CSMD1 CUB and Sushi multiple domains 1 is a protein that in humans is encoded by the CSMD1gene.[5]
Structure
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.[6]
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.[6]
Clinical significance
It is a potential tumour suppressor, the deletion of which may result in head and neck carcinomas behaving more aggressively.[7] CSMD1 protein expression was found to be reduced in patients with invasive breast cancer.[8] 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.[9]
Certain CSMD1 genetic variants have been found to show an association with risk of developing schizophrenia, consistent with emerging evidence that some forms of schizophrenia may result from dysregulated complement activation in the central nervous system resulting in excessive synaptic pruning.[10]
^* 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. S2CID22088084.
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.
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. S2CID7193505.
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. Bibcode:2003Sci...302.1960C. doi:10.1126/science.1088821. PMID14671302. S2CID6682593.
