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CUB domain-containing protein 1 (CDCP1) is a protein that in humans is encoded by the CDCP1gene.[5][6] CDCP1 has also been designated as CD318 (cluster of differentiation 318) and Trask (Transmembrane and associated with src kinases). Alternatively spliced transcript variants encoding distinct isoforms have been reported.[6]
Function
CDCP1/Trask is a 140 kD transmembrane glycoprotein with a large extracellular domain (ECD) containing two CUB domains, and a smaller intracellular domain (ICD) containing five tyrosines. The tyrosine phosphorylation of Trask is tightly regulated and reciprocally linked with the state of cell adhesion.[7] The tyrosine phosphorylation of CDCP1 in cultured cells occurs when cells are induced to detach by trypsin or EDTA, or seen spontaneously during mitotic detachment. The overexpression of CDCP1 leads to the loss of cell adhesion and a detached phenotype. CDCP1 is widely expressed in human epithelial tissues, but its phosphorylation is only seen in mitotically detached or shedding cells, consistent with its role in the negative regulation of cell adhesion.
Clinical significance
The phosphorylation of CDCP1 is seen in many cancers, including some pre-invasive cancers as well as in invasive tumors and in tumor metastases.[8]
^Wortmann A, He Y, Deryugina EI, Quigley JP, Hooper JD (July 2009). "The cell surface glycoprotein CDCP1 in cancer--insights, opportunities, and challenges". IUBMB Life. 61 (7): 723–30. doi:10.1002/iub.198. PMID19514048.
Hooper JD, Zijlstra A, Aimes RT, Liang H, Claassen GF, Tarin D, Testa JE, Quigley JP (March 2003). "Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen". Oncogene. 22 (12): 1783–94. doi:10.1038/sj.onc.1206220. PMID12660814.
Conze T, Lammers R, Kuci S, Scherl-Mostageer M, Schweifer N, Kanz L, Buhring HJ (May 2003). "CDCP1 is a novel marker for hematopoietic stem cells". Annals of the New York Academy of Sciences. 996 (1): 222–6. doi:10.1111/j.1749-6632.2003.tb03249.x. PMID12799299.
Brown TA, Yang TM, Zaitsevskaia T, Xia Y, Dunn CA, Sigle RO, Knudsen B, Carter WG (April 2004). "Adhesion or plasmin regulates tyrosine phosphorylation of a novel membrane glycoprotein p80/gp140/CUB domain-containing protein 1 in epithelia". The Journal of Biological Chemistry. 279 (15): 14772–83. doi:10.1074/jbc.M309678200. PMID14739293.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Bühring HJ, Kuçi S, Conze T, Rathke G, Bartolović K, Grünebach F, Scherl-Mostageer M, Brümmendorf TH, Schweifer N, Lammers R (2005). "CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin". Stem Cells. 22 (3): 334–43. doi:10.1634/stemcells.22-3-334. PMID15153610.
Benes CH, Wu N, Elia AE, Dharia T, Cantley LC, Soltoff SP (April 2005). "The C2 domain of PKCdelta is a phosphotyrosine binding domain". Cell. 121 (2): 271–80. doi:10.1016/j.cell.2005.02.019. PMID15851033.
André M, Le Caer JP, Greco C, Planchon S, El Nemer W, Boucheix C, Rubinstein E, Chamot-Rooke J, Le Naour F (March 2006). "Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS". Proteomics. 6 (5): 1437–49. doi:10.1002/pmic.200500180. PMID16404722.
Kimura H, Morii E, Ikeda JI, Ezoe S, Xu JX, Nakamichi N, Tomita Y, Shibayama H, Kanakura Y, Aozasa K (September 2006). "Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells". Leukemia. 20 (9): 1551–6. doi:10.1038/sj.leu.2404312. PMID16926850.
Perry SE, Robinson P, Melcher A, Quirke P, Bühring HJ, Cook GP, Blair GE (March 2007). "Expression of the CUB domain containing protein 1 (CDCP1) gene in colorectal tumour cells". FEBS Letters. 581 (6): 1137–42. doi:10.1016/j.febslet.2007.02.025. PMID17335815.
