CCBE1 explained

Collagen and calcium-binding EGF domain-containing protein 1 is a protein that in humans is encoded by the CCBE1 gene.^{[1] [2]}

Function

CCBE1 is a regulator of the development and growth of the lymphatic system. CCBE1 is necessary for the proteolytic activation of VEGF-C by ADAMTS3,^[3] which is the main growth factor for the lymphatic system.^[4]

Clinical significance

Hennekam syndrome type I (a generalized lymphatic dysplasia in humans) is associated with mutations in the CCBE1 gene,^[5] and the molecular etiology of the disease has been elucidated.

Further reading

• Barton CA, Gloss BS, Qu W . Collagen and calcium-binding EGF domains 1 is frequently inactivated in ovarian cancer by aberrant promoter hypermethylation and modulates cell migration and survival . Br. J. Cancer . 102 . 1 . 87–96 . 2010 . 19935792 . 2813742 . 10.1038/sj.bjc.6605429 . etal.
• Browning SR, Thomas J . Multilocus analysis of GAW15 NARAC chromosome 18 case-control data . BMC Proceedings . 1. S11 . 2007 . Suppl 1 . 18466450 . 2367534 . 10.1186/1753-6561-1-S1-S11 . free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Uhl GR, Liu QR, Drgon T . Molecular Genetics of Successful Smoking Cessation: Convergent Genome-Wide Association Study Results . Arch. Gen. Psychiatry . 65 . 6 . 683–93 . 2008 . 18519826 . 2430596 . 10.1001/archpsyc.65.6.683 . etal.
• Hogan BM, Bos FL, Bussmann J . Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting . Nat. Genet. . 41 . 4 . 396–8 . 2009 . 19287381 . 10.1038/ng.321 . 205349555 . etal. free .
• Clark HF, Gurney AL, Abaya E . The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 403697 . 10.1101/gr.1293003 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . etal. free .
• Connell F, Kalidas K, Ostergaard P . Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia . Hum. Genet. . 127 . 2 . 231–41 . 2010 . 19911200 . 10.1007/s00439-009-0766-y . 6076175 . etal.

Notes and References

1. Web site: Entrez Gene: collagen and calcium binding EGF domains 1.
2. Nagase T, Kikuno R, Ohara O . Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins . DNA Res. . 8 . 6 . 319–27 . December 2001 . 11853319 . 10.1093/dnares/8.6.319. free .
3. 10.1161/CIRCULATIONAHA.113.002779. 129. 19. 1962–71. Jeltsch. Michael. Jha. Sawan Kumar. Tvorogov. Denis. Anisimov. Andrey. Leppänen. Veli-Matti. Holopainen. Tanja. Kivelä. Riikka. Ortega. Sagrario. Kärpanen. Terhi. Alitalo. Kari. CCBE1 Enhances Lymphangiogenesis via A Disintegrin and Metalloprotease With Thrombospondin Motifs-3-Mediated Vascular Endothelial Growth Factor-C Activation. Circulation. 2014. 24552833. free.
4. 10.1126/science.276.5317.1423. 9162011 . 276. 5317. 1423–25. Jeltsch. Michael. Kaipainen. Arja. Joukov. Vladimir. Meng. Xiaojuan. Lakso. Merja. Rauvala. Heikki. Swartz. Melody. Fukumura. Dai. Jain. Rakesh K.. Alitalo. Kari. Hyperplasia of Lymphatic Vessels in VEGF-C Transgenic Mice. Science. 1997.
5. Alders M, Hogan BM, Gjini E, Salehi F, Al-Gazali L, Hennekam EA, Holmberg EE, Mannens MM, Mulder MF, Offerhaus GJ, Prescott TE, Schroor EJ, Verheij JB, Witte M, Zwijnenburg PJ, Vikkula M, Schulte-Merker S, Hennekam RC . Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans . Nat. Genet. . 41 . 12 . 1272–4 . December 2009 . 19935664 . 10.1038/ng.484 . 205356254 .