CDCP1

CUB domain-containing protein 1 (CDCP1) is a protein that in humans is encoded by the CDCP1 gene.^[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 not important for the development of the mouse.^[7] 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.^[7] 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.^[8]

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.^[9] 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.^[7]

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.^[10][11] 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.^[11] 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.^[12]

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.^[13]

References

Further reading

• Xia Y, Gil SG, Carter WG (February 1996). "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.
  PMID 8647901
  .
• 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.
  S2CID 2608191
  .
• 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.
  S2CID 12794175
  .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (October 2003). "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.
  PMID 12975309
  .
• 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.
  PMID 14739293
  .
• 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.
  S2CID 11997172
  .
• 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.
  S2CID 1498824
  .
• Bhatt AS, Erdjument-Bromage H, Tempst P, Craik CS, Moasser MM (August 2005). "Adhesion signaling by a novel mitotic substrate of src kinases". Oncogene. 24 (34): 5333–43.
  PMID 16007225
  .
• 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.
  S2CID 46542257
  .
• 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.
  S2CID 6809573
  .
• 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.
  S2CID 30701692
  .
• Uekita T, Jia L, Narisawa-Saito M, Yokota J, Kiyono T, Sakai R (November 2007). "CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma". Molecular and Cellular Biology. 27 (21): 7649–60.
  PMID 17785447
  .

External links

• CDCP1+protein,+human at the U.S. 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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