CSMD1 contains 14 N-terminalCUB domains that are separated from each other by a Sushi domains followed by an additional 15 tandem Sushi domain segment.[2]
Function
Based on analogy to other proteins that contain Sushi domains, it is believed that the gene product of CSMD1 functions as a Complement control protein.[2]
Clinical significance
It is a potential tumour suppressor, the deletion of which may result in head and neck carcinomas behaving more aggressively.[3] CSMD1 protein expression was found to be reduced in patients with invasive breast cancer.[4] Functional studies showed that CSMD1 reduction causes cells to transform to a cancer form by increasing their ability to divide, migrate and invade. In a three dimensional model of breast ducts, reduced CSMD1 expression failed breast duct formation.[5]
↑ 2.02.1Kraus DM, Elliott GS, Chute H, Horan T, Pfenninger KH, Sanford SD, Foster S, Scully S, Welcher AA, Holers VM (April 2006). "CSMD1 is a novel multiple domain complement-regulatory protein highly expressed in the central nervous system and epithelial tissues". Journal of Immunology. 176 (7): 4419–30. doi:10.4049/jimmunol.176.7.4419. PMID16547280.
↑* Toomes C, Jackson A, Maguire K, Wood J, Gollin S, Ishwad C, Paterson I, Prime S, Parkinson K, Bell S, Woods G, Markham A, Oliver R, Woodward R, Sloan P, Dixon M, Read A, Thakker N (June 2003). "The presence of multiple regions of homozygous deletion at the CSMD1 locus in oral squamous cell carcinoma question the role of CSMD1 in head and neck carcinogenesis". Genes, Chromosomes & Cancer. 37 (2): 132–40. doi:10.1002/gcc.10191. PMID12696061.
Kamal M, Shaaban AM, Zhang L, Walker C, Gray S, Thakker N, Toomes C, Speirs V, Bell SM (June 2010). "Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma". Breast Cancer Research and Treatment. 121 (3): 555–63. doi:10.1007/s10549-009-0500-4. PMID19669408.
Smith DI, Zhu Y, McAvoy S, Kuhn R (January 2006). "Common fragile sites, extremely large genes, neural development and cancer". Cancer Letters. 232 (1): 48–57. doi:10.1016/j.canlet.2005.06.049. PMID16221525.
Nagase T, Kikuno R, Ohara O (August 2001). "Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins". DNA Research. 8 (4): 179–87. doi:10.1093/dnares/8.4.179. PMID11572484.
Henshall SM, Afar DE, Hiller J, Horvath LG, Quinn DI, Rasiah KK, Gish K, Willhite D, Kench JG, Gardiner-Garden M, Stricker PD, Scher HI, Grygiel JJ, Agus DB, Mack DH, Sutherland RL (July 2003). "Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse". Cancer Research. 63 (14): 4196–203. PMID12874026.
Scholnick SB, Richter TM (November 2003). "The role of CSMD1 in head and neck carcinogenesis". Genes, Chromosomes & Cancer. 38 (3): 281–3. doi:10.1002/gcc.10279. PMID14506705.
Clark AG, Glanowski S, Nielsen R, Thomas PD, Kejariwal A, Todd MA, Tanenbaum DM, Civello D, Lu F, Murphy B, Ferriera S, Wang G, Zheng X, White TJ, Sninsky JJ, Adams MD, Cargill M (December 2003). "Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios". Science. 302 (5652): 1960–3. doi:10.1126/science.1088821. PMID14671302.
Paris PL, Andaya A, Fridlyand J, Jain AN, Weinberg V, Kowbel D, Brebner JH, Simko J, Watson JE, Volik S, Albertson DG, Pinkel D, Alers JC, van der Kwast TH, Vissers KJ, Schroder FH, Wildhagen MF, Febbo PG, Chinnaiyan AM, Pienta KJ, Carroll PR, Rubin MA, Collins C, van Dekken H (July 2004). "Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors". Human Molecular Genetics. 13 (13): 1303–13. doi:10.1093/hmg/ddh155. PMID15138198.
