Literature summary for 2.7.7.7 extracted from

Stern, H.R.; Sefcikova, J.; Chaparro, V.E.; Beuning, P.J.
Mammalian DNA polymerase kappa activity and specificity (2019), Molecules, 24, 2805 .

Protein Variants

Protein Variants	Comment	Organism
A329A	not meaningfully associated with breast cancer risk; more likely to respond to Pt-based chemotherapy	Homo sapiens
A471V	moderate decrease in activity	Homo sapiens
D189G	impaired for extension step of TLS	Homo sapiens
E292K	similar activity as wild-type enzyme	Homo sapiens
E29K	decreased insertion opposite abasic site (2-20)	Homo sapiens
E419G	20fold decrease in kcat/Km on dG and 670fold decrease on N2-CH2-Anth-dG, extension defect	Homo sapiens
E430G	low activity on AP site	Homo sapiens
E449K	low activity on AP site, low fidelity	Homo sapiens
F155S	decreased activity on model abasic site	Homo sapiens
F192C	slight increase in activity with N2-furfuryl-dG-containing templates	Homo sapiens
G154E	decreased activity opposite model abasic site, pathogenic	Homo sapiens
I39T	similar activity to WT with several types of DNA damage	Homo sapiens
L21F	30fold decrease in incorporation opposite N2-CH2-(9-anthracenyl)-dG (N2-CH2-Anth-dG)	Homo sapiens
L442F	low activity on AP site	Homo sapiens
P169T	slight decrease in activity on undamaged DNA	Homo sapiens
R219I	slight decrease in activity	Homo sapiens
R246X	5-10fold less active with 8-oxo-dG-, N2-CH2-Anth-dG-, O6-Me-dG- and abasic-containing templates	Homo sapiens
R298H	less active than wild-type on several different lesions	Homo sapiens
R512W	decreased activity on undamaged and damaged DNA	Homo sapiens
S423R	1.6fold more effcient than wild-type, 2fold increased DNA binding affinity, pathogenic	Homo sapiens
T44M	lesion-specific reduction in activity. Reduced activity with N2-CH2-Anth-dG, O6-Me-dG and abasic sites	Homo sapiens
T473A	decreased activity on undamaged and damaged DNA	Homo sapiens
V130I	mutant has relaxed discrimination against the major groove adduct N6-furfuryl-dA	Homo sapiens
Y432S	less active on undamaged and damaged DNA, extension defect, decreased DNA binding affinity	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
MK886	-	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9UBT6	-	-

Synonyms

Synonyms	Comment	Organism
DNA polymerase kappa	-	Homo sapiens

General Information

General Information	Comment	Organism
drug target	the enzyme is an attractive target for cancer therapies because it has been correlated with a shorter survival time in patients with glioblastoma as well as poor chemotherapy responses in some cases	Homo sapiens
malfunction	many cancer-associated single-nucleotide polymorphisms have been reported in the Pol kappa gene, some of which are associated with poor survival and altered chemotherapy response	Homo sapiens
physiological function	the enzyme has roles both in maintaining and compromising genomic integrity. The expression of pol kappa is altered in several different cancer types, which can lead to genome instability	Homo sapiens