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Q13231 (CHIT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chitotriosidase-1

EC=3.2.1.14
Alternative name(s):
Chitinase-1
Gene names
Name:CHIT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length466 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity. Ref.1 Ref.5 Ref.6

Catalytic activity

Random hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and chitodextrins. Ref.5 Ref.9 Ref.11

Subunit structure

Monomer.

Subcellular location

Secreted. Lysosome. Note: A small proportion is lysosomal. Ref.1 Ref.7 Ref.11

Tissue specificity

Detected in spleen. Secreted by cultured macrophages. Ref.5

Polymorphism

A 24 bp duplication in exon 10 leads to the activation of an alternative splice site and the production of an inactive protein resulting in chitotriosidase deficiency [MIM:614122]. 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.

Miscellaneous

Very high plasma levels of CHIT1 are found in patients with Gaucher disease type 1 (GD I). Can be used as diagnostic aid and to evaluate the success of treatment that brings levels back to normal.

Sequence similarities

Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.

Contains 1 chitin-binding type-2 domain.

Sequence caution

The sequence BAG51478.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 4 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.
Isoform 4 (identifier: Q13231-4)

The sequence of this isoform differs from the canonical sequence as follows:
     87-105: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.5
Chain22 – 466445Chitotriosidase-1
PRO_0000011941

Regions

Domain417 – 46650Chitin-binding type-2
Region70 – 712Chitooligosaccharide binding
Region97 – 1004Chitooligosaccharide binding
Region210 – 2134Chitooligosaccharide binding

Sites

Active site1401Proton donor By similarity
Binding site2691Chitooligosaccharide
Binding site3581Chitooligosaccharide

Amino acid modifications

Glycosylation1001N-linked (GlcNAc...); in variant S-102 Ref.11
Disulfide bond26 ↔ 51 Ref.7
Disulfide bond307 ↔ 370 Ref.7
Disulfide bond450 ↔ 463 By similarity

Natural variations

Alternative sequence87 – 10519Missing in isoform 4.
VSP_044816
Alternative sequence344 – 37229Missing in isoform 3.
VSP_008633
Alternative sequence386 – 3872SL → NG in isoform 2.
VSP_008631
Alternative sequence388 – 46679Missing in isoform 2.
VSP_008632
Natural variant401R → H.
Corresponds to variant rs35920428 [ dbSNP | Ensembl ].
VAR_049190
Natural variant741E → K Rare variant detected in patients with Gaucher disease type 1. Ref.10
Corresponds to variant rs137852607 [ dbSNP | Ensembl ].
VAR_065914
Natural variant1021G → S Common variant detected in patients with Gaucher disease type 1 as well as healthy individuals; slightly reduced activity towards 4-methylumbelliferyl-chitotrioside but no effect on activity towards 4-methylumbelliferyl-deoxychitobioside. Ref.4 Ref.10 Ref.11
Corresponds to variant rs2297950 [ dbSNP | Ensembl ].
VAR_022138
Natural variant1711Q → H.
Corresponds to variant rs12562058 [ dbSNP | Ensembl ].
VAR_049191
Natural variant4421A → G. Ref.2 Ref.4
Corresponds to variant rs1065761 [ dbSNP | Ensembl ].
VAR_024458

Secondary structure

........................................................................ 466
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: B4312D1E885E386D

FASTA46651,681
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 03A272B8BC5E0D71
Show »

FASTA38743,133
Isoform 3 [UniParc].

Checksum: 1A073A5F90A43717
Show »

FASTA43748,565
Isoform 4 [UniParc].

Checksum: 4C083E18D767C381
Show »

FASTA44749,613

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION.
Tissue: Macrophage.
[2]"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] (ISOFORM 4), VARIANT GLY-442.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 1), VARIANTS SER-102 AND GLY-442.
[5]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-43 AND 178-198, FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
Tissue: Spleen.
[6]"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] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM, FUNCTION (ISOFORM 3).
[7]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 22-386 IN COMPLEX WITH CHITOBIOSE AND ALLOSAMIDIN, SUBCELLULAR LOCATION, DISULFIDE BONDS.
[8]"Crystal structures of allosamidin derivatives in complex with human macrophage chitinase."
Rao F.V., Houston D.R., Boot R.G., Aerts J.M., Sakuda S., van Aalten D.M.
J. Biol. Chem. 278:20110-20116(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 22-385 IN COMPLEX WITH ALLOSAMIDIN.
[9]"Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases."
Rao F.V., Houston D.R., Boot R.G., Aerts J.M., Hodkinson M., Adams D.J., Shiomi K., Omura S., van Aalten D.M.
Chem. Biol. 12:65-76(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 22-466 IN COMPLEX WITH THE CYCLOPENTAPEPTIDE INHIBITOR ARGADIN, CATALYTIC ACTIVITY.
[10]"Type 1 Gaucher disease: null and hypomorphic novel chitotriosidase mutations-implications for diagnosis and therapeutic monitoring."
Grace M.E., Balwani M., Nazarenko I., Prakash-Cheng A., Desnick R.J.
Hum. Mutat. 28:866-873(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-74 AND SER-102.
[11]"Common G102S polymorphism in chitotriosidase differentially affects activity towards 4-methylumbelliferyl substrates."
Bussink A.P., Verhoek M., Vreede J., Ghauharali-van der Vlugt K., Donker-Koopman W.E., Sprenger R.R., Hollak C.E., Aerts J.M., Boot R.G.
FEBS J. 276:5678-5688(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT SER-102, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-100.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U29615 mRNA. Translation: AAC50246.1.
U62662 mRNA. Translation: AAG10644.1.
AK055165 mRNA. Translation: BAG51478.1. Different initiation.
AC105940 Genomic DNA. No translation available.
AL359090 Genomic DNA. No translation available.
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.
CCDSCCDS1436.1. [Q13231-1]
CCDS58057.1. [Q13231-4]
RefSeqNP_001243054.2. NM_001256125.1. [Q13231-4]
NP_003456.1. NM_003465.2. [Q13231-1]
UniGeneHs.201688.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GUVX-ray2.35A22-387[»]
1HKIX-ray2.55A22-386[»]
1HKJX-ray2.60A22-386[»]
1HKKX-ray1.85A22-385[»]
1HKMX-ray2.55A22-386[»]
1LG1X-ray2.78A22-386[»]
1LG2X-ray2.10A22-386[»]
1LQ0X-ray2.20A22-386[»]
1WAWX-ray1.75A22-466[»]
1WB0X-ray1.65A22-466[»]
ProteinModelPortalQ13231.
SMRQ13231. Positions 22-385.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000255427.

Chemistry

BindingDBQ13231.
ChEMBLCHEMBL3080.

Protein family/group databases

CAZyCBM14. Carbohydrate-Binding Module Family 14.
GH18. Glycoside Hydrolase Family 18.

Polymorphism databases

DMDM37999493.

Proteomic databases

PaxDbQ13231.
PRIDEQ13231.

Protocols and materials databases

DNASU1118.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000255427; ENSP00000255427; ENSG00000133063. [Q13231-4]
ENST00000367229; ENSP00000356198; ENSG00000133063. [Q13231-1]
ENST00000491855; ENSP00000423778; ENSG00000133063. [Q13231-2]
GeneID1118.
KEGGhsa:1118.
UCSCuc001gzn.2. human. [Q13231-1]
uc009xal.2. human. [Q13231-3]

Organism-specific databases

CTD1118.
GeneCardsGC01M203181.
HGNCHGNC:1936. CHIT1.
HPAHPA010575.
MIM600031. gene.
614122. phenotype.
neXtProtNX_Q13231.
PharmGKBPA26467.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3325.
HOVERGENHBG011684.
InParanoidQ13231.
KOK01183.
OMAPGQDTFC.
OrthoDBEOG7ZGX3G.
PhylomeDBQ13231.
TreeFamTF315610.

Gene expression databases

ArrayExpressQ13231.
BgeeQ13231.
CleanExHS_CHIT1.
GenevestigatorQ13231.

Family and domain databases

Gene3D2.170.140.10. 1 hit.
3.10.50.10. 1 hit.
3.20.20.80. 2 hits.
InterProIPR002557. Chitin-bd_dom.
IPR011583. Chitinase_II.
IPR029070. Chitinase_insertion.
IPR001223. Glyco_hydro18cat.
IPR001579. Glyco_hydro_18_chit_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PfamPF01607. CBM_14. 1 hit.
PF00704. Glyco_hydro_18. 1 hit.
[Graphical view]
SMARTSM00494. ChtBD2. 1 hit.
SM00636. Glyco_18. 1 hit.
[Graphical view]
SUPFAMSSF51445. SSF51445. 2 hits.
SSF54556. SSF54556. 1 hit.
SSF57625. SSF57625. 1 hit.
PROSITEPS50940. CHIT_BIND_II. 1 hit.
PS01095. CHITINASE_18. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCHIT1. human.
EvolutionaryTraceQ13231.
GenomeRNAi1118.
NextBio35534786.
PROQ13231.
SOURCESearch...

Entry information

Entry nameCHIT1_HUMAN
AccessionPrimary (citable) accession number: Q13231
Secondary accession number(s): B3KNW6 expand/collapse secondary AC list , J3KN09, Q0VGG5, Q0VGG6, Q3ZAR1, Q6ISC2, Q9H3V8, Q9UDJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 144 of the entry and version 1 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