CCBE1

Summary

Gene Symbol: CCBE1
Description: collagen and calcium binding EGF domains 1
Alias: HKLLS1, collagen and calcium-binding EGF domain-containing protein 1, full of fluid protein homolog
Species: human
Products:     CCBE1

Top Publications

  1. Connell F, Kalidas K, Ostergaard P, Brice G, Homfray T, Roberts L, et al. Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia. Hum Genet. 2010;127:231-41 pubmed publisher
    ..Linkage analysis produced two loci on chromosome 18, covering 22 Mb and containing 150 genes, one of which is CCBE1. A homozygous cysteine to serine change in CCBE1 has been identified in the proband, in a residue that is ..
  2. Alders M, Hogan B, Gjini E, Salehi F, Al Gazali L, Hennekam E, et al. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nat Genet. 2009;41:1272-4 pubmed publisher
    ..Homozygosity mapping identified a critical chromosomal region containing CCBE1, the human ortholog of a gene essential for lymphangiogenesis in zebrafish...
  3. Hogan B, Bos F, Bussmann J, Witte M, Chi N, Duckers H, et al. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet. 2009;41:396-8 pubmed publisher
    ..Using a genetic screen in zebrafish we identify ccbe1 (collagen and calcium-binding EGF domain-1) as indispensible for embryonic lymphangiogenesis...
  4. Bos F, Caunt M, Peterson Maduro J, Planas Paz L, Kowalski J, Karpanen T, et al. CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo. Circ Res. 2011;109:486-91 pubmed publisher
    Collagen- and calcium-binding EGF domains 1 (CCBE1) has been associated with Hennekam syndrome, in which patients have lymphedema, lymphangiectasias, and other cardiovascular anomalies...
  5. Ye Z, Huang Y, Wang Y, Lu J, Wu J, Yu Z. Phenotype and Genotype of a Cohort of Chinese Children with Early-Onset Protein-Losing Enteropathy. J Pediatr. 2019;208:38-42.e3 pubmed publisher
    ..Next-generation sequencing in 9 patients with available DNA showed 1 patient had compound heterozygous CCBE1 mutations and 2 had novel homozygous DGAT1 mutations...
  6. Zhao Y, Liu H, Xiao L, Jin C, Zhang Z, Yang C. The clinical significance of CCBE1 expression in human colorectal cancer. Cancer Manag Res. 2018;10:6581-6590 pubmed publisher
    ..b>CCBE1 is expressed in various tumors and its expression correlates with lymphangiogenesis and angiogenesis...
  7. Bonet F, Pereira P, Bover O, Marques S, Inácio J, Belo J. CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart. Dev Dyn. 2018;247:1135-1145 pubmed publisher
    ..b>CCBE1 plays an important role during lymphangiogenesis, enhancing VEGF-C signaling, which is also required for coronary ..
  8. Silva M, Gomes Alves P, Rosa S, Simão D, Inácio J, Peixoto C, et al. Full-length human CCBE1 production and purification: leveraging bioprocess development for high quality glycosylation attributes and functionality. J Biotechnol. 2018;285:6-14 pubmed publisher
    Collagen and calcium-binding EGF domain-1 (CCBE1) is a secreted protein critical for lymphatic/cardiac vascular development and regeneration...
  9. Michelini S, Vettori A, Maltese P, Cardone M, Bruson A, Fiorentino A, et al. Genetic Screening in a Large Cohort of Italian Patients Affected by Primary Lymphedema Using a Next Generation Sequencing (NGS) Approach. Lymphology. 2016;49:57-72 pubmed
    ..library, we were able to analyze simultaneously in each patient all the coding exons of 10 genes (FLT4, FOXC2, CCBE1, GJC2, MET, HGF, GATA2, SOX18, VEGFC, KIF11) associated with primary lymphedema...

More Information

Publications36

  1. Deng X, Yin F, Zhang G, Duan Y. [A complicated case study: Hennekam syndrome]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17:77-80 pubmed
    ..Mutations in CCBE1 and FAT4 have been found responsible for the syndrome in a part of patients...
  2. Frosk P, Chodirker B, Simard L, El Matary W, Hanlon Dearman A, Schwartzentruber J, et al. A novel CCBE1 mutation leading to a mild form of hennekam syndrome: case report and review of the literature. BMC Med Genet. 2015;16:28 pubmed publisher
    Mutations in CCBE1 have been found to be responsible for a subset of families with autosomal recessive Hennekam syndrome. Hennekam syndrome is defined as the combination of generalized lymphatic dysplasia (ie...
  3. Pichol Thievend C, Betterman K, Liu X, Ma W, Skoczylas R, Lesieur E, et al. A blood capillary plexus-derived population of progenitor cells contributes to genesis of the dermal lymphatic vasculature during embryonic development. Development. 2018;145: pubmed publisher
    ..We describe a novel mechanism whereby rare PROX1-positive endothelial cells exit the capillary plexus in a Ccbe1-dependent manner to establish discrete LEC clusters...
  4. Furtado J, Bento M, Correia E, Inácio J, Belo J. Expression and function of Ccbe1 in the chick early cardiogenic regions are required for correct heart development. PLoS ONE. 2014;9:e115481 pubmed publisher
    ..screen to identify transcripts specific for chick heart/hemangioblast precursor cells, we have identified Ccbe1 (Collagen and calcium-binding EGF-like domain 1)...
  5. Jha S, Rauniyar K, Jeltsch M. Key molecules in lymphatic development, function, and identification. Ann Anat. 2018;219:25-34 pubmed publisher
    ..activated by an extracellular protein complex comprised of Collagen and calcium binding EGF domains 1 (CCBE1) protein and the protease A disintegrin and metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3)...
  6. Crawford J, Bower N, Hogan B, Taft R, Gabbett M, McGaughran J, et al. Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome. Am J Med Genet A. 2016;170:2694-7 pubmed publisher
    ..lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder, with 25% of patients having mutations in CCBE1. We identified a family with two brothers presenting with primary lymphedema, and performed exome sequencing to ..
  7. Burger N, Haak M, Kok E, de Groot C, Shou W, Scambler P, et al. Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. Early Hum Dev. 2016;101:39-48 pubmed publisher
    ..Mouse embryos with anomalous lymphatic development and nuchal edema (Ccbe1(-/-) embryos), mouse embryos with cardiac defects and nuchal edema (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, ..
  8. Cervera Juanes R, Wilhelm L, Park B, Grant K, Ferguson B. Genome-wide analysis of the nucleus accumbens identifies DNA methylation signals differentiating low/binge from heavy alcohol drinking. Alcohol. 2017;60:103-113 pubmed publisher
    ..However, two other DMRs, linked to the CCBE1 and FZD5 genes, had L/BD methylation levels that significantly differed from both ANs and H/VHDs...
  9. Guo R, Wang X, Wang Q, Li Z, Lu X, Miao R, et al. The regulatory role of SLP-2 and mechanism on CCBE1 gene expression in rectal carcinoma and adjacent lymphatic tube tissues. Eur Rev Med Pharmacol Sci. 2018;22:87-94 pubmed publisher
    ..Collagen and calcium-binding EGF domain (CCBE1) belongs to lymphatic tube genesis factor...
  10. Bui H, Enis D, Robciuc M, Nurmi H, Cohen J, Chen M, et al. Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD. J Clin Invest. 2016;126:2167-80 pubmed publisher
    ..with thrombospondin motifs 3 (ADAMTS3) and the secreted factor collagen and calcium binding EGF domains 1 (CCBE1) in this process...
  11. Hasselhof V, Sperling A, Buttler K, Strobel P, Becker J, Aung T, et al. Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors. PLoS ONE. 2016;11:e0164964 pubmed publisher
    ..Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1)...
  12. Zhang L, Liu F. Expression of SLP-2 gene and CCBE1 are associated with prognosis of rectal cancer. Eur Rev Med Pharmacol Sci. 2017;21:1214-1218 pubmed
    ..To analyze the effect of CCBE1 (Collagen and calcium-binding EGF domain-containing protein 1) on rectal cancer tissue and lymph vessels of para-..
  13. Jha S, Rauniyar K, Karpanen T, Leppänen V, Brouillard P, Vikkula M, et al. Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C-terminal domain of VEGF-C and the N-terminal domain of CCBE1. Sci Rep. 2017;7:4916 pubmed publisher
    The collagen- and calcium-binding EGF domains 1 (CCBE1) protein is necessary for lymphangiogenesis...
  14. Jackson C, Best L, Lorenzo L, Casanova J, Wacker J, Bertz S, et al. A Multiplex Kindred with Hennekam Syndrome due to Homozygosity for a CCBE1 Mutation that does not Prevent Protein Expression. J Clin Immunol. 2016;36:19-27 pubmed publisher
    Collagen and calcium-binding EGF domain-containing protein 1 (CCBE1) bi-allelic mutations have been associated with syndromes of widespread congenital lymphatic dysplasia, including Hennekam Syndrome (HS)...
  15. Connell F, Kalidas K, Ostergaard P, Brice G, Murday V, Mortimer P, et al. CCBE1 mutations can cause a mild, atypical form of generalized lymphatic dysplasia but are not a common cause of non-immune hydrops fetalis. Clin Genet. 2012;81:191-7 pubmed publisher
  16. Tian G, Zhu C, Zhang X, Zhu L, Yang X, Jiang S, et al. CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib. Sci Rep. 2016;6:31071 pubmed publisher
    ..In this study, we first found that collagen and calcium binding EGF domains 1 (CCBE1) expression gradually elevated along with the risk degree of NIH classification, and poor prognosis emerged in the ..
  17. Fransen E, Bonneux S, Corneveaux J, Schrauwen I, Di Berardino F, White C, et al. Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment. Eur J Hum Genet. 2015;23:110-5 pubmed publisher
    ..We estimated that 22% of the variance in our data set can be explained by the collective effect of all genotyped SNPs. A score analysis showed a modest enrichment in causative SNPs among the SNPs with a P-value below 0.01. ..
  18. Shah S, Conlin L, Gomez L, Aagenaes Ø, Eiklid K, Knisely A, et al. CCBE1 mutation in two siblings, one manifesting lymphedema-cholestasis syndrome, and the other, fetal hydrops. PLoS ONE. 2013;8:e75770 pubmed publisher
    ..6cM region on chromosome 15. Mutations in CCBE1 on chromosome 18 have been reported in some cases of lymphatic dysplasia, but not in LCS...
  19. Barton C, Gloss B, Qu W, Statham A, Hacker N, Sutherland R, et al. 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. 2010;102:87-96 pubmed publisher
    Collagen and calcium-binding EGF domains 1 (CCBE1) is an uncharacterised gene that has down-regulated expression in breast cancer. As CCBE1 maps to 18q21...
  20. Mesci A, Huang X, Taeb S, Jahangiri S, Kim Y, Fokas E, et al. Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis. Br J Cancer. 2017;116:1350-1357 pubmed publisher
    ..luciferase assays, we validate a novel target gene for miR-330-3p, Collagen And Calcium Binding EGF Domains 1 (CCBE1)...
  21. Sharma B, Ho L, Ford G, Chen H, Goldstone A, Woo Y, et al. Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts. Dev Cell. 2017;42:655-666.e3 pubmed publisher
    ..An upregulation of endocardial SOX17 accompanied compensation in Apj mutants, which was also seen in Ccbe1 knockouts, indicating that the endocardium is activated in multiple cases where sinus venosus angiogenesis is ..
  22. Brouillard P, Dupont L, Helaers R, Coulie R, Tiller G, Peeden J, et al. Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3. Hum Mol Genet. 2017;26:4095-4104 pubmed publisher
    ..VEGFC processing is also affected by CCBE1 mutations that cause the Hennekam lymphangiectasia-lymphedema syndrome syndrome type1...
  23. Power R, Cohen Woods S, Ng M, Butler A, Craddock N, Korszun A, et al. Genome-wide association analysis accounting for environmental factors through propensity-score matching: application to stressful live events in major depressive disorder. Am J Med Genet B Neuropsychiatr Genet. 2013;162B:521-9 pubmed publisher
  24. Browning S, Thomas J. Multilocus analysis of GAW15 NARAC chromosome 18 case-control data. BMC Proc. 2007;1 Suppl 1:S11 pubmed
    ..This haplotype was located less than 500 base pairs upstream of the CCBE1 gene...
  25. Li P, Cong Z, Qiang Y, Xiong L, Tang L, Zhang Y, et al. Clinical significance of CCBE1 expression in lung cancer. Mol Med Rep. 2017;: pubmed publisher
    ..between the expression of collagen and calcium?binding epidermal growth factor domain?containing protein 1 (CCBE1) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in tumor tissue with the clinical prognosis of ..
  26. Roukens M, Peterson Maduro J, Padberg Y, Jeltsch M, Leppänen V, Bos F, et al. Functional Dissection of the CCBE1 Protein: A Crucial Requirement for the Collagen Repeat Domain. Circ Res. 2015;116:1660-9 pubmed publisher
    Collagen- and calcium-binding EGF domain-containing protein 1 (CCBE1) is essential for lymphangiogenesis in vertebrates and has been associated with Hennekam syndrome...
  27. Jeltsch M, Jha S, Tvorogov D, Anisimov A, Lepp nen V, Holopainen T, et al. CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation. Circulation. 2014;129:1962-71 pubmed publisher
    ..Inheritance in Man 235510) is a rare autosomal recessive disease, which is associated with mutations in the CCBE1 gene...