TRYB2_HUMAN
ID TRYB2_HUMAN Reviewed; 275 AA.
AC P20231; D2E6S0; D2E6S2; O95827; Q15664; Q9UQI6; Q9UQI7;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Tryptase beta-2;
DE Short=Tryptase-2;
DE EC=3.4.21.59;
DE AltName: Full=Tryptase II;
DE Flags: Precursor;
GN Name=TPSB2; Synonyms=TPS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (VARIANT BETA-2).
RC TISSUE=Lung;
RX PubMed=2203827; DOI=10.1172/jci114786;
RA Miller J.S., Moxley G., Schwartz L.B.;
RT "Cloning and characterization of a second complementary DNA for human
RT tryptase.";
RL J. Clin. Invest. 86:864-870(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (VARIANT BETA-2).
RX PubMed=8434231; DOI=10.1111/j.1365-3083.1993.tb01757.x;
RA Blom T., Hellman L.;
RT "Characterization of a tryptase mRNA expressed in the human basophil cell
RT line KU812.";
RL Scand. J. Immunol. 37:203-208(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (VARIANTS BETA-2 AND BETA-3).
RX PubMed=9920877; DOI=10.1074/jbc.274.6.3355;
RA Pallaoro M., Fejzo M.S., Shayesteh L., Blount J.L., Caughey G.H.;
RT "Characterization of genes encoding known and novel human mast cell
RT tryptases on chromosome 16p13.3.";
RL J. Biol. Chem. 274:3355-3362(1999).
RN [4]
RP SEQUENCE REVISION.
RA Pallaoro M., Fejzo M.S., Shayesteh L., Blount J.L., Caughey G.H.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (VARIANT BETA-2), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 50-275 (VARIANT BETA-3).
RX PubMed=19748655; DOI=10.1016/j.jaci.2009.07.026;
RA Trivedi N.N., Tamraz B., Chu C., Kwok P.Y., Caughey G.H.;
RT "Human subjects are protected from mast cell tryptase deficiency despite
RT frequent inheritance of loss-of-function mutations.";
RL J. Allergy Clin. Immunol. 124:1099-1105(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (VARIANT BETA-2).
RC TISSUE=Lung;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-275 (VARIANT BETA-2), AND NUCLEOTIDE
RP SEQUENCE [MRNA] OF 9-275 (VARIANT BETA-3).
RX PubMed=2187193; DOI=10.1073/pnas.87.10.3811;
RA Vanderslice P., Ballinger S.M., Tam E.K., Goldstein S.M., Craik C.S.,
RA Caughey G.H.;
RT "Human mast cell tryptase: multiple cDNAs and genes reveal a multigene
RT serine protease family.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:3811-3815(1990).
RN [9]
RP FORMATION OF A COMPLEX WITH SERPINB6.
RX PubMed=14670919; DOI=10.1182/blood-2003-08-2981;
RA Strik M.C., Wolbink A., Wouters D., Bladergroen B.A., Verlaan A.R.,
RA van Houdt I.S., Hijlkema S., Hack C.E., Kummer J.A.;
RT "Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast
RT cells and forms complexes with beta-tryptase monomers.";
RL Blood 103:2710-2717(2004).
RN [10]
RP SUBUNIT.
RX PubMed=18039527; DOI=10.1016/j.intimp.2007.07.007;
RA Fukuoka Y., Schwartz L.B.;
RT "Active monomers of human beta-tryptase have expanded substrate
RT specificities.";
RL Int. Immunopharmacol. 7:1900-1908(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=9521329; DOI=10.1038/32703;
RA Pereira P.J.B., Bergner A., Macedo-Ribeiro S., Huber R., Matschiner G.,
RA Fritz H., Sommerhoff C.P., Bode W.;
RT "Human beta-tryptase is a ring-like tetramer with active sites facing a
RT central pore.";
RL Nature 392:306-311(1998).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS).
RX PubMed=10500112; DOI=10.1073/pnas.96.20.10984;
RA Sommerhoff C.P., Bode W., Pereira P.J.B., Stubbs M.T., Stuerzebecher J.,
RA Piechottka G.P., Matschiner G., Bergner A.;
RT "The structure of the human betaII-tryptase tetramer: fo(u)r better or
RT worse.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10984-10991(1999).
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. May play a role in innate immunity. {ECO:0000250,
CC ECO:0000250|UniProtKB:P21845}.
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. {ECO:0000269|PubMed:18039527}.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Released from the secretory
CC granules upon mast cell activation.
CC -!- POLYMORPHISM: There are two alleles; beta-II and beta-III. The sequence
CC shown corresponds to allele beta-II, as beta-II is the most common
CC allele. There are two forms of the beta-III allele, a short and a long
CC form. The short form (also named frameshifted form) is carried by 23%
CC and 19% of individuals of European and African ancestry but 0% of Asian
CC subjects. In the human genome reference version GRCh38/p12, the allele
CC beta-III short form is represented. {ECO:0000269|PubMed:19748655,
CC ECO:0000269|PubMed:2187193, ECO:0000269|PubMed:2203827,
CC ECO:0000269|PubMed:8434231, ECO:0000269|PubMed:9920877}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Tryptase subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; M37488; AAA51843.1; -; mRNA.
DR EMBL; S55551; AAD13876.1; -; mRNA.
DR EMBL; AF099143; AAD17859.2; -; Genomic_DNA.
DR EMBL; AF099145; AAD17857.1; -; Genomic_DNA.
DR EMBL; AF099146; AAD17858.1; -; Genomic_DNA.
DR EMBL; FJ931117; ACZ98911.1; -; Genomic_DNA.
DR EMBL; FJ931120; ACZ98913.1; -; mRNA.
DR EMBL; AC120498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029356; AAH29356.1; -; mRNA.
DR EMBL; M33492; AAA36779.1; -; mRNA.
DR EMBL; M33493; AAA36780.1; -; mRNA.
DR PIR; B35863; B35863.
DR PIR; C35863; C35863.
DR RefSeq; NP_003285.2; NM_003294.3.
DR RefSeq; NP_077078.5; NM_024164.5.
DR PDB; 1A0L; X-ray; 3.00 A; A/B/C/D=31-274.
DR PDB; 2BM2; X-ray; 2.20 A; A/B/C/D=31-275.
DR PDB; 2FPZ; X-ray; 2.00 A; A/B/C/D=31-275.
DR PDB; 2FS8; X-ray; 2.50 A; A/B/C/D=31-275.
DR PDB; 2FS9; X-ray; 2.30 A; A/B/C/D=31-275.
DR PDB; 2FWW; X-ray; 2.25 A; A/B/C/D=31-275.
DR PDB; 2FXR; X-ray; 2.50 A; A/B/C/D=31-275.
DR PDB; 2GDD; X-ray; 2.35 A; A/B/C/D=31-275.
DR PDB; 2ZA5; X-ray; 2.30 A; A/B/C/D=31-275.
DR PDB; 3V7T; X-ray; 2.09 A; A/B/C/D=31-275.
DR PDBsum; 1A0L; -.
DR PDBsum; 2BM2; -.
DR PDBsum; 2FPZ; -.
DR PDBsum; 2FS8; -.
DR PDBsum; 2FS9; -.
DR PDBsum; 2FWW; -.
DR PDBsum; 2FXR; -.
DR PDBsum; 2GDD; -.
DR PDBsum; 2ZA5; -.
DR PDBsum; 3V7T; -.
DR AlphaFoldDB; P20231; -.
DR SMR; P20231; -.
DR BioGRID; 113029; 15.
DR BioGRID; 122201; 99.
DR ComplexPortal; CPX-3805; Tryptase beta-2 complex.
DR IntAct; P20231; 16.
DR MINT; P20231; -.
DR BindingDB; P20231; -.
DR ChEMBL; CHEMBL4523196; -.
DR DrugBank; DB04654; 4-PIPERIDIN-4-YLBUTANAL.
DR DrugBank; DB04764; [4-(3-AMINOMETHYL-PHENYL)-PIPERIDIN-1-YL]-(5-PHENETHYL- PYRIDIN-3-YL)-METHANONE.
DR DrugBank; DB02018; Amido Phenyl Pyruvic Acid.
DR DrugBank; DB06962; JNJ-27390467.
DR MEROPS; S01.015; -.
DR MEROPS; S01.143; -.
DR GlyConnect; 1862; 10 N-Linked glycans (1 site).
DR GlyGen; P20231; 1 site, 9 N-linked glycans (1 site).
DR iPTMnet; P20231; -.
DR PhosphoSitePlus; P20231; -.
DR BioMuta; TPSB2; -.
DR DMDM; 116242830; -.
DR jPOST; P20231; -.
DR MassIVE; P20231; -.
DR PeptideAtlas; P20231; -.
DR PRIDE; P20231; -.
DR Antibodypedia; 4287; 117 antibodies from 21 providers.
DR DNASU; 7177; -.
DR Ensembl; ENST00000606293.5; ENSP00000482743.1; ENSG00000197253.13.
DR GeneID; 64499; -.
DR GeneID; 7177; -.
DR KEGG; hsa:64499; -.
DR KEGG; hsa:7177; -.
DR MANE-Select; ENST00000338844.8; ENSP00000343577.3; NM_003294.4; NP_003285.2.
DR UCSC; uc032dnv.1; human.
DR CTD; 64499; -.
DR CTD; 7177; -.
DR DisGeNET; 64499; -.
DR DisGeNET; 7177; -.
DR GeneCards; TPSB2; -.
DR HGNC; HGNC:14120; TPSB2.
DR HPA; ENSG00000197253; Low tissue specificity.
DR MIM; 191081; gene.
DR neXtProt; NX_P20231; -.
DR OpenTargets; ENSG00000172236; -.
DR PharmGKB; PA36698; -.
DR VEuPathDB; HostDB:ENSG00000197253; -.
DR HOGENOM; CLU_006842_13_1_1; -.
DR InParanoid; P20231; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P20231; -.
DR BRENDA; 3.4.21.59; 2681.
DR PathwayCommons; P20231; -.
DR SignaLink; P20231; -.
DR BioGRID-ORCS; 64499; 2 hits in 168 CRISPR screens.
DR BioGRID-ORCS; 7177; 14 hits in 1026 CRISPR screens.
DR ChiTaRS; TPSB2; human.
DR EvolutionaryTrace; P20231; -.
DR GeneWiki; TPSAB1; -.
DR GeneWiki; TPSB2; -.
DR Pharos; P20231; Tchem.
DR PRO; PR:P20231; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P20231; protein.
DR Bgee; ENSG00000197253; Expressed in mucosa of stomach and 86 other tissues.
DR ExpressionAtlas; P20231; baseline and differential.
DR Genevisible; P20231; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:1905368; C:peptidase complex; IPI:ComplexPortal.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal.
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 3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Phosphoprotein;
KW Protease; Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..30
FT /note="Activation peptide"
FT /id="PRO_0000027481"
FT CHAIN 31..275
FT /note="Tryptase beta-2"
FT /id="PRO_0000027482"
FT DOMAIN 31..272
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 74
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 121
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 224
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT MOD_RES 97
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P21845"
FT CARBOHYD 233
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 59..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 155..230
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 188..211
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 220..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VARIANT 51..53
FT /note="HGP -> RDR (beta-III short form and long form)"
FT /evidence="ECO:0000269|PubMed:19748655,
FT ECO:0000269|PubMed:2187193"
FT /id="VAR_012104"
FT CONFLICT 132
FT /note="N -> K (in Ref. 1; AAA51843, 2; AAD13876, 3;
FT AAD17858, 5; ACZ98911, 7; AAH29356 and 8; AAA36779/
FT AAA36780)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="T -> A (in Ref. 5; ACZ98913)"
FT /evidence="ECO:0000305"
FT CONFLICT 240
FT /note="G -> D (in Ref. 5; ACZ98913)"
FT /evidence="ECO:0000305"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:3V7T"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:2BM2"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 56..65
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:2FPZ"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:2FPZ"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:2FPZ"
FT TURN 95..98
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 102..109
FT /evidence="ECO:0007829|PDB:2FPZ"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 123..129
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 176..183
FT /evidence="ECO:0007829|PDB:2FPZ"
FT HELIX 185..193
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:2FPZ"
FT TURN 221..225
FT /evidence="ECO:0007829|PDB:2ZA5"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 235..244
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:2FPZ"
FT STRAND 255..259
FT /evidence="ECO:0007829|PDB:2FPZ"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:2FPZ"
FT HELIX 264..267
FT /evidence="ECO:0007829|PDB:2FPZ"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:2FPZ"
SQ SEQUENCE 275 AA; 30515 MW; ADC48FDC51F37112 CRC64;
MLNLLLLALP VLASRAYAAP APGQALQRVG IVGGQEAPRS KWPWQVSLRV HGPYWMHFCG
GSLIHPQWVL TAAHCVGPDV KDLAALRVQL REQHLYYQDQ LLPVSRIIVH PQFYTAQIGA
DIALLELEEP VNVSSHVHTV TLPPASETFP PGMPCWVTGW GDVDNDERLP PPFPLKQVKV
PIMENHICDA KYHLGAYTGD DVRIVRDDML CAGNTRRDSC QGDSGGPLVC KVNGTWLQAG
VVSWGEGCAQ PNRPGIYTRV TYYLDWIHHY VPKKP
