GenomeNet

Database: UniProt/SWISS-PROT
Entry: TRY1_HUMAN
LinkDB: TRY1_HUMAN
Original site: TRY1_HUMAN 
ID   TRY1_HUMAN              Reviewed;         247 AA.
AC   P07477; A1A509; A6NJ71; B2R5I5; Q5NV57; Q7M4N3; Q7M4N4; Q92955;
AC   Q9HAN4; Q9HAN5; Q9HAN6; Q9HAN7;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   13-FEB-2019, entry version 204.
DE   RecName: Full=Trypsin-1;
DE            EC=3.4.21.4;
DE   AltName: Full=Beta-trypsin;
DE   AltName: Full=Cationic trypsinogen;
DE   AltName: Full=Serine protease 1;
DE   AltName: Full=Trypsin I;
DE   Contains:
DE     RecName: Full=Alpha-trypsin chain 1;
DE   Contains:
DE     RecName: Full=Alpha-trypsin chain 2;
DE   Flags: Precursor;
GN   Name=PRSS1; Synonyms=TRP1, TRY1, TRYP1;
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   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8650574; DOI=10.1126/science.272.5269.1755;
RA   Rowen L., Koop B.F., Hood L.;
RT   "The complete 685-kilobase DNA sequence of the human beta T cell
RT   receptor locus.";
RL   Science 272:1755-1762(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA   Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA   Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA   Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA   Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA   Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA   Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA   Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA   Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA   Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA   Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA   Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA   Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA   Mural R.J., Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 15-67, AND VARIANT PCTT GLY-22.
RX   PubMed=10930381; DOI=10.1053/gast.2000.9312;
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   [9]
RP   PROTEIN SEQUENCE OF 16-43 AND 123-142, FUNCTION, AND
RP   POST-TRANSLATIONAL PROCESSING.
RC   TISSUE=Gastric adenocarcinoma;
RX   PubMed=7945238; DOI=10.1042/bj3030187;
RA   Koshikawa N., Yasumitsu H., Nagashima Y., Umeda M., Miyazaki K.;
RT   "Identification of one- and two-chain forms of trypsinogen 1 produced
RT   by a human gastric adenocarcinoma cell line.";
RL   Biochem. J. 303:187-190(1994).
RN   [10]
RP   PROTEIN SEQUENCE OF 16-43.
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   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 68-151, AND VARIANT PCTT HIS-122.
RX   PubMed=8841182; DOI=10.1038/ng1096-141;
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   [12]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 68-151, AND VARIANTS PCTT ILE-29;
RP   PRO-104; CYS-116; HIS-122 AND PHE-139.
RX   PubMed=11866271; DOI=10.1111/j.1572-0241.2002.05467.x;
RA   Teich N., Bauer N., Mossner J., Keim V.;
RT   "Mutational screening of patients with nonalcoholic chronic
RT   pancreatitis: identification of further trypsinogen variants.";
RL   Am. J. Gastroenterol. 97:341-346(2002).
RN   [13]
RP   PROTEIN SEQUENCE OF 73-92, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Brain, and Cajal-Retzius cell;
RA   Lubec G., Afjehi-Sadat L.;
RL   Submitted (MAR-2007) to UniProtKB.
RN   [14]
RP   SULFATION AT TYR-154, AND MUTAGENESIS OF TYR-154.
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   [15]
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   [16]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND MASS SPECTROMETRY.
RX   PubMed=8683601; DOI=10.1006/jmbi.1996.0376;
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   [17]
RP   VARIANTS PCTT ILE-29 AND HIS-122.
RX   PubMed=9322498; DOI=10.1053/gast.1997.v113.pm9322498;
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   [18]
RP   VARIANT PCTT ILE-29.
RX   PubMed=9633818;
RX   DOI=10.1002/(SICI)1098-1004(1998)12:1<39::AID-HUMU6>3.0.CO;2-P;
RA   Teich N., Mossner J., Keim V.;
RT   "Mutations of the cationic trypsinogen in hereditary pancreatitis.";
RL   Hum. Mutat. 12:39-43(1998).
RN   [19]
RP   VARIANTS PCTT VAL-16 AND HIS-122.
RX   PubMed=10381903; DOI=10.1016/S0016-5085(99)70543-3;
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   [20]
RP   VARIANT PCTT ARG-23.
RX   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   [21]
RP   VARIANT PCTT HIS-122.
RX   PubMed=11073545; DOI=10.1136/jmg.37.11.e36;
RA   Chen J.-M., Raguenes O., Ferec C., Deprez P.H., Verellen-Dumoulin C.;
RT   "A CGC>CAT gene conversion-like event resulting in the R122H mutation
RT   in the cationic trypsinogen gene and its implication in the genotyping
RT   of pancreatitis.";
RL   J. Med. Genet. 37:E36-E36(2000).
RN   [22]
RP   VARIANTS PCTT THR-29 AND CYS-122.
RX   PubMed=11788572; DOI=10.1136/gut.50.2.271;
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).
RN   [23]
RP   VARIANT PCTT LYS-79, AND CHARACTERIZATION OF VARIANT PCTT LYS-79.
RX   PubMed=14695529; DOI=10.1002/humu.10285;
RA   Teich N., Le Marechal C., Kukor Z., Caca K., Witzigmann H.,
RA   Chen J.-M., Toth M., Moessner J., Keim V., Ferec C., Sahin-Toth M.;
RT   "Interaction between trypsinogen isoforms in genetically determined
RT   pancreatitis: mutation E79K in cationic trypsin (PRSS1) causes
RT   increased transactivation of anionic trypsinogen (PRSS2).";
RL   Hum. Mutat. 23:22-31(2004).
RN   [24]
RP   VARIANTS PCTT ILE-29 AND SER-54, AND CHARACTERIZATION OF VARIANTS PCTT
RP   ILE-29 AND SER-54.
RX   PubMed=15776435; DOI=10.1002/humu.20148;
RA   Teich N., Nemoda Z., Koehler H., Heinritz W., Moessner J., Keim V.,
RA   Sahin-Toth M.;
RT   "Gene conversion between functional trypsinogen genes PRSS1 and PRSS2
RT   associated with chronic pancreatitis in a six-year-old girl.";
RL   Hum. Mutat. 25:343-347(2005).
RN   [25]
RP   VARIANT [LARGE SCALE ANALYSIS] MET-137.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Has activity against the synthetic substrates Boc-Phe-
CC       Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-
CC       Pro-Arg-Mec. The single-chain form is more active than the two-
CC       chain form against all of these substrates.
CC       {ECO:0000269|PubMed:7945238}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.;
CC         EC=3.4.21.4;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC       Note=Binds 1 Ca(2+) ion per subunit.;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC   -!- PTM: Occurs in a single-chain form and a two-chain form, produced
CC       by proteolytic cleavage after Arg-122.
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   -!- MASS SPECTROMETRY: Mass=24348; Mass_error=2; Method=Electrospray;
CC       Range=24-247; Evidence={ECO:0000269|PubMed:8683601};
CC   -!- DISEASE: Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease
CC       characterized by pancreas inflammation, permanent destruction of
CC       the pancreatic parenchyma, maldigestion, and severe abdominal pain
CC       attacks. {ECO:0000269|PubMed:10204851,
CC       ECO:0000269|PubMed:10381903, ECO:0000269|PubMed:10930381,
CC       ECO:0000269|PubMed:11073545, ECO:0000269|PubMed:11788572,
CC       ECO:0000269|PubMed:11866271, ECO:0000269|PubMed:14695529,
CC       ECO:0000269|PubMed:15776435, ECO:0000269|PubMed:8841182,
CC       ECO:0000269|PubMed:9322498, ECO:0000269|PubMed:9633818}.
CC       Note=Disease susceptibility is associated with variations
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC   -!- CAUTION: Tyr-154 was proposed to be phosphorylated
CC       (PubMed:8683601) but it has been shown (PubMed:17087724) to be
CC       sulfated instead. Phosphate and sulfate groups are similar in mass
CC       and size, and this can lead to erroneous interpretation of the
CC       results. {ECO:0000305|PubMed:17087724,
CC       ECO:0000305|PubMed:8683601}.
DR   EMBL; M22612; AAA61231.1; -; mRNA.
DR   EMBL; L36092; AAC80207.1; -; Genomic_DNA.
DR   EMBL; AK312199; BAG35132.1; -; mRNA.
DR   EMBL; AC231380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH236959; EAL23773.1; -; Genomic_DNA.
DR   EMBL; CH471198; EAW51925.1; -; Genomic_DNA.
DR   EMBL; BC128226; AAI28227.1; -; mRNA.
DR   EMBL; AF314534; AAG30943.1; -; Genomic_DNA.
DR   EMBL; U70137; AAC50728.1; -; Genomic_DNA.
DR   EMBL; AF315309; AAG30947.1; -; Genomic_DNA.
DR   EMBL; AF315310; AAG30948.1; -; Genomic_DNA.
DR   EMBL; AF315311; AAG30949.1; -; Genomic_DNA.
DR   CCDS; CCDS5872.1; -.
DR   PIR; A25852; A25852.
DR   PIR; S50020; S50020.
DR   PIR; S50021; S50021.
DR   RefSeq; NP_002760.1; NM_002769.4.
DR   UniGene; Hs.382212; -.
DR   UniGene; Hs.449276; -.
DR   UniGene; Hs.449281; -.
DR   PDB; 1FXY; X-ray; 2.15 A; A=127-247.
DR   PDB; 1TRN; X-ray; 2.20 A; A/B=24-247.
DR   PDB; 2RA3; X-ray; 1.46 A; A/B=24-247.
DR   PDB; 4WWY; X-ray; 1.70 A; A/B=24-247.
DR   PDB; 4WXV; X-ray; 2.10 A; A/B=24-247.
DR   PDBsum; 1FXY; -.
DR   PDBsum; 1TRN; -.
DR   PDBsum; 2RA3; -.
DR   PDBsum; 4WWY; -.
DR   PDBsum; 4WXV; -.
DR   ProteinModelPortal; P07477; -.
DR   SMR; P07477; -.
DR   BioGrid; 111626; 27.
DR   IntAct; P07477; 6.
DR   MINT; P07477; -.
DR   STRING; 9606.ENSP00000308720; -.
DR   BindingDB; P07477; -.
DR   ChEMBL; CHEMBL209; -.
DR   DrugBank; DB06850; (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclohexylamino)ethanoyl)pyrrolidine-2-carboxamide.
DR   DrugBank; DB07091; (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclohexyloxy)ethanoyl)pyrrolidine-2-carboxamide.
DR   DrugBank; DB06845; (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclopentylamino)ethanoyl)pyrrolidine-2-carboxamide.
DR   DrugBank; DB07088; (S)-N-(4-carbamimidoylbenzyl)-1-(2-(cyclopentyloxy)ethanoyl)pyrrolidine-2-carboxamide.
DR   DrugBank; DB07131; (S)-N-(4-carbamimidoylbenzyl)-1-(3-cyclohexylpropanoyl)pyrrolidine-2-carboxamide.
DR   DrugBank; DB07095; (S)-N-(4-carbamimidoylbenzyl)-1-(3-cyclopentylpropanoyl)pyrrolidine-2-carboxamide.
DR   DrugBank; DB07985; +/-METHYL 4-(AMINOIMINOMETHYL)-BETA-[3- INH (AMINOIMINO)PHENYL]BENZENE PENTANOATE.
DR   DrugBank; DB03337; 1-(2-Amidinophenyl)-3-(Phenoxyphenyl)Urea.
DR   DrugBank; DB04336; 1-(4-Amidinophenyl)-3-(4-Chlorophenyl)Urea.
DR   DrugBank; DB03417; 1-(4-Tert-Butylcarbamoyl-Piperazine-1-Carbonyl)-3-(3-Guanidino-Propyl)-4-Oxo-Azetidine-2-Carboxylic Acid.
DR   DrugBank; DB08420; 1-{[1-(2-AMINO-3-PHENYL-PROPIONYL)-PYRROLIDINE-2-CARBONYL]-AMINO}-2-(3-CYANO-PHENYL)-ETHANEBORONIC ACID.
DR   DrugBank; DB01905; 2-(2-Hydroxy-5-Methoxy-Phenyl)-1h-Benzoimidazole-5-Carboxamidine.
DR   DrugBank; DB02193; 2-(2-Hydroxy-Phenyl)-1h-Benzoimidazole-5-Carboxamidine.
DR   DrugBank; DB02463; 2-(2-Hydroxy-Phenyl)-1h-Indole-5-Carboxamidine.
DR   DrugBank; DB02287; 2-(2-Hydroxy-Phenyl)-3h-Benzoimidazole-5-Carboxamidine.
DR   DrugBank; DB08184; 2-(2-METHYLPHENYL)-1H-INDOLE-5-CARBOXIMIDAMIDE.
DR   DrugBank; DB06918; 2-(2-METHYLPHENYL)-1H-INDOLE-6-CARBOXIMIDAMIDE.
DR   DrugBank; DB06923; 2-(3-METHYLPHENYL)-1H-INDOLE-5-CARBOXIMIDAMIDE.
DR   DrugBank; DB08254; 2-NAPHTHALENESULFONIC ACID.
DR   DrugBank; DB04325; 2-Phenylethylamine.
DR   DrugBank; DB04410; 3-Phenylpropylamine.
DR   DrugBank; DB07368; 4-(METHYLSULFONYL)BENZENECARBOXIMIDAMIDE.
DR   DrugBank; DB03243; 4-Fluorobenzylamine.
DR   DrugBank; DB03136; 4-Iodobenzo[B]Thiophene-2-Carboxamidine.
DR   DrugBank; DB04311; 4-Phenylbutylamine.
DR   DrugBank; DB04654; 4-PIPERIDIN-4-YLBUTANAL.
DR   DrugBank; DB02354; 4-{[1-Methyl-5-(2-Methyl-Benzoimidazol-1-Ylmethyl)-1h-Benzoimidazol-2-Ylmethyl]-Amino}-Benzamidine.
DR   DrugBank; DB01939; 5-Amidino-Benzimidazole.
DR   DrugBank; DB03865; 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine.
DR   DrugBank; DB04107; [(1-{2[(4-Carbamimidoyl-Phenylamino)-Methyl]-1-Methyl-1h-Benzoimidazol-5-Yl}-Cyclopropyl)-Pyridin-2-Yl-Methyleneaminooxy]-Acetic Acid Ethyl Ester.
DR   DrugBank; DB02269; [4-({[5-Benzyloxy-1-(3-Carbamimidoyl-Benzyl)-1h-Indole-2-Carbonyl]-Amino}-Methyl)-Phenyl]-Trimethyl-Ammonium.
DR   DrugBank; DB08763; [N-(BENZYLOXYCARBONYL)AMINO](4-AMIDINOPHENYL)METHANE-PHOSPHONATE.
DR   DrugBank; DB04391; Aeruginosin 98-B.
DR   DrugBank; DB02435; Aminomethylcyclohexane.
DR   DrugBank; DB02045; Amylamine.
DR   DrugBank; DB06692; Aprotinin.
DR   DrugBank; DB03127; Benzamidine.
DR   DrugBank; DB04446; Benzo[B]Thiophene-2-Carboxamidine.
DR   DrugBank; DB02464; Benzylamine.
DR   DrugBank; DB03213; Bis(5-Amidino-2-Benzimidazolyl)Methane Ketone.
DR   DrugBank; DB04301; Bis(5-Amidino-2-Benzimidazolyl)Methane Ketone Hydrate.
DR   DrugBank; DB01876; Bis(5-Amidino-2-Benzimidazolyl)Methanone.
DR   DrugBank; DB01705; Bis(5-Amidino-Benzimidazolyl)Methane.
DR   DrugBank; DB04008; Bis(5-Amidino-Benzimidazolyl)Methane Zinc.
DR   DrugBank; DB03443; Bis(5-Amidino-Benzimidazolyl)Methanone Zinc.
DR   DrugBank; DB02081; Bis-Benzamidine.
DR   DrugBank; DB03173; CRA_10433.
DR   DrugBank; DB02526; CRA_10655.
DR   DrugBank; DB04470; CRA_10656.
DR   DrugBank; DB02366; CRA_10762.
DR   DrugBank; DB03494; CRA_10950.
DR   DrugBank; DB02989; CRA_10972.
DR   DrugBank; DB01771; CRA_10991.
DR   DrugBank; DB03555; CRA_11092.
DR   DrugBank; DB03643; CRA_1144.
DR   DrugBank; DB02063; CRA_16847.
DR   DrugBank; DB02084; CRA_17312.
DR   DrugBank; DB01741; CRA_17693.
DR   DrugBank; DB03016; CRA_1801.
DR   DrugBank; DB02875; CRA_1802.
DR   DrugBank; DB04246; CRA_23653.
DR   DrugBank; DB01725; CRA_7806.
DR   DrugBank; DB03159; CRA_8696.
DR   DrugBank; DB04215; CRA_9076.
DR   DrugBank; DB02288; CRA_9334.
DR   DrugBank; DB04563; CRA_9678.
DR   DrugBank; DB03595; CRA_9785.
DR   DrugBank; DB03081; Crc200 (Chiron-Behring).
DR   DrugBank; DB04269; Cyclotheonamide A.
DR   DrugBank; DB03608; Diminazene.
DR   DrugBank; DB01767; Hemi-Babim.
DR   DrugBank; DB01805; Monoisopropylphosphorylserine.
DR   DrugBank; DB04125; N-Alpha-(2-Naphthylsulfonyl)-N(3-Amidino-L-Phenylalaninyl)-4-Acetyl-Piperazine.
DR   DrugBank; DB01745; N-Alpha-(2-Naphthylsulfonyl)-N(3-Amidino-L-Phenylalaninyl)Isopipecolinic Acid Methyl Ester.
DR   DrugBank; DB04238; N-Alpha-(2-Naphthylsulfonyl)-N-(3-Amidino-L-Phenylalaninyl)-D-Pipecolinic Acid.
DR   DrugBank; DB06853; N-cycloheptylglycyl-N-(4-carbamimidoylbenzyl)-L-prolinamide.
DR   DrugBank; DB06858; N-cyclooctylglycyl-N-(4-carbamimidoylbenzyl)-L-prolinamide.
DR   DrugBank; DB03976; Phosphorylisopropane.
DR   DrugBank; DB04424; RPR128515.
DR   DrugBank; DB02744; RPR131247.
DR   DrugBank; DB03251; RWJ-51084.
DR   DrugBank; DB02665; Trans-2-Phenylcyclopropylamine.
DR   DrugBank; DB01665; ZK-800270.
DR   DrugBank; DB04432; ZK-805623.
DR   DrugBank; DB02112; Zk-806450.
DR   DrugBank; DB03373; ZK-806711.
DR   GuidetoPHARMACOLOGY; 2397; -.
DR   MEROPS; S01.127; -.
DR   iPTMnet; P07477; -.
DR   PhosphoSitePlus; P07477; -.
DR   BioMuta; PRSS1; -.
DR   DMDM; 136408; -.
DR   EPD; P07477; -.
DR   jPOST; P07477; -.
DR   PaxDb; P07477; -.
DR   PeptideAtlas; P07477; -.
DR   PRIDE; P07477; -.
DR   ProteomicsDB; 52006; -.
DR   Ensembl; ENST00000311737; ENSP00000308720; ENSG00000204983.
DR   Ensembl; ENST00000616256; ENSP00000479217; ENSG00000274247.
DR   GeneID; 5644; -.
DR   KEGG; hsa:5644; -.
DR   UCSC; uc003wak.3; human.
DR   CTD; 5644; -.
DR   DisGeNET; 5644; -.
DR   EuPathDB; HostDB:ENSG00000204983.12; -.
DR   GeneCards; PRSS1; -.
DR   GeneReviews; PRSS1; -.
DR   HGNC; HGNC:9475; PRSS1.
DR   HPA; CAB025487; -.
DR   HPA; CAB025538; -.
DR   HPA; HPA062452; -.
DR   HPA; HPA063471; -.
DR   MalaCards; PRSS1; -.
DR   MIM; 167800; phenotype.
DR   MIM; 276000; gene.
DR   neXtProt; NX_P07477; -.
DR   OpenTargets; ENSG00000204983; -.
DR   Orphanet; 676; Hereditary chronic pancreatitis.
DR   PharmGKB; PA33828; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   eggNOG; COG5640; LUCA.
DR   GeneTree; ENSGT00940000153485; -.
DR   HOVERGEN; HBG013304; -.
DR   InParanoid; P07477; -.
DR   KO; K01312; -.
DR   OrthoDB; 1314811at2759; -.
DR   PhylomeDB; P07477; -.
DR   TreeFam; TF331065; -.
DR   Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR   Reactome; R-HSA-196741; Cobalamin (Cbl, vitamin B12) transport and metabolism.
DR   ChiTaRS; PRSS1; human.
DR   EvolutionaryTrace; P07477; -.
DR   GeneWiki; Trypsin_1; -.
DR   GenomeRNAi; 5644; -.
DR   PMAP-CutDB; P07477; -.
DR   PRO; PR:P07477; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000204983; Expressed in 87 organ(s), highest expression level in body of pancreas.
DR   ExpressionAtlas; P07477; baseline and differential.
DR   Genevisible; P07477; HS.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008236; F:serine-type peptidase activity; TAS:Reactome.
DR   GO; GO:0009235; P:cobalamin metabolic process; TAS:Reactome.
DR   GO; GO:0007586; P:digestion; IEA:UniProtKB-KW.
DR   GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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   3D-structure; Calcium; Complete proteome; Digestion;
KW   Direct protein sequencing; Disease mutation; Disulfide bond;
KW   Hydrolase; Metal-binding; Polymorphism; Protease; Reference proteome;
KW   Secreted; Serine protease; Signal; Sulfation; Zymogen.
FT   SIGNAL        1     15       {ECO:0000269|PubMed:2598466,
FT                                ECO:0000269|PubMed:7945238}.
FT   PROPEP       16     23       Activation peptide.
FT                                /FTId=PRO_0000028197.
FT   CHAIN        24    247       Trypsin-1.
FT                                /FTId=PRO_0000028198.
FT   CHAIN        24    122       Alpha-trypsin chain 1.
FT                                /FTId=PRO_0000313570.
FT   CHAIN       123    247       Alpha-trypsin chain 2.
FT                                /FTId=PRO_0000313571.
FT   DOMAIN       24    244       Peptidase S1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00274}.
FT   ACT_SITE     63     63       Charge relay system.
FT   ACT_SITE    107    107       Charge relay system.
FT   ACT_SITE    200    200       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   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
FT   DISULFID     48     64
FT   DISULFID    139    206
FT   DISULFID    171    185
FT   DISULFID    196    220
FT   VARIANT      16     16       A -> V (in PCTT; disrupts signal sequence
FT                                cleavage site; dbSNP:rs202003805).
FT                                {ECO:0000269|PubMed:10381903}.
FT                                /FTId=VAR_011693.
FT   VARIANT      22     22       D -> G (in PCTT; increased rate of
FT                                activation; dbSNP:rs397507442).
FT                                {ECO:0000269|PubMed:10930381}.
FT                                /FTId=VAR_011652.
FT   VARIANT      23     23       K -> R (in PCTT; increased rate of
FT                                activation; dbSNP:rs111033567).
FT                                {ECO:0000269|PubMed:10204851}.
FT                                /FTId=VAR_011653.
FT   VARIANT      29     29       N -> I (in PCTT; dbSNP:rs111033566).
FT                                {ECO:0000269|PubMed:11866271,
FT                                ECO:0000269|PubMed:15776435,
FT                                ECO:0000269|PubMed:9322498,
FT                                ECO:0000269|PubMed:9633818}.
FT                                /FTId=VAR_006720.
FT   VARIANT      29     29       N -> T (in PCTT; dbSNP:rs111033566).
FT                                {ECO:0000269|PubMed:11788572}.
FT                                /FTId=VAR_012712.
FT   VARIANT      54     54       N -> S (in PCTT; associated with Ile-29;
FT                                the double mutant shows increased
FT                                autocatalytic activation which is solely
FT                                due to the Ile-29 mutation;
FT                                dbSNP:rs144422014).
FT                                {ECO:0000269|PubMed:15776435}.
FT                                /FTId=VAR_037908.
FT   VARIANT      79     79       E -> K (in PCTT; Lys-79 trypsin activates
FT                                anionic trypsinogen PRSS2 2-fold while
FT                                the common pancreatitis-associated
FT                                mutants His-122 or Ile-29 have no such
FT                                effect; dbSNP:rs111033564).
FT                                {ECO:0000269|PubMed:14695529}.
FT                                /FTId=VAR_037909.
FT   VARIANT     104    104       L -> P (in PCTT).
FT                                {ECO:0000269|PubMed:11866271}.
FT                                /FTId=VAR_011654.
FT   VARIANT     116    116       R -> C (in PCTT; dbSNP:rs387906698).
FT                                {ECO:0000269|PubMed:11866271}.
FT                                /FTId=VAR_011655.
FT   VARIANT     122    122       R -> C (in PCTT; suppresses an
FT                                autocleavage site; dbSNP:rs111033568).
FT                                {ECO:0000269|PubMed:11788572}.
FT                                /FTId=VAR_012713.
FT   VARIANT     122    122       R -> H (in PCTT; 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                                dbSNP:rs267606982).
FT                                {ECO:0000269|PubMed:10381903,
FT                                ECO:0000269|PubMed:11073545,
FT                                ECO:0000269|PubMed:11866271,
FT                                ECO:0000269|PubMed:8841182,
FT                                ECO:0000269|PubMed:9322498}.
FT                                /FTId=VAR_006721.
FT   VARIANT     137    137       T -> M (in a colorectal cancer sample;
FT                                somatic mutation; dbSNP:rs117497341).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_036299.
FT   VARIANT     139    139       C -> F (in PCTT).
FT                                {ECO:0000269|PubMed:11866271}.
FT                                /FTId=VAR_011656.
FT   MUTAGEN     154    154       Y->F: Lack of sulfation.
FT                                {ECO:0000269|PubMed:17087724}.
FT   CONFLICT      4      4       L -> F (in Ref. 7; AAI28227).
FT                                {ECO:0000305}.
FT   STRAND       38     54       {ECO:0000244|PDB:2RA3}.
FT   STRAND       57     60       {ECO:0000244|PDB:2RA3}.
FT   HELIX        62     64       {ECO:0000244|PDB:2RA3}.
FT   STRAND       70     74       {ECO:0000244|PDB:2RA3}.
FT   TURN         78     80       {ECO:0000244|PDB:1FXY}.
FT   STRAND       86     95       {ECO:0000244|PDB:2RA3}.
FT   TURN        101    103       {ECO:0000244|PDB:2RA3}.
FT   STRAND      109    115       {ECO:0000244|PDB:2RA3}.
FT   STRAND      120    122       {ECO:0000244|PDB:2RA3}.
FT   STRAND      138    144       {ECO:0000244|PDB:2RA3}.
FT   STRAND      149    151       {ECO:0000244|PDB:2RA3}.
FT   STRAND      159    165       {ECO:0000244|PDB:2RA3}.
FT   HELIX       168    174       {ECO:0000244|PDB:2RA3}.
FT   TURN        176    178       {ECO:0000244|PDB:2RA3}.
FT   STRAND      183    187       {ECO:0000244|PDB:2RA3}.
FT   STRAND      192    194       {ECO:0000244|PDB:1TRN}.
FT   STRAND      203    206       {ECO:0000244|PDB:2RA3}.
FT   STRAND      209    216       {ECO:0000244|PDB:2RA3}.
FT   STRAND      218    222       {ECO:0000244|PDB:2RA3}.
FT   STRAND      227    231       {ECO:0000244|PDB:2RA3}.
FT   HELIX       232    235       {ECO:0000244|PDB:2RA3}.
FT   HELIX       236    245       {ECO:0000244|PDB:2RA3}.
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
//
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