AIICITVGKP EDIEAFKNYT
   181  LDSSAAPTPQ AAPAPTPAAT ASPPTPSAQA PGSSYPPHMQ VLLPALSPTM TMGTVQRWEK
   241  KVGEKLSEGD LLAEIETDKA TIGFEVQEEG YLAKILVPEG TRDVPLGTPL CIIVEKEADI
   301  SAFADYRPTE VTDLKPQVPP PTPPPVAAVP PTPQPLAPTP SAPCPATPAG PKGRVFVSPL
   361  AKKLAVEKGI DLTQVKGTGP DGRITKKDID SFVPSKVAPA PAAVVPPTGP GMAPVPTGVF
   421  TDIPISNIRR VIAQRLMQSK QTIPHYYLSI DVNMGEVLLV RKELNKILEG RSKISVNDFI
   481  IKASALACLK VPEANSSWMD TVIRQNHVVD VSVAVSTPAG LITPIVFNAH IKGVETIAND
   541  VVSLATKARE GKLQPHEFQG GTFTISNLGM FGIKNFSAII NPPQACILAI GASEDKLVPA
   601  DNEKGFDVAS MMSVTLSCDH RVVDGAVGAQ WLAEFRKYLE KPITMLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DLAT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.44

Highest tissue expression

84 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DLAT.

Disease | AllUniProt

Conditions DLAT is implicated in, by any mechanism.

• Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) MIM:245348

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 401 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pyruvate dehydrogenase E2 deficiency
• Inborn genetic diseases
• Pancreatic adenocarcinoma

Disease | ImmuneIEDB

Conditions an epitope on DLAT was assayed in.

• primary biliary cholangitis B and T cell
• type 1 diabetes mellitus B cell
• rheumatoid arthritis B cell
• systemic scleroderma B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against DLAT are reported. Each links to that disease's full target list.

• Liver Cirrhosis, Biliary 56
• Scleroderma, Systemic 3

Showing 2 of 3 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for DLAT from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.86

gnomAD pLI

0

gnomAD missense Z

0.42

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• glucose metabolic process
• pyruvate catabolic process
• pyruvate decarboxylation to acetyl-CoA
• tricarboxylic acid cycle

Molecular functions

• dihydrolipoyllysine-residue acetyltransferase activity
• identical protein binding

Cellular components

• mitochondrial matrix
• mitochondrion
• pyruvate dehydrogenase complex
• sperm head-tail coupling apparatus

Protein domainsUniProt · Pfam · InterPro

• Biotin/lipoyl attachment
• 2-oxoacid dehydrogenase acyltransferase, catalytic domain
• 2-oxo acid dehydrogenase, lipoyl-binding site
• Peripheral subunit-binding domain
• Single hybrid motif
• Chloramphenicol acetyltransferase-like domain superfamily
• E3-binding domain superfamily
• Dihydrolipoamide acetyltransferase/Pyruvate dehydrogenase protein X component
• 2-oxoacid dehydrogenases acyltransferase (catalytic domain)
• Biotin-requiring enzyme
• e3 binding domain
• Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex

KeywordsUniProt

• Acetylation
• Acyltransferase
• Carbohydrate metabolism
• Glucose metabolism
• Lipoyl
• Mitochondrion
• Phosphoprotein
• Repeat
• Transferase
• Transit peptide
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of DLAT in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PDHB
• PDK2
• PDK3
• SIRT4
• PDHA1
• PDHA2
• STAT5A