DLAT (dihydrolipoamide S-acetyltransferase)

Gene

• Entrez ID: 1737
• Gene name: Dihydrolipoamide S-acetyltransferase
• Gene symbol: DLAT
• Synonyms: DLTA, E2, PBC, PDC-E2, PDCE2
• Chromosome: 11
• Chromosome location: 11q23.1
• 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs138505899	T>G	Likely-pathogenic	Coding sequence variant, intron variant, 5 prime UTR variant, missense variant, non coding transcript variant
rs140678772	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, intron variant, missense variant
rs367875541	G>A	Likely-pathogenic	Splice acceptor variant
rs781936816	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, intron variant, non coding transcript variant, coding sequence variant, 5 prime UTR variant
rs782070173	T>C	Likely-pathogenic	Splice donor variant
rs782704553	AT>-	Likely-pathogenic	Frameshift variant, coding sequence variant, intron variant
rs797044957	T>G	Pathogenic, uncertain-significance	Missense variant, non coding transcript variant, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT032242	hsa-let-7b-5p	Proteomics	18668040
MIRT040451	hsa-miR-615-3p	CLASH	23622248
MIRT047485	hsa-miR-10b-5p	CLASH	23622248
MIRT447437	hsa-miR-8085	PAR-CLIP	22100165
MIRT447438	hsa-miR-5192	PAR-CLIP	22100165
MIRT447439	hsa-miR-6731-5p	PAR-CLIP	22100165

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004742	Function	Dihydrolipoyllysine-residue acetyltransferase activity	IBA	21873635
GO:0004742	Function	Dihydrolipoyllysine-residue acetyltransferase activity	IDA	9045657
GO:0004742	Function	Dihydrolipoyllysine-residue acetyltransferase activity	NAS	3191998
GO:0005515	Function	Protein binding	IPI	15861126, 17683942, 18206651, 25525879, 28514442
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	IDA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005967	Component	Mitochondrial pyruvate dehydrogenase complex	IBA	21873635
GO:0005967	Component	Mitochondrial pyruvate dehydrogenase complex	NAS	3191998
GO:0006006	Process	Glucose metabolic process	IEA
GO:0006086	Process	Acetyl-CoA biosynthetic process from pyruvate	IBA	21873635
GO:0006090	Process	Pyruvate metabolic process	TAS
GO:0006099	Process	Tricarboxylic acid cycle	IEA
GO:0018215	Process	Protein phosphopantetheinylation	IEA
GO:0030431	Process	Sleep	IEA
GO:0034604	Function	Pyruvate dehydrogenase (NAD+) activity	IBA	21873635
GO:0034604	Function	Pyruvate dehydrogenase (NAD+) activity	IC	9045657
GO:0034604	Function	Pyruvate dehydrogenase (NAD+) activity	IDA	9242632
GO:0042802	Function	Identical protein binding	IPI	18184587, 18184588
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0045254	Component	Pyruvate dehydrogenase complex	IDA	9242632, 25525879

Other IDs

• MIM: 608770
• HGNC: 2896
• e!Ensembl: ENSG00000150768

Protein

• UniProt ID: P10515
• Protein name: Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (EC 2.3.1.12) (70 kDa mitochondrial autoantigen of primary biliary cirrhosis) (PBC) (Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex) (M2 antigen complex 70 kDa subunit) (Pyruvate dehydrogenase complex component E2) (PDC-E2) (PDCE2)
• Protein function: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
• PDB: 1FYC, 1Y8N, 1Y8O, 1Y8P, 2DNE, 2PNR, 2Q8I, 3B8K, 3CRK, 3CRL, 6CT0, 6H55
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00364	Biotin_lipoyl	92 → 165	Biotin-requiring enzyme	Domain
  PF00364	Biotin_lipoyl	219 → 293	Biotin-requiring enzyme	Domain
  PF02817	E3_binding	355 → 390	e3 binding domain	Family
  PF00198	2-oxoacid_dh	417 → 647	2-oxoacid dehydrogenases acyltransferase (catalytic domain)	Domain

• Sequence:

  MWRVCARRAQNVAPWAGLEARWTALQEVPGTPRVTSRSGPAPARRNSVTTGYGGVRALCG
  WTPSSGATPRNRLLLQLLGSPGRRYYSLPPHQKVPLPSLSPTMQAGTIARWEKKEGDKIN
  EGDLIAEVETDKATVGFESLEECYMAKILVAEGTRDVPIGAIICITVGKPEDIEAFKNYT
  LDSSAAPTPQAAPAPTPAATASPPTPSAQAPGSSYPPHMQVLLPALSPTMTMGTVQRWEK
  KVGEKLSEGDLLAEIETDKATIGFEVQEEGYLAKILVPEGTRDVPLGTPLCIIVEKEADI
  SAFADYRPTEVTDLKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPATPAGPKGRVFVSPL
  AKKLAVEKGIDLTQVKGTGPDGRITKKDIDSFVPSKVAPAPAAVVPPTGPGMAPVPTGVF
  TDIPISNIRRVIAQRLMQSKQTIPHYYLSIDVNMGEVLLVRKELNKILEGRSKISVNDFI
  IKASALACLKVPEANSSWMDTVIRQNHVVDVSVAVSTPAGLITPIVFNAHIKGVETIAND
  VVSLATKAREGKLQPHEFQGGTFTISNLGMFGIKNFSAIINPPQACILAIGASEDKLVPA
  DNEKGFDVASMMSVTLSCDHRVVDGAVGAQWLAEFRKYLEKPITMLL

• Sequence length: 647