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P36222 (CH3L1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chitinase-3-like protein 1
Alternative name(s):
39 kDa synovial protein
Cartilage glycoprotein 39
Short name=CGP-39
Short name=GP-39
Short name=hCGP-39
YKL-40
Gene names
Name:CHI3L1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length383 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their environment. Plays a role in T-helper cell type 2 (Th2) inflammatory response and IL-13-induced inflammation, regulating allergen sensitization, inflammatory cell apoptosis, dendritic cell accumulation and M2 macrophage differentiation. Facilitates invasion of pathogenic enteric bacteria into colonic mucosa and lymphoid organs. Mediates activation of AKT1 signaling pathway and subsequent IL8 production in colonic epithelial cells. Regulates antibacterial responses in lung by contributing to macrophage bacterial killing, controlling bacterial dissemination and augmenting host tolerance. Also regulates hyperoxia-induced injury, inflammation and epithelial apoptosis in lung. Ref.8 Ref.9 Ref.10 Ref.11

Subunit structure

Monomer.

Subcellular location

Secretedextracellular space. Cytoplasm By similarity. Cytoplasmperinuclear region By similarity. Endoplasmic reticulum By similarity Ref.8.

Tissue specificity

Present in activated macrophages, articular chondrocytes, synovial cells as well as in liver. Very low or undetectable expression in non-inflammatory colon. Undetectable in muscle tissues, lung, pancreas, mononuclear cells, or fibroblasts. Ref.8 Ref.9

Induction

Up-regulated in colon under several inflammatory conditions. Down-regulated by hyperoxia in bronchial epithelial cells. Ref.9 Ref.11

Post-translational modification

Glycosylated. Ref.12

Involvement in disease

Asthma-related traits 7 (ASRT7) [MIM:611960]: Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, dyspnea, bronchial hyperresponsiveness as assessed by methacholine challenge test, serum IgE levels, atopy and atopic dermatitis.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Sequence similarities

Belongs to the glycosyl hydrolase 18 family.

Caution

Although it belongs to the glycosyl hydrolase 18 family, Leu-140 is present instead of the conserved Glu which is an active site residue. Therefore this protein lacks chitinase activity.

Ontologies

Keywords
   Biological processApoptosis
Inflammatory response
   Cellular componentCytoplasm
Endoplasmic reticulum
Secreted
   Coding sequence diversityPolymorphism
   DiseaseAsthma
   DomainSignal
   LigandLectin
   Molecular functionAntimicrobial
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of NF-kappaB-inducing kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

carbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

cartilage development

Non-traceable author statement Ref.1. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from sequence or structural similarity. Source: UniProtKB

chitin catabolic process

Inferred from electronic annotation. Source: InterPro

inflammatory response

Inferred from expression pattern PubMed 16234240. Source: UniProtKB

interleukin-8 secretion

Inferred from sequence or structural similarity. Source: UniProtKB

lung development

Inferred from mutant phenotype Ref.14. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype PubMed 21385870. Source: UniProtKB

positive regulation of angiogenesis

Inferred from mutant phenotype PubMed 21385870. Source: UniProtKB

positive regulation of peptidyl-threonine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 21385870. Source: UniProtKB

response to interleukin-1

Inferred from expression pattern PubMed 16234240. Source: UniProtKB

response to interleukin-6

Inferred from expression pattern PubMed 21478032. Source: UniProtKB

response to mechanical stimulus

Inferred from expression pattern PubMed 20650887. Source: UniProtKB

response to tumor necrosis factor

Inferred from expression pattern PubMed 16234240. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular space

Inferred from direct assay Ref.1Ref.8. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

proteinaceous extracellular matrix

Non-traceable author statement Ref.1. Source: UniProtKB

   Molecular_functionchitin binding

Inferred from direct assay Ref.12Ref.8. Source: UniProtKB

extracellular matrix structural constituent

Non-traceable author statement Ref.1. Source: UniProtKB

hydrolase activity, hydrolyzing O-glycosyl compounds

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.7 Ref.8
Chain22 – 383362Chitinase-3-like protein 1
PRO_0000011965

Regions

Region70 – 712Chitooligosaccharide binding
Region97 – 1004Chitooligosaccharide binding
Region204 – 2074Chitooligosaccharide binding
Region324 – 33815Important for AKT1 activation and IL8 production By similarity

Sites

Binding site1411Chitooligosaccharide
Binding site2631Chitooligosaccharide
Binding site3521Chitooligosaccharide

Amino acid modifications

Glycosylation601N-linked (GlcNAc...) Ref.12
Disulfide bond26 ↔ 51 Ref.12 Ref.13
Disulfide bond300 ↔ 364 Ref.12 Ref.13

Natural variations

Natural variant1451R → G. Ref.3 Ref.6
Corresponds to variant rs880633 [ dbSNP | Ensembl ].
VAR_019838
Natural variant3111I → T. Ref.1 Ref.2
Corresponds to variant rs1049407 [ dbSNP | Ensembl ].
VAR_019839

Secondary structure

............................................................................. 383
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P36222 [UniParc].

Last modified December 20, 2005. Version 2.
Checksum: 6C9EF133BDC7C2D1

FASTA38342,625
        10         20         30         40         50         60 
MGVKASQTGF VVLVLLQCCS AYKLVCYYTS WSQYREGDGS CFPDALDRFL CTHIIYSFAN 

        70         80         90        100        110        120 
ISNDHIDTWE WNDVTLYGML NTLKNRNPNL KTLLSVGGWN FGSQRFSKIA SNTQSRRTFI 

       130        140        150        160        170        180 
KSVPPFLRTH GFDGLDLAWL YPGRRDKQHF TTLIKEMKAE FIKEAQPGKK QLLLSAALSA 

       190        200        210        220        230        240 
GKVTIDSSYD IAKISQHLDF ISIMTYDFHG AWRGTTGHHS PLFRGQEDAS PDRFSNTDYA 

       250        260        270        280        290        300 
VGYMLRLGAP ASKLVMGIPT FGRSFTLASS ETGVGAPISG PGIPGRFTKE AGTLAYYEIC 

       310        320        330        340        350        360 
DFLRGATVHR ILGQQVPYAT KGNQWVGYDD QESVKSKVQY LKDRQLAGAM VWALDLDDFQ 

       370        380 
GSFCGQDLRF PLTNAIKDAL AAT 

« Hide

References

« Hide 'large scale' references
[1]"Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family."
Hakala B.E., White C., Recklies A.D.
J. Biol. Chem. 268:25803-25810(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT THR-311.
Tissue: Cartilage.
[2]"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."
Rehli M., Krause S.W., Andressen R.
Genomics 43:221-225(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-311.
Tissue: Blood.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-145.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-145.
Tissue: Brain.
[7]"Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period."
Nyirkos P., Golds E.E.
Biochem. J. 269:265-268(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-45.
[8]"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."
Renkema G.H., Boot R.G., Au F.L., Donker-Koopman W.E., Strijland A., Muijsers A.O., Hrebicek M., Aerts J.M.F.G.
Eur. J. Biochem. 251:504-509(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells."
Mizoguchi E.
Gastroenterology 130:398-411(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[10]"Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis."
Lee C.G., Hartl D., Lee G.R., Koller B., Matsuura H., Da Silva C.A., Sohn M.H., Cohn L., Homer R.J., Kozhich A.A., Humbles A., Kearley J., Coyle A., Chupp G., Reed J., Flavell R.A., Elias J.A.
J. Exp. Med. 206:1149-1166(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"The chitinase-like proteins breast regression protein-39 and YKL-40 regulate hyperoxia-induced acute lung injury."
Sohn M.H., Kang M.J., Matsuura H., Bhandari V., Chen N.Y., Lee C.G., Elias J.A.
Am. J. Respir. Crit. Care Med. 182:918-928(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[12]"Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes."
Houston D.R., Recklies A.D., Krupa J.C., van Aalten D.M.F.
J. Biol. Chem. 278:30206-30212(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 22-383 IN COMPLEX WITH CHITIN OLIGOMERS, DISULFIDE BONDS, GLYCOSYLATION AT ASN-60.
[13]"Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39."
Fusetti F., Pijning T., Kalk K.H., Bos E., Dijkstra B.W.
J. Biol. Chem. 278:37753-37760(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 22-383 IN COMPLEX WITH CHITIN OLIGOMERS, DISULFIDE BONDS.
[14]"Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function."
Ober C., Tan Z., Sun Y., Possick J.D., Pan L., Nicolae R., Radford S., Parry R.R., Heinzmann A., Deichmann K.A., Lester L.A., Gern J.E., Lemanske R.F. Jr., Nicolae D.L., Elias J.A., Chupp G.L.
N. Engl. J. Med. 358:1682-1691(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA-RELATED TRAITS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M80927 mRNA. Translation: AAA16074.1.
Y08374 expand/collapse EMBL AC list , Y08375, Y08376, Y08377, Y08378 Genomic DNA. Translation: CAA69661.1.
BT007223 mRNA. Translation: AAP35887.1.
AK312911 mRNA. Translation: BAG35757.1.
CH471067 Genomic DNA. Translation: EAW91467.1.
BC008568 mRNA. Translation: AAH08568.1.
BC038354 mRNA. Translation: AAH38354.1.
BC039132 mRNA. Translation: AAH39132.1.
CCDSCCDS1435.1.
PIRA49562.
RefSeqNP_001267.2. NM_001276.2.
UniGeneHs.382202.
Hs.733359.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HJVX-ray2.75A/B/C/D22-383[»]
1HJWX-ray2.30A/B22-383[»]
1HJXX-ray1.85A/B/C/D22-383[»]
1LA7model-A22-383[»]
1NWRX-ray2.70A/B/C/D22-383[»]
1NWSX-ray2.70A/B/C/D22-383[»]
1NWTX-ray2.50A/B/C/D22-383[»]
1NWUX-ray2.20A/B/C/D22-383[»]
ProteinModelPortalP36222.
SMRP36222. Positions 22-382.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000255409.

Protein family/group databases

CAZyGH18. Glycoside Hydrolase Family 18.

PTM databases

PhosphoSiteP36222.

Polymorphism databases

DMDM84028186.

Proteomic databases

PaxDbP36222.
PeptideAtlasP36222.
PRIDEP36222.

Protocols and materials databases

DNASU1116.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000255409; ENSP00000255409; ENSG00000133048.
GeneID1116.
KEGGhsa:1116.
UCSCuc001gzi.2. human.

Organism-specific databases

CTD1116.
GeneCardsGC01M203148.
HGNCHGNC:1932. CHI3L1.
MIM601525. gene.
611960. phenotype.
neXtProtNX_P36222.
PharmGKBPA26463.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3325.
HOGENOMHOG000111109.
HOVERGENHBG011684.
InParanoidP36222.
KOK17523.
OMASNDHIDT.
OrthoDBEOG7ZGX3G.
PhylomeDBP36222.
TreeFamTF315610.

Gene expression databases

ArrayExpressP36222.
BgeeP36222.
CleanExHS_CHI3L1.
GenevestigatorP36222.

Family and domain databases

Gene3D3.10.50.10. 1 hit.
3.20.20.80. 2 hits.
InterProIPR028538. CHI3L1.
IPR011583. Chitinase_II.
IPR029070. Chitinase_insertion.
IPR001223. Glyco_hydro18cat.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERPTHR11177:SF81. PTHR11177:SF81. 1 hit.
PfamPF00704. Glyco_hydro_18. 1 hit.
[Graphical view]
SMARTSM00636. Glyco_18. 1 hit.
[Graphical view]
SUPFAMSSF51445. SSF51445. 2 hits.
SSF54556. SSF54556. 1 hit.
ProtoNetSearch...

Other

ChiTaRSCHI3L1. human.
EvolutionaryTraceP36222.
GeneWikiCHI3L1.
GenomeRNAi1116.
NextBio4626.
PROP36222.
SOURCESearch...

Entry information

Entry nameCH3L1_HUMAN
AccessionPrimary (citable) accession number: P36222
Secondary accession number(s): B2R7B0 expand/collapse secondary AC list , P30923, Q8IVA4, Q96HI7
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: December 20, 2005
Last modified: July 9, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries