CCBE1

Collagen and calcium-binding EGF domain-containing protein 1 is a protein that in humans is encoded by the CCBE1 gene.[5][6]

CCBE1
Identifiers
Aliases	CCBE1, HKLLS1, collagen and calcium binding EGF domains 1
External IDs	OMIM: 612753 MGI: 2445053 HomoloGene: 15852 GeneCards: CCBE1
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q21.32 Start 59,430,939 bp[1] End 59,697,662 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18|18 E1 Start 66,045,302 bp[2] End 66,302,741 bp[2]
Gene ontology Molecular function • protease binding • calcium ion binding • GO:0001948 protein binding • collagen binding Cellular component • extracellular region • collagen • extracellular • extracellular matrix Biological process • positive regulation of endothelial cell migration • multicellular organism development • positive regulation of vascular endothelial growth factor production • sprouting angiogenesis • positive regulation of lymphangiogenesis • positive regulation of protein processing • angiogenesis • positive regulation of vascular endothelial growth factor signaling pathway • venous blood vessel morphogenesis • lymphangiogenesis • positive regulation of angiogenesis • lymph vessel development • lung development • respiratory gaseous exchange • respiratory system process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	147372	320924
Ensembl	ENSG00000183287	ENSMUSG00000046318
UniProt	Q6UXH8	Q3MI99
RefSeq (mRNA)	NM_133459	NM_178793
RefSeq (protein)	NP_597716	NP_848908
Location (UCSC)	Chr 18: 59.43 – 59.7 Mb	Chr 18: 66.05 – 66.3 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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,[7] which is the main growth factor for the lymphatic system.[8]

Clinical significance

Hennekam syndrome type I (a generalized lymphatic dysplasia in humans) is associated with mutations in the CCBE1 gene,[9] and the molecular etiology of the disease has been elucidated.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000183287 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000046318 - 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. "Entrez Gene: collagen and calcium binding EGF domains 1".
6. Nagase T, Kikuno R, Ohara O (December 2001). "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. doi:10.1093/dnares/8.6.319. PMID 11853319.
7. Jeltsch, Michael; Jha, Sawan Kumar; Tvorogov, Denis; Anisimov, Andrey; Leppänen, Veli-Matti; Holopainen, Tanja; Kivelä, Riikka; Ortega, Sagrario; Kärpanen, Terhi; Alitalo, Kari (2014). "CCBE1 Enhances Lymphangiogenesis via A Disintegrin and Metalloprotease With Thrombospondin Motifs-3-Mediated Vascular Endothelial Growth Factor-C Activation". Circulation. 129 (19): 1962–71. doi:10.1161/CIRCULATIONAHA.113.002779. PMID 24552833.
8. Jeltsch, Michael; Kaipainen, Arja; Joukov, Vladimir; Meng, Xiaojuan; Lakso, Merja; Rauvala, Heikki; Swartz, Melody; Fukumura, Dai; Jain, Rakesh K.; Alitalo, Kari (1997). "Hyperplasia of Lymphatic Vessels in VEGF-C Transgenic Mice". Science. 276 (5317): 1423–25. doi:10.1126/science.276.5317.1423. PMID 9162011.
9. 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 (December 2009). "Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans". Nat. Genet. 41 (12): 1272–4. doi:10.1038/ng.484. PMID 19935664. S2CID 205356254.

External links

• Human CCBE1 genome location and CCBE1 gene details page in the UCSC Genome Browser.

Further reading

• Barton CA, Gloss BS, Qu W, et al. (2010). "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. doi:10.1038/sj.bjc.6605429. PMC 2813742. PMID 19935792.
• Browning SR, Thomas J (2007). "Multilocus analysis of GAW15 NARAC chromosome 18 case-control data". BMC Proceedings. 1 Suppl 1: S11. doi:10.1186/1753-6561-1-S1-S11. PMC 2367534. PMID 18466450.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Uhl GR, Liu QR, Drgon T, et al. (2008). "Molecular Genetics of Successful Smoking Cessation: Convergent Genome-Wide Association Study Results". Arch. Gen. Psychiatry. 65 (6): 683–93. doi:10.1001/archpsyc.65.6.683. PMC 2430596. PMID 18519826.
• Hogan BM, Bos FL, Bussmann J, et al. (2009). "Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting". Nat. Genet. 41 (4): 396–8. doi:10.1038/ng.321. PMID 19287381. S2CID 205349555.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "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. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Connell F, Kalidas K, Ostergaard P, et al. (2010). "Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia" (PDF). Hum. Genet. 127 (2): 231–41. doi:10.1007/s00439-009-0766-y. PMID 19911200. S2CID 6076175.

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