ID   TRY3_HUMAN              Reviewed;         304 AA.
AC   P35030; A8CED1; A8CED3; A9Z1Y4; E7ES07; F8W7P3; P15951; Q15665; Q5VXV0;
AC   Q6ISJ4; Q9UQV3;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2008, sequence version 2.
DT   27-MAR-2024, entry version 218.
DE   RecName: Full=Trypsin-3;
DE            EC=3.4.21.4 {ECO:0000269|PubMed:11827488, ECO:0000269|PubMed:14507909, ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:27810896, ECO:0000269|PubMed:6698368, ECO:0000269|PubMed:9099703};
DE   AltName: Full=Brain trypsinogen {ECO:0000303|PubMed:8294000};
DE   AltName: Full=Mesotrypsin {ECO:0000303|PubMed:14507909};
DE   AltName: Full=Mesotrypsinogen {ECO:0000303|PubMed:9099703};
DE   AltName: Full=Serine protease 3;
DE   AltName: Full=Serine protease 4;
DE   AltName: Full=Trypsin III;
DE   AltName: Full=Trypsin IV {ECO:0000303|PubMed:8294000};
DE   Flags: Precursor;
GN   Name=PRSS3; Synonyms=PRSS4, TRY3, TRY4;
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] (ISOFORMS 1 AND 2), VARIANT ALA-188, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=8294000; DOI=10.1016/0378-1119(93)90460-k;
RA   Wiegand U., Corbach S., Minn A., Kang J., Mueller-Hill B.;
RT   "Cloning of the cDNA encoding human brain trypsinogen and characterization
RT   of its product.";
RL   Gene 136:167-175(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND VARIANTS ALA-188 AND CYS-232.
RC   TISSUE=Pancreas;
RX   PubMed=2326201; DOI=10.1093/nar/18.6.1631;
RA   Tani T., Kawashima I., Mita K., Takiguchi Y.;
RT   "Nucleotide sequence of the human pancreatic trypsinogen III cDNA.";
RL   Nucleic Acids Res. 18:1631-1631(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, CATALYTIC ACTIVITY,
RP   ACTIVITY REGULATION, AND VARIANT ALA-188.
RC   TISSUE=Pancreas;
RX   PubMed=9099703; DOI=10.1074/jbc.272.16.10573;
RA   Nyaruhucha C.N., Kito M., Fukuoka S.I.;
RT   "Identification and expression of the cDNA-encoding human
RT   mesotrypsin(ogen), an isoform of trypsin with inhibitor resistance.";
RL   J. Biol. Chem. 272:10573-10578(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), AND VARIANT ALA-188.
RA   Rowen L., Trask B., Boysen C., Qin S., Wang K., Ahearn M.E., Hood L.;
RT   "Sequence of a large duplication from human chromosome 7 to chromosome 9
RT   containing a portion of the T cell receptor beta locus and trypsinogen
RT   locus.";
RL   Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 5), AND VARIANT ALA-188.
RX   PubMed=19924134; DOI=10.1038/jid.2009.364;
RA   Nakanishi J., Yamamoto M., Koyama J., Sato J., Hibino T.;
RT   "Keratinocytes synthesize enteropeptidase and multiple forms of trypsinogen
RT   during terminal differentiation.";
RL   J. Invest. Dermatol. 130:944-952(2010).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-188.
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ALA-188.
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   [9]
RP   TISSUE SPECIFICITY.
RX   PubMed=12021776; DOI=10.1038/ni797;
RA   Ghosh D., Porter E., Shen B., Lee S.K., Wilk D., Drazba J., Yadav S.P.,
RA   Crabb J.W., Ganz T., Bevins C.L.;
RT   "Paneth cell trypsin is the processing enzyme for human defensin-5.";
RL   Nat. Immunol. 3:583-590(2002).
RN   [10]
RP   CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP   LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=6698368;
RA   Rinderknecht H., Renner I.G., Abramson S.B., Carmack C.;
RT   "Mesotrypsin: a new inhibitor-resistant protease from a zymogen in human
RT   pancreatic tissue and fluid.";
RL   Gastroenterology 86:681-692(1984).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX   PubMed=14507909; DOI=10.1074/jbc.m310301200;
RA   Szmola R., Kukor Z., Sahin-Toth M.;
RT   "Human mesotrypsin is a unique digestive protease specialized for the
RT   degradation of trypsin inhibitors.";
RL   J. Biol. Chem. 278:48580-48589(2003).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 81-304 (ISOFORM A) IN COMPLEX WITH
RP   CALCIUM IONS, COFACTOR, CATALYTIC ACTIVITY, AND DISULFIDE BONDS.
RX   PubMed=11827488; DOI=10.1006/jmbi.2001.5305;
RA   Katona G., Berglund G.I., Hajdu J., Graf L., Szilagyi L.;
RT   "Crystal structure reveals basis for the inhibitor resistance of human
RT   brain trypsin.";
RL   J. Mol. Biol. 315:1209-1218(2002).
RN   [13] {ECO:0007744|PDB:2R9P}
RP   X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 81-304 OF MUTANT ALA-257,
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND DISULFIDE BONDS.
RX   PubMed=18077447; DOI=10.1074/jbc.m708268200;
RA   Salameh M.A., Soares A.S., Hockla A., Radisky E.S.;
RT   "Structural basis for accelerated cleavage of bovine pancreatic trypsin
RT   inhibitor (BPTI) by human mesotrypsin.";
RL   J. Biol. Chem. 283:4115-4123(2008).
RN   [14] {ECO:0007744|PDB:4U30, ECO:0007744|PDB:4U32}
RP   X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 81-304 IN COMPLEX WITH CALCIUM,
RP   CATALYTIC ACTIVITY, FUNCTION, COFACTOR, AND DISULFIDE BONDS.
RX   PubMed=25301953; DOI=10.1074/jbc.m114.609560;
RA   Pendlebury D., Wang R., Henin R.D., Hockla A., Soares A.S., Madden B.J.,
RA   Kazanov M.D., Radisky E.S.;
RT   "Sequence and conformational specificity in substrate recognition: several
RT   human Kunitz protease inhibitor domains are specific substrates of
RT   mesotrypsin.";
RL   J. Biol. Chem. 289:32783-32797(2014).
RN   [15] {ECO:0007744|PDB:5JBT}
RP   X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 81-304 OF MUTANT ALA-257 IN
RP   COMPLEX WITH CALCIUM, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DISULFIDE
RP   BONDS, ACTIVE SITE, AND MUTAGENESIS OF SER-257.
RX   PubMed=27810896; DOI=10.1074/jbc.m116.758417;
RA   Kayode O., Wang R., Pendlebury D.F., Cohen I., Henin R.D., Hockla A.,
RA   Soares A.S., Papo N., Caulfield T.R., Radisky E.S.;
RT   "An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate
RT   Conformational Dynamics in Trypsin Proteolysis.";
RL   J. Biol. Chem. 291:26304-26319(2016).
CC   -!- FUNCTION: Digestive protease that cleaves proteins preferentially after
CC       an Arg residue and has proteolytic activity toward Kunitz-type trypsin
CC       inhibitors. {ECO:0000269|PubMed:11827488, ECO:0000269|PubMed:14507909,
CC       ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953,
CC       ECO:0000269|PubMed:27810896, ECO:0000269|PubMed:9099703}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.; EC=3.4.21.4;
CC         Evidence={ECO:0000269|PubMed:11827488, ECO:0000269|PubMed:14507909,
CC         ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953,
CC         ECO:0000269|PubMed:27810896, ECO:0000269|PubMed:6698368,
CC         ECO:0000269|PubMed:9099703};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000269|PubMed:14507909, ECO:0000269|PubMed:6698368};
CC       Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:11827488,
CC       ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:27810896};
CC   -!- ACTIVITY REGULATION: Not inhibited by Kunitz-type trypsin inhibitors.
CC       {ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:9099703}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 8.5. {ECO:0000269|PubMed:6698368};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:6698368}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1; Synonyms=A;
CC         IsoId=P35030-1; Sequence=Displayed;
CC       Name=2; Synonyms=B;
CC         IsoId=P35030-2; Sequence=VSP_042074;
CC       Name=3; Synonyms=C;
CC         IsoId=P35030-3; Sequence=VSP_005410;
CC       Name=4; Synonyms=D;
CC         IsoId=P35030-4; Sequence=VSP_005409;
CC       Name=5; Synonyms=E;
CC         IsoId=P35030-5; Sequence=VSP_053779;
CC   -!- TISSUE SPECIFICITY: Detected in pancreas and pancreatic fluid (at
CC       protein level) (PubMed:6698368). Expressed in pancreas and brain
CC       (PubMed:8294000). Detected in ileum (PubMed:12021776).
CC       {ECO:0000269|PubMed:12021776, ECO:0000269|PubMed:6698368,
CC       ECO:0000269|PubMed:8294000}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00274}.
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DR   EMBL; X72781; CAB58178.1; -; mRNA.
DR   EMBL; X71345; CAA50484.1; -; mRNA.
DR   EMBL; X15505; CAA33527.1; -; mRNA.
DR   EMBL; D45417; BAA08257.1; -; mRNA.
DR   EMBL; AF029308; AAC13322.1; -; Genomic_DNA.
DR   EMBL; AB298285; BAF80324.1; -; mRNA.
DR   EMBL; AB298286; BAF80325.1; -; mRNA.
DR   EMBL; AL139113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL356489; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL358573; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471071; EAW58482.1; -; Genomic_DNA.
DR   EMBL; CH471071; EAW58484.1; -; Genomic_DNA.
DR   EMBL; BC069476; AAH69476.1; -; mRNA.
DR   EMBL; BC069494; AAH69494.1; -; mRNA.
DR   CCDS; CCDS56570.1; -. [P35030-5]
DR   CCDS; CCDS6545.1; -. [P35030-3]
DR   PIR; S12764; S12764.
DR   PIR; S33496; S33496.
DR   RefSeq; NP_001184026.2; NM_001197097.2. [P35030-4]
DR   RefSeq; NP_001184027.1; NM_001197098.1.
DR   RefSeq; NP_002762.2; NM_002771.3. [P35030-3]
DR   RefSeq; NP_031369.2; NM_007343.3.
DR   PDB; 1H4W; X-ray; 1.70 A; A=81-304.
DR   PDB; 2R9P; X-ray; 1.40 A; A/B/C/D=81-304.
DR   PDB; 3L33; X-ray; 2.48 A; A/B/C/D=81-304.
DR   PDB; 3L3T; X-ray; 2.38 A; A/B/C/D=81-304.
DR   PDB; 3P92; X-ray; 1.60 A; A=81-304.
DR   PDB; 3P95; X-ray; 1.30 A; A=81-304.
DR   PDB; 4DG4; X-ray; 1.40 A; A/B/D/G=81-304.
DR   PDB; 4U30; X-ray; 2.50 A; A/B/C/D=81-304.
DR   PDB; 4U32; X-ray; 1.65 A; A=81-304.
DR   PDB; 5C67; X-ray; 1.83 A; A/B=81-304.
DR   PDB; 5JBT; X-ray; 1.40 A; A=81-304.
DR   PDB; 5TP0; X-ray; 1.25 A; A=81-304.
DR   PDB; 6BX8; X-ray; 1.98 A; A/C/E/G=81-304.
DR   PDB; 6GFI; X-ray; 2.30 A; A/B=81-304.
DR   PDBsum; 1H4W; -.
DR   PDBsum; 2R9P; -.
DR   PDBsum; 3L33; -.
DR   PDBsum; 3L3T; -.
DR   PDBsum; 3P92; -.
DR   PDBsum; 3P95; -.
DR   PDBsum; 4DG4; -.
DR   PDBsum; 4U30; -.
DR   PDBsum; 4U32; -.
DR   PDBsum; 5C67; -.
DR   PDBsum; 5JBT; -.
DR   PDBsum; 5TP0; -.
DR   PDBsum; 6BX8; -.
DR   PDBsum; 6GFI; -.
DR   AlphaFoldDB; P35030; -.
DR   SMR; P35030; -.
DR   BioGRID; 111628; 52.
DR   IntAct; P35030; 26.
DR   MINT; P35030; -.
DR   STRING; 9606.ENSP00000354280; -.
DR   BindingDB; P35030; -.
DR   ChEMBL; CHEMBL4551; -.
DR   DrugBank; DB04369; 1,3,2-Dioxaborolan-2-Ol.
DR   DrugBank; DB02308; 4-(1,3,2-Dioxaborolan-2-Yloxy)Butan-1-Aminium.
DR   DrugBank; DB02585; 4-(Hydroxymethyl)Benzamidine.
DR   DrugBank; DB02541; 4-Hydroxybutan-1-Aminium.
DR   DrugBank; DB04109; [4-(1,3,2-Dioxaborolan-2-Yloxy)Methyl]Benzamidine.
DR   DrugBank; DB03127; Benzamidine.
DR   DrugBank; DB03129; Diamino-N-[3-(1,3,2-dioxaborolan-2-yloxy)propyl]methaniminium.
DR   DrugBank; DB03637; Guanidine-3-propanol.
DR   DrugCentral; P35030; -.
DR   GuidetoPHARMACOLOGY; 2399; -.
DR   MEROPS; S01.174; -.
DR   GlyGen; P35030; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P35030; -.
DR   PhosphoSitePlus; P35030; -.
DR   BioMuta; PRSS3; -.
DR   DMDM; 209572698; -.
DR   EPD; P35030; -.
DR   jPOST; P35030; -.
DR   MassIVE; P35030; -.
DR   MaxQB; P35030; -.
DR   PaxDb; 9606-ENSP00000354280; -.
DR   PeptideAtlas; P35030; -.
DR   ProteomicsDB; 29982; -.
DR   ProteomicsDB; 54972; -. [P35030-1]
DR   ProteomicsDB; 54973; -. [P35030-2]
DR   ProteomicsDB; 54974; -. [P35030-3]
DR   ProteomicsDB; 54975; -. [P35030-4]
DR   Antibodypedia; 11047; 382 antibodies from 29 providers.
DR   DNASU; 5646; -.
DR   Ensembl; ENST00000379405.4; ENSP00000368715.3; ENSG00000010438.17. [P35030-3]
DR   Ensembl; ENST00000429677.8; ENSP00000401828.3; ENSG00000010438.17. [P35030-5]
DR   GeneID; 5646; -.
DR   KEGG; hsa:5646; -.
DR   MANE-Select; ENST00000379405.4; ENSP00000368715.3; NM_002771.4; NP_002762.3. [P35030-3]
DR   UCSC; uc003zti.5; human. [P35030-1]
DR   AGR; HGNC:9486; -.
DR   CTD; 5646; -.
DR   DisGeNET; 5646; -.
DR   GeneCards; PRSS3; -.
DR   HGNC; HGNC:9486; PRSS3.
DR   HPA; ENSG00000010438; Tissue enriched (pancreas).
DR   MIM; 613578; gene.
DR   neXtProt; NX_P35030; -.
DR   OpenTargets; ENSG00000010438; -.
DR   PharmGKB; PA33838; -.
DR   VEuPathDB; HostDB:ENSG00000010438; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT01050000244883; -.
DR   HOGENOM; CLU_006842_7_1_1; -.
DR   InParanoid; P35030; -.
DR   OMA; ECSEAYP; -.
DR   OrthoDB; 4629979at2759; -.
DR   PhylomeDB; P35030; -.
DR   TreeFam; TF331065; -.
DR   PathwayCommons; P35030; -.
DR   Reactome; R-HSA-1462054; Alpha-defensins.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   Reactome; R-HSA-6803157; Antimicrobial peptides.
DR   Reactome; R-HSA-9758881; Uptake of dietary cobalamins into enterocytes.
DR   SignaLink; P35030; -.
DR   SIGNOR; P35030; -.
DR   BioGRID-ORCS; 5646; 19 hits in 1118 CRISPR screens.
DR   ChiTaRS; PRSS3; human.
DR   EvolutionaryTrace; P35030; -.
DR   GenomeRNAi; 5646; -.
DR   Pharos; P35030; Tchem.
DR   PRO; PR:P35030; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; P35030; Protein.
DR   Bgee; ENSG00000010438; Expressed in body of pancreas and 165 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR   GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProtKB.
DR   GO; GO:0019730; P:antimicrobial humoral response; TAS:Reactome.
DR   GO; GO:0007586; P:digestion; TAS:UniProtKB.
DR   GO; GO:0043542; P:endothelial cell migration; IMP:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR   GO; GO:0031638; P:zymogen activation; IDA:UniProtKB.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 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   PANTHER; PTHR24264:SF48; TRYPSIN-3; 1.
DR   PANTHER; PTHR24264; TRYPSIN-RELATED; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   Genevisible; P35030; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Calcium; Digestion; Disulfide bond;
KW   Hydrolase; Metal-binding; Protease; Reference proteome; Secreted;
KW   Serine protease; Signal; Sulfation; Zymogen.
FT   SIGNAL          1..?
FT                   /evidence="ECO:0000255"
FT   PROPEP          ?..80
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028201"
FT   CHAIN           81..304
FT                   /note="Trypsin-3"
FT                   /id="PRO_0000028202"
FT   DOMAIN          81..301
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        120
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT                   ECO:0000305|PubMed:27810896"
FT   ACT_SITE        164
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT                   ECO:0000305|PubMed:27810896"
FT   ACT_SITE        257
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT                   ECO:0000305|PubMed:27810896"
FT   BINDING         132
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:27810896,
FT                   ECO:0007744|PDB:1H4W, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4U30,
FT                   ECO:0007744|PDB:4U32, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   BINDING         134
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:27810896,
FT                   ECO:0007744|PDB:1H4W, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4U30,
FT                   ECO:0007744|PDB:4U32, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   BINDING         137
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:27810896,
FT                   ECO:0007744|PDB:1H4W, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4U30,
FT                   ECO:0007744|PDB:4U32, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   BINDING         139
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:27810896,
FT                   ECO:0007744|PDB:1H4W, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4U30,
FT                   ECO:0007744|PDB:4U32, ECO:0007744|PDB:5JBT"
FT   BINDING         142
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:27810896,
FT                   ECO:0007744|PDB:1H4W, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4U32,
FT                   ECO:0007744|PDB:5JBT, ECO:0007744|PDB:5TP0"
FT   SITE            251
FT                   /note="Required for specificity"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         211
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000250"
FT   DISULFID        87..217
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953,
FT                   ECO:0000269|PubMed:27810896, ECO:0007744|PDB:1H4W,
FT                   ECO:0007744|PDB:2R9P, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4DG4,
FT                   ECO:0007744|PDB:4U30, ECO:0007744|PDB:4U32,
FT                   ECO:0007744|PDB:5C67, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   DISULFID        105..121
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953,
FT                   ECO:0000269|PubMed:27810896, ECO:0007744|PDB:1H4W,
FT                   ECO:0007744|PDB:2R9P, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4DG4,
FT                   ECO:0007744|PDB:4U30, ECO:0007744|PDB:4U32,
FT                   ECO:0007744|PDB:5C67, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   DISULFID        196..263
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953,
FT                   ECO:0000269|PubMed:27810896, ECO:0007744|PDB:1H4W,
FT                   ECO:0007744|PDB:2R9P, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4DG4,
FT                   ECO:0007744|PDB:4U30, ECO:0007744|PDB:4U32,
FT                   ECO:0007744|PDB:5C67, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   DISULFID        228..242
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953,
FT                   ECO:0000269|PubMed:27810896, ECO:0007744|PDB:1H4W,
FT                   ECO:0007744|PDB:2R9P, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4DG4,
FT                   ECO:0007744|PDB:4U30, ECO:0007744|PDB:4U32,
FT                   ECO:0007744|PDB:5C67, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   DISULFID        253..277
FT                   /evidence="ECO:0000269|PubMed:11827488,
FT                   ECO:0000269|PubMed:18077447, ECO:0000269|PubMed:25301953,
FT                   ECO:0000269|PubMed:27810896, ECO:0007744|PDB:1H4W,
FT                   ECO:0007744|PDB:2R9P, ECO:0007744|PDB:3L33,
FT                   ECO:0007744|PDB:3L3T, ECO:0007744|PDB:3P92,
FT                   ECO:0007744|PDB:3P95, ECO:0007744|PDB:4DG4,
FT                   ECO:0007744|PDB:4U30, ECO:0007744|PDB:4U32,
FT                   ECO:0007744|PDB:5C67, ECO:0007744|PDB:5JBT,
FT                   ECO:0007744|PDB:5TP0"
FT   VAR_SEQ         1..71
FT                   /note="MCGPDDRCPARWPGPGRAVKCGKGLAAARPGRVERGGAQRGGAGLELHPLLG
FT                   GRTWRAARDADGCEALGTV -> MHMRETSGFTLKKGRSAPLVFHPPDALI (in
FT                   isoform 4)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_005409"
FT   VAR_SEQ         1..70
FT                   /note="MCGPDDRCPARWPGPGRAVKCGKGLAAARPGRVERGGAQRGGAGLELHPLLG
FT                   GRTWRAARDADGCEALGT -> MNPFLILAFVGAA (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:2326201, ECO:0000303|PubMed:9099703"
FT                   /id="VSP_005410"
FT   VAR_SEQ         1..70
FT                   /note="MCGPDDRCPARWPGPGRAVKCGKGLAAARPGRVERGGAQRGGAGLELHPLLG
FT                   GRTWRAARDADGCEALGT -> MGPAGE (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:19924134"
FT                   /id="VSP_053779"
FT   VAR_SEQ         1..45
FT                   /note="MCGPDDRCPARWPGPGRAVKCGKGLAAARPGRVERGGAQRGGAGL -> M
FT                   (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:8294000"
FT                   /id="VSP_042074"
FT   VARIANT         174
FT                   /note="A -> V (in dbSNP:rs11547028)"
FT                   /id="VAR_067459"
FT   VARIANT         188
FT                   /note="T -> A (in dbSNP:rs855581)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:19924134, ECO:0000269|PubMed:2326201,
FT                   ECO:0000269|PubMed:8294000, ECO:0000269|PubMed:9099703,
FT                   ECO:0000269|Ref.4, ECO:0000269|Ref.7"
FT                   /id="VAR_046794"
FT   VARIANT         224
FT                   /note="T -> S (in dbSNP:rs1063273)"
FT                   /id="VAR_059788"
FT   VARIANT         232
FT                   /note="Y -> C (in dbSNP:rs1048379)"
FT                   /evidence="ECO:0000269|PubMed:2326201"
FT                   /id="VAR_046795"
FT   MUTAGEN         257
FT                   /note="S->A: Loss of catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:27810896"
FT   CONFLICT        89
FT                   /note="Missing (in Ref. 1; CAA50484)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        224..225
FT                   /note="TQ -> RE (in Ref. 2; CAA33527)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        253..254
FT                   /note="CQ -> WK (in Ref. 2; CAA33527)"
FT                   /evidence="ECO:0000305"
FT   STRAND          89..91
FT                   /evidence="ECO:0007829|PDB:3L3T"
FT   STRAND          95..111
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          114..117
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   HELIX           119..121
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          127..131
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          133..137
FT                   /evidence="ECO:0007829|PDB:2R9P"
FT   STRAND          143..152
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   TURN            158..160
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          166..172
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          177..180
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          195..201
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          206..208
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          216..222
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   HELIX           225..231
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   TURN            233..235
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          240..244
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          246..249
FT                   /evidence="ECO:0007829|PDB:3P92"
FT   TURN            254..258
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          260..263
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          266..273
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          275..278
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   STRAND          284..288
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   HELIX           289..292
FT                   /evidence="ECO:0007829|PDB:5TP0"
FT   HELIX           293..302
FT                   /evidence="ECO:0007829|PDB:5TP0"
SQ   SEQUENCE   304 AA;  32529 MW;  4C4303C310B7BFFC CRC64;
     MCGPDDRCPA RWPGPGRAVK CGKGLAAARP GRVERGGAQR GGAGLELHPL LGGRTWRAAR
     DADGCEALGT VAVPFDDDDK IVGGYTCEEN SLPYQVSLNS GSHFCGGSLI SEQWVVSAAH
     CYKTRIQVRL GEHNIKVLEG NEQFINAAKI IRHPKYNRDT LDNDIMLIKL SSPAVINARV
     STISLPTTPP AAGTECLISG WGNTLSFGAD YPDELKCLDA PVLTQAECKA SYPGKITNSM
     FCVGFLEGGK DSCQRDSGGP VVCNGQLQGV VSWGHGCAWK NRPGVYTKVY NYVDWIKDTI
     AANS
//