Reviewed, UniProtKB/Swiss-Prot P36222 (CH3L1_HUMAN)

Names and origin

Protein names

Recommended name:
    Chitinase-3-like protein 1
Alternative name(s):
    Cartilage glycoprotein 39
      Short name=CGP-39
      Short name=GP-39
      Short name=hCGP-39
    39 kDa synovial protein
    YKL-40

Gene names

Name:

CHI3L1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	383 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Carbohydrate-binding lectin with a preference for chitin. May play a role in defense against pathogens, or in tissue remodeling. May play an important role in the capacity of cells to respond to and cope with changes in their environment.
Subunit structure	Monomer.
Subcellular location	Secreted › extracellular space.
Tissue specificity	Present in activated macrophages, articular chondrocytes, synovial cells as well as in liver. Undetectable in muscle tissues, lung, pancreas, mononuclear cells, or fibroblasts.
Post-translational modification	Glycosylated.
Involvement in disease	A genetic variation in CHI3L1 is associated with susceptibility to asthma-related traits type 7 (ASRT7) [MIM:611960]. Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing and dyspnea, bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test, serum IgE levels, atopy, and atopic dermatitis.
Sequence similarities	Belongs to the glycosyl hydrolase 18 family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Lectin
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	chitin catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular space Ref.1 Traceable author statement. Source: ProtInc proteinaceous extracellular matrix Ref.1 Traceable author statement. Source: ProtInc
Molecular function	cation binding Inferred from electronic annotation. Source: InterPro chitinase activity Inferred from electronic annotation. Source: InterPro extracellular matrix structural constituent Ref.1 Traceable author statement. Source: ProtInc sugar binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Ref.7

Chain

22 – 383

362

Chitinase-3-like protein 1

PRO_0000011965

Regions

Region

70 – 71

2

Chitooligosaccharide binding

Region

97 – 100

4

Chitooligosaccharide binding

Region

204 – 207

4

Chitooligosaccharide

Sites

Binding site

141

1

Chitooligosaccharide

Binding site

263

1

Chitooligosaccharide

Binding site

352

1

Chitooligosaccharide

Amino acid modifications

Glycosylation

60

1

N-linked (GlcNAc...)

Disulfide bond

26 ↔ 51

Disulfide bond

300 ↔ 364

Natural variations

Natural variant

145

1

R → G: dbSNP rs880633. Ref.3 Ref.6

VAR_019838

Natural variant

311

1

I → T: dbSNP rs1049407. Ref.1 Ref.2

VAR_019839

Secondary structure

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383

Helix Strand Turn

Details...

Beta strand

23 – 29

7

Helix

30 – 34

5

Helix

37 – 39

3

Helix

43 – 45

3

Turn

48 – 50

3

Beta strand

52 – 62

11

Beta strand

65 – 67

3

Helix

73 – 82

10

Beta strand

91 – 97

7

Turn

99 – 101

3

Helix

103 – 111

9

Helix

113 – 129

17

Beta strand

133 – 138

6

Helix

144 – 146

3

Helix

147 – 165

19

Turn

166 – 168

3

Beta strand

173 – 179

7

Helix

182 – 188

7

Helix

191 – 197

7

Beta strand

199 – 204

6

Helix

211 – 213

3

Helix

227 – 229

3

Beta strand

233 – 236

4

Helix

237 – 247

11

Helix

251 – 253

3

Beta strand

254 – 270

17

Beta strand

277 – 281

5

Turn

286 – 288

3

Beta strand

293 – 295

3

Helix

296 – 302

7

Turn

303 – 305

3

Beta strand

307 – 310

4

Turn

312 – 314

3

Beta strand

317 – 321

5

Beta strand

324 – 327

4

Helix

331 – 343

13

Beta strand

347 – 352

6

Helix

354 – 356

3

Beta strand

359 – 361

3

Beta strand

363 – 367

5

Helix

371 – 381

11

Sequences

	Sequence		Length	Mass (Da)
	P36222-1 [UniParc]. Last modified December 20, 2005. Version 2. Checksum: 6C9EF133BDC7C2D1	FASTA	383	42,625
	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

References

	« Hide 'large scale' referencesShow '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: 8245017] [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: 9244440] [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. , 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: 14702039] [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. , 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: 15489334] [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: 2375755] [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: 9492324] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"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: 12775711] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 22-383 IN COMPLEX WITH CHITIN OLIGOMERS, DISULFIDE BONDS, GLYCOSYLATION AT ASN-60.
[10]	"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: 12851408] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 22-383 IN COMPLEX WITH CHITIN OLIGOMERS, DISULFIDE BONDS.
[11]	"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: 18403759] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA-RELATED TRAITS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M80927 mRNA. Translation: AAA16074.1.
Y08374 , 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.

IPI

IPI00002147.

PIR

A49562.

RefSeq

NP_001267.2.

UniGene

Hs.382202

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HJV	X-ray	2.75	A/B/C/D	22-383	[»]
1HJW	X-ray	2.30	A/B	22-383	[»]
1HJX	X-ray	1.85	A/B/C/D	22-383	[»]
1LA7	model	-	A	22-383	[»]
1NWR	X-ray	2.70	A/B/C/D	22-383	[»]
1NWS	X-ray	2.70	A/B/C/D	22-383	[»]
1NWT	X-ray	2.50	A/B/C/D	22-383	[»]
1NWU	X-ray	2.20	A/B/C/D	22-383	[»]

ModBase

Search...

Protein family/group databases

CAZy

GH18. Glycoside Hydrolase Family 18.

PTM databases

PhosphoSite

P36222.

Proteomic databases

PeptideAtlas

P36222.

PRIDE

P36222.

Genome annotation databases

Ensembl

ENSG00000133048. Homo sapiens. [Contig view]

GeneID

1116.

KEGG

hsa:1116.

Organism-specific databases

GeneCards

GC01M201414.

H-InvDB

HIX0001487.

HGNC

HGNC:1932. CHI3L1.

MIM

601525. gene.
611960. phenotype.

PharmGKB

PA26463.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P36222.

HOVERGEN

P36222.

OMA

P36222. FPLTNAI.

Gene expression databases

ArrayExpress

P36222.

Bgee

P36222.

CleanEx

HS_CHI3L1.

GermOnline

ENSG00000133048. Homo sapiens.

Family and domain databases

InterPro

IPR011583. Chitinase_II.
IPR001223. Glyco_hydro18cat.
IPR001579. Glyco_hydro_18_chit_AS.
IPR013781. Glyco_hydro_sg_catalytic.
[Graphical view]

Gene3D

G3DSA:3.20.20.80. Glyco_hydro_cat. 1 hit.

Pfam

PF00704. Glyco_hydro_18. 1 hit.
[Graphical view]

ProDom

PD000471. Chitinase_II. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00636. Glyco_18. 1 hit.
[Graphical view]

PROSITE

PS01095. CHITINASE_18. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

4626.

SOURCE

Search...

Entry information

Entry name

CH3L1_HUMAN

Accession

Primary (citable) accession number: P36222
Secondary accession number(s): B2R7B0 , P30923, Q8IVA4, Q96HI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	December 20, 2005
Last modified:	June 16, 2009
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)