P10515 · ODP2_HUMAN
- ProteinDihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
- GeneDLAT
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids647 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
As part of the pyruvate dehydrogenase complex, catalyzes the transfers of an acetyl group to a lipoic acid moiety (Probable). The pyruvate dehydrogenase complex, catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle (Probable).
Catalytic activity
- acetyl-CoA + N6-[(R)-dihydrolipoyl]-L-lysyl-[protein] = CoA + N6-[(R)-S8-acetyldihydrolipoyl]-L-lysyl-[protein]This reaction proceeds in the forward direction.
Cofactor
Note: Binds 2 lipoyl cofactors covalently.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 461 | CoA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 475 | CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 566 | CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 567 | CoA (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 591 | CoA (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Active site | 620 | |||||
Sequence: H | ||||||
Active site | 624 | |||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Cellular Component | pyruvate dehydrogenase complex | |
Molecular Function | dihydrolipoyllysine-residue acetyltransferase activity | |
Molecular Function | identical protein binding | |
Biological Process | acetyl-CoA biosynthetic process from pyruvate | |
Biological Process | glucose metabolic process | |
Biological Process | tricarboxylic acid cycle |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP10515
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency)
- Note
- DescriptionPyruvate 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.
- See alsoMIM:245348
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_047410 | 43 | in dbSNP:rs2303436 | |||
Sequence: A → V | ||||||
Natural variant | VAR_047411 | 98 | in dbSNP:rs537057 | |||
Sequence: S → F | ||||||
Natural variant | VAR_047412 | 99 | in dbSNP:rs537060 | |||
Sequence: L → F | ||||||
Natural variant | VAR_047413 | 209 | in dbSNP:rs11553595 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_047414 | 313 | in dbSNP:rs11553592 | |||
Sequence: D → V | ||||||
Natural variant | VAR_047415 | 318 | in dbSNP:rs627441 | |||
Sequence: V → A | ||||||
Natural variant | VAR_047416 | 451 | in dbSNP:rs10891314 | |||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 753 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-86 | UniProt | Mitochondrion | ||||
Sequence: MWRVCARRAQNVAPWAGLEARWTALQEVPGTPRVTSRSGPAPARRNSVTTGYGGVRALCGWTPSSGATPRNRLLLQLLGSPGRRYY | |||||||
Chain | PRO_0000020479 | 87-647 | UniProt | Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial | |||
Sequence: SLPPHQKVPLPSLSPTMQAGTIARWEKKEGDKINEGDLIAEVETDKATVGFESLEECYMAKILVAEGTRDVPIGAIICITVGKPEDIEAFKNYTLDSSAAPTPQAAPAPTPAATASPPTPSAQAPGSSYPPHMQVLLPALSPTMTMGTVQRWEKKVGEKLSEGDLLAEIETDKATIGFEVQEEGYLAKILVPEGTRDVPLGTPLCIIVEKEADISAFADYRPTEVTDLKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPATPAGPKGRVFVSPLAKKLAVEKGIDLTQVKGTGPDGRITKKDIDSFVPSKVAPAPAAVVPPTGPGMAPVPTGVFTDIPISNIRRVIAQRLMQSKQTIPHYYLSIDVNMGEVLLVRKELNKILEGRSKISVNDFIIKASALACLKVPEANSSWMDTVIRQNHVVDVSVAVSTPAGLITPIVFNAHIKGVETIANDVVSLATKAREGKLQPHEFQGGTFTISNLGMFGIKNFSAIINPPQACILAIGASEDKLVPADNEKGFDVASMMSVTLSCDHRVVDGAVGAQWLAEFRKYLEKPITMLL | |||||||
Modified residue | 100 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 100 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 132 | UniProt | N6-lipoyllysine | ||||
Sequence: K | |||||||
Modified residue | 259 | UniProt | N6-lipoyllysine | ||||
Sequence: K | |||||||
Modified residue | 466 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 473 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 475 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 547 | UniProt | N6-succinyllysine | ||||
Sequence: K |
Post-translational modification
Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation decreases the PHD complex activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Part of the pyruvate dehydrogenase complex (PDHc) that is a multi-enzyme complex composed of multiple copies of three enzymes, pyruvate dehydrogenase (subunits PDH1A and PDHB, E1 component), dihydrolipoamide acetyltransferase (DLAT, E2 component), and dihydrolipoamide dehydrogenase (DLD, E3 component) to which is added an additional protein the E3-binding protein (PDHX, E3BP) (By similarity).
In terms of structural architecture, the E2 and E3BP components assemble into a 60meric central core with icosahedral symmetry (PubMed:14638692, PubMed:20361979).
The central core is decorated with E1 and E3 proteins (By similarity).
Currently, two alternative models for the E2:E3BP stoichiometry are considered as being either 48:12 (E248-E3BP12) or 40:20 (E240-E3BP20) (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).
In terms of structural architecture, the E2 and E3BP components assemble into a 60meric central core with icosahedral symmetry (PubMed:14638692, PubMed:20361979).
The central core is decorated with E1 and E3 proteins (By similarity).
Currently, two alternative models for the E2:E3BP stoichiometry are considered as being either 48:12 (E248-E3BP12) or 40:20 (E240-E3BP20) (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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P10515 | DLAT P10515 | 2 | EBI-2959723, EBI-2959723 | |
BINARY | P10515 | PDHB P11177 | 8 | EBI-2959723, EBI-1035872 | |
BINARY | P10515 | PDK3 Q15120 | 3 | EBI-2959723, EBI-1383915 | |
BINARY | P10515 | SIRT4 Q9Y6E7 | 6 | EBI-2959723, EBI-2606540 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 29-49 | Disordered | ||||
Sequence: PGTPRVTSRSGPAPARRNSVT | ||||||
Domain | 91-167 | Lipoyl-binding 1 | ||||
Sequence: HQKVPLPSLSPTMQAGTIARWEKKEGDKINEGDLIAEVETDKATVGFESLEECYMAKILVAEGTRDVPIGAIICITV | ||||||
Region | 184-219 | Disordered | ||||
Sequence: SAAPTPQAAPAPTPAATASPPTPSAQAPGSSYPPHM | ||||||
Compositional bias | 190-204 | Pro residues | ||||
Sequence: QAAPAPTPAATASPP | ||||||
Domain | 218-294 | Lipoyl-binding 2 | ||||
Sequence: HMQVLLPALSPTMTMGTVQRWEKKVGEKLSEGDLLAEIETDKATIGFEVQEEGYLAKILVPEGTRDVPLGTPLCIIV | ||||||
Region | 312-346 | Disordered | ||||
Sequence: TDLKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPA | ||||||
Compositional bias | 314-346 | Pro residues | ||||
Sequence: LKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPA | ||||||
Domain | 356-393 | Peripheral subunit-binding (PSBD) | ||||
Sequence: FVSPLAKKLAVEKGIDLTQVKGTGPDGRITKKDIDSFV |
Sequence similarities
Belongs to the 2-oxoacid dehydrogenase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length647
- Mass (Da)68,997
- Last updated2008-11-25 v3
- ChecksumDD93A8E666E377C2
Computationally mapped potential isoform sequences
There are 13 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H0YDD4 | H0YDD4_HUMAN | DLAT | 520 | ||
A0A7P0T9N8 | A0A7P0T9N8_HUMAN | DLAT | 243 | ||
A0A7P0T997 | A0A7P0T997_HUMAN | DLAT | 636 | ||
A0A7P0TAX2 | A0A7P0TAX2_HUMAN | DLAT | 640 | ||
A0A7P0TBE2 | A0A7P0TBE2_HUMAN | DLAT | 645 | ||
A0A7P0TBK2 | A0A7P0TBK2_HUMAN | DLAT | 554 | ||
A0A7P0TA47 | A0A7P0TA47_HUMAN | DLAT | 446 | ||
A0A7P0TAG1 | A0A7P0TAG1_HUMAN | DLAT | 611 | ||
E9PKC7 | E9PKC7_HUMAN | DLAT | 65 | ||
A0A7P0Z423 | A0A7P0Z423_HUMAN | DLAT | 225 | ||
A0A7P0Z459 | A0A7P0Z459_HUMAN | DLAT | 294 | ||
A0A7P0Z4G4 | A0A7P0Z4G4_HUMAN | DLAT | 562 | ||
E9PEJ4 | E9PEJ4_HUMAN | DLAT | 542 |
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 112 | in Ref. 4; CAA68787 | ||||
Sequence: E → K | ||||||
Compositional bias | 190-204 | Pro residues | ||||
Sequence: QAAPAPTPAATASPP | ||||||
Compositional bias | 314-346 | Pro residues | ||||
Sequence: LKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPA | ||||||
Sequence conflict | 342 | in Ref. 3; AAA62253 | ||||
Sequence: A → T | ||||||
Sequence conflict | 358 | in Ref. 3; AAA62253 | ||||
Sequence: S → D |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK223596 EMBL· GenBank· DDBJ | BAD97316.1 EMBL· GenBank· DDBJ | mRNA | ||
AP000907 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
J03866 EMBL· GenBank· DDBJ | AAA62253.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
Y00978 EMBL· GenBank· DDBJ | CAA68787.1 EMBL· GenBank· DDBJ | mRNA |