CLCA2 Human Protein

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. [provided by RefSeq, Jul 2008]

Function: Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner, and cell adhesion. Involved in basal cell adhesion and/or stratification of squamous epithelia. May act as a tumor suppressor in breast and colorectal cancer. Plays a key role for cell adhesion in the beginning stages of lung metastasis via the binding to ITGB4. Ref.7 Ref.8 Ref.9 Ref.11 Ref.12

Subcellular location: Cell membrane; Single-pass type I membrane protein. Basal cell membrane; Single-pass type I membrane protein. Cell junction Ref.1 Ref.10 Ref.11 Ref.13. Calcium-activated chloride channel regulator 2, 109 kDa form: Secreted. Note: Remains associated to the 35 kDa form until an unidentified event triggers the release. Ref.1 Ref.10 Ref.11 Ref.13

Tissue specificity: Expressed in cornea, skin, vagina, esophagus, and larynx (at protein level). Expressed in trachea and mammary gland. Weakly expressed in testis and kidney. Highly expressed in corneal epithelium, colon and trachea. Moderately expressed in brain, urogenital organs, bladder, uterus and prostate. Highly expressed in tissues containing stratified epithelium including cornea, esophagus, larynx, skin and vagina than those tissues which contain only epithelial monolayers. Expressed in normal breast epithelium but not in breast cancer. Highly expressed during epithelial stratification. Expressed in endothelial cells of lung. Expressed selectively in endothelia of small pulmonary arteries, arterioles, and subpleural and interlobular venules. Ref.1 Ref.2 Ref.3 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12

Induction: Significantly down-regulated in breast and colorectal cancer. Ref.7 Ref.8

Post-translational modification: The 141 kDa mature form is shedded, producing a 109 kDa form and a 35 kDa form.N-glycosylated. Ref.1 Ref.13

Sequence similarities: Belongs to the CLCR family.Contains 1 VWFA domain.