The name is misleading — although STK19 was initially identified as aserine/threonine kinase, analysis of the crystal structure revealed absence of the kinase domain[10] and it does not seem to possess any kinase activity.[11]
Structure of STK19 showing the CSA, RNAPII, and UVSSA interacting domains. Based on figure and domain identification by Heuvel, et al.,[9] with accompanying protein structure (PDB: 7XRB).[12][13]
STK19 contains 3 different protein-interaction domains, which are essential to its function in DNA repair: theCSA interacting domain,RNA polymerase II (RNAPII) interacting domain, andUVSSA interacting domain.[9] 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.[9]
Part of the UVSAA binding domain may also interact withXPD, 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.[9]
Role in transcription coupled nucleotide excision repair
STK19 is involved intranscription-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 activelytranscribed (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 (GG-NER).[8]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Sargent CA, Anderson MJ, Hsieh SL, Kendall E, Gomez-Escobar N, Campbell RD (Jul 1994). "Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex".Human Molecular Genetics.3 (3):481–488.doi:10.1093/hmg/3.3.481.PMID8012361.
Yu CY (1991). "The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene".Journal of Immunology.146 (3). Baltimore, Md.:1057–1066.doi:10.4049/jimmunol.146.3.1057.PMID1988494.
Ulgiati D, Townend DC, Christiansen FT, Dawkins RL, Abraham LJ (1996). "Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype".Immunogenetics.43 (4):250–252.doi:10.1007/BF00587313.PMID8575831.
Yang Z, Shen L, Dangel AW, Wu LC, Yu CY (1998). "Four ubiquitously expressed genes, RD (D6S45)-SKI2W (SKIV2L)-DOM3Z-RP1 (D6S60E), are present between complement component genes factor B and C4 in the class III region of the HLA".Genomics.53 (3):338–347.doi:10.1006/geno.1998.5499.PMID9799600.
Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region".Genomics.83 (1):153–167.doi:10.1016/S0888-7543(03)00235-0.PMID14667819.
Wadle A, Mischo A, Henrich PP, Stenner-Liewen F, Scherer C, Imig J, et al. (2005). "Characterization of Hap/BAG-1 variants as RP1 binding proteins with antiapoptotic activity".International Journal of Cancer.117 (6):896–904.doi:10.1002/ijc.21259.PMID15986447.S2CID36464436.
