UniProt functional annotation for P10515



	UniProt functional annotation for P10515

UniProt code: P10515.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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.

Catalytic activity: Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + acetyl-CoA = (R)- N(6)-(S(8)-acetyldihydrolipoyl)-L-lysyl-[protein] + CoA; Xref=Rhea:RHEA:17017, Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:10478, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:83100, ChEBI:CHEBI:83111; EC=2.3.1.12;

Cofactor: Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088; Note=Binds 2 lipoyl cofactors covalently.;

Subunit: Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (PubMed:14638692). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (PubMed:14638692, PubMed:20361979). Interacts with PDK2 and PDK3 (PubMed:15861126, PubMed:17532006, PubMed:17683942, PubMed:18387944). Interacts with SIRT4 (PubMed:25525879). Interacts with PDHB (PubMed:20160912). {ECO:0000269|PubMed:14638692, ECO:0000269|PubMed:15861126, ECO:0000269|PubMed:17532006, ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:18387944, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:20361979, ECO:0000269|PubMed:25525879}.

Subcellular location: Mitochondrion matrix.

Ptm: Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation decreases the PHD complex activity. {ECO:0000269|PubMed:25525879}.

Disease: Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.

Disease: Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:245348]: Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent. {ECO:0000269|PubMed:16049940}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the 2-oxoacid dehydrogenase family. {ECO:0000305}.

Sequence caution: Sequence=AAA62253.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAA62253.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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.


Catalytic activity:		Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + acetyl-CoA = (R)- N(6)-(S(8)-acetyldihydrolipoyl)-L-lysyl-[protein] + CoA; Xref=Rhea:RHEA:17017, Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:10478, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:83100, ChEBI:CHEBI:83111; EC=2.3.1.12;
Cofactor:		Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088; Note=Binds 2 lipoyl cofactors covalently.;
Subunit:		Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (PubMed:14638692). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (PubMed:14638692, PubMed:20361979). Interacts with PDK2 and PDK3 (PubMed:15861126, PubMed:17532006, PubMed:17683942, PubMed:18387944). Interacts with SIRT4 (PubMed:25525879). Interacts with PDHB (PubMed:20160912). {ECO:0000269\|PubMed:14638692, ECO:0000269\|PubMed:15861126, ECO:0000269\|PubMed:17532006, ECO:0000269\|PubMed:17683942, ECO:0000269\|PubMed:18387944, ECO:0000269\|PubMed:20160912, ECO:0000269\|PubMed:20361979, ECO:0000269\|PubMed:25525879}.
Subcellular location:		Mitochondrion matrix.
Ptm:		Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation decreases the PHD complex activity. {ECO:0000269\|PubMed:25525879}.
Disease:		Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.
Disease:		Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:245348]: Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent. {ECO:0000269\|PubMed:16049940}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the 2-oxoacid dehydrogenase family. {ECO:0000305}.
Sequence caution:		Sequence=AAA62253.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAA62253.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};