ID CHIA_HUMAN Reviewed; 476 AA.
AC Q9BZP6; Q32W79; Q32W80; Q3B866; Q5U5Z5; Q5VUV4; Q86UD8; Q9ULY3;
AC Q9ULY4;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 01-MAY-2013, entry version 119.
DE RecName: Full=Acidic mammalian chitinase;
DE Short=AMCase;
DE EC=3.2.1.14;
DE AltName: Full=Lung-specific protein TSA1902;
DE Flags: Precursor;
GN Name=CHIA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND VARIANTS VAL-339
RP AND GLY-432.
RC TISSUE=Lung;
RX PubMed=10548734; DOI=10.1016/S0378-1119(99)00394-7;
RA Saito A., Ozaki K., Fujiwara T., Nakamura Y., Tanigami A.;
RT "Isolation and mapping of a human lung-specific gene, TSA1902,
RT encoding a novel chitinase family member.";
RL Gene 239:325-331(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11085997; DOI=10.1074/jbc.M009886200;
RA Boot R.G., Blommaart E.F.C., Swart E., Ghauharali-van der Vlugt K.,
RA Bijl N., Moe C., Place A., Aerts J.M.F.G.;
RT "Identification of a novel acidic mammalian chitinase distinct from
RT chitotriosidase.";
RL J. Biol. Chem. 276:6770-6778(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Kidney;
RA Chen X.H., Cai G.P.;
RT "A novel chitinase family member.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=15192232; DOI=10.1126/science.1095336;
RA Zhu Z., Zheng T., Homer R.J., Kim Y.K., Chen N.Y., Cohn L., Hamid Q.,
RA Elias J.A.;
RT "Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13
RT pathway activation.";
RL Science 304:1678-1682(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH EGFR, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18824549; DOI=10.1074/jbc.M805574200;
RA Hartl D., He C.H., Koller B., Da Silva C.A., Homer R., Lee C.G.,
RA Elias J.A.;
RT "Acidic mammalian chitinase is secreted via an ADAM17/epidermal growth
RT factor receptor-dependent pathway and stimulates chemokine production
RT by pulmonary epithelial cells.";
RL J. Biol. Chem. 283:33472-33482(2008).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF ASP-138.
RX PubMed=19342690; DOI=10.4049/jimmunol.0803446;
RA Hartl D., He C.H., Koller B., Da Silva C.A., Kobayashi Y., Lee C.G.,
RA Flavell R.A., Elias J.A.;
RT "Acidic mammalian chitinase regulates epithelial cell apoptosis via a
RT chitinolytic-independent mechanism.";
RL J. Immunol. 182:5098-5106(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 22-408 IN COMPLEX WITH
RP METHYLALLOSAMIDIN, CATALYTIC ACTIVITY, AND DISULFIDE BONDS.
RX PubMed=19241384; DOI=10.1002/pro.63;
RA Olland A.M., Strand J., Presman E., Czerwinski R., Joseph-McCarthy D.,
RA Krykbaev R., Schlingmann G., Chopra R., Lin L., Fleming M., Kriz R.,
RA Stahl M., Somers W., Fitz L., Mosyak L.;
RT "Triad of polar residues implicated in pH specificity of acidic
RT mammalian chitinase.";
RL Protein Sci. 18:569-578(2009).
RN [10]
RP VARIANTS ASP-45; ASN-47; MET-61; ARG-102; ARG-125; VAL-339; SER-354
RP AND GLY-432, CATALYTIC ACTIVITY, FUNCTION, AND CHARACTERIZATION OF
RP VARIANTS ASP-45; ASN-47 AND MET-61.
RX PubMed=19435888; DOI=10.1074/jbc.M109.012443;
RA Seibold M.A., Reese T.A., Choudhry S., Salam M.T., Beckman K., Eng C.,
RA Atakilit A., Meade K., Lenoir M., Watson H.G., Thyne S., Kumar R.,
RA Weiss K.B., Grammer L.C., Avila P., Schleimer R.P., Fahy J.V.,
RA Rodriguez-Santana J., Rodriguez-Cintron W., Boot R.G., Sheppard D.,
RA Gilliland F.D., Locksley R.M., Burchard E.G.;
RT "Differential enzymatic activity of common haplotypic versions of the
RT human acidic mammalian chitinase protein.";
RL J. Biol. Chem. 284:19650-19658(2009).
CC -!- FUNCTION: Degrades chitin and chitotriose. May participate in the
CC defense against nematodes, fungi and other pathogens. Plays a role
CC in T-helper cell type 2 (Th2) immune response. Contributes to the
CC response to IL-13 and inflammation in response to IL-13.
CC Stimulates chemokine production by pulmonary epithelial cells.
CC Protects lung epithelial cells against apoptosis and promotes
CC phosphorylation of AKT1. Its function in the inflammatory response
CC and in protecting cells against apoptosis is inhibited by
CC allosamidin, suggesting that the function of this protein depends
CC on carbohydrate binding.
CC -!- CATALYTIC ACTIVITY: Random hydrolysis of N-acetyl-beta-D-
CC glucosaminide (1->4)-beta-linkages in chitin and chitodextrins.
CC -!- SUBUNIT: Interacts with EGFR.
CC -!- SUBCELLULAR LOCATION: Isoform 1: Secreted. Note=Secretion depends
CC on EGFR activity.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: Isoform 3: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9BZP6-1; Sequence=Displayed;
CC Name=2; Synonyms=TSA1902-L;
CC IsoId=Q9BZP6-2; Sequence=VSP_008635;
CC Name=3; Synonyms=TSA1902-S;
CC IsoId=Q9BZP6-3; Sequence=VSP_008634;
CC -!- TISSUE SPECIFICITY: Detected in lung epithelial cells from asthma
CC patients (at protein level). Highly expressed in stomach. Detected
CC at lower levels in lung.
CC -!- INDUCTION: Up-regulated in lung epithelial cells from asthma
CC patients.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 18 family. Chitinase
CC class II subfamily.
CC -!- SIMILARITY: Contains 1 chitin-binding type-2 domain.
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DR EMBL; AB025008; BAA86980.1; -; mRNA.
DR EMBL; AB025009; BAA86981.1; -; mRNA.
DR EMBL; AF290004; AAG60019.1; -; mRNA.
DR EMBL; AY789444; AAX81431.1; -; mRNA.
DR EMBL; AY789445; AAX81432.1; -; mRNA.
DR EMBL; AL513202; CAH70803.1; -; Genomic_DNA.
DR EMBL; AL356387; CAH70803.1; JOINED; Genomic_DNA.
DR EMBL; AL356387; CAI19265.1; -; Genomic_DNA.
DR EMBL; AL513202; CAI19265.1; JOINED; Genomic_DNA.
DR EMBL; BC047336; AAH47336.2; -; mRNA.
DR EMBL; BC036339; AAH36339.2; -; mRNA.
DR EMBL; BC106910; AAI06911.1; -; mRNA.
DR IPI; IPI00033102; -.
DR IPI; IPI00374037; -.
DR IPI; IPI00374038; -.
DR RefSeq; NP_001035713.1; NM_001040623.2.
DR RefSeq; NP_001244930.1; NM_001258001.1.
DR RefSeq; NP_001244931.1; NM_001258002.1.
DR RefSeq; NP_001244932.1; NM_001258003.1.
DR RefSeq; NP_001244933.1; NM_001258004.1.
DR RefSeq; NP_001244934.1; NM_001258005.1.
DR RefSeq; NP_068569.2; NM_021797.3.
DR RefSeq; NP_970615.2; NM_201653.3.
DR UniGene; Hs.128814; -.
DR PDB; 2YBT; X-ray; 2.22 A; A/B/C/D/E/F=21-398.
DR PDB; 2YBU; X-ray; 2.25 A; A/B/C/D/E/F=21-398.
DR PDB; 3FXY; X-ray; 2.00 A; A/B/C/D=22-408.
DR PDB; 3FY1; X-ray; 1.70 A; A/B=22-408.
DR PDB; 3RM4; X-ray; 1.90 A; A/B=22-408.
DR PDB; 3RM8; X-ray; 1.80 A; A/B=22-408.
DR PDB; 3RM9; X-ray; 2.10 A; A/B=22-408.
DR PDB; 3RME; X-ray; 1.80 A; A/B=22-408.
DR PDBsum; 2YBT; -.
DR PDBsum; 2YBU; -.
DR PDBsum; 3FXY; -.
DR PDBsum; 3FY1; -.
DR PDBsum; 3RM4; -.
DR PDBsum; 3RM8; -.
DR PDBsum; 3RM9; -.
DR PDBsum; 3RME; -.
DR ProteinModelPortal; Q9BZP6; -.
DR CAZy; CBM14; Carbohydrate-Binding Module Family 14.
DR CAZy; GH18; Glycoside Hydrolase Family 18.
DR PhosphoSite; Q9BZP6; -.
DR DMDM; 37999771; -.
DR PaxDb; Q9BZP6; -.
DR PRIDE; Q9BZP6; -.
DR Ensembl; ENST00000343320; ENSP00000341828; ENSG00000134216.
DR Ensembl; ENST00000353665; ENSP00000338970; ENSG00000134216.
DR Ensembl; ENST00000369740; ENSP00000358755; ENSG00000134216.
DR Ensembl; ENST00000430615; ENSP00000391132; ENSG00000134216.
DR Ensembl; ENST00000451398; ENSP00000390476; ENSG00000134216.
DR Ensembl; ENST00000483391; ENSP00000436946; ENSG00000134216.
DR GeneID; 27159; -.
DR KEGG; hsa:27159; -.
DR UCSC; uc001eaq.3; human.
DR CTD; 27159; -.
DR GeneCards; GC01P111833; -.
DR HGNC; HGNC:17432; CHIA.
DR MIM; 606080; gene.
DR neXtProt; NX_Q9BZP6; -.
DR PharmGKB; PA142672117; -.
DR eggNOG; COG3325; -.
DR HOVERGEN; HBG011684; -.
DR InParanoid; Q9BZP6; -.
DR KO; K01183; -.
DR OMA; GLGRFMP; -.
DR PhylomeDB; Q9BZP6; -.
DR BRENDA; 3.2.1.14; 2681.
DR BindingDB; Q9BZP6; -.
DR ChEMBL; CHEMBL1293197; -.
DR EvolutionaryTrace; Q9BZP6; -.
DR GenomeRNAi; 27159; -.
DR NextBio; 49937; -.
DR ArrayExpress; Q9BZP6; -.
DR Bgee; Q9BZP6; -.
DR Genevestigator; Q9BZP6; -.
DR GermOnline; ENSG00000134216; Homo sapiens.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; NAS:UniProtKB.
DR GO; GO:0008061; F:chitin binding; TAS:UniProtKB.
DR GO; GO:0004568; F:chitinase activity; IDA:UniProtKB.
DR GO; GO:0003796; F:lysozyme activity; NAS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006037; P:cell wall chitin metabolic process; TAS:UniProtKB.
DR GO; GO:0006032; P:chitin catabolic process; IDA:UniProtKB.
DR GO; GO:0007586; P:digestion; NAS:UniProtKB.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0000272; P:polysaccharide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0090197; P:positive regulation of chemokine secretion; IDA:UniProtKB.
DR GO; GO:0002532; P:production of molecular mediator involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0001101; P:response to acid; TAS:UniProtKB.
DR GO; GO:0009620; P:response to fungus; TAS:UniProtKB.
DR Gene3D; 2.170.140.10; -; 1.
DR Gene3D; 3.20.20.80; -; 2.
DR InterPro; IPR002557; Chitin-bd_dom.
DR InterPro; IPR011583; Chitinase_II.
DR InterPro; IPR001223; Glyco_hydro18cat.
DR InterPro; IPR001579; Glyco_hydro_18_chit_AS.
DR InterPro; IPR013781; Glyco_hydro_catalytic_dom.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR Pfam; PF01607; CBM_14; 1.
DR Pfam; PF00704; Glyco_hydro_18; 1.
DR SMART; SM00494; ChtBD2; 1.
DR SMART; SM00636; Glyco_18; 1.
DR SUPFAM; SSF57625; Chitin_bind_PerA; 1.
DR SUPFAM; SSF51445; Glyco_hydro_cat; 1.
DR PROSITE; PS50940; CHIT_BIND_II; 1.
DR PROSITE; PS01095; CHITINASE_18; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis;
KW Carbohydrate metabolism; Chitin degradation; Chitin-binding;
KW Complete proteome; Cytoplasm; Disulfide bond; Glycosidase; Hydrolase;
KW Immunity; Inflammatory response; Polymorphism;
KW Polysaccharide degradation; Reference proteome; Secreted; Signal.
FT SIGNAL 1 21 By similarity.
FT CHAIN 22 476 Acidic mammalian chitinase.
FT /FTId=PRO_0000011944.
FT DOMAIN 427 476 Chitin-binding type-2.
FT REGION 70 71 Chitooligosaccharide binding (Probable).
FT REGION 97 100 Chitooligosaccharide binding (Probable).
FT REGION 210 213 Chitooligosaccharide binding (Probable).
FT COMPBIAS 415 420 Poly-Ser.
FT ACT_SITE 140 140 Proton donor (Probable).
FT BINDING 141 141 Chitooligosaccharide (By similarity).
FT BINDING 360 360 Chitooligosaccharide (By similarity).
FT DISULFID 26 51
FT DISULFID 49 394
FT DISULFID 307 372
FT VAR_SEQ 1 161 Missing (in isoform 3).
FT /FTId=VSP_008634.
FT VAR_SEQ 1 108 Missing (in isoform 2).
FT /FTId=VSP_008635.
FT VARIANT 45 45 N -> D (increased chitinase activity;
FT when associated with N-47 and M-61;
FT dbSNP:rs41282492).
FT /FTId=VAR_063030.
FT VARIANT 47 47 D -> N (increased chitinase activity;
FT when associated with N-47 and M-61;
FT dbSNP:rs41282494).
FT /FTId=VAR_063031.
FT VARIANT 61 61 R -> M (increased chitinase activity;
FT when associated with N-47 and M-61;
FT dbSNP:rs41282496).
FT /FTId=VAR_063032.
FT VARIANT 102 102 G -> R (in dbSNP:rs3818822).
FT /FTId=VAR_049192.
FT VARIANT 125 125 K -> R.
FT /FTId=VAR_063033.
FT VARIANT 324 324 V -> G (in dbSNP:rs2256721).
FT /FTId=VAR_033730.
FT VARIANT 339 339 I -> V (in dbSNP:rs2275253).
FT /FTId=VAR_049193.
FT VARIANT 354 354 F -> S (in dbSNP:rs2275254).
FT /FTId=VAR_049194.
FT VARIANT 377 377 F -> L (in dbSNP:rs36011905).
FT /FTId=VAR_049195.
FT VARIANT 432 432 V -> G (in dbSNP:rs2256721).
FT /FTId=VAR_049196.
FT MUTAGEN 138 138 D->A: Loss of chitinase activity. No
FT effect on protection against apoptosis or
FT on AKT1 activation.
FT CONFLICT 203 203 Y -> C (in Ref. 3; AAX81431).
FT STRAND 23 29
FT HELIX 32 34
FT HELIX 37 39
FT HELIX 43 45
FT TURN 48 50
FT STRAND 52 62
FT STRAND 65 67
FT HELIX 73 82
FT HELIX 83 85
FT STRAND 91 97
FT HELIX 99 101
FT HELIX 104 110
FT HELIX 113 130
FT STRAND 133 138
FT HELIX 151 173
FT STRAND 179 184
FT HELIX 188 194
FT HELIX 197 203
FT STRAND 205 209
FT HELIX 217 219
FT HELIX 236 240
FT HELIX 243 252
FT HELIX 257 259
FT STRAND 260 275
FT STRAND 284 288
FT TURN 293 295
FT STRAND 300 302
FT HELIX 303 311
FT STRAND 315 319
FT TURN 320 323
FT STRAND 324 329
FT STRAND 332 335
FT HELIX 339 351
FT STRAND 355 360
FT HELIX 362 364
FT STRAND 367 369
FT TURN 370 372
FT HELIX 378 386
FT HELIX 392 394
SQ SEQUENCE 476 AA; 52271 MW; 92B27BAD2F7EB4CC CRC64;
MTKLILLTGL VLILNLQLGS AYQLTCYFTN WAQYRPGLGR FMPDNIDPCL CTHLIYAFAG
RQNNEITTIE WNDVTLYQAF NGLKNKNSQL KTLLAIGGWN FGTAPFTAMV STPENRQTFI
TSVIKFLRQY EFDGLDFDWE YPGSRGSPPQ DKHLFTVLVQ EMREAFEQEA KQINKPRLMV
TAAVAAGISN IQSGYEIPQL SQYLDYIHVM TYDLHGSWEG YTGENSPLYK YPTDTGSNAY
LNVDYVMNYW KDNGAPAEKL IVGFPTYGHN FILSNPSNTG IGAPTSGAGP AGPYAKESGI
WAYYEICTFL KNGATQGWDA PQEVPYAYQG NVWVGYDNIK SFDIKAQWLK HNKFGGAMVW
AIDLDDFTGT FCNQGKFPLI STLKKALGLQ SASCTAPAQP IEPITAAPSG SGNGSGSSSS
GGSSGGSGFC AVRANGLYPV ANNRNAFWHC VNGVTYQQNC QAGLVFDTSC DCCNWA
//
