ID TRY1_HUMAN STANDARD; PRT; 247 AA. AC P07477; Q92955; Q9HAN4; Q9HAN5; Q9HAN6; Q9HAN7; DT 01-APR-1988 (Rel. 07, Created) DT 01-APR-1988 (Rel. 07, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Trypsin I precursor (EC 3.4.21.4) (Cationic trypsinogen). GN PRSS1 OR TRY1 OR TRP1 OR TRYP1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=86221712; PubMed=3011602; 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 SEQUENCE OF 16-43. RX MEDLINE=90091010; PubMed=2598466; 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 SEQUENCE OF 68-151 FROM N.A., AND VARIANT HPC HIS-122. RX MEDLINE=96438847; PubMed=8841182; RA Whitcomb D.C., Gorry M.C., Preston R.A., Furey W., Sossenheimer M.J., RA Ulrich C.D., Martin S.P., Gates L.K. Jr., Amann S.T., Toskes P.P., RA Liddle R., McGrath K., Uomo G., Post J.C., Ehrlich G.D.; RT "Hereditary pancreatitis is caused by a mutation in the cationic RT trypsinogen gene."; RL Nat. Genet. 14:141-145(1996). RN [4] RP SEQUENCE OF 15-67 FROM N.A., AND VARIANT HPC GLY-22. RX MEDLINE=20389982; PubMed=10930381; RA Teich N., Ockenga J., Hoffmeister A., Manns M., Mossner J., Keim V.; RT "Chronic pancreatitis associated with an activation peptide mutation RT that facilitates trypsin activation."; RL Gastroenterology 119:461-465(2000). RN [5] RP SEQUENCE OF 68-151 FROM N.A., AND VARIANTS HPC PRO-104; CYS-116 AND RP PHE-139. RA Teich N., Bauer N., Mossner J., Keim V.; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND PHOSPHORYLATION. RX MEDLINE=96266496; PubMed=8683601; RA Gaboriaud C., Serre L., Guy-Crotte O., Forest E., RA Fontecilla-Camps J.-C.; RT "Crystal structure of human trypsin 1: unexpected phosphorylation of RT Tyr151."; RL J. Mol. Biol. 259:995-1010(1996). RN [7] RP VARIANTS HPC ILE-29 AND HIS-122. RX MEDLINE=97463797; PubMed=9322498; RA Gorry M.C., Gabbaizedeh D., Furey W., Gates L.K. Jr., Preston R.A., RA Aston C.E., Zhang Y., Ulrich C., Ehrlich G.D., Whitcomb D.C.; RT "Mutations in the cationic trypsinogen gene are associated with RT recurrent acute and chronic pancreatitis."; RL Gastroenterology 113:1063-1068(1997). RN [8] RP VARIANT HPC ILE-29. RX MEDLINE=98295575; PubMed=9633818; RA Teich N., Mossner J., Keim V.; RT "Mutations of the cationic trypsinogen in hereditary pancreatitis."; RL Hum. Mutat. 12:39-43(1998). RN [9] RP VARIANTS HPC VAL-16 AND HIS-122. RX MEDLINE=99315544; PubMed=10381903; RA Witt H., Luck W., Becker M.; RT "A signal peptide cleavage site mutation in the cationic trypsinogen RT gene is strongly associated with chronic pancreatitis."; RL Gastroenterology 117:7-10(1999). RN [10] RP VARIANT HPC ARG-23. RX MEDLINE=99219545; PubMed=10204851; RA Ferec C., Raguenes O., Salomon R., Roche C., Bernard J.P., Guillot M., RA Quere I., Faure C., Mercier B., Audrezet M.P., Guillausseau P.J., RA Dupont C., Munnich A., Bignon J.D., Le Bodic L.; RT "Mutations in the cationic trypsinogen gene and evidence for genetic RT heterogeneity in hereditary pancreatitis."; RL J. Med. Genet. 36:228-232(1999). RN [11] RP VARIANTS HPC THR-29 AND CYS-122. RX MEDLINE=21648565; PubMed=11788572; RA Pfutzer R., Myers E., Applebaum-Shapiro S., Finch R., Ellis I., RA Neoptolemos J., Kant J.A., Whitcomb D.C.; RT "Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause RT autosomal dominant hereditary pancreatitis."; RL Gut 50:271-272(2002). CC -!- CATALYTIC ACTIVITY: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa. CC -!- COFACTOR: Binds 1 calcium ion per subunit. CC -!- SUBCELLULAR LOCATION: Extracellular. CC -!- MASS SPECTROMETRY: MW=24348; MW_ERR=2; METHOD=Electrospray; CC RANGE=24-247. CC -!- DISEASE: Defects in PRSS1 are a cause of hereditary pancreatitis CC (HPC) [MIM:167800]; also known as chronic pancreatitis (CP). HPC CC is an autosomal dominant disease characterized by the presence of CC calculi in pancreatic ducts. It causes severe abdominal pain CC attacks. CC -!- SIMILARITY: Belongs to peptidase family S1. 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; M22612; AAA61231.1; -. DR EMBL; U70137; AAC50728.1; -. DR EMBL; AF314534; AAG30943.1; -. DR EMBL; AF315309; AAG30947.1; -. DR EMBL; AF315310; AAG30948.1; -. DR EMBL; AF315311; AAG30949.1; -. DR PIR; A25852; A25852. DR PDB; 1TRN; 03-JUN-95. DR PDB; 1FXY; 17-JUN-98. DR MEROPS; S01.151; -. DR Genew; HGNC:9475; PRSS1. DR MIM; 276000; -. DR MIM; 167800; -. DR GO; GO:0004295; F:trypsin activity; TAS. DR InterPro; IPR009003; Cys_Ser_trypsin. DR InterPro; IPR001254; Peptidase_S1. DR InterPro; IPR001314; Peptidase_S1A. DR Pfam; PF00089; trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. KW Hydrolase; Serine protease; Digestion; Pancreas; Zymogen; KW Calcium-binding; Signal; Multigene family; Phosphorylation; KW 3D-structure; Disease mutation. FT SIGNAL 1 15 FT PROPEP 16 23 Activation peptide. FT CHAIN 24 247 Trypsin I. FT ACT_SITE 63 63 Charge relay system. FT METAL 75 75 Calcium. FT METAL 77 77 Calcium (via carbonyl oxygen). FT METAL 80 80 Calcium (via carbonyl oxygen). FT METAL 85 85 Calcium. FT ACT_SITE 107 107 Charge relay system. FT ACT_SITE 200 200 Charge relay system. FT DISULFID 30 160 FT DISULFID 48 64 FT DISULFID 139 206 FT DISULFID 171 185 FT DISULFID 196 220 FT MOD_RES 154 154 PHOSPHORYLATION. FT SITE 194 194 REQUIRED FOR SPECIFICITY (BY SIMILARITY). FT VARIANT 16 16 A -> V (in HPC; disrupts signal sequence FT cleavage site). FT /FTId=VAR_011693. FT VARIANT 22 22 D -> G (in HPC; increased rate of FT activation). FT /FTId=VAR_011652. FT VARIANT 23 23 K -> R (in HPC; increased rate of FT activation). FT /FTId=VAR_011653. FT VARIANT 29 29 N -> I (in HPC). FT /FTId=VAR_006720. FT VARIANT 29 29 N -> T (in HPC). FT /FTId=VAR_012712. FT VARIANT 104 104 L -> P (in HPC). FT /FTId=VAR_011654. FT VARIANT 116 116 R -> C (in HPC). FT /FTId=VAR_011655. FT VARIANT 122 122 R -> C (in HPC; suppresses an FT autocleavage site). FT /FTId=VAR_012713. FT VARIANT 122 122 R -> H (in HPC; suppresses an FT autocleavage site which is probably part FT of a fail-safe mechanism by which FT trypsin, which is activated within the FT pancreas, may be inactivated; loss of FT this cleavage site would permit FT autodigestion resulting in pancreatitis). FT /FTId=VAR_006721. FT VARIANT 139 139 C -> F (in HPC). FT /FTId=VAR_011656. SQ SEQUENCE 247 AA; 26558 MW; DD49A487B8062813 CRC64; MNPLLILTFV AAALAAPFDD DDKIVGGYNC EENSVPYQVS LNSGYHFCGG SLINEQWVVS AGHCYKSRIQ VRLGEHNIEV LEGNEQFINA AKIIRHPQYD RKTLNNDIML IKLSSRAVIN ARVSTISLPT APPATGTKCL ISGWGNTASS GADYPDELQC LDAPVLSQAK CEASYPGKIT SNMFCVGFLE GGKDSCQGDS GGPVVCNGQL QGVVSWGDGC AQKNKPGVYT KVYNYVKWIK NTIAANS //