CLCAs self cleave

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
19307298 Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents

Hamann, M, Gibson, A, Davies, N, Jowett, A, Walhin, JP, Partington, L, Affleck, K, Trezise, D, Main, M

J. Physiol. (Lond.) 2009
11842292 A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma

Toda, M, Tulic, MK, Levitt, RC, Hamid, Q

J. Allergy Clin. Immunol. 2002
15919655 hCLCA1 and mCLCA3 are secreted non-integral membrane proteins and therefore are not ion channels

Gibson, A, Lewis, AP, Affleck, K, Aitken, AJ, Meldrum, E, Thompson, N

J. Biol. Chem. 2005
15318163 Association of the hCLCA1 gene with childhood and adult asthma

Kamada, F, Suzuki, Y, Shao, C, Tamari, M, Hasegawa, K, Hirota, T, Shimizu, M, Takahashi, N, Mao, XQ, Doi, S, Fujiwara, H, Miyatake, A, Fujita, K, Chiba, Y, Aoki, Y, Kure, S, Tamura, G, Shirakawa, T, Matsubara, Y

Genes Immun. 2004
23112050 Self-cleavage of human CLCA1 protein by a novel internal metalloprotease domain controls calcium-activated chloride channel activation

Yurtsever, Z, Sala-Rabanal, M, Randolph, DT, Scheaffer, SM, Roswit, WT, Alevy, YG, Patel, AC, Heier, RF, Romero, AG, Nichols, CG, Holtzman, MJ, Brett, TJ

J. Biol. Chem. 2012
11956057 Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway

Hoshino, M, Morita, S, Iwashita, H, Sagiya, Y, Nagi, T, Nakanishi, A, Ashida, Y, Nishimura, O, Fujisawa, Y, Fujino, M

Am. J. Respir. Crit. Care Med. 2002
Catalyst Activity

metalloendopeptidase activity of CLCAs [plasma membrane]

This event is regulated
Positively by
Orthologous Events
Cite Us!