POLH
entrez
5429
canonical
uniprot
Q9Y253
canonical
ensembl
ENSG00000170734
resolver
ensp
ENSP00000361300
resolver
ensp
ENSP00000361310
resolver
genesymbol
POLH
resolver
genesymbol_syn
RAD30
resolver
genesymbol_syn
RAD30A
resolver
genesymbol_syn
XPV
resolver
hgnc
HGNC:9181
resolver
uniprot
B3KN75
resolver
uniprot
Q7L8E3
resolver
uniprot
Q96BC4
resolver
uniprot
Q9BX13
resolver
uniprot_entry
B3KN75_HUMAN
resolver
uniprot_entry
POLH_HUMAN
resolver
uniprot_sec
Q7L8E3
resolver
uniprot_sec
Q96BC4
resolver
uniprot_sec
Q9BX13
resolver
activity_regulation
ACTIVITY REGULATION: The enzyme in complex with the DNA substrate binds a third divalent metal cation (PubMed:27284197). The binding of this third divalent cation, which is coordinated by water molecules and two oxygen atoms from DNA and dNTP, is essential for catalyzing the DNA synthesis (PubMed:27284197). {ECO:0000269|PubMed:27284197}.
uniprot
proteins
amino_acid_sequence
MATGQDRVVALVDMDCFFVQVEQRQNPHLRNKPCAVVQYKSWKGGGIIAVSYEARAFGVTRSMWADDAKKLCPDLLLAQVRESRGKANLTKYREASVEVMEIMSRFAVIERASIDEAYVDLTSAVQERLQKLQGQPISADLLPSTYIEGLPQGPTTAEETVQKEGMRKQGLFQWLDSLQIDNLTSPDLQLTVGAVIVEEMRAAIERETGFQCSAGISHNKVLAKLACGLNKPNRQTLVSHGSVPQLFSQMPIRKIRSLGGKLGASVIEILGIEYMGELTQFTESQLQSHFGEKNGSWLYAMCRGIEHDPVKPRQLPKTIGCSKNFPGKTALATREQVQWWLLQLAQELEERLTKDRNDNDRVATQLVVSIRVQGDKRLSSLRRCCALTRYDAHKMSHDAFTVIKNCNTSGIQTEWSPPLTMLFLCATKFSASAPSSSTDITSFLSSDPSSLPKVPVTSSEAKTQGSGPAVTATKKATTSLESFFQKAAERQKVKEASLSSLTAPTQAPMSNSPSKPSLPFQTSQSTGTEPFFKQKSLLLKQKQLNNSSVSSPQQNPWSNCKALPNSLPTEYPGCVPVCEGVSKLEESSKATPAEMDLAHNSQSMHASSASKSVLEVTQKATPNPSLLAAEDQVPCEKCGSLVPVWDMPEHMDYHFALELQKSFLQPHSSNPQVVSAVSHQGKRNPKSPLACTNKRPRPEGMQTLESFFKPLTH
uniprot
proteins
disease_involvement
DISEASE: Xeroderma pigmentosum variant type (XPV) [MIM:278750]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most patients with the variant type of xeroderma pigmentosum do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes. {ECO:0000269|PubMed:10385124, ECO:0000269|PubMed:10398605, ECO:0000269|PubMed:11032022, ECO:0000269|PubMed:11121129, ECO:0000269|PubMed:11773631, ECO:0000269|PubMed:24130121, ECO:0000269|PubMed:38212351}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.7.7
uniprot
proteins
function
FUNCTION: DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS) (PubMed:10385124, PubMed:11743006, PubMed:16357261, PubMed:20388628, PubMed:24449906, PubMed:24553286, PubMed:38212351). Due to low processivity on both damaged and normal DNA, cooperates with the heterotetrameric (REV3L, REV7, POLD2 and POLD3) POLZ complex for complete bypass of DNA lesions. Inserts one or 2 nucleotide(s) opposite the lesion, the primer is further extended by the tetrameric POLZ complex. In the case of 1,2-intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3' guanine (PubMed:24449906). Particularly important for the repair of UV-induced pyrimidine dimers (PubMed:10385124, PubMed:11743006). Although inserts the correct base, may cause base transitions and transversions depending upon the context. May play a role in hypermutation at immunoglobulin genes (PubMed:11376341, PubMed:14734526). Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have any lyase activity, preventing the release of the 5'-deoxyribose phosphate (5'-dRP) residue. This covalent trapping of the enzyme by the 5'-dRP residue inhibits its DNA synthetic activity during base excision repair, thereby avoiding high incidence of mutagenesis (PubMed:14630940). Targets POLI to replication foci (PubMed:12606586). {ECO:0000269|PubMed:10385124, ECO:0000269|PubMed:11376341, ECO:0000269|PubMed:11743006, ECO:0000269|PubMed:12606586, ECO:0000269|PubMed:14630940, ECO:0000269|PubMed:14734526, ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:20388628, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:24553286, ECO:0000269|PubMed:38212351}.
uniprot
proteins
mass_dalton
78413
uniprot
proteins
mutagenesis
MUTAGEN 52; /note="Y->A,F: Reduces DNA polymerase activity."; /evidence="ECO:0000269|PubMed:12644469"; MUTAGEN 52; /note="Y->E: Reduces DNA polymerase activity. Increases fidelity of replication and reduces translesion bypass."; /evidence="ECO:0000269|PubMed:12644469"; MUTAGEN 61; /note="R->A: Reduces enzymatic activity by two-thirds."; /evidence="ECO:0000269|PubMed:27284197"; MUTAGEN 62; /note="S->G: Increased DNA polymerase activity and translesion bypass compared to wild-type."; /evidence="ECO:0000269|PubMed:11743006"; MUTAGEN 68; /note="A->S,V: Severe reduction in thymine dimer translesion bypass."; /evidence="ECO:0000269|PubMed:11743006"; MUTAGEN 324..326; /note="NFP->AAA: Reduces binding to chromatin and to monoubiquitinated PCNA. Abolishes binding to monoubiquitinated PCNA; when associated with 705-E--H-713 Del."; /evidence="ECO:0000269|PubMed:15149598"; MUTAGEN 638; /note="C->A: Reduces cell resistance to UV-induced DNA damage."; /evidence="ECO:0000269|PubMed:16357261"; MUTAGEN 652; /note="D->A: Abolishes ubiquitin binding and localization to nuclear foci after UV-induced DNA damage but does not affect catalytic activity."; /evidence="ECO:0000269|PubMed:16357261"; MUTAGEN 705..713; /note="Missing: Reduces cell resistance to UV-induced DNA damage. Reduces binding to chromatin and to monoubiquitinated PCNA. Abolishes binding to monoubiquitinated PCNA; when associated with 324-A--A-326."; /evidence="ECO:0000269|PubMed:15149598, ECO:0000269|PubMed:16357261
uniprot
proteins
post_translational_modification
PTM: Monoubiquitinated by RCHY1/PIRH2 (PubMed:20159558, PubMed:21791603). Ubiquitination depends on integrity of the UBZ3-type zinc finger domain and is enhanced by TRAIP (PubMed:16357261, PubMed:24553286). Ubiquitination inhibits the ability of PolH to interact with PCNA and to bypass UV-induced lesions (PubMed:20159558, PubMed:21791603, PubMed:24553286). {ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:20159558, ECO:0000269|PubMed:21791603, ECO:0000269|PubMed:24553286}.
uniprot
proteins
protein_family
DNA polymerase type-Y family
uniprot
proteins
pubmed
10385124
uniprot
proteins
pubmed
10398605
uniprot
proteins
pubmed
11032022
uniprot
proteins
pubmed
11121129
uniprot
proteins
pubmed
11376341
uniprot
proteins
pubmed
11743006
uniprot
proteins
pubmed
11773631
uniprot
proteins
pubmed
12606586
uniprot
proteins
pubmed
12644469
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14630940
uniprot
proteins
pubmed
14734526
uniprot
proteins
pubmed
15149598
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16357261
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
20159558
uniprot
proteins
pubmed
20388628
uniprot
proteins
pubmed
20554254
uniprot
proteins
pubmed
21791603
uniprot
proteins
pubmed
22691049
uniprot
proteins
pubmed
22801543
uniprot
proteins
pubmed
24130121
uniprot
proteins
pubmed
24449906
uniprot
proteins
pubmed
24485656
uniprot
proteins
pubmed
24553286
uniprot
proteins
pubmed
27062441
uniprot
proteins
pubmed
27284197
uniprot
proteins
pubmed
38212351
uniprot
proteins
sequence_length
713
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12606586, ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:22801543, ECO:0000269|PubMed:24553286}. Note=Binding to ubiquitinated PCNA mediates colocalization to replication foci during DNA replication and persists at sites of stalled replication forks following UV irradiation (PubMed:12606586, PubMed:16357261, PubMed:24553286). After UV irradiation, recruited to DNA damage sites within 1 hour, to a maximum of about 80%; this recruitment may not be not restricted to cells active in DNA replication (PubMed:22801543). Colocalizes with TRAIP to nuclear foci (PubMed:24553286). {ECO:0000269|PubMed:12606586, ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:22801543, ECO:0000269|PubMed:24553286}.
uniprot
proteins