Chloride channel accessory 2 is a protein that in humans is encoded by the CLCA2gene.
The protein encoded by this gene belongs to the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same site on chromosome 1p31-p22 and share high degrees of homology in size, sequence and predicted structure, but differ significantly in their tissue distributions. Since this protein is expressed predominantly in trachea and lung, it is suggested to play a role in the complex pathogenesis of cystic fibrosis. It may also serve as adhesion molecule for lung metastatic cancer cells, mediating vascular arrest and colonization, and furthermore, it has been implicated to act as a tumor suppressor gene for breast cancer. Protein structure prediction methods suggest the N-terminal region of CLCA2 protein is a zinc metalloprotease.
^Pawłowski K, Lepistö M, Meinander N, et al. (2006). "Novel conserved hydrolase domain in the CLCA family of alleged calcium-activated chloride channels". Proteins63 (3): 424–39. doi:10.1002/prot.20887. PMID16470849.
Gruber AD, Schreur KD, Ji HL, et al. (1999). "Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland". Am. J. Physiol.276 (6 Pt 1): C1261–70. PMID10362588.
Agnel M, Vermat T, Culouscou JM (1999). "Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea". FEBS Lett.455 (3): 295–301. doi:10.1016/S0014-5793(99)00891-1. PMID10437792.
Gruber AD, Pauli BU (1999). "Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2". Cancer Res.59 (21): 5488–91. PMID10554024.
Koegel H, Alzheimer C (2001). "Expression and biological significance of Ca2+-activated ion channels in human keratinocytes". FASEB J.15 (1): 145–154. doi:10.1096/fj.00-0055com. PMID11149902.
Itoh R, Kawamoto S, Miyamoto Y, et al. (2001). "Isolation and characterization of a Ca2+-activated chloride channel from human corneal epithelium". Curr. Eye Res.21 (6): 918–25. doi:10.1076/ceyr.21.6.918.6983. PMID11262615.
Abdel-Ghany M, Cheng HC, Elble RC, Pauli BU (2001). "The breast cancer beta 4 integrin and endothelial human CLCA2 mediate lung metastasis". J. Biol. Chem.276 (27): 25438–46. doi:10.1074/jbc.M100478200. PMID11320086.
Abdel-Ghany M, Cheng HC, Elble RC, Pauli BU (2002). "Focal adhesion kinase activated by beta(4) integrin ligation to mCLCA1 mediates early metastatic growth". J. Biol. Chem.277 (37): 34391–400. doi:10.1074/jbc.M205307200. PMID12110680.
Mall M, Gonska T, Thomas J, et al. (2003). "Modulation of Ca2+-activated Cl− secretion by basolateral K+ channels in human normal and cystic fibrosis airway epithelia". Pediatr. Res.53 (4): 608–18. doi:10.1203/01.PDR.0000057204.51420.DC. PMID12612194.
Abdel-Ghany M, Cheng HC, Elble RC, et al. (2004). "The interacting binding domains of the beta(4) integrin and calcium-activated chloride channels (CLCAs) in metastasis". J. Biol. Chem.278 (49): 49406–16. doi:10.1074/jbc.M309086200. PMID14512419.
Connon CJ, Kawasaki S, Yamasaki K, et al. (2005). "The quantification of hCLCA2 and colocalisation with integrin beta4 in stratified human epithelia". Acta Histochem.106 (6): 421–5. doi:10.1016/j.acthis.2004.08.003. PMID15707651.
Connon CJ, Kawasaki S, Liles M, et al. (2006). "Gene expression and immunolocalisation of a calcium-activated chloride channel during the stratification of cultivated and developing corneal epithelium". Cell Tissue Res.323 (1): 177–82. doi:10.1007/s00441-005-0059-2. PMID16158324.
Elble RC, Walia V, Cheng HC, et al. (2006). "The putative chloride channel hCLCA2 has a single C-terminal transmembrane segment". J. Biol. Chem.281 (40): 29448–54. doi:10.1074/jbc.M605919200. PMID16873362.