Reviewed, UniProtKB/Swiss-Prot Q13231 (CHIT1_HUMAN)

Names and origin

Protein names

Recommended name:
    Chitotriosidase-1
    EC=3.2.1.14
Alternative name(s):
    Chitinase-1

Gene names

Name:

CHIT1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	466 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	Degrades chitin and chitotriose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity. Ref.1 Ref.3 Ref.4
Catalytic activity	Random hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and chitodextrins.
Subunit structure	Monomer.
Subcellular location	Secreted. Lysosome. Note: A small proportion is lysosomal. Ref.1
Tissue specificity	Detected in spleen. Secreted by cultured macrophages. Ref.3
Polymorphism	A 24 bp duplication in exon 10 leads to the activation of an alternative splice site and the production of an inactive protein. About 6% of the population are deficient for CHIT1 activity, while 35% are carriers and show reduced enzyme levels. People with CHIT1 deficiency appear perfectly healthy.
Involvement in disease	Very high plasma levels of CHIT1 are found in patients with Gaucher disease type 1 (GD I). This can be used as diagnostic aid and to evaluate the success of treatment. Successful therapy brings the CHIT1 activity levels back to normal.
Sequence similarities	Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily. Contains 1 chitin-binding type-2 domain.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Chitin degradation Polysaccharide degradation
Cellular component	Lysosome Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Chitin-binding
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	chitin catabolic process Ref.4 Traceable author statement. Source: UniProtKB immune response Ref.4 Non-traceable author statement. Source: UniProtKB response to bacterium Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.1 Ref.4 Inferred by curator. Source: UniProtKB lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cation binding Inferred from electronic annotation. Source: InterPro chitin binding Ref.4 Traceable author statement. Source: UniProtKB chitinase activity Ref.3 Ref.4 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13231-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q13231-2)

The sequence of this isoform differs from the canonical sequence as follows:
     386-387: SL → NG
     388-466: Missing.

Isoform 3 (identifier: Q13231-3)

The sequence of this isoform differs from the canonical sequence as follows:
     344-372: Missing.

Note: Duplication of 24 bp in exon 10 leads to the use of a cryptic splice site. The normal splice site is still present but not used.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Ref.3

Chain

22 – 466

445

Chitotriosidase-1

PRO_0000011941

Regions

Domain

417 – 466

50

Chitin-binding type-2

Sites

Active site

140

1

Proton donor By similarity

Amino acid modifications

Disulfide bond

26 ↔ 51

Disulfide bond

307 ↔ 370

Disulfide bond

450 ↔ 463

By similarity

Natural variations

Alternative sequence

344 – 372

29

Missing in isoform 3.

VSP_008633

Alternative sequence

386 – 387

2

SL → NG in isoform 2.

VSP_008631

Alternative sequence

388 – 466

79

Missing in isoform 2.

VSP_008632

Natural variant

40

1

R → H: dbSNP rs35920428.

VAR_049190

Natural variant

102

1

G → S: dbSNP rs2297950. Ref.2

VAR_022138

Natural variant

171

1

Q → H: dbSNP rs12562058.

VAR_049191

Natural variant

442

1

A → G: dbSNP rs1065761. Ref.2

VAR_024458

Secondary structure

1

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466

Helix Strand Turn

Details...

Beta strand

23 – 29

7

Helix

32 – 34

3

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

Helix

83 – 85

3

Beta strand

91 – 97

7

Turn

99 – 101

3

Helix

104 – 109

6

Beta strand

110 – 113

4

Helix

114 – 130

17

Beta strand

134 – 138

5

Helix

151 – 173

23

Beta strand

179 – 184

6

Helix

188 – 194

7

Helix

197 – 203

7

Beta strand

205 – 209

5

Beta strand

219 – 221

3

Helix

236 – 240

5

Helix

243 – 252

10

Helix

257 – 259

3

Beta strand

260 – 277

18

Beta strand

284 – 288

5

Turn

293 – 295

3

Beta strand

300 – 302

3

Helix

303 – 306

4

Beta strand

313 – 316

4

Helix

318 – 320

3

Beta strand

323 – 327

5

Beta strand

330 – 333

4

Helix

337 – 350

14

Beta strand

353 – 358

6

Helix

360 – 362

3

Beta strand

367 – 372

6

Helix

376 – 384

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: B4312D1E885E386D	FASTA	466	51,681
	10 20 30 40 50 60 MVRSVAWAGF MVLLMIPWGS AAKLVCYFTN WAQYRQGEAR FLPKDLDPSL CTHLIYAFAG 70 80 90 100 110 120 MTNHQLSTTE WNDETLYQEF NGLKKMNPKL KTLLAIGGWN FGTQKFTDMV ATANNRQTFV 130 140 150 160 170 180 NSAIRFLRKY SFDGLDLDWE YPGSQGSPAV DKERFTTLVQ DLANAFQQEA QTSGKERLLL 190 200 210 220 230 240 SAAVPAGQTY VDAGYEVDKI AQNLDFVNLM AYDFHGSWEK VTGHNSPLYK RQEESGAAAS 250 260 270 280 290 300 LNVDAAVQQW LQKGTPASKL ILGMPTYGRS FTLASSSDTR VGAPATGSGT PGPFTKEGGM 310 320 330 340 350 360 LAYYEVCSWK GATKQRIQDQ KVPYIFRDNQ WVGFDDVESF KTKVSYLKQK GLGGAMVWAL 370 380 390 400 410 420 DLDDFAGFSC NQGRYPLIQT LRQELSLPYL PSGTPELEVP KPGQPSEPEH GPSPGQDTFC 430 440 450 460 QGKADGLYPN PRERSSFYSC AAGRLFQQSC PTGLVFSNSC KCCTWN
	Isoform 2. Checksum: 03A272B8BC5E0D71	FASTA	387	43,133
	10 20 30 40 50 60 MVRSVAWAGF MVLLMIPWGS AAKLVCYFTN WAQYRQGEAR FLPKDLDPSL CTHLIYAFAG 70 80 90 100 110 120 MTNHQLSTTE WNDETLYQEF NGLKKMNPKL KTLLAIGGWN FGTQKFTDMV ATANNRQTFV 130 140 150 160 170 180 NSAIRFLRKY SFDGLDLDWE YPGSQGSPAV DKERFTTLVQ DLANAFQQEA QTSGKERLLL 190 200 210 220 230 240 SAAVPAGQTY VDAGYEVDKI AQNLDFVNLM AYDFHGSWEK VTGHNSPLYK RQEESGAAAS 250 260 270 280 290 300 LNVDAAVQQW LQKGTPASKL ILGMPTYGRS FTLASSSDTR VGAPATGSGT PGPFTKEGGM 310 320 330 340 350 360 LAYYEVCSWK GATKQRIQDQ KVPYIFRDNQ WVGFDDVESF KTKVSYLKQK GLGGAMVWAL 370 380 DLDDFAGFSC NQGRYPLIQT LRQELNG
	Isoform 3. Checksum: 1A073A5F90A43717	FASTA	437	48,565
	10 20 30 40 50 60 MVRSVAWAGF MVLLMIPWGS AAKLVCYFTN WAQYRQGEAR FLPKDLDPSL CTHLIYAFAG 70 80 90 100 110 120 MTNHQLSTTE WNDETLYQEF NGLKKMNPKL KTLLAIGGWN FGTQKFTDMV ATANNRQTFV 130 140 150 160 170 180 NSAIRFLRKY SFDGLDLDWE YPGSQGSPAV DKERFTTLVQ DLANAFQQEA QTSGKERLLL 190 200 210 220 230 240 SAAVPAGQTY VDAGYEVDKI AQNLDFVNLM AYDFHGSWEK VTGHNSPLYK RQEESGAAAS 250 260 270 280 290 300 LNVDAAVQQW LQKGTPASKL ILGMPTYGRS FTLASSSDTR VGAPATGSGT PGPFTKEGGM 310 320 330 340 350 360 LAYYEVCSWK GATKQRIQDQ KVPYIFRDNQ WVGFDDVESF KTKGRYPLIQ TLRQELSLPY 370 380 390 400 410 420 LPSGTPELEV PKPGQPSEPE HGPSPGQDTF CQGKADGLYP NPRERSSFYS CAAGRLFQQS 430 CPTGLVFSNS CKCCTWN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages." Boot R.G., Renkema G.H., Strijland A., van Zonneveld A.J., Aerts J.M.F.G. J. Biol. Chem. 270:26252-26256(1995) [PubMed: 7592832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION. Tissue: Macrophage.
[2]	"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] (ISOFORM 1), VARIANTS SER-102 AND GLY-442.
[3]	"Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins." Renkema G.H., Boot R.G., Muijsers A.O., Donker-Koopman W.E., Aerts J.M.F.G. J. Biol. Chem. 270:2198-2202(1995) [PubMed: 7836450] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-42 AND 178-198, FUNCTION, TISSUE SPECIFICITY.
[4]	"The human chitotriosidase gene. Nature of inherited enzyme deficiency." Boot R.G., Renkema G.H., Verhoek M., Strijland A., Bliek J., de Meulemeester T.M.A.M.O., Mannens M.M.A.M., Aerts J.M.F.G. J. Biol. Chem. 273:25680-25685(1998) [PubMed: 9748235] [Abstract] Cited for: POLYMORPHISM, FUNCTION (ISOFORM 3).
[5]	"Structure of human chitotriosidase. Implications for specific inhibitor design and function of mammalian chitinase-like lectins." Fusetti F., von Moeller H., Houston D., Rozeboom H.J., Dijkstra B.W., Boot R.G., Aerts J.M.F.G., van Aalten D.M.F. J. Biol. Chem. 277:25537-25544(2002) [PubMed: 11960986] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 22-386 IN COMPLEX WITH CHITOBIOSE AND ALLOSAMIDIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U29615 mRNA. Translation: AAC50246.1.
U62662 mRNA. Translation: AAG10644.1.
BC069614 mRNA. Translation: AAH69614.1.
BC103695 mRNA. Translation: AAI03696.1.
BC105680 mRNA. Translation: AAI05681.1.
BC105681 mRNA. Translation: AAI05682.1.
BC105682 mRNA. Translation: AAI05683.1.

IPI

IPI00375364.
IPI00478217.
IPI00852865.

RefSeq

NP_003456.1.

UniGene

Hs.201688

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GUV	X-ray	2.35	A	22-387	[»]
1HKI	X-ray	2.55	A	22-386	[»]
1HKJ	X-ray	2.60	A	22-386	[»]
1HKK	X-ray	1.85	A	22-385	[»]
1HKM	X-ray	2.55	A	22-386	[»]
1LG1	X-ray	2.78	A	22-386	[»]
1LG2	X-ray	2.10	A	22-386	[»]
1LQ0	X-ray	2.20	A	22-386	[»]
1WAW	X-ray	1.75	A	22-466	[»]
1WB0	X-ray	1.65	A	22-466	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q13231.

Protein family/group databases

CAZy

CBM14. Carbohydrate-Binding Module Family 14.
GH18. Glycoside Hydrolase Family 18.

Proteomic databases

PRIDE

Q13231.

Genome annotation databases

Ensembl

ENST00000255427; ENSP00000255427; ENSG00000133063; Homo sapiens. [Genome view]
ENST00000362046; ENSP00000355262; ENSG00000133063; Homo sapiens. [Genome view]
ENST00000367229; ENSP00000356198; ENSG00000133063; Homo sapiens. [Genome view]

GeneID

1118.

KEGG

hsa:1118.

UCSC

uc001gzn.2. human.

Organism-specific databases

CTD

1118.

GeneCards

GC01M201451.

H-InvDB

HIX0001488.

HGNC

HGNC:1936. CHIT1.

HPA

HPA010575.

MIM

600031. gene.

PharmGKB

PA26467.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q13231.

HOVERGEN

Q13231.

Enzyme and pathway databases

BRENDA

3.2.1.14. 247.

Gene expression databases

ArrayExpress

Q13231.

Bgee

Q13231.

CleanEx

HS_CHIT1.

Genevestigator

Q13231.

GermOnline

ENSG00000133063. Homo sapiens.

Family and domain databases

InterPro

IPR002557. Chitin-bd_peritrophin-A.
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

PF01607. CBM_14. 1 hit.
PF00704. Glyco_hydro_18. 1 hit.
[Graphical view]

ProDom

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

SMART

SM00494. ChtBD2. 1 hit.
SM00636. Glyco_18. 1 hit.
[Graphical view]

PROSITE

PS50940. CHIT_BIND_II. 1 hit.
PS01095. CHITINASE_18. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

4638.

SOURCE

Search...

Entry information

Entry name

CHIT1_HUMAN

Accession

Primary (citable) accession number: Q13231
Secondary accession number(s): Q0VGG5 , Q0VGG6, Q3ZAR1, Q6ISC2, Q9H3V8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	November 1, 1996
Last modified:	November 3, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.