Chitinase 3-like-1-tmem219-interleukin-13 receptor-ligand alpha-2 signalling complex

ComplexAc: CPX-9184

Homo sapiens; 9606

Curated by:

IntAct

Components

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ComplexViewer 2.2.4by Rappsilber LaboratoryTMEM219IL13RA2CHI3L1IL13tooltip
Legend Description Stoichiometry
protein - IL13 (unspecified role)
Interleukin-13
protein - TMEM219 (unspecified role)
Insulin-like growth factor-binding protein 3 receptor
protein - IL13RA2 (unspecified role)
Interleukin-13 receptor subunit alpha-2
protein - CHI3L1 (unspecified role)
Chitinase-3-like protein 1

Complex formed upon Chitinase-3-like protein 1 (CHI3L1) binding to interleukin-13 receptor alpha-2 (IL13RA2) by associating with TMEM219 which is a cell-death receptor for IGFBP-3 (P17936). CHI3L1 interaction with IL13RA2 through a TMEM219-dependent pathway prevents cell death by activating the MAP kinases, ERK1/2 and AKT pathways, while direct interaction with IL13RA2 results in apoptosis through activation of Wnt/beta-catenin (P35222). Functional effects of this complex is also moderated by LGALS3 (P17931), which physically interacts with IL13RA2 and CHI3L1 to compete with TMEM219 for IL13RA2 binding, thereby diminishing the anti-apoptotic role of CHI3L1. IL13RA2 also forms a complex with IL13 and TMEM219 (CPX847) which largely acts as a decoy to diminish IL13 activity. IL13RA2 N-glycosylation is a critical determinant of whether it binds CHI3L1 or IL13; CHI3L1 binding to IL13RA2 and signalling is increased if IL13RA2 N-glycosylation is diminished. CHI3L1 is a carbohydrate-binding lectin with a preference for chitin, produced by immune cells, osteoclasts, chondrocytes, smooth muscle cells, astrocytes and cancer cells upon stimulation from several interleukins including IL13, IL6, IL1B and TNF. CHI3L1 expression is inhibited by miR-24, miR-342-3p, miR-449a, miR125a-3p and miR-96-5p. CHI3L1 binding to IL13RA2 leads to inflammasome activation, melanoma metastasis, apoptosis, oxidative damage, allergic inflammation, wound healing, fibrosis, and TGFB1 production. CH3L1 also plays a key role in antipathogenic responses and is involved in stimulating disease tolerance by controlling cell death, inflammation and remodelling.

Properties

CHI3L1, the ligand component of this complex is a 40 kDa glycoprotein consisting of a (beta/alpha)x8-barrel fold with a beta+alpha domain insertion which are essential in mediating its physiological and pathological processes. CHI3L1 belongs to the glycosyl hydrolase 18 (GH 18) family, but it lacks chitinase enzymatic activity as a result of a Glu140Leu substitution. CHI3L1 does not compete with IL13 for IL13RA2 binding and there is no abrogative effect on each other’s signaling because they bind to different locations on the receptor. CHI3L1, IL13RA2 and IL13 are thought to interact to form a multimeric complex.

Expression and Cellular Location

Gene Expression Map

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GO - Cellular Component (1)

receptor complex

Diseases and Pathologies

Disease Cross References (1)

Identifier Name
MONDO:0004992 cancer

Additional Information

Further Reading

Identifier Title Author(s)
27629921 IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses. Lee CM, He CH, Nour AM, Zhou Y, Ma B, Park JW, Kim KH, Dela Cruz C, Sharma L, Nasr ML, Modis Y, Lee CG, Elias JA.
32402213 <i>N</i>-Glycosylation Regulates Chitinase 3-like-1 and IL-13 Ligand Binding to IL-13 Receptor α2. He CH, Lee CG, Ma B, Kamle S, Choi AMK, Elias JA.
36152905 Interleukin 13 receptor alpha 2 (IL13Rα2): Expression, signaling pathways and therapeutic applications in cancer. Jaén M, Martín-Regalado Á, Bartolomé RA, Robles J, Casal JI.
32929074 Chitinase-3 like-protein-1 function and its role in diseases. Zhao T, Su Z, Li Y, Zhang X, You Q.
23972995 Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. He CH, Lee CG, Dela Cruz CS, Lee CM, Zhou Y, Ahangari F, Ma B, Herzog EL, Rosenberg SA, Li Y, Nour AM, Parikh CR, Schmidt I, Modis Y, Cantley L, Elias JA.
38177294 Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer. Yu JE, Yeo IJ, Han SB, Yun J, Kim B, Yong YJ, Lim YS, Kim TH, Son DJ, Hong JT.

Synonyms (2)

YKL40-IGFBP-3R-IL13-IL13RA2 complex
BRP-39-TMEM219-IL13-IL13RA2 complex

Systematic Name

TMEM219:CHI3L1:IL13:IL13RA2