Reactome | CLCAs self cleave

CLCAs self cleave

Stable Identifier

R-HSA-5333671

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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Calcium-activated chloride channel regulators 1,2,3P and 4 (CLCA1,2,3P and 4), originally named as CLCAs based on the observation that overexpression of them all induced chloride current in response to cytosolic calcium flux. More recent evidence points to them being secreted proteins (Gibson et al. 2005) and being responsible for chloride channel modulation rather that forming chloride channels per se (Hamann et al. 2009). CLCA1 has been found to be overexpressed in aiways of patients suffering from asthma and chronic obstructive pulmonary disease (Hoshino et al. 2002, Toda et al. 2002, Kamada et al. 2004). All CLCAs contain a consensus cleavage motif which is recognised by an internal zincin metalloprotease domain within the N terminus. Self-proteolysis within the secretory pathway yields N- and C-terminal fragments, a step critical for CLCA activation of calcium-activated chloride channels (CaCCs) mediated through the N-terminal fragment (Yurtsever et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
11842292	A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma Hamid, Q, Toda, M, Tulic, MK, Levitt, RC	J. Allergy Clin. Immunol.	2002
19307298	Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents Affleck, K, Main, M, Davies, N, Jowett, A, Hamann, M, Partington, L, Gibson, A, Trezise, D, Walhin, JP	J. Physiol. (Lond.)	2009
15919655	hCLCA1 and mCLCA3 are secreted non-integral membrane proteins and therefore are not ion channels Aitken, AJ, Affleck, K, Thompson, N, Lewis, AP, Meldrum, E, Gibson, A	J. Biol. Chem.	2005
15318163	Association of the hCLCA1 gene with childhood and adult asthma Tamari, M, Suzuki, Y, Hasegawa, K, Kure, S, Fujita, K, Mao, XQ, Matsubara, Y, Takahashi, N, Aoki, Y, Kamada, F, Tamura, G, Hirota, T, Miyatake, A, Fujiwara, H, Chiba, Y, Shao, C, Doi, S, Shimizu, M, Shirakawa, T	Genes Immun.	2004
23112050	Self-cleavage of human CLCA1 protein by a novel internal metalloprotease domain controls calcium-activated chloride channel activation Heier, RF, Patel, AC, Scheaffer, SM, Sala-Rabanal, M, Roswit, WT, Romero, AG, Alevy, YG, Randolph, DT, Brett, TJ, Yurtsever, Z, Holtzman, MJ, Nichols, CG	J. Biol. Chem.	2012
11956057	Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway Ashida, Y, Fujino, M, Nakanishi, A, Nishimura, O, Morita, S, Sagiya, Y, Iwashita, H, Hoshino, M, Nagi, T, Fujisawa, Y	Am. J. Respir. Crit. Care Med.	2002