TRYB2_MOUSE
ID TRYB2_MOUSE Reviewed; 276 AA.
AC P21845; Q61962;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 2.
DT 25-MAY-2022, entry version 154.
DE RecName: Full=Tryptase beta-2;
DE Short=Tryptase-2;
DE EC=3.4.21.59;
DE AltName: Full=Mast cell protease 6;
DE Short=mMCP-6;
DE Flags: Precursor;
GN Name=Tpsb2; Synonyms=Mcpt6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1995638; DOI=10.1016/s0021-9258(19)67871-3;
RA Reynolds D.S., Gurley D.S., Austen K.F., Serafin W.E.;
RT "Cloning of the cDNA and gene of mouse mast cell protease-6. Transcription
RT by progenitor mast cells and mast cells of the connective tissue
RT subclass.";
RL J. Biol. Chem. 266:3847-3853(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Leaden X A1;
RX PubMed=8210998; DOI=10.1111/j.1365-3083.1993.tb01738.x;
RA Huang R., Abrink M., Gobl A.E., Nilsson G., Aveskogh M., Larsson L.G.,
RA Nilsson K., Hellman L.;
RT "Expression of a mast cell tryptase in the human monocytic cell lines U-937
RT and Mono Mac 6.";
RL Scand. J. Immunol. 38:359-367(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC STRAIN=Leaden X A1;
RX PubMed=7959952; DOI=10.1007/bf00177823;
RA Huang R., Hellman L.T.;
RT "Genes for mast-cell serine protease and their molecular evolution.";
RL Immunogenetics 40:397-414(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC STRAIN=FVB/N; TISSUE=Colon;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 32-54.
RX PubMed=2326280; DOI=10.1073/pnas.87.8.3230;
RA Reynolds D.S., Stevens R.L., Lane W.S., Carr M.H., Austen K.F.,
RA Serafin W.E.;
RT "Different mouse mast cell populations express various combinations of at
RT least six distinct mast cell serine proteases.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:3230-3234(1990).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17456473; DOI=10.1074/jbc.m611842200;
RA Thakurdas S.M., Melicoff E., Sansores-Garcia L., Moreira D.C., Petrova Y.,
RA Stevens R.L., Adachi R.;
RT "The mast cell-restricted tryptase mMCP-6 has a critical immunoprotective
RT role in bacterial infections.";
RL J. Biol. Chem. 282:20809-20815(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-98, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [8]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16777228; DOI=10.1016/j.molimm.2006.04.019;
RA Abraham D., Oster H., Huber M., Leitges M.;
RT "The expression pattern of three mast cell specific proteases during mouse
RT development.";
RL Mol. Immunol. 44:732-740(2007).
CC -!- FUNCTION: Tryptase is the major neutral protease present in mast cells
CC and is secreted upon the coupled activation-degranulation response of
CC this cell type. Plays a role in innate immunity.
CC {ECO:0000269|PubMed:17456473}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa, but with more
CC restricted specificity than trypsin.; EC=3.4.21.59;
CC -!- SUBUNIT: Homotetramer. The active tetramer is converted to inactive
CC monomers at neutral and acidic pH in the absence of heparin. Low
CC concentrations of inactive monomers become active monomers at pH 6.0 in
CC the presence of heparin. When the concentration of active monomers is
CC higher, they convert to active monomers and then to active tetramers.
CC These monomers are active and functionally distinct from the tetrameric
CC enzyme. In contrast to the hidden active sites in the tetrameric form,
CC the active site of the monomeric form is accessible for macromolecular
CC proteins and inhibitors eg: fibrinogen which is a substrate for the
CC monomeric but not for the tetrameric form. The monomeric form forms a
CC complex with SERPINB6 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Note=Released from the
CC secretory granules upon mast cell activation. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P21845-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P21845-2; Sequence=VSP_005376, VSP_005377;
CC -!- TISSUE SPECIFICITY: During embryogenesis, detected primarily in skin.
CC {ECO:0000269|PubMed:16777228}.
CC -!- DEVELOPMENTAL STAGE: Not detected at early embryonic stages but is
CC abundantly expressed in later stages with a peak at 17.5 dpc-18.5 dpc.
CC {ECO:0000269|PubMed:16777228}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice do not exhibit any visible phenotype
CC when maintained in pathogen-free facilities. However, after peritoneal
CC inoculation of Klebsiella pneumoniae, they cannot efficiently fight the
CC infection and show increased lethality. {ECO:0000269|PubMed:17456473}.
CC -!- MISCELLANEOUS: [Isoform Short]: Probably non functional. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Tryptase subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M57626; AAA39988.1; -; mRNA.
DR EMBL; M57625; AAA39987.1; -; mRNA.
DR EMBL; L31853; AAA39725.1; -; mRNA.
DR EMBL; X78542; CAA55288.1; -; mRNA.
DR EMBL; BC024374; AAH24374.1; -; mRNA.
DR CCDS; CCDS28517.1; -. [P21845-1]
DR PIR; A38654; A38654.
DR PIR; I48685; I48685.
DR AlphaFoldDB; P21845; -.
DR SMR; P21845; -.
DR ComplexPortal; CPX-3806; Tryptase beta-2 complex.
DR STRING; 10090.ENSMUSP00000063499; -.
DR BindingDB; P21845; -.
DR ChEMBL; CHEMBL4523201; -.
DR MEROPS; S01.025; -.
DR GlyGen; P21845; 1 site.
DR iPTMnet; P21845; -.
DR PhosphoSitePlus; P21845; -.
DR MaxQB; P21845; -.
DR PaxDb; P21845; -.
DR PRIDE; P21845; -.
DR ProteomicsDB; 298244; -. [P21845-1]
DR ProteomicsDB; 298245; -. [P21845-2]
DR MGI; MGI:96942; Tpsb2.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; P21845; -.
DR PhylomeDB; P21845; -.
DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR ChiTaRS; Tpsb2; mouse.
DR PRO; PR:P21845; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P21845; protein.
DR GO; GO:0005576; C:extracellular region; TAS:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:1905368; C:peptidase complex; ISO:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0022617; P:extracellular matrix disassembly; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; TAS:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Phosphoprotein; Protease; Reference proteome;
KW Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..21
FT PROPEP 22..31
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:2326280"
FT /id="PRO_0000027490"
FT CHAIN 32..276
FT /note="Tryptase beta-2"
FT /id="PRO_0000027491"
FT DOMAIN 32..273
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 75
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 122
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 225
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT MOD_RES 98
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 60..76
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 156..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 189..212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 221..249
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VAR_SEQ 223..230
FT /note="GDSGGPLV -> PFCIGDDI (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:7959952"
FT /id="VSP_005376"
FT VAR_SEQ 231..276
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:7959952"
FT /id="VSP_005377"
SQ SEQUENCE 276 AA; 30927 MW; 525B2C9A04A72200 CRC64;
MLKRRLLLLW ALSLLASLVY SAPRPANQRV GIVGGHEASE SKWPWQVSLR FKLNYWIHFC
GGSLIHPQWV LTAAHCVGPH IKSPQLFRVQ LREQYLYYGD QLLSLNRIVV HPHYYTAEGG
ADVALLELEV PVNVSTHIHP ISLPPASETF PPGTSCWVTG WGDIDNDEPL PPPYPLKQVK
VPIVENSLCD RKYHTGLYTG DDFPIVHDGM LCAGNTRRDS CQGDSGGPLV CKVKGTWLQA
GVVSWGEGCA QPNKPGIYTR VTYYLDWIHR YVPEHS
