RIPK5

DSTYK
Identifiers
Aliases	DSTYK , CAKUT1, DustyPK, RIP5, RIPK5, HDCMD38P, dual serine/threonine and tyrosine protein kinase, SPG23
External IDs	OMIM: 612666 MGI: 1925064 HomoloGene: 19711 GeneCards: DSTYK
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1q32.1 Start 205,142,505 bp [1] End 205,211,702 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1|1 E4 Start 132,345,293 bp [2] End 132,394,696 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in internal globus pallidus superior vestibular nucleus inferior ganglion of vagus nerve ventral tegmental area pons cerebellar vermis subthalamic nucleus renal medulla parietal lobe external globus pallidus Top expressed in ciliary body habenula secondary oocyte utricle iris retinal pigment epithelium stria vascularis olfactory tubercle conjunctival fornix nucleus accumbens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein serine/threonine/tyrosine kinase activity protein tyrosine kinase activity protein kinase activity ATP binding kinase activity protein serine/threonine kinase activity Cellular component cytoplasm cell junction plasma membrane basolateral plasma membrane apical plasma membrane membrane cytosol Biological process positive regulation of fibroblast growth factor receptor signaling pathway positive regulation of kinase activity peptidyl-tyrosine phosphorylation protein phosphorylation cellular response to fibroblast growth factor stimulus phosphorylation positive regulation of ERK1 and ERK2 cascade negative regulation of apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 25778 213452 Ensembl ENSG00000133059 ENSMUSG00000042046 UniProt Q6XUX3 Q6XUX1 RefSeq (mRNA) NM_015375 NM_199462 NM_172516 RefSeq (protein) NP_056190 NP_955749 NP_766104 Location (UCSC) Chr 1: 205.14 – 205.21 Mb Chr 1: 132.35 – 132.39 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dual serine/threonine and tyrosine protein kinase is an enzyme that in humans is encoded by the DSTYK gene. ^{[5] [6]}

This protein is also known as the Dusty protein kinase and the Receptor interacting protein 5 (RIP5).

This gene encodes a dual serine/threonine and tyrosine protein kinase which is expressed in multiple tissues. Multiple alternatively spliced transcript variants have been found, but the biological validity of some variants has not been determined. ^[6]

In melanocytic cells RIPK5 gene expression may be regulated by MITF. ^[7]

Mutations in this gene have been associated with hereditary spastic paraplegia type 23. ^[8]

"Diagram of HsInv0006 (orange bar) genomic region showing the effect of the inverted allele on the expression of neighboring genes in different tissues according to the GTEx data and the inversion tag SNP in Europeans associated to increased risk of Glaucoma"

It has also seen that DSTYK deletion causes pigmentation problems and high cell death after ultraviolet irradiation. In a study conducted by Giner-Delgado, Carla, et al. ^[10] it has been observed that the inversion of the first intron has been associated with changes in expression in the proximal genes and with an increase in the expression of DSTKY itself. Due to the deleterious effect caused by the absence of expression, the positive selection of this investment could explain its increase in the African population. They also noted that the investment has been linked to an increased risk of glaucoma in Europeans (which again shows the possible positive selection, since glaucoma is more common and severe in individuals of African descent.

References

1. GRCh38: Ensembl release 89: ENSG00000133059 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042046 - 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. Zha J, Zhou Q, Xu LG, Chen D, Li L, Zhai Z, Shu HB (Jun 2004). "RIP5 is a RIP-homologous inducer of cell death". Biochem Biophys Res Commun. 319 (2): 298–303. doi:10.1016/j.bbrc.2004.04.194. PMID   15178406.
6. "Entrez Gene: RIPK5 receptor interacting protein kinase 5".
7. Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi: 10.1111/j.1755-148X.2008.00505.x . PMID   19067971.
8. Lee JYW, Hsu CK, Michael M, Nanda A, Liu L, McMillan JR, Pourreyron C, Takeichi T, Tolar J, Reid E, Hayday T, Blumen SC, Abu-Mouch S, Straussberg R, Basel-Vanagaite L, Barhum Y, Zouabi Y, Al-Ajmi H, Huang HY, Lin TC, Akiyama M, Lee JYY, McLean WHI, Simpson MA, Parsons M, McGrath JA (2017) Large intragenic deletion in DSTYK underlies autosomal-recessive complicated spastic paraparesis, SPG23. Am J Hum Genet 100(2):364-370
9. Giner-Delgado, Carla, et al. "Evolutionary and functional impact of common polymorphic inversions in the human genome." Nature communications 10.1 (2019): 1-14.
10. Giner-Delgado, C., Villatoro, S., Lerga-Jaso, J., Gayà-Vidal, M., Oliva, M., Castellano, D., ... & Olalde, I. (2019). Evolutionary and functional impact of common polymorphic inversions in the human genome. Nature communications, 10(1), 1-14.

Further reading

• Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, et al. (1995). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics. 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID   7829101.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Seki N, Ohira M, Nagase T, et al. (1998). "Characterization of cDNA clones in size-fractionated cDNA libraries from human brain". DNA Res. 4 (5): 345–9. doi: 10.1093/dnares/4.5.345 . PMID   9455484.
• Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. Bibcode:2000PNAS...97.3491D. doi: 10.1073/pnas.97.7.3491 . PMC   16267 . PMID   10737800.
• 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.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Peng J, Dong W, Chen Y, et al. (2007). "Dusty protein kinases: primary structure, gene evolution, tissue specific expression and unique features of the catalytic domain". Biochim. Biophys. Acta. 1759 (11–12): 562–72. doi:10.1016/j.bbaexp.2006.10.004. PMC   4277547 . PMID   17123648.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.