CLCA2 Membrane Protein Introduction

Introduction of CLCA2

Calcium-activated chloride channel regulator 2 (CLCA2) which is encoded by CLCA2 gene is a member of the calcium sensitive chloride conductance protein family. CLCA2 gene is located on chromosome 1p31-p22 and is expressed predominantly in trachea and lung. The metalloprotease domain autoproteolytically cleaves into 141 kDa mature form which is divided into a 109 kDa form and a 35 kDa form. The cleavage is essential to activate calcium-activated chloride channel (CaCC). Based on protein structure prediction methods, the N-terminal region of CLCA2 protein is a zinc metalloprotease.

Basic Information of CLCA2
Protein Name	Calcium-activated chloride channel regulator 2
Gene Name	CLCA2
Aliases	Calcium-activated chloride channel family member (hCLCA2), Calcium-activated chloride channel protein 3 (CaCC-3, hCaCC-3)
Organism	Homo sapiens (Human)
UniProt ID	Q9UQC9
Transmembrane Times	1
Length (aa)	943
Sequence	MTQRSIAGPICNLKFVTLLVALSSELPFLGAGVQLQDNGYNGLLIAINPQVPENQNLISNIKEMITEASFYLFNATKRRVFFRNIKILIPATWKANNNSKIKQESYEKANVIVTDWYGAHGDDPYTLQYRGCGKEGKYIHFTPNFLLNDNLTAGYGSRGRVFVHEWAHLRWGVFDEYNNDKPFYINGQNQIKVTRCSSDITGIFVCEKGPCPQENCIISKLFKEGCTFIYNSTQNATASIMFMQSLSSVVEFCNASTHNQEAPNLQNQMCSLRSAWDVITDSADFHHSFPMNGTELPPPPTFSLVQAGDKVVCLVLDVSSKMAEADRLLQLQQAAEFYLMQIVEIHTFVGIASFDSKGEIRAQLHQINSNDDRKLLVSYLPTTVSAKTDISICSGLKKGFEVVEKLNGKAYGSVMILVTSGDDKLLGNCLPTVLSSGSTIHSIALGSSAAPNLEELSRLTGGLKFFVPDISNSNSMIDAFSRISSGTGDIFQQHIQLESTGENVKPHHQLKNTVTVDNTVGNDTMFLVTWQASGPPEIILFDPDGRKYYTNNFITNLTFRTASLWIPGTAKPGHWTYTLNNTHHSLQALKVTVTSRASNSAVPPATVEAFVERDSLHFPHPVMIYANVKQGFYPILNATVTATVEPETGDPVTLRLLDDGAGADVIKNDGIYSRYFFSFAANGRYSLKVHVNHSPSISTPAHSIPGSHAMYVPGYTANGNIQMNAPRKSVGRNEEERKWGFSRVSSGGSFSVLGVPAGPHPDVFPPCKIIDLEAVKVEEELTLSWTAPGEDFDQGQATSYEIRMSKSLQNIQDDFNNAILVNTSKRNPQQAGIREIFTFSPQISTNGPEHQPNGETHESHRIYVAIRAMDRNSLQSAVSNIAQAPLFIPPNSDPVPARDYLILKGVLTAMGLIGIICLIIVVTHHTLSRKKRADKKENGTKLL

Function of CLCA2 Membrane Protein

CLCA2 is a type I integral transmembrane protein. Its coding gene is a stress-inducible gene, and is strongly induced by p53 in response to cell detachment, DNA damage, and other stressors. CLCA2 is frequently down-regulated in breast cancers by promoter methylation, and ectopic expression in a breast cancer cell line inhibited tumor formation, therefore CLCA2 can act as a tumor suppressor in breast and colorectal cancer. In a calcium-dependent manner, and cell adhesion CLCA2 modulates chloride current across the plasma membrane. CLCA2 is also involved in basal cell adhesion and/or stratification of squamous epithelia. In the beginning stages of lung metastasis via the binding to ITGB4, CLA2 plays a key role for cell adhesion.

Fig.1 Proposed model for action of CLCA2 and EVA1 at cell-cell junctions. (Ramena, 2016)

Application of CLCA2 Membrane Protein in Literature

Shinmura K., et al. CLCA2 as a novel immunohistochemical marker for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the lung. Disease Markers. 2014, 2014:1-11. PubMed ID: 25548429

This article finds that CLCA2 can be a novel good immunohistochemical marker for differentiating between primary ADC and primary SCC of the lung.
Ramena G., et al. CLCA2 Interactor EVA1 is required for mammary epithelial cell differentiation. PLoS One. 2016, 11(3):e0147489. PubMed ID: 26930581

This article suggests the mechnism of attenuation of CLCA2 causing EMT and explains why CLCA2 and EVA1 are frequently down-regulated in metastatic breast cancer cell lines.
Tanikawa C., et al. CLCA2 as a p53-inducible senescence mediator. Neoplasia. 2012, 14(2):141-9. PubMed ID: 22431922

This article suggests that the reduced expression of CLCA2 is related to the inhibition of oxidative stress-induced senescence. Besides, the decreased CLCA2 expression is also observed in various cancers like prostate cancer.
Sasaki Y., et al. TCLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion. Cancer Biology & Therapy. 2012, 13(14):1512-21. PubMed ID: 22990203

This article reveals that CLCA2 plays a role in the p53 tumor suppressor network and has an essential effect on cell migration and invasion.
Amélie G and Josée H. CLCA2, a novel RUNX1 partner gene in a therapy-related leukemia with t(1;21)(p22;q22). Cancer Genet Cytogenet. 2010, 202(2):94-100. PubMed ID: 20875871

This article reveals that the RUNX1-CLCA2 fusion is another example of out-of-frame fusion generating truncated RUNX1 isoforms that represent a recurrent molecular mechanism in RUNX1-related leukemias.

CLCA2 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CLCA2 antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

Ramena G, et al. (2016). CLCA2 interactor EVA1 is required for mammary epithelial cell differentiation. PLoS One. 11(3), e0147489.

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