Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

POLH (Q9Y253) - Overview - Molecular Target Synopsis

Protein


POLH, DNA polymerase eta
Enzyme Classification 2.7.7.7
UniProt Q9Y253

Also Known as POLH_HUMAN, POLH, RAD30, RAD30A, XPV

DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS) (PubMed:10385124, PubMed:11743006, PubMed:24449906). 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). Interacts with REV1 (By similarity). Interacts with monoubiquitinated PCNA, but not unmodified PCNA (PubMed:15149598). Interacts with POLI; this interaction targets POLI to the replication machinery (PubMed:12606586). Interacts with PALB2 and BRCA2; the interactions are direct and are required to sustain the recruitment of POLH at blocked replication forks and to stimulate POLH-dependent DNA synthesis on D loop substrates (PubMed:24485656).

6MXO
STRUCTURE OF HPOLETA INCORPORATING DCTP OPPOSITE THE 3-PRIME PT(DACH)- GG
RCSB/PDB
Inspect Structure
See all 3D Structures for POLH

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: POLH is active in the following subcellular-locations: nucleus.
GO terms: POLH is active in the following subcellular-locations: cytosol, nucleoplasm, nucleus, replication fork, site of double-strand break.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project POLH has gain in 2 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H226, OVCAR_4, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: YAPC, HCC4011, TK

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HMEC, SK-N-SH, NHLF

(see details)

3D Structures


For POLH there are:
123 structures (123 chains) solved
93 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


POLH has been screened with 12 compounds (14 bioactivities). (see details)