ID   TRY2_HUMAN              Reviewed;         247 AA.
AC   P07478;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   27-MAR-2024, entry version 206.
DE   RecName: Full=Trypsin-2;
DE            EC=3.4.21.4;
DE   AltName: Full=Anionic trypsinogen;
DE   AltName: Full=Serine protease 2;
DE   AltName: Full=Trypsin II;
DE   Flags: Precursor;
GN   Name=PRSS2; Synonyms=TRY2, TRYP2;
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].
RX   PubMed=3011602; DOI=10.1016/0378-1119(86)90111-3;
RA   Emi M., Nakamura Y., Ogawa M., Yamamoto T., Nishide T., Mori T.,
RA   Matsubara K.;
RT   "Cloning, characterization and nucleotide sequences of two cDNAs encoding
RT   human pancreatic trypsinogens.";
RL   Gene 41:305-310(1986).
RN   [2]
RP   PROTEIN SEQUENCE OF 16-49.
RX   PubMed=2598466; DOI=10.1016/0009-8981(89)90254-4;
RA   Kimland M., Russick C., Marks W.H., Borgstroem A.;
RT   "Immunoreactive anionic and cationic trypsin in human serum.";
RL   Clin. Chim. Acta 184:31-46(1989).
RN   [3]
RP   FUNCTION, AND 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   [4]
RP   SULFATION.
RX   PubMed=17087724; DOI=10.1111/j.1742-4658.2006.05501.x;
RA   Sahin-Toth M., Kukor Z., Nemoda Z.;
RT   "Human cationic trypsinogen is sulfated on Tyr154.";
RL   FEBS J. 273:5044-5050(2006).
RN   [5]
RP   SULFATION AT TYR-154.
RX   PubMed=25010489; DOI=10.1371/journal.pone.0102063;
RA   Szabo A., Salameh M.A., Ludwig M., Radisky E.S., Sahin-Toth M.;
RT   "Tyrosine sulfation of human trypsin steers S2' subsite selectivity towards
RT   basic amino acids.";
RL   PLoS ONE 9:E102063-E102063(2014).
RN   [6]
RP   VARIANT HIS-153, AND CHARACTERIZATION OF VARIANT HIS-153.
RX   PubMed=18986305; DOI=10.1042/bj20081848;
RA   Ronai Z., Witt H., Rickards O., Destro-Bisol G., Bradbury A.R.,
RA   Sahin-Toth M.;
RT   "A common African polymorphism abolishes tyrosine sulfation of human
RT   anionic trypsinogen (PRSS2).";
RL   Biochem. J. 418:155-161(2009).
CC   -!- FUNCTION: In the ileum, may be involved in defensin processing,
CC       including DEFA5. {ECO:0000269|PubMed:12021776}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.; EC=3.4.21.4;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC       Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC   -!- TISSUE SPECIFICITY: Expressed in Paneth cells, at the base of small
CC       intestinal crypts. {ECO:0000269|PubMed:12021776}.
CC   -!- PTM: Sulfated on tyrosine. {ECO:0000269|PubMed:17087724}.
CC   -!- PTM: Sulfation at Tyr-154 increases selectivity towards basic versus
CC       apolar residues at the P2' position of inhibitors that bind in a
CC       substrate-like fashion. Although the increase in selectivity is
CC       relatively small, it may facilitate digestion of a broader range of
CC       dietary proteins. {ECO:0000269|PubMed:25010489}.
CC   -!- POLYMORPHISM: His-153 variation is a common polymorphism in African
CC       populations with a minor allele frequency of 9.2%, it eliminates
CC       sulfation at Tyr-154, with no consequences on digestive physiology.
CC       {ECO:0000269|PubMed:18986305}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC       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; M27602; AAA61232.1; -; mRNA.
DR   CCDS; CCDS83236.1; -.
DR   PIR; B25852; B25852.
DR   RefSeq; NP_002761.1; NM_002770.3.
DR   AlphaFoldDB; P07478; -.
DR   SMR; P07478; -.
DR   BioGRID; 111627; 41.
DR   IntAct; P07478; 14.
DR   MINT; P07478; -.
DR   STRING; 9606.ENSP00000488437; -.
DR   BindingDB; P07478; -.
DR   ChEMBL; CHEMBL3159; -.
DR   DrugBank; DB04410; 3-Phenylpropylamine.
DR   DrugBank; DB03127; Benzamidine.
DR   DrugBank; DB02464; Benzylamine.
DR   DrugBank; DB01805; Monoisopropylphosphorylserine.
DR   DrugBank; DB01973; O-Benzylsulfonyl-Serine.
DR   DrugBank; DB04325; Phenethylamine.
DR   DrugBank; DB03976; Phosphorylisopropane.
DR   DrugCentral; P07478; -.
DR   MEROPS; S01.258; -.
DR   GlyGen; P07478; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P07478; -.
DR   PhosphoSitePlus; P07478; -.
DR   BioMuta; PRSS2; -.
DR   DMDM; 136413; -.
DR   jPOST; P07478; -.
DR   MassIVE; P07478; -.
DR   PaxDb; 9606-ENSP00000485444; -.
DR   PeptideAtlas; P07478; -.
DR   ProteomicsDB; 52007; -.
DR   TopDownProteomics; P07478; -.
DR   Antibodypedia; 74627; 189 antibodies from 21 providers.
DR   DNASU; 5645; -.
DR   Ensembl; ENST00000539842.6; ENSP00000488338.1; ENSG00000275896.7.
DR   Ensembl; ENST00000632112.1; ENSP00000487952.1; ENSG00000282049.1.
DR   GeneID; 5645; -.
DR   KEGG; hsa:5645; -.
DR   MANE-Select; ENST00000539842.6; ENSP00000488338.1; NM_002770.4; NP_002761.1.
DR   AGR; HGNC:9483; -.
DR   CTD; 5645; -.
DR   DisGeNET; 5645; -.
DR   GeneCards; PRSS2; -.
DR   HGNC; HGNC:9483; PRSS2.
DR   HPA; ENSG00000275896; Tissue enriched (pancreas).
DR   MalaCards; PRSS2; -.
DR   MIM; 601564; gene.
DR   neXtProt; NX_P07478; -.
DR   OpenTargets; ENSG00000275896; -.
DR   Orphanet; 676; Hereditary chronic pancreatitis.
DR   PharmGKB; PA33833; -.
DR   VEuPathDB; HostDB:ENSG00000275896; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT01050000244883; -.
DR   InParanoid; P07478; -.
DR   OrthoDB; 4629979at2759; -.
DR   PhylomeDB; P07478; -.
DR   PathwayCommons; P07478; -.
DR   Reactome; R-HSA-1442490; Collagen degradation.
DR   Reactome; R-HSA-1462054; Alpha-defensins.
DR   Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   Reactome; R-HSA-6803157; Antimicrobial peptides.
DR   SignaLink; P07478; -.
DR   SIGNOR; P07478; -.
DR   BioGRID-ORCS; 5645; 6 hits in 217 CRISPR screens.
DR   ChiTaRS; PRSS2; human.
DR   GenomeRNAi; 5645; -.
DR   Pharos; P07478; Tchem.
DR   PRO; PR:P07478; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P07478; Protein.
DR   Bgee; ENSG00000275896; Expressed in body of pancreas and 89 other cell types or tissues.
DR   ExpressionAtlas; P07478; baseline and differential.
DR   GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR   GO; GO:0031012; C:extracellular matrix; TAS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IMP:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR   GO; GO:0004222; F:metalloendopeptidase activity; TAS:Reactome.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008236; F:serine-type peptidase activity; TAS:Reactome.
DR   GO; GO:0019730; P:antimicrobial humoral response; TAS:Reactome.
DR   GO; GO:0030574; P:collagen catabolic process; IDA:UniProtKB.
DR   GO; GO:0007586; P:digestion; IEA:UniProtKB-KW.
DR   GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; TAS:UniProtKB.
DR   GO; GO:0030307; P:positive regulation of cell growth; TAS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; 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   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24264:SF57; TRYPSIN-2; 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   PROSITE; PS00135; TRYPSIN_SER; 1.
DR   Genevisible; P07478; HS.
PE   1: Evidence at protein level;
KW   Calcium; Digestion; Direct protein sequencing; Disulfide bond; Hydrolase;
KW   Metal-binding; Protease; Reference proteome; Secreted; Serine protease;
KW   Signal; Sulfation; Zymogen.
FT   SIGNAL          1..15
FT                   /evidence="ECO:0000269|PubMed:2598466"
FT   PROPEP          16..23
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028199"
FT   CHAIN           24..247
FT                   /note="Trypsin-2"
FT                   /id="PRO_0000028200"
FT   DOMAIN          24..244
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        63
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        107
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        200
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   BINDING         75
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250"
FT   BINDING         77
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250"
FT   BINDING         80
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250"
FT   BINDING         85
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250"
FT   SITE            194
FT                   /note="Required for specificity"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         154
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000305|PubMed:17087724,
FT                   ECO:0000305|PubMed:25010489"
FT   DISULFID        30..160
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        48..64
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        171..185
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        196..220
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   VARIANT         117
FT                   /note="A -> V (in dbSNP:rs11547028)"
FT                   /id="VAR_051858"
FT   VARIANT         153
FT                   /note="D -> H (abolishes tyrosine sulfation;
FT                   dbSNP:rs1804564)"
FT                   /evidence="ECO:0000269|PubMed:18986305"
FT                   /id="VAR_071761"
SQ   SEQUENCE   247 AA;  26488 MW;  82B0F41EB8E3D5DB CRC64;
     MNLLLILTFV AAAVAAPFDD DDKIVGGYIC EENSVPYQVS LNSGYHFCGG SLISEQWVVS
     AGHCYKSRIQ VRLGEHNIEV LEGNEQFINA AKIIRHPKYN SRTLDNDILL IKLSSPAVIN
     SRVSAISLPT APPAAGTESL ISGWGNTLSS GADYPDELQC LDAPVLSQAE CEASYPGKIT
     NNMFCVGFLE GGKDSCQGDS GGPVVSNGEL QGIVSWGYGC AQKNRPGVYT KVYNYVDWIK
     DTIAANS
//