STK19

STK19
Identifiers
Aliases	STK19 , D6S60, D6S60E, G11, HLA-RP1, RP1, serine/threonine kinase 19
External IDs	OMIM: 604977; MGI: 1860085; HomoloGene: 10449; GeneCards: STK19; OMA:STK19 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6p21.33 Start 31,971,091 bp [1] End 31,982,821 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17|17 B1 Start 35,042,969 bp [2] End 35,055,921 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left adrenal gland left adrenal cortex right adrenal gland right adrenal cortex right lobe of liver skin of leg anterior pituitary skin of abdomen left ovary right ovary Top expressed in bone marrow lip superior frontal gyrus islet of Langerhans duodenum jejunum primary visual cortex proximal tubule adrenal gland granulocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein serine/threonine kinase activity ATP binding kinase activity protein binding Cellular component nucleus nuclear speck Biological process protein phosphorylation phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8859 54402 Ensembl ENSG00000226257 ENSG00000206342 ENSG00000236250 ENSG00000226033 ENSG00000204344 ENSG00000234947 ENSMUSG00000061207 UniProt P49842 Q9JHN8 RefSeq (mRNA) NM_004197 NM_032454 NM_019442 RefSeq (protein) NP_004188 NP_115830 NP_062315 Location (UCSC) Chr 6: 31.97 – 31.98 Mb Chr 17: 35.04 – 35.06 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Serine/threonine-protein kinase 19 is a protein that in humans is encoded by the STK19 gene ^{[5] [6] [7]} and is involved in DNA repair, specifically the Transcription Coupled Nucleotide Excision Repair Pathway (TC-NER). ^{[8] [9]}

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 ^[10] and it does not seem to possess any kinase activity. ^[11]

This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants. ^[7]

Structure

Structure of STK19 showing the CSA, RNAPII, and UVSSA interacting domains. Based on figure and domain identification by Heuvel, et al., with accompanying protein structure (PDB: 7XRB). Image created using BioRender.

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. ^[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 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. ^[9]

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). ^[8]

See also

• RCCX

References

1. ENSG00000206342, ENSG00000236250, ENSG00000226033, ENSG00000204344, ENSG00000234947 GRCh38: Ensembl release 89: ENSG00000226257, ENSG00000206342, ENSG00000236250, ENSG00000226033, ENSG00000204344, ENSG00000234947 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000061207 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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". Hum Mol Genet. 3 (3): 481–8. doi:10.1093/hmg/3.3.481. PMID   8012361.
6. Gomez-Escobar N, Chou CF, Lin WW, Hsieh SL, Campbell RD (Dec 1998). "The G11 gene located in the major histocompatibility complex encodes a novel nuclear serine/threonine protein kinase". J Biol Chem. 273 (47): 30954–60. doi: 10.1074/jbc.273.47.30954 . PMID   9812991.
7. "Entrez Gene: STK19 serine/threonine kinase 19".
8. Mevissen, Tycho E. T.; Kümmecke, Maximilian; Schmid, Ernst W.; Farnung, Lucas; Walter, Johannes C. (2024-12-12). "STK19 positions TFIIH for cell-free transcription-coupled DNA repair". Cell. 187 (25): 7091–7106.e24. doi:10.1016/j.cell.2024.10.020. ISSN   0092-8674. PMID   39547228.
9. Heuvel, Diana van den; Rodríguez-Martínez, Marta; Meer, Paula J. van der; Moreno, Nicolas Nieto; Park, Jiyoung; Kim, Hyun-Suk; Schie, Janne J. M. van; Wondergem, Annelotte P.; D'Souza, Areetha; Yakoub, George; Herlihy, Anna E.; Kashyap, Krushanka; Boissière, Thierry; Walker, Jane; Mitter, Richard (2024-12-12). "STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair". Cell. 187 (25): 7107–7125.e25. doi:10.1016/j.cell.2024.10.018. ISSN   0092-8674. PMID   39547229.
10. Li, Yuling; Gong, Yanqiu; Zhou, Yue; Xiao, Yuzhou; Huang, Wenxin; Zhou, Qiao; Tu, Yingfeng; Zhao, Yinglan; Zhang, Shuyu; Dai, Lunzhi; Sun, Qingxiang (2024-01-22). "STK19 is a DNA/RNA-binding protein critical for DNA damage repair and cell proliferation". Journal of Cell Biology. 223 (2): e202301090. doi:10.1083/jcb.202301090. ISSN   0021-9525. PMC   10806857 . PMID   38252411.
11. Rodríguez-Martínez, Marta; Boissiére, Thierry; Gonzalez, Melvin Noe; Litchfield, Kevin; Mitter, Richard; Walker, Jane; Kjœr, Svend; Ismail, Mohamed; Downward, Julian; Swanton, Charles; Svejstrup, Jesper Q. (2020-06-11). "Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver". Cell. 181 (6): 1395–1405.e11. doi:10.1016/j.cell.2020.04.014. ISSN   0092-8674. PMC   7298618 . PMID   32531245.
12. Sun, Q.; Li, Y. (2023-06-07). "human STK19 dimer". www.wwpdb.org. doi:10.2210/pdb7xrb/pdb . Retrieved 2024-12-13.
13. Sipes, Jared (12 December 2024). "Domains of STK19". Biorender.com.

Further reading

• 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". J. Immunol. 146 (3): 1057–66. doi:10.4049/jimmunol.146.3.1057. PMID   1988494.
• Shen L, Wu LC, Sanlioglu S, et al. (1994). "Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplication". J. Biol. Chem. 269 (11): 8466–76. doi: 10.1016/S0021-9258(17)37217-4 . PMID   8132574.
• Ulgiati D, Townend DC, Christiansen FT, et al. (1996). "Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype". Immunogenetics. 43 (4): 250–2. doi:10.1007/BF00587313. PMID   8575831.
• Yang Z, Shen L, Dangel AW, et al. (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): 338–47. doi:10.1006/geno.1998.5499. PMID   9799600.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–11. Bibcode:2003Natur.425..805M. doi: 10.1038/nature02055 . PMID   14574404.
• Xie T, Rowen L, Aguado B, et al. (2004). "Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse". Genome Res. 13 (12): 2621–36. doi:10.1101/gr.1736803. PMC   403804 . PMID   14656967.
• Lehner B, Semple JI, Brown SE, et al. (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): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID   14667819.
• Wadle A, Mischo A, Henrich PP, et al. (2005). "Characterization of Hap/BAG-1 variants as RP1 binding proteins with antiapoptotic activity". Int. J. Cancer. 117 (6): 896–904. doi:10.1002/ijc.21259. PMID   15986447. S2CID   36464436.

STK19 involvement in DNA repair

• Mevissen, Tycho E. T.; Kümmecke, Maximilian; Schmid, Ernst W.; Farnung, Lucas; Walter, Johannes C. (2024-12-12). "STK19 positions TFIIH for cell-free transcription-coupled DNA repair". Cell. 187 (25): 7091–7106.e24. doi:10.1016/j.cell.2024.10.020. ISSN   0092-8674. PMID   39547228.
• Heuvel, Diana van den; Rodríguez-Martínez, Marta; Meer, Paula J. van der; Moreno, Nicolas Nieto; Park, Jiyoung; Kim, Hyun-Suk; Schie, Janne J. M. van; Wondergem, Annelotte P.; D'Souza, Areetha; Yakoub, George; Herlihy, Anna E.; Kashyap, Krushanka; Boissière, Thierry; Walker, Jane; Mitter, Richard (2024-12-12). "STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair". Cell. 187 (25): 7107–7125.e25. doi:10.1016/j.cell.2024.10.018. ISSN   0092-8674. PMID   39547229.