Q15054 · DPOD3_HUMAN
- ProteinDNA polymerase delta subunit 3
- GenePOLD3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids466 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200).
Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433).
Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200).
Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374).
Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611).
Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888).
Also involved in TLS, as a component of the tetrametric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | delta DNA polymerase complex | |
Cellular Component | nucleoplasm | |
Cellular Component | zeta DNA polymerase complex | |
Molecular Function | protein-macromolecule adaptor activity | |
Biological Process | DNA biosynthetic process | |
Biological Process | DNA strand elongation involved in DNA replication | |
Biological Process | DNA synthesis involved in DNA repair | |
Biological Process | DNA synthesis involved in UV-damage excision repair | |
Biological Process | DNA-templated DNA replication | |
Biological Process | error-prone translesion synthesis | |
Biological Process | mismatch repair | |
Biological Process | nucleotide-excision repair, DNA gap filling |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA polymerase delta subunit 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ15054
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_064745 | 194 | found in a renal cell carcinoma sample; somatic mutation | |||
Sequence: G → V | ||||||
Natural variant | VAR_064746 | 195 | found in a renal cell carcinoma sample; somatic mutation | |||
Sequence: M → L | ||||||
Mutagenesis | 258 | Partially loss of sumoylation. Complete loss of sumoylation; when associated with R-433. | ||||
Sequence: K → R | ||||||
Mutagenesis | 325 | No effect on sumoylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 433 | Partially loss of sumoylation. Complete loss of SUMO3-sumoylation; when associated with R-285. | ||||
Sequence: K → R | ||||||
Mutagenesis | 456-466 | Complete loss of PCNA binding. | ||||
Sequence: Missing | ||||||
Mutagenesis | 458 | Partial loss of PCNA binding (60% of wild-type) and strong decrease of PCNA stimulation of Pol-delta4 polymerase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 459-463 | Complete loss of PCNA binding. | ||||
Sequence: ITGFF → ATGAA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 477 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 initiator methionine, modified residue, chain, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000186047 | 2-466 | UniProt | DNA polymerase delta subunit 3 | |||
Sequence: ADQLYLENIDEFVTDQNKIVTYKWLSYTLGVHVNQAKQMLYDYVERKRKENSGAQLHVTYLVSGSLIQNGHSCHKVAVVREDKLEAVKSKLAVTASIHVYSIQKAMLKDSGPLFNTDYDILKSNLQNCSKFSAIQCAAAVPRAPAESSSSSKKFEQSHLHMSSETQANNELTTNGHGPPASKQVSQQPKGIMGMFASKAAAKTQETNKETKTEAKEVTNASAAGNKAPGKGNMMSNFFGKAAMNKFKVNLDSEQAVKEEKIVEQPTVSVTEPKLATPAGLKKSSKKAEPVKVLQKEKKRGKRVALSDDETKETENMRKKRRRIKLPESDSSEDEVFPDSPGAYEAESPSPPPPPSPPLEPVPKTEPEPPSVKSSSGENKRKRKRVLKSKTYLDGEGCIVTEKVYESESCTDSEEELNMKTSSVHRPPAMTVKKEPREERKGPKKGTAALGKANRQVSITGFFQRK | |||||||
Cross-link | 258 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | |||||||
Cross-link | 258 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | |||||||
Cross-link | 261 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 269 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 277 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 307 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 307 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 311 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 407 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 407 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 409 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 409 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 411 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 411 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 413 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 413 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 423 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 433 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | |||||||
Cross-link | 433 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | |||||||
Modified residue | 458 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 458 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Sumoylated (PubMed:16934752, PubMed:25218447).
Sumoylation with SUMO3 may be predominant (PubMed:16934752).
Can also be phosphorylated in vitro by CDK1-cyclin-A complex, as well as CDK2-cyclin-A and CDK2-cyclin-E complexes. PCNA interferes with CDK-cyclin phosphorylation (PubMed:11595739).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Developmental stage
Gene expression databases
Organism-specific databases
Interaction
Subunit
The tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:11328591, PubMed:11595739, PubMed:17317665, PubMed:22801543).
Within this complex, directly interacts with POLD2 (PubMed:11328591, PubMed:16510448, PubMed:18818516).
Following stress caused by DNA damaging agents or by replication stress, POLD4 is degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3), which consists of POLD1, POLD2 and POLD3. Pol-delta3 is the major form occurring at S phase replication sites, as well as DNA damage sites (PubMed:11595739, PubMed:17317665, PubMed:22801543, PubMed:23913683).
Directly interacts with PCNA, as do POLD1 and POLD4; this interaction stimulates Pol-delta polymerase activity (PubMed:11328591, PubMed:11595739, PubMed:12403614, PubMed:16510448, PubMed:22148433).
POLD3 phosphorylation at Ser-458 impairs PCNA binding (PubMed:22148433).
Component of the DNA polymerase zeta complex (POLZ), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity (PubMed:24449906).
The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q15054 | PCNA P12004 | 7 | EBI-864956, EBI-358311 | |
BINARY | Q15054 | POLD2 P49005 | 10 | EBI-864956, EBI-372354 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 169-188 | Disordered | ||||
Sequence: NNELTTNGHGPPASKQVSQQ | ||||||
Region | 199-232 | Disordered | ||||
Sequence: KAAAKTQETNKETKTEAKEVTNASAAGNKAPGKG | ||||||
Region | 274-393 | Disordered | ||||
Sequence: KLATPAGLKKSSKKAEPVKVLQKEKKRGKRVALSDDETKETENMRKKRRRIKLPESDSSEDEVFPDSPGAYEAESPSPPPPPSPPLEPVPKTEPEPPSVKSSSGENKRKRKRVLKSKTYL | ||||||
Compositional bias | 285-332 | Basic and acidic residues | ||||
Sequence: SKKAEPVKVLQKEKKRGKRVALSDDETKETENMRKKRRRIKLPESDSS | ||||||
Compositional bias | 345-368 | Pro residues | ||||
Sequence: EAESPSPPPPPSPPLEPVPKTEPE | ||||||
Region | 406-466 | Disordered | ||||
Sequence: ESESCTDSEEELNMKTSSVHRPPAMTVKKEPREERKGPKKGTAALGKANRQVSITGFFQRK | ||||||
Compositional bias | 407-421 | Basic and acidic residues | ||||
Sequence: SESCTDSEEELNMKT | ||||||
Compositional bias | 430-446 | Basic and acidic residues | ||||
Sequence: MTVKKEPREERKGPKKG | ||||||
Motif | 456-463 | PIP-box | ||||
Sequence: QVSITGFF |
Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q15054-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length466
- Mass (Da)51,400
- Last updated2001-09-26 v2
- ChecksumE9625E0188725F45
Q15054-2
- Name2
- Differences from canonical
- 1-39: Missing
Q15054-3
- Name3
- Differences from canonical
- 1-106: Missing
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_054150 | 1-39 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_054149 | 1-106 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 285-332 | Basic and acidic residues | ||||
Sequence: SKKAEPVKVLQKEKKRGKRVALSDDETKETENMRKKRRRIKLPESDSS | ||||||
Compositional bias | 345-368 | Pro residues | ||||
Sequence: EAESPSPPPPPSPPLEPVPKTEPE | ||||||
Compositional bias | 407-421 | Basic and acidic residues | ||||
Sequence: SESCTDSEEELNMKT | ||||||
Compositional bias | 430-446 | Basic and acidic residues | ||||
Sequence: MTVKKEPREERKGPKKG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D26018 EMBL· GenBank· DDBJ | BAA05039.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK316301 EMBL· GenBank· DDBJ | BAH14672.1 EMBL· GenBank· DDBJ | mRNA | ||
AP001104 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP001324 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP001372 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471076 EMBL· GenBank· DDBJ | EAW74942.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC108908 EMBL· GenBank· DDBJ | AAI08909.1 EMBL· GenBank· DDBJ | mRNA | ||
BC108909 EMBL· GenBank· DDBJ | AAI08910.1 EMBL· GenBank· DDBJ | mRNA |