CLCA1 Membrane Protein Introduction

Introduction of CLCA1

CLCA1 encoding calcium-activated chloride channel regulator 1 is member of calcium-activated chloride channel regulator family (CLCA, previously known as chloride channel calcium activated). CLCA proteins are a group of secreted self-cleaving metalloproteases that activate calcium-dependent chloride currents (ICaCC) in mammalian cells. To date, all members of this gene family map to the same region on chromosome 1p31-p22 and share a high degree of homology in size and sequence, but differ significantly in their tissue distributions. CLCA1 is highly expressed in small intestine and colon namely in intestinal basal crypt epithelia and goblet cells, and appendix. And it is weakly expressed in uterus, testis and kidney.

Basic Information of CLCA1
Protein Name	Calcium-activated chloride channel regulator 1
Gene Name	CLCA1
Aliases	Calcium-activated chloride channel family member 1(hCLCA1), Calcium-activated chloride channel protein 1(CaCC-1, hCaCC-1)
Organism	Homo sapiens (Human)
UniProt ID	A8K7I4
Transmembrane Times	/
Length (aa)	914
Sequence	MGPFKSSVFILILHLLEGALSNSLIQLNNNGYEGIVVAIDPNVPEDETLIQQIKDMVTQASLYLLEATGKRFYFKNVAILIPETWKTKADYVRPKLETYKNADVLVAESTPPGNDEPYTEQMGNCGEKGERIHLTPDFIAGKKLAEYGPQGRAFVHEWAHLRWGVFDEYNNDEKFYLSNGRIQAVRCSAGITGTNVVKKCQGGSCYTKRCTFNKVTGLYEKGCEFVLQSRQTEKASIMFAQHVDSIVEFCTEQNHNKEAPNKQNQKCNLRSTWEVIRDSEDFKKTTPMTTQPPNPTFSLLQIGQRIVCLVLDKSGSMATGNRLNRLNQAGQLFLLQTVELGSWVGMVTFDSAAHVQNELIQINSGSDRDTLAKRLPAAASGGTSICSGLRSAFTVIRKKYPTDGSEIVLLTDGEDNTISGCFNEVKQSGAIIHTVALGPSAAQELEELSKMTGGLQTYASDQVQNNGLIDAFGALSSGNGAVSQRSIQLESKGLTLQNSQWMNGTVIVDSTVGKDTLFLITWTMQPPQILLWDPSGQKQGGFVVDKNTKMAYLQIPGIAKVGTWKYSLQASSQTLTLTVTSRASNATLPPITVTSKTNKDTSKFPSPLVVYANIRQGASPILRASVTALIESVNGKTVTLELLDNGAGADATKDDGVYSRYFTTYDTNGRYSVKVRALGGVNAARRRVIPQQSGALYIPGWIENDEIQWNPPRPEINKDDVQHKQVCFSRTSSGGSFVASDVPNAPIPDLFPPGQITDLKAEIHGGSLINLTWTAPGDDYDHGTAHKYIIRISTSILDLRDKFNESLQVNTTALIPKEANSEEVFLFKPENITFENGTDLFIAIQAVDKVDLKSEISNIARVSLFIPPQTPPETPSPDETSAPCPNIHINSTIPGIHILKIMWKWIGELQLSIA

Function of CLCA1 Membrane Protein

The goblet cell-derived protein CLCA1 (chloride channel regulator, calcium-activated is thought to act as a multifunctional signaling protein via as yet unidentified molecular pathways. Originally, CLCA1 had been thought to modulate epithelial cell chloride conductance. However, subsequent work has shown that it may also induce airway mucus production through an interleukin (IL)-13-mediated cascade and promote spontaneous differentiation while reducing proliferation of Caco-2 cells. In a similar context, CLCA1 expression was proposed as a prognostic factor in colorectal cancer. In early immune responses, CLCA1 was shown to modulate pulmonary cytokine expression, specifically the pro-inflammatory response of human airway macrophages in vitro.

Fig.1 Model for CLCA1 modulation of TMEM16A-mediated calcium-dependent chloride currents (Sala-Rabanal, 2015)

Application of CLCA1 Membrane Protein in Literature

Erickson N.A., et al. The goblet cell protein Clca1 (Alias mClca3 or Gob-5) is not required for intestinal mucus synthesis, structure and barrier function in naive or DSS-challenged mice. PLoS One. 2015, 10(7):e0131991. PubMed ID: 26162072

This article finds that no relevant differences between wild-type and Clca1-deficient mice under steady state or DSS-challenged conditions in mouse colon. Clca1 is not required for mucus synthesis, structure and barrier function in the murine colon.
Erickson N.A., et al. Role of goblet cell protein CLCA1 in murine DSS colitis. Journal of Inflammation-London. 2016, 13:5. PubMed ID: 26855614

This article suggests that CLCA1 is involved in the modulation of cytokine responses in the colon, albeit differently than what had been observed in the lungs.
Brett T.J. CLCA1 and TMEM16A: the link towards a potential cure for airway diseases. Expert Review of Respiratory Medicine. 2015, 9(5):503-6. PubMed ID: 26296094

This article recently reveals the function of CLCA1 and mechanistically how it activates chloride currents through TMEM16A.
Mishina K., et al. HO-1 inhibits IL-13-induced goblet cell hyperplasia associated with CLCA1 suppression in normal human bronchial epithelial cells. International Immunopharmacology. 2015, 29(2):448-453. PubMed ID: 26507166

This article reveals that HO-1 overexpression suppresses IL-13-induced goblet cell hyperplasia and MUC5AC production, and involvement of CLCA1 in the mechanism is suggested.
Musrap N., et al. Comparative proteomics of ovarian cancer aggregate formation reveals an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). The Journal of Biological Chemistry. 2015, 290(28):17218-27. PubMed ID: 26004777

This article suggests an apparent effect of CLCA1 on cancer cell aggregation by inhibitor and siRNA transfection studies.

CLCA1 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-CLCA1 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

Sala-Rabanal M, et al. (2015). Secreted CLCA1 modulates TMEM16A to activate Ca(2+)-dependent chloride currents in human cells. Elife. 4.

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