POLD3
entrez
10714
canonical
uniprot
Q15054
canonical
ensembl
ENSG00000077514
resolver
ensp
ENSP00000263681
resolver
ensp
ENSP00000432951
resolver
ensp
ENSP00000787301
resolver
genesymbol
POLD3
resolver
genesymbol_syn
KIAA0039
resolver
hgnc
HGNC:20932
resolver
uniprot
B7ZAI6
resolver
uniprot
Q32MZ9
resolver
uniprot
Q32N00
resolver
uniprot_entry
DPOD3_HUMAN
resolver
uniprot_sec
B7ZAI6
resolver
uniprot_sec
Q32MZ9
resolver
uniprot_sec
Q32N00
resolver
amino_acid_sequence
MADQLYLENIDEFVTDQNKIVTYKWLSYTLGVHVNQAKQMLYDYVERKRKENSGAQLHVTYLVSGSLIQNGHSCHKVAVVREDKLEAVKSKLAVTASIHVYSIQKAMLKDSGPLFNTDYDILKSNLQNCSKFSAIQCAAAVPRAPAESSSSSKKFEQSHLHMSSETQANNELTTNGHGPPASKQVSQQPKGIMGMFASKAAAKTQETNKETKTEAKEVTNASAAGNKAPGKGNMMSNFFGKAAMNKFKVNLDSEQAVKEEKIVEQPTVSVTEPKLATPAGLKKSSKKAEPVKVLQKEKKRGKRVALSDDETKETENMRKKRRRIKLPESDSSEDEVFPDSPGAYEAESPSPPPPPSPPLEPVPKTEPEPPSVKSSSGENKRKRKRVLKSKTYLDGEGCIVTEKVYESESCTDSEEELNMKTSSVHRPPAMTVKKEPREERKGPKKGTAALGKANRQVSITGFFQRK
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 122 (IMD122) [MIM:620869]: An autosomal recessive, severe immunologic disorder characterized by recurrent viral and bacterial infections of the respiratory tract and skin, appearing in early infancy. Additional clinical features include poor overall growth, global developmental delay with poor motor skills, impaired intellectual development, and poor or absent speech acquisition. Some patients have diffuse skin rash, erythroderma, sensorineural hearing loss, lymphadenopathy, dysmorphic facial features, and tooth abnormalities. Death in early childhood may occur. {ECO:0000269|PubMed:37030525, ECO:0000269|PubMed:38099988}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). 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 tetrameric 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). {ECO:0000269|PubMed:10219083, ECO:0000269|PubMed:10852724, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:25628356, ECO:0000269|PubMed:27185888, ECO:0000269|PubMed:38099988}.
uniprot
proteins
mass_dalton
51400
uniprot
proteins
mutagenesis
MUTAGEN 258; /note="K->R: Partially loss of sumoylation. Complete loss of sumoylation; when associated with R-433."; /evidence="ECO:0000269|PubMed:16934752"; MUTAGEN 325; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:16934752"; MUTAGEN 433; /note="K->R: Partially loss of sumoylation. Complete loss of SUMO3-sumoylation; when associated with R-285."; /evidence="ECO:0000269|PubMed:16934752"; MUTAGEN 456..466; /note="Missing: Complete loss of PCNA binding."; /evidence="ECO:0000269|PubMed:22148433"; MUTAGEN 458; /note="S->A: Partial loss of PCNA binding (60% of wild-type) and strong decrease of PCNA stimulation of Pol-delta4 polymerase activity."; /evidence="ECO:0000269|PubMed:22148433"; MUTAGEN 459..463; /note="ITGFF->ATGAA: Complete loss of PCNA binding."; /evidence="ECO:0000269|PubMed:22148433
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated, but not targeted to the proteasome (PubMed:16934752). Sumoylated (PubMed:16934752, PubMed:25218447). Sumoylation with SUMO3 may be predominant (PubMed:16934752). {ECO:0000269|PubMed:16934752}.; PTM: Phosphorylation at Ser-458 is catalyzed in vitro by PKA. It is thought to decrease the affinity for PCNA and Pol-delta4 processivity (PubMed:22148433). 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). {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:22148433}.
uniprot
proteins
pubmed
10219083
uniprot
proteins
pubmed
10852724
uniprot
proteins
pubmed
11328591
uniprot
proteins
pubmed
11595739
uniprot
proteins
pubmed
12403614
uniprot
proteins
pubmed
12522211
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16510448
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16934752
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17317665
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18818516
uniprot
proteins
pubmed
19074196
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20227374
uniprot
proteins
pubmed
20334433
uniprot
proteins
pubmed
21248752
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22148433
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22801543
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23913683
uniprot
proteins
pubmed
24035200
uniprot
proteins
pubmed
24310611
uniprot
proteins
pubmed
24449906
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25628356
uniprot
proteins
pubmed
26982350
uniprot
proteins
pubmed
27185888
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
37030525
uniprot
proteins
pubmed
38099988
uniprot
proteins
pubmed
7584026
uniprot
proteins
sequence_length
466
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9EQ28}. Nucleus {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22801543}. Note=Partially colocalizes with PCNA and POLD1 at S phase replication sites (PubMed:11595739). Recruited to DNA damage sites within 2 hours following UV irradiation (PubMed:20227374, PubMed:22801543). {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22801543}.
uniprot
proteins