CDCP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | CDCP1 , CD318, SIMA135, TRASK, CUB domain containing protein 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 611735 MGI: 2442010 HomoloGene: 11276 GeneCards: CDCP1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
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]
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]
Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus.
Growth factor receptor-bound protein 7, also known as GRB7, is a protein that in humans is encoded by the GRB7 gene.
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Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.
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RAS p21 protein activator 1 or RasGAP, also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:
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Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.
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A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.
David Schlaepfer is a California-born scientist known for his studies on cell migration and cancer metastasis. His early research focused on signaling by protein kinases, with a subsequent focus on the proteins that regulate the turnover of cell contacts with the extracellular matrix. In particular, Schlaepfer is well known for his studies on focal adhesion kinase (FAK).
Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs in invertebrates such as flies and worms, and Src homologs exist in organisms as diverse as unicellular choanoflagellates, but the SrcA and SrcB subfamilies are specific to vertebrates. Src family kinases contain six conserved domains: a N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.