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{{Infobox_gene}}
{{PBB_Controls
'''Chitinase-3-like protein 1''' ('''CHI3L1'''), also known as '''YKL-40''', is a [[Secretion|secreted]] [[glycoprotein]] that is approximately 40k[[Atomic mass unit|Da]] in size that in humans is encoded by the ''CHI3L1'' [[gene]].<ref name="pmid8245017">{{cite journal | vauthors = Hakala BE, White C, Recklies AD | title = Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family | journal = The Journal of Biological Chemistry | volume = 268 | issue = 34 | pages = 25803–10 | date = December 1993 | pmid = 8245017 | pmc =  | doi =  }}</ref><ref name="pmid9244440">{{cite journal | vauthors = Rehli M, Krause SW, Andreesen R | title = 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 | journal = Genomics | volume = 43 | issue = 2 | pages = 221–5 | date = July 1997 | pmid = 9244440 | doi = 10.1006/geno.1997.4778 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CHI3L1 chitinase 3-like 1 (cartilage glycoprotein-39)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1116| accessdate = }}</ref> The name YKL-40 is derived from the three N-terminal [[amino acid]]s present on the secreted form and its [[molecular mass]]. YKL-40 is expressed and secreted by various [[cell type|cell-types]] including [[macrophage]]s, [[chondrocyte]]s, fibroblast-like synovial cells, vascular smooth muscle cells, and hepatic stellate cells. The biological function of YKL-40 is unclear. It is not known to have a specific receptor. Its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, [[fibrosis]] and solid carcinomas<ref name=":0">{{cite journal | vauthors = Kazakova MH, Sarafian VS | title = YKL-40--a novel biomarker in clinical practice? | journal = Folia Medica | volume = 51 | issue = 1 | pages = 5–14 | date = 2009-03-01 | pmid = 19437893 }}</ref> and [[asthma]].<ref name="pmid18403759">{{cite journal | vauthors = Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, Lester LA, Gern JE, Lemanske RF, Nicolae DL, Elias JA, Chupp GL | title = Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function | journal = The New England Journal of Medicine | volume = 358 | issue = 16 | pages = 1682–91 | date = April 2008 | pmid = 18403759 | pmc = 2629486 | doi = 10.1056/NEJMoa0708801 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_CHI3L1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1hjv.
| PDB = {{PDB2|1hjv}}, {{PDB2|1hjw}}, {{PDB2|1hjx}}, {{PDB2|1nwr}}, {{PDB2|1nws}}, {{PDB2|1nwt}}, {{PDB2|1nwu}}
| Name = Chitinase 3-like 1 (cartilage glycoprotein-39)
| HGNCid = 1932
| Symbol = CHI3L1
| AltSymbols =; GP39; HC-gp39; HCGP-3P; YKL40; YYL-40
| OMIM = 601525
| ECnumber = 
| Homologene = 55569
| MGIid = 1340899
| GeneAtlas_image1 = PBB_GE_CHI3L1_209396_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_CHI3L1_209395_at_tn.png
| GeneAtlas_image3 = PBB_GE_CHI3L1_216546_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003824 |text = catalytic activity}} {{GNF_GO|id=GO:0004553 |text = hydrolase activity, hydrolyzing O-glycosyl compounds}} {{GNF_GO|id=GO:0004568 |text = chitinase activity}} {{GNF_GO|id=GO:0005201 |text = extracellular matrix structural constituent}} {{GNF_GO|id=GO:0005529 |text = sugar binding}} {{GNF_GO|id=GO:0043169 |text = cation binding}}
| Component = {{GNF_GO|id=GO:0005578 |text = proteinaceous extracellular matrix}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0006032 |text = chitin catabolic process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1116
    | Hs_Ensembl = ENSG00000133048
    | Hs_RefseqProtein = NP_001267
    | Hs_RefseqmRNA = NM_001276
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 201414553
    | Hs_GenLoc_end = 201422500
    | Hs_Uniprot = P36222
    | Mm_EntrezGene = 12654
    | Mm_Ensembl = ENSMUSG00000064246
    | Mm_RefseqmRNA = NM_007695
    | Mm_RefseqProtein = NP_031721
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 135998875
    | Mm_GenLoc_end = 136006439
    | Mm_Uniprot = Q3U291
  }}
}}
'''Chitinase 3-like 1 (cartilage glycoprotein-39)''', also known as '''CHI3L1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CHI3L1 chitinase 3-like 1 (cartilage glycoprotein-39)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1116| accessdate = }}</ref> It has been implicated in [[asthma]], with the discovery of an allele that doubles the risk.<ref>[http://content.nejm.org/cgi/content/full/NEJMoa0708801v1 New England Journal of Medicine article]</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
[[Chitinase]]s catalyze the hydrolysis of [[chitin]], which is an abundant [[glycopolymer]] found in insect [[exoskeleton]]s and fungal cell walls. The [[glycoside hydrolase]] 18 family of chitinases includes eight human family members. This gene encodes a [[glycoprotein]] member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated [[macrophage]]s, [[chondrocyte]]s, [[neutrophil]]s and [[synovial membrane|synovial cells]]. The protein is thought to play a role in the process of inflammation and tissue remodeling.<ref name="entrez"/> YKL-40 lacks [[chitinase]] activity due to mutations within the active site (conserved sequence: DXXDXDXE ; YKL-40 sequence: DGLDLAWL).<ref name=":0" />
{{PBB_Summary
 
| section_title =  
== Regulation and mechanism ==
| summary_text =  
 
}}
YKL-40 has been linked to activation of the [[AKT]] pro-survival (anti-[[Apoptosis|apoptotic]]) signaling pathway. YKL-40 promotes [[angiogenesis]] through [[Vascular endothelial growth factor|VEGF]]-dependent and independent pathways.<ref name="pmid21385870">{{cite journal|date=April 2011|title=Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma|journal=J. Biol. Chem.|volume=286|issue=17|pages=15332–43|doi=10.1074/jbc.M110.212514|pmc=3083166|pmid=21385870|vauthors=Francescone RA, Scully S, Faibish M, Taylor SL, Oh D, Moral L, Yan W, Bentley B, Shao R}}</ref>
 
YKL-40 is a migration factor for primary [[astrocyte]]s and its expression is controlled by [[NFIX|NFI-X3]], [[STAT3]], and [[AP-1 transcription factor|AP-1]].<ref name="pmid21953450">{{cite journal | vauthors = Singh SK, Bhardwaj R, Wilczynska KM, Dumur CI, Kordula T | title = A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40 | journal = J. Biol. Chem. | volume = 286 | issue = 46 | pages = 39893–903 |date=November 2011 | pmid = 21953450 | doi = 10.1074/jbc.M111.257451 | pmc=3220556}}</ref>
 
CHI3l1 is induced by a variety of cancers and in the presence of [[SEMA7A|semaphorin 7A]] (protein) can inhibit multiple anti-tumor immune system responses. Activating an antiviral immune pathway known as the RIG-like helicase (RLH) has the ability to counter CHI3l1 induction. Cancer cells can offset RLH by stimulating [[NLRX1]]. [[Polyinosinic:polycytidylic acid|Poly(I:C)]], an RNA-like molecule, can stimulate RLH activation. RLH activation can also inhibit the expression of receptor [[IL13RA2|IL-13Rα2]]<nowiki/>pand lmonary metastasisre. It stores [[Natural killer cell|NK cell]] accumulation and activation. It augments the expression of [[Interferon type I|IFN-α/β]], [[chemerin]] and its receptor ChemR23, p-cofilin, [[LIMK2]] and [[PTEN (gene)|PTEN]] and inhibiting [[BRAF (gene)|BRAF]] and [[NLRX1]] in a MAVS-dependent manner.<ref name=":1">{{cite journal | vauthors = Ma B, Herzog EL, Moore M, Lee CM, Na SH, Lee CG, Elias JA | title = RIG-like Helicase Regulation of Chitinase 3-like 1 Axis and Pulmonary Metastasis | journal = Scientific Reports | volume = 6 | pages = 26299 | date = 2016-05-20 | pmid = 27198666 | pmc = 4873814 | doi = 10.1038/srep26299 }}</ref>
 
== Cancer ==
 
It is assumed that YKL-40 plays a role in cancer cell proliferation, survival, invasiveness and in the regulation of cell-matrix interactions. It is suggested that YKL-40 is a marker associated with a poorer clinical outcome in genetically defined subgroups of different tumors. YKL-40 was recently introduced into (restricted) clinical practice. A few techniques are available for its detection.<ref name=":0" />
 
YKL-40 is a [[T helper cell|Th2]] promoting [[cytokine]] that is present at high levels in the [[tumor microenvironment]] and in the serum of cancer patients.<ref name="pmid19134206">{{cite journal | vauthors = Høgdall EV, Ringsholt M, Høgdall CK, Christensen IJ, Johansen JS, Kjaer SK, Blaakaer J, Ostenfeld-Møller L, Price PA, Christensen LH | title = YKL-40 tissue expression and plasma levels in patients with ovarian cancer | journal = BMC Cancer | volume = 9 | issue = | pages = 8 | year = 2009 | pmid = 19134206 | pmc = 2645422 | doi = 10.1186/1471-2407-9-8 }}</ref><ref name="pmid22102082">{{cite journal | vauthors = Bernardi D, Padoan A, Ballin A, Sartori M, Manara R, Scienza R, Plebani M, Della Puppa A | title = Serum YKL-40 following resection for cerebral glioblastoma | journal = J. Neurooncol. | volume = 107 | issue = 2 | pages = 299–305 |date=April 2012 | pmid = 22102082 | doi = 10.1007/s11060-011-0762-7 }}</ref> Elevated levels of YKL-40 correlate strongly with stage and outcome of various types of cancer, which establish YKL-40 as a biomarker of disease severity.<ref name="pmid12889595">{{cite journal | vauthors = Johansen JS, Christensen IJ, Riisbro R, Greenall M, Han C, Price PA, Smith K, Brünner N, Harris AL | title = High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival | journal = Breast Cancer Res. Treat. | volume = 80 | issue = 1 | pages = 15–21 |date=July 2003 | pmid = 12889595 | doi = 10.1023/A:1024431000710 }}</ref> Targeting YKL-40 with [[Neutralizing antibody|neutralizing antibodies]] is effective as a treatment in animal models of [[glioblastoma multiforme]].<ref name="pmid21357475">{{cite journal | vauthors = Faibish M, Francescone R, Bentley B, Yan W, Shao R | title = A YKL-40-neutralizing antibody blocks tumor angiogenesis and progression: a potential therapeutic agent in cancers | journal = Mol. Cancer Ther. | volume = 10 | issue = 5 | pages = 742–51 |date=May 2011 | pmid = 21357475 | pmc = 3091949 | doi = 10.1158/1535-7163.MCT-10-0868 }}</ref>
 
YKL-40 also enhances tumor survival in response to [[Radiation therapy|gamma-irradiation]].<ref name="pmid21385870"/>


==References==
==References==
{{reflist|2}}
{{reflist|30em}}
{{Clear}}
 
==External links==
* {{UCSC gene info|CHI3L1}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  | vauthors=Rathcke CN, Vestergaard H |title=YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. |journal=Inflamm. Res. |volume=55 |issue= 6 |pages= 221–7 |year= 2007 |pmid= 16955240 |doi= 10.1007/s00011-006-0076-y }}
| citations =
*{{cite journal  | vauthors=Nyirkos P, Golds EE |title=Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period. |journal=Biochem. J. |volume=269 |issue= 1 |pages= 265–8 |year= 1990 |pmid= 2375755 |doi= | pmc=1131563 }}
*{{cite journal  | author=Rathcke CN, Vestergaard H |title=YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. |journal=Inflamm. Res. |volume=55 |issue= 6 |pages= 221-7 |year= 2007 |pmid= 16955240 |doi= 10.1007/s00011-006-0076-y }}
*{{cite journal  | vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
*{{cite journal  | author=Nyirkos P, Golds EE |title=Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period. |journal=Biochem. J. |volume=269 |issue= 1 |pages= 265-8 |year= 1990 |pmid= 2375755 |doi=  }}
*{{cite journal  | vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 |display-authors=etal}}
*{{cite journal  | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
*{{cite journal  | vauthors=Kirkpatrick RB, Emery JG, Connor JR |title=Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. |journal=Exp. Cell Res. |volume=237 |issue= 1 |pages= 46–54 |year= 1998 |pmid= 9417865 |doi= 10.1006/excr.1997.3764 |display-authors=etal}}
*{{cite journal  | author=Hakala BE, White C, Recklies AD |title=Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. |journal=J. Biol. Chem. |volume=268 |issue= 34 |pages= 25803-10 |year= 1994 |pmid= 8245017 |doi=  }}
*{{cite journal  | vauthors=Renkema GH, Boot RG, Au FL |title=Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages. |journal=Eur. J. Biochem. |volume=251 |issue= 1-2 |pages= 504–9 |year= 1998 |pmid= 9492324 |doi=10.1046/j.1432-1327.1998.2510504.x  |display-authors=etal}}
*{{cite journal  | author=Rehli M, Krause SW, Andreesen R |title=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. |journal=Genomics |volume=43 |issue= 2 |pages= 221-5 |year= 1997 |pmid= 9244440 |doi= 10.1006/geno.1997.4778 }}
*{{cite journal  | vauthors=Johansen JS, Stoltenberg M, Hansen M |title=Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity. |journal=Rheumatology (Oxford) |volume=38 |issue= 7 |pages= 618–26 |year= 1999 |pmid= 10461474 |doi=10.1093/rheumatology/38.7.618  |display-authors=etal}}
*{{cite journal  | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
*{{cite journal  | vauthors=Nordenbaek C, Johansen JS, Junker P |title=YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization. |journal=J. Infect. Dis. |volume=180 |issue= 5 |pages= 1722–6 |year= 1999 |pmid= 10515841 |doi=10.1086/315050 |display-authors=etal}}
*{{cite journal  | author=Kirkpatrick RB, Emery JG, Connor JR, ''et al.'' |title=Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. |journal=Exp. Cell Res. |volume=237 |issue= 1 |pages= 46-54 |year= 1998 |pmid= 9417865 |doi= 10.1006/excr.1997.3764 }}
*{{cite journal  | vauthors=Connor JR, Dodds RA, Emery JG |title=Human cartilage glycoprotein 39 (HC gp-39) mRNA expression in adult and fetal chondrocytes, osteoblasts and osteocytes by in-situ hybridization. |journal=Osteoarthr. Cartil. |volume=8 |issue= 2 |pages= 87–95 |year= 2000 |pmid= 10772238 |doi= 10.1053/joca.1999.0276 |display-authors=etal}}
*{{cite journal  | author=Renkema GH, Boot RG, Au FL, ''et al.'' |title=Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages. |journal=Eur. J. Biochem. |volume=251 |issue= 1-2 |pages= 504-9 |year= 1998 |pmid= 9492324 |doi=  }}
*{{cite journal  | vauthors=Østergaard C, Johansen JS, Benfield T |title=YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis. |journal=Clin. Diagn. Lab. Immunol. |volume=9 |issue= 3 |pages= 598–604 |year= 2002 |pmid= 11986266 |doi=10.1128/CDLI.9.3.598-604.2002  | pmc=119997  |display-authors=etal}}
*{{cite journal  | author=Johansen JS, Stoltenberg M, Hansen M, ''et al.'' |title=Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity. |journal=Rheumatology (Oxford) |volume=38 |issue= 7 |pages= 618-26 |year= 1999 |pmid= 10461474 |doi= }}
*{{cite journal  | vauthors=Kronborg G, Ostergaard C, Weis N |title=Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease. |journal=Scand. J. Infect. Dis. |volume=34 |issue= 5 |pages= 323–6 |year= 2003 |pmid= 12069012 |doi=10.1080/00365540110080233  |display-authors=etal}}
*{{cite journal  | author=Nordenbaek C, Johansen JS, Junker P, ''et al.'' |title=YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization. |journal=J. Infect. Dis. |volume=180 |issue= 5 |pages= 1722-6 |year= 1999 |pmid= 10515841 |doi= }}
*{{cite journal  | vauthors=Recklies AD, White C, Ling H |title=The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. |journal=Biochem. J. |volume=365 |issue= Pt 1 |pages= 119–26 |year= 2002 |pmid= 12071845 |doi= 10.1042/BJ20020075 | pmc=1222662 }}
*{{cite journal  | author=Connor JR, Dodds RA, Emery JG, ''et al.'' |title=Human cartilage glycoprotein 39 (HC gp-39) mRNA expression in adult and fetal chondrocytes, osteoblasts and osteocytes by in-situ hybridization. |journal=Osteoarthr. Cartil. |volume=8 |issue= 2 |pages= 87-95 |year= 2000 |pmid= 10772238 |doi= 10.1053/joca.1999.0276 }}
*{{cite journal  | vauthors=Cintin C, Johansen JS, Christensen IJ |title=High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. |journal=Cancer |volume=95 |issue= 2 |pages= 267–74 |year= 2002 |pmid= 12124825 |doi= 10.1002/cncr.10644 |display-authors=etal}}
*{{cite journal  | author=Østergaard C, Johansen JS, Benfield T, ''et al.'' |title=YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis. |journal=Clin. Diagn. Lab. Immunol. |volume=9 |issue= 3 |pages= 598-604 |year= 2002 |pmid= 11986266 |doi=  }}
*{{cite journal  | vauthors=Steck E, Breit S, Breusch SJ |title=Enhanced expression of the human chitinase 3-like 2 gene (YKL-39) but not chitinase 3-like 1 gene (YKL-40) in osteoarthritic cartilage. |journal=Biochem. Biophys. Res. Commun. |volume=299 |issue= 1 |pages= 109–15 |year= 2003 |pmid= 12435396 |doi=10.1016/S0006-291X(02)02585-8  |display-authors=etal}}
*{{cite journal  | author=Kronborg G, Ostergaard C, Weis N, ''et al.'' |title=Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease. |journal=Scand. J. Infect. Dis. |volume=34 |issue= 5 |pages= 323-6 |year= 2003 |pmid= 12069012 |doi= }}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
*{{cite journal  | author=Recklies AD, White C, Ling H |title=The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. |journal=Biochem. J. |volume=365 |issue= Pt 1 |pages= 119-26 |year= 2002 |pmid= 12071845 |doi= 10.1042/BJ20020075 }}
*{{cite journal  | vauthors=Steenbakkers PG, Baeten D, Rovers E |title=Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies. |journal=J. Immunol. |volume=170 |issue= 11 |pages= 5719–27 |year= 2003 |pmid= 12759455 |doi=  10.4049/jimmunol.170.11.5719|display-authors=etal}}
*{{cite journal  | author=Cintin C, Johansen JS, Christensen IJ, ''et al.'' |title=High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. |journal=Cancer |volume=95 |issue= 2 |pages= 267-74 |year= 2002 |pmid= 12124825 |doi= 10.1002/cncr.10644 }}
*{{cite journal  | vauthors=Houston DR, Recklies AD, Krupa JC, van Aalten DM |title=Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes. |journal=J. Biol. Chem. |volume=278 |issue= 32 |pages= 30206–12 |year= 2003 |pmid= 12775711 |doi= 10.1074/jbc.M303371200 }}
*{{cite journal  | author=Steck E, Breit S, Breusch SJ, ''et al.'' |title=Enhanced expression of the human chitinase 3-like 2 gene (YKL-39) but not chitinase 3-like 1 gene (YKL-40) in osteoarthritic cartilage. |journal=Biochem. Biophys. Res. Commun. |volume=299 |issue= 1 |pages= 109-15 |year= 2003 |pmid= 12435396 |doi=  }}
*{{cite journal  | vauthors=Nishikawa KC, Millis AJ |title=gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. |journal=Exp. Cell Res. |volume=287 |issue= 1 |pages= 79–87 |year= 2003 |pmid= 12799184 |doi=10.1016/S0014-4827(03)00069-7 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Steenbakkers PG, Baeten D, Rovers E, ''et al.'' |title=Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies. |journal=J. Immunol. |volume=170 |issue= 11 |pages= 5719-27 |year= 2003 |pmid= 12759455 |doi= }}
*{{cite journal  | author=Houston DR, Recklies AD, Krupa JC, van Aalten DM |title=Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes. |journal=J. Biol. Chem. |volume=278 |issue= 32 |pages= 30206-12 |year= 2003 |pmid= 12775711 |doi= 10.1074/jbc.M303371200 }}
*{{cite journal  | author=Nishikawa KC, Millis AJ |title=gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. |journal=Exp. Cell Res. |volume=287 |issue= 1 |pages= 79-87 |year= 2003 |pmid= 12799184 |doi= }}
}}
{{refend}}
{{refend}}


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[[Category:Glycoproteins]]

Latest revision as of 09:38, 30 August 2017

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Identifiers
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Orthologs
SpeciesHumanMouse
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Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a secreted glycoprotein that is approximately 40kDa in size that in humans is encoded by the CHI3L1 gene.[1][2][3] The name YKL-40 is derived from the three N-terminal amino acids present on the secreted form and its molecular mass. YKL-40 is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells, vascular smooth muscle cells, and hepatic stellate cells. The biological function of YKL-40 is unclear. It is not known to have a specific receptor. Its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, fibrosis and solid carcinomas[4] and asthma.[5]

Function

Chitinases catalyze the hydrolysis of chitin, which is an abundant glycopolymer found in insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 family of chitinases includes eight human family members. This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling.[3] YKL-40 lacks chitinase activity due to mutations within the active site (conserved sequence: DXXDXDXE ; YKL-40 sequence: DGLDLAWL).[4]

Regulation and mechanism

YKL-40 has been linked to activation of the AKT pro-survival (anti-apoptotic) signaling pathway. YKL-40 promotes angiogenesis through VEGF-dependent and independent pathways.[6]

YKL-40 is a migration factor for primary astrocytes and its expression is controlled by NFI-X3, STAT3, and AP-1.[7]

CHI3l1 is induced by a variety of cancers and in the presence of semaphorin 7A (protein) can inhibit multiple anti-tumor immune system responses. Activating an antiviral immune pathway known as the RIG-like helicase (RLH) has the ability to counter CHI3l1 induction. Cancer cells can offset RLH by stimulating NLRX1. Poly(I:C), an RNA-like molecule, can stimulate RLH activation. RLH activation can also inhibit the expression of receptor IL-13Rα2pand lmonary metastasisre. It stores NK cell accumulation and activation. It augments the expression of IFN-α/β, chemerin and its receptor ChemR23, p-cofilin, LIMK2 and PTEN and inhibiting BRAF and NLRX1 in a MAVS-dependent manner.[8]

Cancer

It is assumed that YKL-40 plays a role in cancer cell proliferation, survival, invasiveness and in the regulation of cell-matrix interactions. It is suggested that YKL-40 is a marker associated with a poorer clinical outcome in genetically defined subgroups of different tumors. YKL-40 was recently introduced into (restricted) clinical practice. A few techniques are available for its detection.[4]

YKL-40 is a Th2 promoting cytokine that is present at high levels in the tumor microenvironment and in the serum of cancer patients.[9][10] Elevated levels of YKL-40 correlate strongly with stage and outcome of various types of cancer, which establish YKL-40 as a biomarker of disease severity.[11] Targeting YKL-40 with neutralizing antibodies is effective as a treatment in animal models of glioblastoma multiforme.[12]

YKL-40 also enhances tumor survival in response to gamma-irradiation.[6]

References

  1. ↑ Hakala BE, White C, Recklies AD (December 1993). "Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family". The Journal of Biological Chemistry. 268 (34): 25803–10. PMID 8245017.
  2. ↑ Rehli M, Krause SW, Andreesen R (July 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. doi:10.1006/geno.1997.4778. PMID 9244440.
  3. ↑ 3.0 3.1 "Entrez Gene: CHI3L1 chitinase 3-like 1 (cartilage glycoprotein-39)".
  4. ↑ 4.0 4.1 4.2 Kazakova MH, Sarafian VS (2009-03-01). "YKL-40--a novel biomarker in clinical practice?". Folia Medica. 51 (1): 5–14. PMID 19437893.
  5. ↑ Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, Lester LA, Gern JE, Lemanske RF, Nicolae DL, Elias JA, Chupp GL (April 2008). "Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function". The New England Journal of Medicine. 358 (16): 1682–91. doi:10.1056/NEJMoa0708801. PMC 2629486. PMID 18403759.
  6. ↑ 6.0 6.1 Francescone RA, Scully S, Faibish M, Taylor SL, Oh D, Moral L, Yan W, Bentley B, Shao R (April 2011). "Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma". J. Biol. Chem. 286 (17): 15332–43. doi:10.1074/jbc.M110.212514. PMC 3083166. PMID 21385870.
  7. ↑ Singh SK, Bhardwaj R, Wilczynska KM, Dumur CI, Kordula T (November 2011). "A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40". J. Biol. Chem. 286 (46): 39893–903. doi:10.1074/jbc.M111.257451. PMC 3220556. PMID 21953450.
  8. ↑ Ma B, Herzog EL, Moore M, Lee CM, Na SH, Lee CG, Elias JA (2016-05-20). "RIG-like Helicase Regulation of Chitinase 3-like 1 Axis and Pulmonary Metastasis". Scientific Reports. 6: 26299. doi:10.1038/srep26299. PMC 4873814. PMID 27198666.
  9. ↑ Høgdall EV, Ringsholt M, Høgdall CK, Christensen IJ, Johansen JS, Kjaer SK, Blaakaer J, Ostenfeld-Møller L, Price PA, Christensen LH (2009). "YKL-40 tissue expression and plasma levels in patients with ovarian cancer". BMC Cancer. 9: 8. doi:10.1186/1471-2407-9-8. PMC 2645422. PMID 19134206.
  10. ↑ Bernardi D, Padoan A, Ballin A, Sartori M, Manara R, Scienza R, Plebani M, Della Puppa A (April 2012). "Serum YKL-40 following resection for cerebral glioblastoma". J. Neurooncol. 107 (2): 299–305. doi:10.1007/s11060-011-0762-7. PMID 22102082.
  11. ↑ Johansen JS, Christensen IJ, Riisbro R, Greenall M, Han C, Price PA, Smith K, Brünner N, Harris AL (July 2003). "High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival". Breast Cancer Res. Treat. 80 (1): 15–21. doi:10.1023/A:1024431000710. PMID 12889595.
  12. ↑ Faibish M, Francescone R, Bentley B, Yan W, Shao R (May 2011). "A YKL-40-neutralizing antibody blocks tumor angiogenesis and progression: a potential therapeutic agent in cancers". Mol. Cancer Ther. 10 (5): 742–51. doi:10.1158/1535-7163.MCT-10-0868. PMC 3091949. PMID 21357475.

External links

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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