UniProt functional annotation for P03176

UniProt code: P03176.

Organism: Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
Taxonomy: Viruses; dsDNA viruses, no RNA stage; Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
 
Function: Catalyzes the transfer of the gamma-phospho group of ATP to thymidine to generate dTMP in the salvage pathway of pyrimidine synthesis. The dTMP serves as a substrate for DNA polymerase during viral DNA replication. Allows the virus to be reactivated and to grow in non-proliferative cells lacking a high concentration of phosphorylated nucleic acid precursors. {ECO:0000255|HAMAP-Rule:MF_04029}.
 
Catalytic activity: ATP + thymidine = ADP + thymidine 5'- phosphate. {ECO:0000255|HAMAP-Rule:MF_04029, ECO:0000269|PubMed:11056041}.
Subunit: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04029, ECO:0000269|PubMed:11056041}.
Biotechnology: Used in molecular biology as a selectable marker to identify transfected eukaryotic cells. Used in cancer suicide gene therapy to selectively kill transformed cells.
Miscellaneous: Phosphorylates and thereby activates certain drugs like acyclovir (ACV), valacyclovir, and famciclovir to a toxic form, that leads to successful suppression of the infection, while the uninfected cell does not have this ability because it lacks TK. Mutations in thymidine kinase may induce HSV resistance to antiviral therapies in immunocompromised patients. The most frequently observed resistant strains are unable to express TK and are avirulent in animal models of disease. Resistance may be acquired less frequently by selecting variants which no longer recognize ACV or ACV triphosphate as substrates but which retain normal functions.
Similarity: Belongs to the herpesviridae thymidine kinase family. {ECO:0000255|HAMAP-Rule:MF_04029}.

Annotations taken from UniProtKB at the EBI.