Secreted Ly-6/uPAR-related protein 1 is a protein that in humans is encoded by the SLURP1gene.[1][2][3] It exerts anti-inflammatory effects and acts as a tumor suppressor and antagonist of nicotine[4].
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[2] and binds to the α7-acetylcholine receptor[4]. 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[4].
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[5] and an increased secretion of the inflammatory cytokines TNFα, IL1, IL-6, and IL-8[6][7].
This gene maps to the same chromosomal region as several members of the Ly6/uPAR family of glycoprotein receptors.[3]
References
↑Fischer J, Bouadjar B, Heilig R, Huber M, Lefèvre C, Jobard F, Macari F, Bakija-Konsuo A, Ait-Belkacem F, Weissenbach J, Lathrop M, Hohl D, Prud'homme JF (April 2001). "Mutations in the gene encoding SLURP-1 in Mal de Meleda". Human Molecular Genetics. 10 (8): 875–80. doi:10.1093/hmg/10.8.875. PMID11285253.
↑Favre B, Plantard L, Aeschbach L, Brakch N, Christen-Zaech S, de Viragh PA, Sergeant A, Huber M, Hohl D (February 2007). "SLURP1 is a late marker of epidermal differentiation and is absent in Mal de Meleda". The Journal of Investigative Dermatology. 127 (2): 301–8. doi:10.1038/sj.jid.5700551. PMID17008884.
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.
Fischer J, Bouadjar B, Heilig R, Fizames C, Prud'homme JF, Weissenbach J (1999). "Genetic linkage of Meleda disease to chromosome 8qter". European Journal of Human Genetics. 6 (6): 542–7. doi:10.1038/sj.ejhg.5200254. PMID9887370.
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.
Marrakchi S, Audebert S, Bouadjar B, Has C, Lefèvre C, Munro C, Cure S, Jobard F, Morlot S, Hohl D, Prud'homme JF, Zahaf A, Turki H, Fischer J (March 2003). "Novel mutations in the gene encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) and description of five ancestral haplotypes in patients with Mal de Meleda". The Journal of Investigative Dermatology. 120 (3): 351–5. doi:10.1046/j.1523-1747.2003.12062.x. PMID12603845.
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. PMID12787122.
Chimienti F, Hogg RC, Plantard L, Lehmann C, Brakch N, Fischer J, Huber M, Bertrand D, Hohl D (November 2003). "Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda". Human Molecular Genetics. 12 (22): 3017–24. doi:10.1093/hmg/ddg320. PMID14506129.
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.
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.
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.
Arredondo J, Chernyavsky AI, Webber RJ, Grando SA (December 2005). "Biological effects of SLURP-1 on human keratinocytes". The Journal of Investigative Dermatology. 125 (6): 1236–41. doi:10.1111/j.0022-202X.2005.23973.x. PMID16354194.