CDCP1
Identifiers
AliasesCDCP1, CD318, SIMA135, TRASK, CUB domain containing protein 1
External IDsOMIM: 611735 MGI: 2442010 HomoloGene: 11276 GeneCards: CDCP1
Orthologs
SpeciesHumanMouse
Entrez

64866

109332

Ensembl

ENSG00000163814

ENSMUSG00000035498

UniProt

Q9H5V8

Q5U462

RefSeq (mRNA)

NM_022842
NM_178181

NM_133974

RefSeq (protein)

NP_073753
NP_835488

NP_598735

Location (UCSC)Chr 3: 45.08 – 45.15 MbChr 9: 123 – 123.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163814 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035498 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Scherl-Mostageer M, Sommergruber W, Abseher R, Hauptmann R, Ambros P, Schweifer N (July 2001). "Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer". Oncogene. 20 (32): 4402–8. doi:10.1038/sj.onc.1204566. PMID 11466621. S2CID 19987585.
  6. ^ a b "Entrez Gene: CDCP1 CUB domain containing protein 1".
  7. ^ a b c Spassov DS, Wong CH, Wong SY, Reiter JF, Moasser MM (2013). "Trask loss enhances tumorigenic growth by liberating integrin signaling and growth factor receptor cross-talk in unanchored cells". Cancer Research. 73 (3): 1168–79. doi:10.1158/0008-5472.CAN-12-2496. PMC 3563920. PMID 23243018.
  8. ^ Enyindah-Asonye G, Li Y, Ruth JH, Spassov DS, Hebron KE, Zijlstra A, Moasser MM, Wang B, Singer NG, Cui H, Ohara RA, Rasmussen SM, Fox DA, Lin F (2017). "CD318 is a ligand for CD6". Proc Natl Acad Sci U S A. 114 (33): E6912–E6921. Bibcode:2017PNAS..114E6912E. doi:10.1073/pnas.1704008114. PMC 5565428. PMID 28760953.
  9. ^ Bhatt AS, Erdjument-Bromage H, Tempst P, Craik CS, Moasser MM (2005). "Adhesion signaling by a novel mitotic substrate of src kinases". Oncogene. 24 (34): 5333–43. doi:10.1038/sj.onc.1208582. PMC 3023961. PMID 16007225.
  10. ^ Spassov DS, Ahuja D, Wong CH, Moasser MM (2011). "The structural features of Trask that mediate its anti-adhesive functions". PLOS ONE. 6 (4): e19154. Bibcode:2011PLoSO...619154S. doi:10.1371/journal.pone.0019154. PMC 3084758. PMID 21559459.
  11. ^ a b Spassov DS, Baehner FL, Wong CH, McDonough S, Moasser MM (2009). "The transmembrane src substrate Trask is an epithelial protein that signals during anchorage deprivation". Am J Pathol. 174 (5): 1756–65. doi:10.2353/ajpath.2009.080890. PMC 2671264. PMID 19349359.
  12. ^ Spassov DS, Wong CH, Sergina N, Ahuja D, Fried M, Sheppard D, Moasser MM (2011). "Phosphorylation of Trask by Src kinases inhibits integrin clustering and functions in exclusion with focal adhesion signaling". Mol Cell Biol. 31 (4): 766–82. doi:10.1128/MCB.00841-10. PMC 3028653. PMID 21189288.
  13. ^ 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. PMID 19514048. S2CID 9630579.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


Proteins: clusters of differentiation (see also list of human clusters of differentiation)
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