Alternative titles; symbols
HGNC Approved Gene Symbol: CLCA2
Cytogenetic location: 1p22.3 Genomic coordinates (GRCh38) : 1:86,424,171-86,456,553 (from NCBI)
CLCA2 belongs to the calcium-dependent chloride channel family. Chloride channels are involved in the regulation of electrolytic fluxes and thereby modulate secretion, absorption, cell volume, and membrane potential (summary by Agnel et al., 1999).
By screening a human lung cDNA library with a Lu-ECAM-1 cDNA, Gruber et al. (1999) isolated cDNAs encoding CLCA2. The 943-amino acid protein deduced from the CLCA2 cDNAs is 76% and 51% identical to Lu-ECAM-1 and human CLCA1 (603906), respectively. Glycosylation site scanning and protease protection assays predicted that CLCA2 has 5 transmembrane domains and a large N-terminal extracellular domain. CLCA2 also contains a signal sequence, conserved cysteine residues within its N-terminal extracellular domain, a conserved consensus site for monobasic proteolytic cleavage, several potential glycosylation sites, and a number of potential phosphorylation sites for protein kinase C (see 176982). Northern blot analysis detected a 3.6-kb CLCA2 transcript in trachea and mammary gland; in addition to these tissues, RT-PCR showed expression in lung. Recombinant CLCA2 was expressed in mammalian cells as a 120-kD primary translation product that was cleaved into an 86-kD N-terminal polypeptide and a 34-kD C-terminal polypeptide, both of which were associated with the outer cell surface.
Using bovine Cacc1 (CLCA1) to query a human EST database, Agnel et al. (1999) identified CLCA2, which they called CACC3. The deduced 943-amino acid protein has an N-terminal signal peptide and a highly conserved HExxH zinc-binding motif. CACC3 shares 45% amino identity with CACC1 and CACC2 (CLCA4; 616857). Northern blot analysis detected a 4.2-kb transcript that was highly expressed in bladder and prostate, with weaker expression in stomach. RNA dot blot analysis of 50 human tissues showed additional CACC3 expression in trachea, uterus, testis, and kidney.
Gruber et al. (1999) found that expression of recombinant human CLCA2 in HEK293 cells resulted in a slightly outwardly rectifying anion conductance that was increased in the presence of the calcium ionophore ionomycin and inhibited by DIDS, dithiothreitol, niflumic acid, and tamoxifen.
By radiation hybrid analysis, Gruber and Pauli (1999) determined that the CLCA2 and CLCA3 genes map to 1p31-p22, where the CLCA1 gene had been assigned. Thus, all human CLCA family members known to that time were shown to be clustered on the short arm of chromosome 1 despite their moderately low levels of sequence homology and their heterogeneous expression patterns.
Pauli et al. (2000) reported that CLCA2 maps to a cluster of CLCA genes on chromosome 1p31-p22. The mouse Clca1 gene maps to a syntenic gene cluster on chromosome 3H2-H3.
Gross (2016) mapped the CLCA2 gene to chromosome 1p22.3 based on an alignment of the CLCA2 sequence (GenBank AF127980) with the genomic sequence (GRCh38).
Agnel, M., Vermat, T., Culouscou, J.-M. Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea. FEBS Lett. 455: 295-301, 1999. [PubMed: 10437792] [Full Text: https://doi.org/10.1016/s0014-5793(99)00891-1]
Gross, M. B. Personal Communication. Baltimore, Md. 3/11/2016.
Gruber, A. D., Pauli, B. U. Clustering of the human CLCA gene family on the short arm of chromosome 1 (1p22-31). Genome 42: 1030-1032, 1999. [PubMed: 10584316] [Full Text: https://doi.org/10.1139/g99-006]
Gruber, A. D., Schreur, K. D., Ji, H.-L., Fuller, C. M., Pauli, B. U. Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland. Am. J. Physiol. 276: C1261-C1270, 1999. [PubMed: 10362588] [Full Text: https://doi.org/10.1152/ajpcell.1999.276.6.C1261]
Pauli, B. U., Abdel-Ghany, M., Cheng, H.-C., Gruber, A. D., Archibald, H. A., Elble, R. C. Molecular characteristics and functional diversity of CLCA family members. Clin. Exp. Pharm. Physiol. 27: 901-905, 2000. [PubMed: 11071307] [Full Text: https://doi.org/10.1046/j.1440-1681.2000.03358.x]