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Database: UniProt/SWISS-PROT
Entry: TRY2_HUMAN
LinkDB: TRY2_HUMAN
Original site: TRY2_HUMAN 
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   07-NOV-2018, entry version 178.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   encoding 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.,
RA   Yadav S.P., 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
RT   towards 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: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.
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
CC       small 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
CC       versus apolar residues at the P2' position of inhibitors that bind
CC       in a substrate-like fashion. Although the increase in selectivity
CC       is relatively small, it may facilitate digestion of a broader
CC       range of dietary proteins. {ECO:0000269|PubMed:25010489}.
CC   -!- POLYMORPHISM: His-153 variation is a common polymorphism in
CC       African populations with a minor allele frequency of 9.2%, it
CC       eliminates sulfation at Tyr-154, with no consequences on digestive
CC       physiology. {ECO:0000269|PubMed:18986305}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
DR   EMBL; M27602; AAA61232.1; -; mRNA.
DR   CCDS; CCDS83236.1; -.
DR   PIR; B25852; B25852.
DR   RefSeq; NP_002761.1; NM_002770.3.
DR   UniGene; Hs.449281; -.
DR   UniGene; Hs.726742; -.
DR   UniGene; Hs.728780; -.
DR   ProteinModelPortal; P07478; -.
DR   SMR; P07478; -.
DR   BioGrid; 111627; 16.
DR   IntAct; P07478; 1.
DR   BindingDB; P07478; -.
DR   ChEMBL; CHEMBL3159; -.
DR   DrugBank; DB04325; 2-Phenylethylamine.
DR   DrugBank; DB04410; 3-Phenylpropylamine.
DR   DrugBank; DB03127; Benzamidine.
DR   DrugBank; DB02464; Benzylamine.
DR   DrugBank; DB02325; Isopropyl Alcohol.
DR   DrugBank; DB01805; Monoisopropylphosphorylserine.
DR   DrugBank; DB01973; O-Benzylsulfonyl-Serine.
DR   DrugBank; DB03976; Phosphorylisopropane.
DR   MEROPS; S01.258; -.
DR   iPTMnet; P07478; -.
DR   PhosphoSitePlus; P07478; -.
DR   DMDM; 136413; -.
DR   PeptideAtlas; P07478; -.
DR   PRIDE; P07478; -.
DR   ProteomicsDB; 52007; -.
DR   TopDownProteomics; P07478; -.
DR   DNASU; 5645; -.
DR   Ensembl; ENST00000539842; ENSP00000488338; ENSG00000275896.
DR   Ensembl; ENST00000632112; ENSP00000487952; ENSG00000282049.
DR   GeneID; 5645; -.
DR   KEGG; hsa:5645; -.
DR   CTD; 5645; -.
DR   DisGeNET; 5645; -.
DR   EuPathDB; HostDB:ENSG00000275896.4; -.
DR   GeneCards; PRSS2; -.
DR   HGNC; HGNC:9483; PRSS2.
DR   HPA; HPA062452; -.
DR   HPA; HPA063471; -.
DR   MalaCards; PRSS2; -.
DR   MIM; 601564; gene.
DR   neXtProt; NX_P07478; -.
DR   OpenTargets; ENSG00000275896; -.
DR   Orphanet; 676; Hereditary chronic pancreatitis.
DR   PharmGKB; PA33833; -.
DR   GeneTree; ENSGT00760000118862; -.
DR   HOGENOM; HOG000251820; -.
DR   HOVERGEN; HBG013304; -.
DR   InParanoid; P07478; -.
DR   KO; K01312; -.
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   GenomeRNAi; 5645; -.
DR   PRO; PR:P07478; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000275896; Expressed in 77 organ(s), highest expression level in body of pancreas.
DR   CleanEx; HS_PRSS2; -.
DR   ExpressionAtlas; P07478; baseline and differential.
DR   Genevisible; P07478; HS.
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:0043312; P:neutrophil degranulation; 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   InterPro; IPR009003; Peptidase_S1_PA.
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   Calcium; Complete proteome; Digestion; Direct protein sequencing;
KW   Disulfide bond; Hydrolase; Metal-binding; Polymorphism; Protease;
KW   Reference proteome; Secreted; Serine protease; Signal; Sulfation;
KW   Zymogen.
FT   SIGNAL        1     15       {ECO:0000269|PubMed:2598466}.
FT   PROPEP       16     23       Activation peptide.
FT                                /FTId=PRO_0000028199.
FT   CHAIN        24    247       Trypsin-2.
FT                                /FTId=PRO_0000028200.
FT   DOMAIN       24    244       Peptidase S1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00274}.
FT   ACT_SITE     63     63       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    107    107       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    200    200       Charge relay system. {ECO:0000250}.
FT   METAL        75     75       Calcium. {ECO:0000250}.
FT   METAL        77     77       Calcium; via carbonyl oxygen.
FT                                {ECO:0000250}.
FT   METAL        80     80       Calcium; via carbonyl oxygen.
FT                                {ECO:0000250}.
FT   METAL        85     85       Calcium. {ECO:0000250}.
FT   SITE        194    194       Required for specificity. {ECO:0000250}.
FT   MOD_RES     154    154       Sulfotyrosine.
FT                                {ECO:0000305|PubMed:17087724,
FT                                ECO:0000305|PubMed:25010489}.
FT   DISULFID     30    160       {ECO:0000255|PROSITE-ProRule:PRU00274}.
FT   DISULFID     48     64       {ECO:0000255|PROSITE-ProRule:PRU00274}.
FT   DISULFID    171    185       {ECO:0000255|PROSITE-ProRule:PRU00274}.
FT   DISULFID    196    220       {ECO:0000255|PROSITE-ProRule:PRU00274}.
FT   VARIANT     117    117       A -> V (in dbSNP:rs11547028).
FT                                /FTId=VAR_051858.
FT   VARIANT     153    153       D -> H (abolishes tyrosine sulfation;
FT                                dbSNP:rs1804564).
FT                                {ECO:0000269|PubMed:18986305}.
FT                                /FTId=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
//
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