chitinase 3 like 1 | Chitinase-like proteins | IUPHAR Guide to IMMUNOPHARMACOLOGY

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chitinase 3 like 1

  Target has curated data in GtoImmuPdb

Target id: 2987

Nomenclature: chitinase 3 like 1

Family: Chitinase-like proteins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 383 1q32.1 CHI3L1 chitinase 3 like 1 7
Mouse - 389 1 E4; 1 58.15 cM Chil1 chitinase-like 1
Rat - 381 13q13 Chi3l1 chitinase 3 like 1
Gene and Protein Information Comments
A longer transcript from the rat gene generating a longer protein isoform (NP_001296749, 931 aa) has been identified.
Previous and Unofficial Names
cartilage glycoprotein-39 | cGP-39 | GP-39 | GP39 | YKL40 | Ym-1
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Immunopharmacology Comments
CHI3L1 is recognised as a proinflammatory mediator in the development and progression of Th2 inflammation, such as in allergic reactions [1]. CHI3L1 negatively regulates Th1 and cytotoxic T lymphocyte (CTL) functions, and silencing the gene enhances Th1 and CTL functions [4]. It is being considered as a novel drug target for immuno-oncology and inflammatory indications.
Chi3l1 is reported to bind to interleukin-13 receptor α2 in a complex that also contains IL-13. It may be formation of this complex that mediates Chi3l1 effector responses [3].
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
Comment:  Highly expressed in macropahges (detected by mRNA expression).
References:  4
Immuno Cell Type:  T cells
Comment:  mRNA and protein levels of Chi3l1 are strongly induced following anti-CD3 and anti-CD28 stimulation of T cells, and Chi3l1 is selectively induced in Th0 and Th2 cells compared to other effector T cell subsets.
References:  4
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0006954 inflammatory response IEP
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 6 GO processes
GO:0034612 response to tumor necrosis factor IEP
GO:0070555 response to interleukin-1 IEP
GO:0070741 response to interleukin-6 IEP
GO:0071356 cellular response to tumor necrosis factor ISS
GO:0072606 interleukin-8 secretion ISS
click arrow to show/hide IEA associations
GO:0071347 cellular response to interleukin-1 IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Biologically Significant Variants
Type:  Naturally occurring SNP
Species:  Human
Description:  The G allele of CHI3L1 rs4950928 might be a protective factor against the development of asthma.
SNP accession: 
General Comments
Despite being included as a member of the chitinase family, CHI3L1 is devoid of chitinase activity, and is included here as a 'Chitinase-like peptide'. It is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. CHI3L1 plays a role in innate immunity against pathogens [2] and has been associated with asthma [8] and cancer [5-6] via regulation of the Th2 inflammatory pathway.

References

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1. Cai Y, Kumar RK, Zhou J, Foster PS, Webb DC. (2009) Ym1/2 promotes Th2 cytokine expression by inhibiting 12/15(S)-lipoxygenase: identification of a novel pathway for regulating allergic inflammation. J. Immunol., 182 (9): 5393-9. [PMID:19380786]

2. Dela Cruz CS, Liu W, He CH, Jacoby A, Gornitzky A, Ma B, Flavell R, Lee CG, Elias JA. (2012) Chitinase 3-like-1 promotes Streptococcus pneumoniae killing and augments host tolerance to lung antibacterial responses. Cell Host Microbe, 12 (1): 34-46. [PMID:22817986]

3. He CH, Lee CG, Dela Cruz CS, Lee CM, Zhou Y, Ahangari F, Ma B, Herzog EL, Rosenberg SA, Li Y et al.. (2013) Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. Cell Rep, 4 (4): 830-41. [PMID:23972995]

4. Kim DH, Park HJ, Lim S, Koo JH, Lee HG, Choi JO, Oh JH, Ha SJ, Kang MJ, Lee CM et al.. (2018) Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis. Nat Commun, 9 (1): 503. [PMID:29403003]

5. Lee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, Sohn MH, Cohn L, Homer RJ, Kozhich AA et al.. (2009) Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. J. Exp. Med., 206 (5): 1149-66. [PMID:19414556]

6. Ma B, Herzog EL, Lee CG, Peng X, Lee CM, Chen X, Rockwell S, Koo JS, Kluger H, Herbst RS et al.. (2015) Role of chitinase 3-like-1 and semaphorin 7a in pulmonary melanoma metastasis. Cancer Res., 75 (3): 487-96. [PMID:25511377]

7. Rehli M, Krause SW, Andreesen R. (1997) Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics, 43 (2): 221-5. [PMID:9244440]

8. Xu Q, Chai SJ, Qian YY, Zhang M, Wang K. (2012) Breast regression protein-39 (BRP-39) promotes dendritic cell maturation in vitro and enhances Th2 inflammation in murine model of asthma. Acta Pharmacol. Sin., 33 (12): 1525-32. [PMID:23178461]

How to cite this page

Chitinase-like proteins: chitinase 3 like 1. Last modified on 13/02/2018. Accessed on 18/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2987.