CSMD1 explained
CSMD1 CUB and Sushi multiple domains 1 is a protein that in humans is encoded by the CSMD1 gene.[1]
Structure
CSMD1 contains 14 N-terminal CUB 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.
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]
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.[6]
Further reading
- Kamal M, Shaaban AM, Zhang L, Walker C, Gray S, Thakker N, Toomes C, Speirs V, Bell SM . 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 . June 2010 . 19669408 . 10.1007/s10549-009-0500-4 . 22958267 .
- Smith DI, Zhu Y, McAvoy S, Kuhn R . Common fragile sites, extremely large genes, neural development and cancer . Cancer Letters . 232 . 1 . 48–57 . January 2006 . 16221525 . 10.1016/j.canlet.2005.06.049 .
- Sun PC, Uppaluri R, Schmidt AP, Pashia ME, Quant EC, Sunwoo JB, Gollin SM, Scholnick SB . Transcript map of the 8p23 putative tumor suppressor region . Genomics . 75 . 1–3 . 17–25 . July 2001 . 11472063 . 10.1006/geno.2001.6587 .
- Nagase T, Kikuno R, Ohara O . 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 . August 2001 . 11572484 . 10.1093/dnares/8.4.179 . free .
- 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 . Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse . Cancer Research . 63 . 14 . 4196–203 . July 2003 . 12874026 .
- Lau WL, Scholnick SB . Identification of two new members of the CSMD gene family . Genomics . 82 . 3 . 412–5 . September 2003 . 12906867 . 10.1016/S0888-7543(03)00149-6 .
- Scholnick SB, Richter TM . The role of CSMD1 in head and neck carcinogenesis . Genes, Chromosomes & Cancer . 38 . 3 . 281–3 . November 2003 . 14506705 . 10.1002/gcc.10279 . 7193505 .
- 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 . 6682593 . Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios . Science . 302 . 5652 . 1960–3 . December 2003 . 14671302 . 10.1126/science.1088821 . 2003Sci...302.1960C .
- 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 . Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors . Human Molecular Genetics . 13 . 13 . 1303–13 . July 2004 . 15138198 . 10.1093/hmg/ddh155 . free .
- Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . September 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
- Richter TM, Tong BD, Scholnick SB . Epigenetic inactivation and aberrant transcription of CSMD1 in squamous cell carcinoma cell lines . Cancer Cell International . 5 . 1 . 29 . September 2005 . 16153303 . 1239921 . 10.1186/1475-2867-5-29 . free .
- Blaveri E, Brewer JL, Roydasgupta R, Fridlyand J, DeVries S, Koppie T, Pejavar S, Mehta K, Carroll P, Simko JP, Waldman FM . Bladder cancer stage and outcome by array-based comparative genomic hybridization . Clinical Cancer Research . 11 . 19 Pt 1 . 7012–22 . October 2005 . 16203795 . 10.1158/1078-0432.CCR-05-0177 . free .
Notes and References
- Web site: Entrez Gene: CSMD1 CUB and Sushi multiple domains 1.
- Kraus DM, Elliott GS, Chute H, Horan T, Pfenninger KH, Sanford SD, Foster S, Scully S, Welcher AA, Holers VM . 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 . April 2006 . 16547280 . 10.4049/jimmunol.176.7.4419 . free .
- 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 . 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 . June 2003 . 12696061 . 10.1002/gcc.10191 . 22088084 .
- Escudero-Esparza A, Bartoschek M, Gialeli C, Okroj M, Owen S, Jirström K, Orimo A, Jiang WG, Pietras K, Blom AM . Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer . Oncotarget . 7 . 47 . 76920–76933 . November 2016 . 27764775 . 5363559 . 10.18632/oncotarget.12729 .
- Kamal M, Holliday DL, Morrison EE, Speirs V, Toomes C, Bell SM . Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion . Oncology Reports . 38 . 1 . 283–292 . July 2017 . 28534981 . 10.3892/or.2017.5656 . free .
- Baum. Matthew L.. 2018-09-16. The Schizophrenia-Associated Gene, CSMD1, Encodes a Brain-Specific Complement Inhibitor. en.