Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT26R3HQ)

DOT Name Chitinase-3-like protein 2 (CHI3L2)
Synonyms Chondrocyte protein 39; YKL-39
Gene Name CHI3L2
Related Disease
Arthropathy ( )
Esophageal cancer ( )
Arthritis ( )
Autoimmune disease ( )
Invasive breast carcinoma ( )
Neoplasm ( )
Osteoarthritis ( )
Amyotrophic lateral sclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Clear cell renal carcinoma ( )
Renal cell carcinoma ( )
UniProt ID
CH3L2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4AY1; 4P8U; 4P8V; 4P8W; 4P8X
Pfam ID
PF00704
Sequence
MGATTMDQKSLWAGVVVLLLLQGGSAYKLVCYFTNWSQDRQEPGKFTPENIDPFLCSHLI
YSFASIENNKVIIKDKSEVMLYQTINSLKTKNPKLKILLSIGGYLFGSKGFHPMVDSSTS
RLEFINSIILFLRNHNFDGLDVSWIYPDQKENTHFTVLIHELAEAFQKDFTKSTKERLLL
TAGVSAGRQMIDNSYQVEKLAKDLDFINLLSFDFHGSWEKPLITGHNSPLSKGWQDRGPS
SYYNVEYAVGYWIHKGMPSEKVVMGIPTYGHSFTLASAETTVGAPASGPGAAGPITESSG
FLAYYEICQFLKGAKITRLQDQQVPYAVKGNQWVGYDDVKSMETKVQFLKNLNLGGAMIW
SIDMDDFTGKSCNQGPYPLVQAVKRSLGSL
Function Lectin that binds chitooligosaccharides and other glycans with high affinity, but not heparin. Has no chitinase activity.
Tissue Specificity Highest expression in chondrocytes, followed by synoviocytes, lung and heart. Not detected in spleen, pancreas, and liver. May also be expressed in developing brain and placenta.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arthropathy DISVEERK Definitive Biomarker [1]
Esophageal cancer DISGB2VN Definitive Biomarker [2]
Arthritis DIST1YEL Strong Biomarker [3]
Autoimmune disease DISORMTM Strong Biomarker [3]
Invasive breast carcinoma DISANYTW Strong Altered Expression [4]
Neoplasm DISZKGEW Strong Genetic Variation [5]
Osteoarthritis DIS05URM Strong Biomarker [6]
Amyotrophic lateral sclerosis DISF7HVM moderate Genetic Variation [7]
Breast cancer DIS7DPX1 Limited Altered Expression [4]
Breast carcinoma DIS2UE88 Limited Altered Expression [4]
Clear cell renal carcinoma DISBXRFJ Limited Biomarker [5]
Renal cell carcinoma DISQZ2X8 Limited Altered Expression [5]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Chitinase-3-like protein 2 (CHI3L2). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Chitinase-3-like protein 2 (CHI3L2). [9]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Chitinase-3-like protein 2 (CHI3L2). [10]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Chitinase-3-like protein 2 (CHI3L2). [11]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Chitinase-3-like protein 2 (CHI3L2). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Chitinase-3-like protein 2 (CHI3L2). [13]
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References

1 YKL-39 (chitinase 3-like protein 2), but not YKL-40 (chitinase 3-like protein 1), is up regulated in osteoarthritic chondrocytes.Ann Rheum Dis. 2003 Oct;62(10):995-8. doi: 10.1136/ard.62.10.995.
2 Enhanced expression of the human chitinase 3-like 2 gene (YKL-39) but not chitinase 3-like 1 gene (YKL-40) in osteoarthritic cartilage.Biochem Biophys Res Commun. 2002 Nov 22;299(1):109-15. doi: 10.1016/s0006-291x(02)02585-8.
3 YKL-39, a human cartilage-related protein, induces arthritis in mice.Clin Exp Rheumatol. 2002 May-Jun;20(3):343-50.
4 Tumor-associated macrophages in human breast cancer produce new monocyte attracting and pro-angiogenic factor YKL-39 indicative for increased metastasis after neoadjuvant chemotherapy.Oncoimmunology. 2018 Mar 13;7(6):e1436922. doi: 10.1080/2162402X.2018.1436922. eCollection 2018.
5 M2 Macrophage Marker Chitinase 3-Like 2 (CHI3L2) Associates With Progression of Conventional Renal Cell Carcinoma.Anticancer Res. 2019 Dec;39(12):6939-6943. doi: 10.21873/anticanres.13915.
6 Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells.Biochem Biophys Res Commun. 2013 Feb 1;431(1):52-7. doi: 10.1016/j.bbrc.2012.12.094. Epub 2013 Jan 3.
7 CSF chitinase proteins in amyotrophic lateral sclerosis.J Neurol Neurosurg Psychiatry. 2019 Nov;90(11):1215-1220. doi: 10.1136/jnnp-2019-320442. Epub 2019 May 23.
8 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
11 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
12 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
13 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.