STK19

Serine/threonine-protein kinase 19 is a protein that in humans is encoded by the STK19 gene{{cite journal | vauthors = Sargent CA, Anderson MJ, Hsieh SL, Kendall E, Gomez-Escobar N, Campbell RD | title = Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex | journal = Human Molecular Genetics | volume = 3 | issue = 3 | pages = 481–488 | date = Jul 1994 | pmid = 8012361 | doi = 10.1093/hmg/3.3.481 }}{{cite journal | vauthors = Gomez-Escobar N, Chou CF, Lin WW, Hsieh SL, Campbell RD | title = The G11 gene located in the major histocompatibility complex encodes a novel nuclear serine/threonine protein kinase | journal = Journal of Biological Chemistry | volume = 273 | issue = 47 | pages = 30954–30960 | date = Dec 1998 | pmid = 9812991 | doi = 10.1074/jbc.273.47.30954 | doi-access = free }}{{cite web | title = Entrez Gene: STK19 serine/threonine kinase 19 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8859 }} and is involved in DNA repair, specifically the Transcription Coupled Nucleotide Excision Repair Pathway (TC-NER).{{Cite journal | vauthors = Mevissen TE, Kummecke M, Schmid EW, Farnung L, Walter JC | title = STK19 positions TFIIH for cell-free transcription-coupled DNA repair | journal = Cell | volume = 187 | issue = 25 | pages = 7091–7106.e24 | date = 2024-12-12 | pmid = 39547228 | pmc = 11645862 | doi = 10.1016/j.cell.2024.10.020 | url = https://linkinghub.elsevier.com/retrieve/pii/S0092867424012029 | language = English | issn = 0092-8674 | doi-access = free }}{{Cite journal | vauthors = van den Heuvel D, Rodriguez-Martinez M, van der Meer PJ, Nieto Moreno N, Park J, Kim HS, van Schie JJ, Wondergem AP, D'Souza A, Yakoub G, Herlihy AE, Kashyap K, Boissiere T, Walker J, Mitter R, Apelt K, de Lint K, Kirdok I, Ljungman M, Wolthuis RM, Cramer P, Scharer OD, Kokic G, Svejstrup JQ, Luijsterburg MS | title = STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair | journal = Cell | volume = 187 | issue = 25 | pages = 7107–7125.e25 | date = 2024-12-12 | pmid = 39547229 | doi = 10.1016/j.cell.2024.10.018 | url = https://linkinghub.elsevier.com/retrieve/pii/S0092867424012005 | language = English | issn = 0092-8674 | doi-access = free }}

The name is misleading — although STK19 was initially identified as a serine/threonine kinase, analysis of the crystal structure revealed absence of the kinase domain {{Cite journal | vauthors = Li Y, Gong Y, Zhou Y, Xiao Y, Huang W, Zhou Q, Tu Y, Zhao Y, Zhang S, Dai L, Sun Q | title = STK19 is a DNA/RNA-binding protein critical for DNA damage repair and cell proliferation | journal = The Journal of Cell Biology | volume = 223 | issue = 2 | pages = e202301090 | date = 2024-01-22 | pmid = 38252411 | pmc = 10806857 | doi = 10.1083/jcb.202301090 | url = https://rupress.org/jcb/article/223/2/e202301090/276514/STK19-is-a-DNA-RNA-binding-protein-critical-for | issn = 0021-9525 }} and it does not seem to possess any kinase activity.{{Cite journal | vauthors = Rodriguez-Martinez M, Boissiere T, Noe Gonzalez M, Litchfield K, Mitter R, Walker J, Kjoer S, Ismail M, Downward J, Swanton C, Svejstrup JQ | title = Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver | journal = Cell | volume = 181 | issue = 6 | pages = 1395–1405.e11 | date = 2020-06-11 | pmid = 32531245 | pmc = 7298618 | doi = 10.1016/j.cell.2020.04.014 | language = English | issn = 0092-8674 }}

This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants.

Structure

File:Domains of STK19.jpg

STK19 contains 3 different protein-interaction domains, which are essential to its function in DNA repair: the CSA interacting domain, RNA Polymerase II (RNAPII) interacting domain, and UVSSA interacting domain. These domains allow STK19 to incorporate into the Transcription-Coupled DNA Repair (TCR) complex, which is recruited to RNA Polymerase II stalled at DNA lesions.

Part of the UVSAA binding domain may also interact with XPD, a protein in the TFIIH (transcription factor IIH) complex. This complex is recruited to the TCR and is involved in excising the damaged DNA. STK19 binding to XPD is theorized to help optimally position the TFIIH ATPase subunits XPD and XPB onto the DNA in front of the lesion.

Role in Transcription Coupled Nucleotide Excision Repair

STK19 is involved in Transcription Coupled Nucleotide Excision Repair (TC-NER), a DNA repair pathway that preferentially detects and removes DNA damage in portions of the genome that are being actively transcribed (copied from DNA into RNA). (By contrast, the non-transcribed strand and portions of the genome not under active transcription are repaired more slowly, using Global Genome Nucleotide Excision Repair or GG-NER).

STK19

Structure

Role in Transcription Coupled Nucleotide Excision Repair

See also

References

Further reading