Tchem POLH DNA polymerase eta

Protein Summary

Description

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). This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

Uniprot Accession IDs

• Q9Y253
• Q7L8E3
• Q96BC4
• Q9BX13

Gene Name

• POLH

Ensembl ID

• ENST00000372226
• ENSP00000361300
• ENSG00000170734
• ENST00000372236
• ENSP00000361310

Symbol

• RAD30
• RAD30A
• XPV
• XPV
• XP-V
• RAD30
• RAD30A

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.98
histone modification site profile	0.91
kinase perturbation	0.88
ligand (protein) perturbation	0.83
small molecule perturbation	0.79

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 134.55   (req: < 5)

Gene RIFs: 121   (req: <= 3)

Antibodies: 182   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 134.55   (req: >= 5)

Gene RIFs: 121   (req: > 3)

Antibodies: 182   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (2)

Explore Active Ligands

1 – 2 of 2

CHEMBL6246

POLHTchem Enzyme

IC50: 7.21

CHEMBL275938

POLHTchem Enzyme

IC50: 7.12

Protein Data Bank (122)

1 – 5 of 122

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (11)

Reactome (9)

KEGG (2)

DNA Damage Bypass (R-HSA-73893)

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Items per page:

5

1 – 5 of 9

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	DNA Damage Bypass	47 targets	R-HSA-73893
Reactome	DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
Reactome	DNA Repair	306 targets	R-HSA-73894
Reactome	HDR through Homologous Recombination (HRR)	66 targets	R-HSA-5685942
Reactome	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	112 targets	R-HSA-5693567

Name	Explore in Pharos	Explore in Source
DNA Damage Bypass	47 targets	R-HSA-73893
DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
DNA Repair	306 targets	R-HSA-73894
HDR through Homologous Recombination (HRR)	66 targets	R-HSA-5685942
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	112 targets	R-HSA-5693567

Gene Ontology Terms (19)

Functions (3)

Components (5)

Processes (11)

Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
DNA-directed DNA polymerase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
damaged DNA binding	Traceable Author Statement (TAS)	ProtInc
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (151)

Explore Interacting Targets

1 – 10 of 151

• See Interactions on String-DB

LSM5

Tbio

Novelty: 0.09756098

p_int: 0.999999988

p_ni: 1.1e-8

p_wrong: 1e-9

Score: 0.181

Data Source: BioPlex,STRINGDB

PIP

Tbio

Novelty: 0.00268794

p_int: 0.999999909

p_ni: 8.8e-8

p_wrong: 3e-9

Data Source: BioPlex

POTEI

Tdark

Novelty: 0.30601093

p_int: 0.999945285

p_ni: 0.000054715

Score: 0.214

Data Source: BioPlex,STRINGDB

ACTBL2

Tbio

Novelty: 0.35273907

p_int: 0.968615606

p_ni: 0.031384394

Data Source: BioPlex

ACTB

Tbio

Novelty: 0.00027728

p_int: 0.916188575

p_ni: 0.083811425

Score: 0.19

Data Source: BioPlex,STRINGDB

TUBA4A

Tchem

Novelty: 0.02626744

p_int: 0.806268415

p_ni: 0.193731585

Data Source: BioPlex

AHNAK

Tbio

Novelty: 0.01530578

p_int: 0.798738745

p_ni: 0.201261255

Score: 0.189

Data Source: BioPlex,STRINGDB

PCNA

Tchem

Novelty: 0.00995674

Score: 0.999

Data Source: Reactome,STRINGDB

REV1

Tbio

Novelty: 0.00340661

Score: 0.99

Data Source: STRINGDB

RAD51

Tchem

Novelty: 0.00014377

Score: 0.981

Data Source: STRINGDB

Publication Statistics

PubMed Score  134.55

PubMed score by year

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PubTator Score  180.78

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MATGQDRVVALVDMDCFFVQVEQRQNPHLRNKPCAVVQYKSWKGGGIIAVSYEARAFGVTRSMWADDAKK

1-70

LCPDLLLAQVRESRGKANLTKYREASVEVMEIMSRFAVIERASIDEAYVDLTSAVQERLQKLQGQPISAD

70-140

LLPSTYIEGLPQGPTTAEETVQKEGMRKQGLFQWLDSLQIDNLTSPDLQLTVGAVIVEEMRAAIERETGF

140-210

QCSAGISHNKVLAKLACGLNKPNRQTLVSHGSVPQLFSQMPIRKIRSLGGKLGASVIEILGIEYMGELTQ

210-280

FTESQLQSHFGEKNGSWLYAMCRGIEHDPVKPRQLPKTIGCSKNFPGKTALATREQVQWWLLQLAQELEE

280-350

RLTKDRNDNDRVATQLVVSIRVQGDKRLSSLRRCCALTRYDAHKMSHDAFTVIKNCNTSGIQTEWSPPLT

350-420

MLFLCATKFSASAPSSSTDITSFLSSDPSSLPKVPVTSSEAKTQGSGPAVTATKKATTSLESFFQKAAER

420-490

QKVKEASLSSLTAPTQAPMSNSPSKPSLPFQTSQSTGTEPFFKQKSLLLKQKQLNNSSVSSPQQNPWSNC

490-560

KALPNSLPTEYPGCVPVCEGVSKLEESSKATPAEMDLAHNSQSMHASSASKSVLEVTQKATPNPSLLAAE

560-630

DQVPCEKCGSLVPVWDMPEHMDYHFALELQKSFLQPHSSNPQVVSAVSHQGKRNPKSPLACTNKRPRPEG

630-700

MQTLESFFKPLTH

700-713

MATGQDRVVALVDMDCFFVQVEQRQNPHLRNKPCAVVQYKSWKGGGIIAVSYEARAFGVTRSMWADDAKKLCPDLLLAQVRESRGKANLTKYREASVEVMEIMSRFAVIERASIDEAYVDLTSAVQERLQKLQGQPISADLLPSTYIEGLPQGPTTAEETVQKEGMRKQGLFQWLDSLQIDNLTSPDLQLTVGAVIVEEMRAAIERETGFQCSAGISHNKVLAKLACGLNKPNRQTLVSHGSVPQLFSQMPIRKIRSLGGKLGASVIEILGIEYMGELTQFTESQLQSHFGEKNGSWLYAMCRGIEHDPVKPRQLPKTIGCSKNFPGKTALATREQVQWWLLQLAQELEERLTKDRNDNDRVATQLVVSIRVQGDKRLSSLRRCCALTRYDAHKMSHDAFTVIKNCNTSGIQTEWSPPLTMLFLCATKFSASAPSSSTDITSFLSSDPSSLPKVPVTSSEAKTQGSGPAVTATKKATTSLESFFQKAAERQKVKEASLSSLTAPTQAPMSNSPSKPSLPFQTSQSTGTEPFFKQKSLLLKQKQLNNSSVSSPQQNPWSNCKALPNSLPTEYPGCVPVCEGVSKLEESSKATPAEMDLAHNSQSMHASSASKSVLEVTQKATPNPSLLAAEDQVPCEKCGSLVPVWDMPEHMDYHFALELQKSFLQPHSSNPQVVSAVSHQGKRNPKSPLACTNKRPRPEGMQTLESFFKPLTH

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Uniprot Keyword

3D-structure
Alternative splicing
Complete proteome
Direct protein sequencing
Disease mutation
DNA damage
DNA repair
DNA replication
DNA synthesis
DNA-binding