POLD4
entrez
57804
canonical
uniprot
Q9HCU8
canonical
ensembl
ENSG00000175482
resolver
ensp
ENSP00000311368
resolver
ensp
ENSP00000444780
resolver
genesymbol
POLD4
resolver
genesymbol_syn
POLDS
resolver
hgnc
HGNC:14106
resolver
uniprot
F5H506
resolver
uniprot
Q6NSD7
resolver
uniprot_entry
DPOD4_HUMAN
resolver
uniprot_entry
Q6NSD7_HUMAN
resolver
uniprot_sec
F5H506
resolver
amino_acid_sequence
MGRKRLITDSYPVVKRREGPAGHSKGELAPELGEEPQPRDEEEAELELLRQFDLAWQYGPCTGITRLQRWCRAKQMGLEPPPEVWQVLKTHPGDPRFQCSLWHLYPL
uniprot
proteins
function
FUNCTION: As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity (PubMed:16510448, PubMed:19074196, PubMed:20334433). Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system (PubMed:24035200). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb (PubMed:24310611). Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival (PubMed:24022480). {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611}.
uniprot
proteins
mass_dalton
12433
uniprot
proteins
mutagenesis
MUTAGEN 1..16; /note="Missing: Complete loss of PCNA binding and of degradation after UV irradiation."; /evidence="ECO:0000269|PubMed:24022480"; MUTAGEN 4; /note="K->A: No effect on PCNA binding."; /evidence="ECO:0000269|PubMed:24022480"; MUTAGEN 4; /note="K->Q: No effect on PCNA binding, nor on degradation after UV irradiation; when associated with Y-10. No effect on PCNA binding, but normal degradation after UV irradiation; when associated with Y-10 and A-15."; /evidence="ECO:0000269|PubMed:24022480"; MUTAGEN 4; /note="K->R: No effect on ubiquitination. Loss of ubiquitination, when associated with R-15, R-25, R-74 and R-89."; /evidence="ECO:0000269|PubMed:16934752"; MUTAGEN 7; /note="I->A: Complete loss of PCNA binding; when associated with 10-AA-11."; /evidence="ECO:0000269|PubMed:16510448"; MUTAGEN 8; /note="T->A: Strongly increased stability following UV irradiation; when associated with A-9."; /evidence="ECO:0000269|PubMed:23913683"; MUTAGEN 8; /note="T->D: Complete loss of PCNA binding."; /evidence="ECO:0000269|PubMed:24022480"; MUTAGEN 9; /note="D->A: Strongly increased stability following UV irradiation; when associated with A-8."; /evidence="ECO:0000269|PubMed:23913683"; MUTAGEN 10..11; /note="SY->AA: Complete loss of PCNA binding; when associated with A-7."; /evidence="ECO:0000269|PubMed:16510448"; MUTAGEN 10; /note="S->Y: No effect on PCNA binding, nor on degradation after UV irradiation; when associated with Q-4. No effect on PCNA binding, but normal degradation after UV irradiation with Q-4 and A-15."; /evidence="ECO:0000269|PubMed:24022480"; MUTAGEN 15; /note="K->A: Decreased PCNA binding. No effect on PCNA binding, but normal degradation after UV irradiation; when associated with Q-4 and Y-10. Increased stability following UV irradiation and no trough during S phase; when associated with A-16 and A-17."; /evidence="ECO:0000269|PubMed:23913683, ECO:0000269|PubMed:24022480"; MUTAGEN 15; /note="K->R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-25, R-74 and R-89."; /evidence="ECO:0000269|PubMed:16934752"; MUTAGEN 16; /note="R->A: Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-17."; /evidence="ECO:0000269|PubMed:23913683"; MUTAGEN 17; /note="R->A: Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-16."; /evidence="ECO:0000269|PubMed:23913683"; MUTAGEN 25; /note="K->R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-74 and R-89."; /evidence="ECO:0000269|PubMed:16934752"; MUTAGEN 74; /note="K->R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-89."; /evidence="ECO:0000269|PubMed:16934752"; MUTAGEN 89; /note="K->R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-74."; /evidence="ECO:0000269|PubMed:16934752
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation (PubMed:16934752, PubMed:17317665, PubMed:23233665, PubMed:23913683). This modification is partly mediated by RNF8 and by the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)) (PubMed:23233665, PubMed:24022480). Efficient degradation requires the presence of PCNA and is required for the inhibition of fork progression after DNA damage (PubMed:24022480). {ECO:0000269|PubMed:16934752, ECO:0000269|PubMed:17317665, ECO:0000269|PubMed:23233665, ECO:0000269|PubMed:23913683, ECO:0000269|PubMed:24022480}.
uniprot
proteins
protein_family
DNA polymerase delta subunit 4 family
uniprot
proteins
pubmed
10751307
uniprot
proteins
pubmed
12403614
uniprot
proteins
pubmed
12522211
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15670210
uniprot
proteins
pubmed
16510448
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16934752
uniprot
proteins
pubmed
17317665
uniprot
proteins
pubmed
19074196
uniprot
proteins
pubmed
20334433
uniprot
proteins
pubmed
22801543
uniprot
proteins
pubmed
23233665
uniprot
proteins
pubmed
23913683
uniprot
proteins
pubmed
24022480
uniprot
proteins
pubmed
24035200
uniprot
proteins
pubmed
24300032
uniprot
proteins
pubmed
24310611
uniprot
proteins
sequence_length
107
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22801543}. Note=Partially recruited to DNA damage sites within 2 hours following UV irradiation, before degradation. {ECO:0000269|PubMed:22801543}.
uniprot
proteins