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 03-AUG-2022, entry version 198.
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}.
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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; 38.
DR IntAct; P07478; 14.
DR MINT; P07478; -.
DR STRING; 9606.ENSP00000485444; -.
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 iPTMnet; P07478; -.
DR PhosphoSitePlus; P07478; -.
DR BioMuta; PRSS2; -.
DR DMDM; 136413; -.
DR jPOST; P07478; -.
DR MassIVE; P07478; -.
DR PeptideAtlas; P07478; -.
DR PRIDE; P07478; -.
DR ProteomicsDB; 52007; -.
DR TopDownProteomics; P07478; -.
DR Antibodypedia; 74627; 157 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 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 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 164 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 87 other tissues.
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: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; -; 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 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
