TRY3_HUMAN
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 03-AUG-2022, entry version 209.
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; CCDS56571.1; -. [P35030-4]
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; 48.
DR IntAct; P35030; 24.
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 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; P35030; -.
DR PeptideAtlas; P35030; -.
DR PRIDE; 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; 350 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 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; HAAKIIC; -.
DR OrthoDB; 1314811at2759; -.
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 1043 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 163 other tissues.
DR Genevisible; P35030; HS.
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; -; 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 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.
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
