Secreted Ly-6/uPAR-related protein 1 is a protein that in humans is encoded by the SLURP1gene.[5][6][7] It exerts anti-inflammatory effects, acts as a tumor suppressor, and antagonizes nicotinic receptors.[8]
Function
The protein encoded by this gene is a member of the Ly6/uPAR family but lacks a GPI-anchoring signal sequence. It is secreted into the blood[6] and is also sometimes found in semen when extracted into the female zygote which binds to the α7-acetylcholine receptor.[8] It is shown to act as an endogenous tumor suppressor by reducing cell migration and invasion by mediating its own anti-tumor effect and by antagonizing the pro-malignant effects of nicotine.[8]
Mutations in this gene have been associated with Mal de Meleda, a rare autosomal recessive skin disorder characterized by an inflammatory palmoplantar hyperkeratosis. This is the consequence of a loss of SLURP1 which leads to a dysfunctional epithelial differentiation[9] and an increased secretion of the inflammatory cytokines TNFα, IL1, IL-6, and IL-8.[10][11]
This gene maps to the same chromosomal region as several members of the Ly6/uPAR family of glycoprotein receptors.[7]
Ridge RJ, Sloane NH (January 1996). "Partial N-terminal amino acid sequence of the anti-neoplastic urinary protein (ANUP) and the anti-tumour effect of the N-terminal nonapeptide of the unique cytokine present in human granulocytes". Cytokine. 8 (1): 1–5. doi:10.1006/cyto.1996.0001. PMID8742060.
Eckl KM, Stevens HP, Lestringant GG, Westenberger-Treumann M, Traupe H, Hinz B, Frossard PM, Stadler R, Leigh IM, Nürnberg P, Reis A, Hennies HC (January 2003). "Mal de Meleda (MDM) caused by mutations in the gene for SLURP-1 in patients from Germany, Turkey, Palestine, and the United Arab Emirates". Human Genetics. 112 (1): 50–6. doi:10.1007/s00439-002-0838-8. PMID12483299. S2CID317308.
Hu G, Yildirim M, Baysal V, Yerebakan O, Yilmaz E, Inaloz HS, Martinez-Mir A, Christiano AM, Celebi JT (June 2003). "A recurrent mutation in the ARS (component B) gene encoding SLURP-1 in Turkish families with mal de Meleda: evidence of a founder effect". The Journal of Investigative Dermatology. 120 (6): 967–9. doi:10.1046/j.1523-1747.2003.12248.x. hdl:10261/39458. PMID12787122.
Charfeddine C, Mokni M, Ben Mousli R, Elkares R, Bouchlaka C, Boubaker S, Ghedamsi S, Baccouche D, Ben Osman A, Dellagi K, Abdelhak S (December 2003). "A novel missense mutation in the gene encoding SLURP-1 in patients with Mal de Meleda from northern Tunisia". The British Journal of Dermatology. 149 (6): 1108–15. doi:10.1111/j.1365-2133.2003.05606.x. PMID14674887. S2CID22999382.
Mastrangeli R, Donini S, Kelton CA, He C, Bressan A, Milazzo F, Ciolli V, Borrelli F, Martelli F, Biffoni M, Serlupi-Crescenzi O, Serani S, Micangeli E, El Tayar N, Vaccaro R, Renda T, Lisciani R, Rossi M, Papoian R (2004). "ARS Component B: structural characterization, tissue expression and regulation of the gene and protein (SLURP-1) associated with Mal de Meleda". European Journal of Dermatology. 13 (6): 560–70. PMID14721776.
Mokni M, Charfeddine C, Ben Mously R, Baccouche D, Kaabi B, Ben Osman A, Dellagi K, Abdelhak S (March 2004). "Heterozygous manifestations in female carriers of Mal de Meleda". Clinical Genetics. 65 (3): 244–6. doi:10.1111/j.0009-9163.2004.00224.x. PMID14756676. S2CID46140052.
Chao SC, Lai FJ, Yang MH, Lee JY (April 2005). "Mal de Meleda in a taiwanese". Journal of the Formosan Medical Association = Taiwan Yi Zhi. 104 (4): 276–8. PMID15909066.