Biology:CDCP1
 Generic protein structure example |
CUB domain-containing protein 1 (CDCP1) is a protein that in humans is encoded by the CDCP1 gene.[1][2] 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.[2]
Function
CDCP1/Trask is not important for the development of the mouse.[3] Adult mice lacking CDCP1 do not exhibit gross morphologic, reproductive or behavioral abnormalities compared with wild-type mice, and histologic examination of multiple organ systems has shown no significant pathology and no observed histologic differences.[3] CDCP1 is a ligand for CD6, a receptor molecule expressed on certain T-cells and may play a role in their migration and chemotaxis. As such CDCP1 may contribute to autoimmune diseases such as encephalomyelitis, multiple sclerosis and inflammatory arthritis.[4]
CDCP1 is a 140 kD transmembrane glycoprotein with a large extracellular domain (ECD) containing two CUB domains, and a smaller intracellular domain (ICD). CDCP1 is cleaved by serine proteases at the extracellular domain next to Arg368 to generate a truncated molecule of 80 kDa size.[5] Different cell lines express different amounts of p140 and p80, depending on the activity of endogenous serine proteases. In vivo, CDCP1 is not cleaved during normal physiological circumstances, but its cleavage can be induced during tumorigenesis or tissue injury.[3]
The intracellular domain of CDCP1 contains five tyrosine residues - Y707, Y734, Y743, Y762 and Y806. Phosphorylation of CDCP1 is exclusively mediated by Src kinases and depends on the adherence state of the cells.[6][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 loss of anchorage or cellular detachment is associated with the phosphorylation of CDCP1 as well as the concomitant dephosphorylation of focal adhesion proteins, consistent with the dismantling of focal adhesions.[7] Contrary, during cellular attachment CDCP1 is dephosphorylated, allowing the phosphorylation of focal adhesion proteins. The anti-adhesion and anti-migratory functions of CDCP1 are mediated through negative regulation on integrin receptors.[8]
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.[9]
References
- ↑ "Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer". Oncogene 20 (32): 4402–8. July 2001. doi:10.1038/sj.onc.1204566. PMID 11466621.
- ↑ 2.0 2.1 "Entrez Gene: CDCP1 CUB domain containing protein 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64866.
- ↑ 3.0 3.1 3.2 "Trask loss enhances tumorigenic growth by liberating integrin signaling and growth factor receptor cross-talk in unanchored cells". Cancer Research 73 (3): 1168–79. 2013. doi:10.1158/0008-5472.CAN-12-2496. PMID 23243018.
- ↑ "CD318 is a ligand for CD6". Proc Natl Acad Sci U S A 114 (33): E6912–E6921. 2017. doi:10.1073/pnas.1704008114. PMID 28760953.
- ↑ "Adhesion signaling by a novel mitotic substrate of src kinases". Oncogene 24 (34): 5333–43. 2005. doi:10.1038/sj.onc.1208582. PMID 16007225.
- ↑ "The structural features of Trask that mediate its anti-adhesive functions". PLOS ONE 6 (4): e19154. 2011. doi:10.1371/journal.pone.0019154. PMID 21559459. Bibcode: 2011PLoSO...619154S.
- ↑ 7.0 7.1 "The transmembrane src substrate Trask is an epithelial protein that signals during anchorage deprivation". Am J Pathol 174 (5): 1756–65. 2009. doi:10.2353/ajpath.2009.080890. PMID 19349359.
- ↑ "Phosphorylation of Trask by Src kinases inhibits integrin clustering and functions in exclusion with focal adhesion signaling". Mol Cell Biol 31 (4): 766–82. 2011. doi:10.1128/MCB.00841-10. PMID 21189288.
- ↑ "The cell surface glycoprotein CDCP1 in cancer--insights, opportunities, and challenges". IUBMB Life 61 (7): 723–30. July 2009. doi:10.1002/iub.198. PMID 19514048.
Further reading
- "Anchorage mediated by integrin alpha6beta4 to laminin 5 (epiligrin) regulates tyrosine phosphorylation of a membrane-associated 80-kD protein". The Journal of Cell Biology 132 (4): 727–40. February 1996. doi:10.1083/jcb.132.4.727. PMID 8647901.
- "Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen". Oncogene 22 (12): 1783–94. March 2003. doi:10.1038/sj.onc.1206220. PMID 12660814.
- "CDCP1 is a novel marker for hematopoietic stem cells". Annals of the New York Academy of Sciences 996 (1): 222–6. May 2003. doi:10.1111/j.1749-6632.2003.tb03249.x. PMID 12799299. Bibcode: 2003NYASA.996..222C.
- "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Research 13 (10): 2265–70. October 2003. doi:10.1101/gr.1293003. PMID 12975309.
- "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. April 2004. doi:10.1074/jbc.M309678200. PMID 14739293.
- "CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin". Stem Cells 22 (3): 334–43. 2005. doi:10.1634/stemcells.22-3-334. PMID 15153610.
- "The C2 domain of PKCdelta is a phosphotyrosine binding domain". Cell 121 (2): 271–80. April 2005. doi:10.1016/j.cell.2005.02.019. PMID 15851033.
- "Adhesion signaling by a novel mitotic substrate of src kinases". Oncogene 24 (34): 5333–43. August 2005. doi:10.1038/sj.onc.1208582. PMID 16007225.
- "Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS". Proteomics 6 (5): 1437–49. March 2006. doi:10.1002/pmic.200500180. PMID 16404722.
- "Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells". Leukemia 20 (9): 1551–6. September 2006. doi:10.1038/sj.leu.2404312. PMID 16926850.
- "Expression of the CUB domain containing protein 1 (CDCP1) gene in colorectal tumour cells". FEBS Letters 581 (6): 1137–42. March 2007. doi:10.1016/j.febslet.2007.02.025. PMID 17335815.
- "CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma". Molecular and Cellular Biology 27 (21): 7649–60. November 2007. doi:10.1128/MCB.01246-07. PMID 17785447.
External links
- CDCP1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human CDCP1 genome location and CDCP1 gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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