ID TRY1_HUMAN Reviewed; 247 AA. AC P07477; A1A509; A6NJ71; B2R5I5; Q5NV57; Q7M4N3; Q7M4N4; Q92955; Q9HAN4; AC Q9HAN5; Q9HAN6; Q9HAN7; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 27-MAR-2024, entry version 232. DE RecName: Full=Serine protease 1 {ECO:0000312|HGNC:HGNC:9475}; DE EC=3.4.21.4; DE AltName: Full=Anionic trypsin I {ECO:0000250|UniProtKB:P00762}; DE AltName: Full=Anionic trypsin-I {ECO:0000250|UniProtKB:P00762}; DE AltName: Full=Beta-trypsin; DE AltName: Full=Cationic trypsinogen; DE AltName: Full=Pretrypsinogen I {ECO:0000250|UniProtKB:P00762}; DE AltName: Full=Trypsin I {ECO:0000312|HGNC:HGNC:9475}; DE AltName: Full=Trypsin-1; DE Contains: DE RecName: Full=Alpha-trypsin chain 1; DE Contains: DE RecName: Full=Alpha-trypsin chain 2; DE Flags: Precursor; GN Name=PRSS1 {ECO:0000312|HGNC:HGNC:9475}; GN Synonyms=TRP1, TRY1 {ECO:0000312|HGNC:HGNC:9475}, TRYP1; 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 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 receptor RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., 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., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA 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., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., 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., Mural R.J., RA 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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 that RT facilitates trypsin activation."; RL Gastroenterology 119:461-465(2000). RN [9] RP PROTEIN SEQUENCE OF 16-43 AND 123-142, FUNCTION, AND POST-TRANSLATIONAL RP 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 by a RT 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 pancreatitis: RT 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 towards RT basic amino acids."; RL PLoS ONE 9:E102063-E102063(2014). RN [16] RP INTERACTION WITH SERPINA1. RX PubMed=11057674; DOI=10.1038/35038119; RA Huntington J.A., Read R.J., Carrell R.W.; RT "Structure of a serpin-protease complex shows inhibition by deformation."; RL Nature 407:923-926(2000). RN [17] 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., 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 [18] 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 recurrent RT acute and chronic pancreatitis."; RL Gastroenterology 113:1063-1068(1997). RN [19] 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 [20] 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 gene RT is strongly associated with chronic pancreatitis."; RL Gastroenterology 117:7-10(1999). RN [21] 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 [22] 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 in RT the cationic trypsinogen gene and its implication in the genotyping of RT pancreatitis."; RL J. Med. Genet. 37:E36-E36(2000). RN [23] 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 [24] 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., Chen J.-M., RA 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 increased RT transactivation of anionic trypsinogen (PRSS2)."; RL Hum. Mutat. 23:22-31(2004). RN [25] 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 [26] 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., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Has activity against the synthetic substrates Boc-Phe-Ser- CC Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg- CC Mec. The single-chain form is more active than the two-chain form CC against all of these substrates. {ECO:0000269|PubMed:7945238}. 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; CC Note=Binds 1 Ca(2+) ion per subunit.; CC -!- SUBUNIT: Interacts with SERPINA1. {ECO:0000269|PubMed:11057674}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space. CC -!- PTM: Occurs in a single-chain form and a two-chain form, produced by CC proteolytic cleavage after Arg-122. 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 -!- MASS SPECTROMETRY: [Serine protease 1]: Mass=24348; Mass_error=2; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:8683601}; CC -!- DISEASE: Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease CC characterized by pancreas inflammation, permanent destruction of the CC pancreatic parenchyma, maldigestion, and severe abdominal pain attacks. CC {ECO:0000269|PubMed:10204851, ECO:0000269|PubMed:10381903, CC ECO:0000269|PubMed:10930381, ECO:0000269|PubMed:11073545, CC ECO:0000269|PubMed:11788572, ECO:0000269|PubMed:11866271, CC ECO:0000269|PubMed:14695529, ECO:0000269|PubMed:15776435, CC ECO:0000269|PubMed:8841182, ECO:0000269|PubMed:9322498, CC ECO:0000269|PubMed:9633818}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. CC -!- CAUTION: Tyr-154 was proposed to be phosphorylated (PubMed:8683601) but CC it has been shown (PubMed:17087724) to be sulfated instead. Phosphate CC and sulfate groups are similar in mass and size, and this can lead to CC erroneous interpretation of the results. {ECO:0000305|PubMed:17087724, CC ECO:0000305|PubMed:8683601}. 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; -; 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 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 PDB; 7QE8; X-ray; 2.90 A; A/B=24-247. DR PDB; 7QE9; X-ray; 2.10 A; A/B=24-247. DR PDB; 8H3S; EM; 4.90 A; C=16-247. DR PDBsum; 1FXY; -. DR PDBsum; 1TRN; -. DR PDBsum; 2RA3; -. DR PDBsum; 4WWY; -. DR PDBsum; 4WXV; -. DR PDBsum; 7QE8; -. DR PDBsum; 7QE9; -. DR PDBsum; 8H3S; -. DR AlphaFoldDB; P07477; -. DR SMR; P07477; -. DR BioGRID; 111626; 78. DR IntAct; P07477; 20. DR MINT; P07477; -. DR STRING; 9606.ENSP00000308720; -. DR BindingDB; P07477; -. DR ChEMBL; CHEMBL209; -. DR DrugBank; DB02665; (1R,2S)-2-Phenylcyclopropanaminium. DR DrugBank; DB03417; (2S,3R)-2-[[4-(Tert-butylcarbamoyl)piperazine-1-carbonyl]amino]-6-(diaminomethylideneamino)-3-formylhexanoic acid. 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; DB04793; 1,4:3,6-Dianhydro-2-O-(3-carbamimidoylphenyl)-5-O-(4-carbamimidoylphenyl)-D-glucitol. DR DrugBank; DB03337; 1-(2-Amidinophenyl)-3-(Phenoxyphenyl)Urea. DR DrugBank; DB04336; 1-(4-Amidinophenyl)-3-(4-Chlorophenyl)Urea. DR DrugBank; DB08420; 1-{[1-(2-AMINO-3-PHENYL-PROPIONYL)-PYRROLIDINE-2-CARBONYL]-AMINO}-2-(3-CYANO-PHENYL)-ETHANEBORONIC ACID. DR DrugBank; DB04790; 2,5-bis-O-{3-[amino(imino)methyl]phenyl}-1,4:3,6-dianhydro-D-glucitol. DR DrugBank; DB04792; 2,5-O,O-BIS-{4',4''-AMIDINOPHENYL}-1,4:3,6-DIANHYDRO-D-SORBITOL. DR DrugBank; DB01905; 2-(2-Hydroxy-5-Methoxy-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; DB04791; 2-O-(4'-AMIDINOPHENYL)-5-O-(3''-AMIDINOPHENYL)-1,4:3,6-DIANHYDRO-D-SORBITOL. DR DrugBank; DB01725; 2-{2-hydroxy-[1,1'-biphenyl]-3-yl}-1H-1,3-benzodiazole-5-carboximidamide. DR DrugBank; DB01665; 2H-Benzimidazol-2-amine. DR DrugBank; DB03374; 3,5-Diiodotyrosine. DR DrugBank; DB04410; 3-Phenylpropylamine. DR DrugBank; DB07229; 3-{5-[AMINO(IMINIO)METHYL]-1H-INDOL-2-YL}-5-METHOXY-1,1'-BIPHENYL-2-OLATE. 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; DB07491; 5-amino-2,4,6-tribromobenzene-1,3-dicarboxylic acid. DR DrugBank; DB03865; 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine. DR DrugBank; DB06855; 6-fluoro-2-(2-hydroxy-3-isobutoxy-phenyl)-1H-benzoimidazole-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; DB01836; [4-(6-Chloro-Naphthalene-2-Sulfonyl)-Piperazin-1-Yl]-(3,4,5,6-Tetrahydro-2h-[1,4']Bipyridinyl-4-Yl)-Methanone. 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; DB03081; [N-[N-(4-Methoxy-2,3,6-trimethylphenylsulfonyl)-L-aspartyl]-D-(4-amidino-phenylalanyl)]-piperidine. 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; DB03443; bis(5-amidino-benzimidazolyl)methanone zinc. DR DrugBank; DB02081; Bis-Benzamidine. DR DrugBank; DB13729; Camostat. DR DrugBank; DB02288; CRA-9334. DR DrugBank; DB03173; CRA_10433. DR DrugBank; DB02526; CRA_10655. DR DrugBank; DB04470; CRA_10656. DR DrugBank; DB02366; CRA_10762. 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; DB03159; CRA_8696. DR DrugBank; DB04215; CRA_9076. DR DrugBank; DB04563; CRA_9678. DR DrugBank; DB03595; CRA_9785. DR DrugBank; DB04269; Cyclotheonamide A. DR DrugBank; DB06840; diethyl [(1R)-1,5-diaminopentyl]boronate. DR DrugBank; DB03608; Diminazene. DR DrugBank; DB12831; Gabexate. DR DrugBank; DB01767; Hemi-Babim. DR DrugBank; DB04442; Imino[2-(2-oxo-1,2-dihydro-3-pyridinyl)-1H-benzimidazol-5-yl]methanaminium. DR DrugBank; DB07985; METHYL 4-(AMINOIMINOMETHYL)-BETA-[3- INH (AMINOIMINO)PHENYL]BENZENE PENTANOATE. 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; DB12598; Nafamostat. DR DrugBank; DB01737; Nalpha-(2-Naphthylsulfonylglycyl)-3-Amidino-D,L-Phenylalanine-Isopropylester. DR DrugBank; DB04325; Phenethylamine. DR DrugBank; DB03976; Phosphorylisopropane. DR DrugBank; DB04424; RPR128515. DR DrugBank; DB02744; RPR131247. DR DrugBank; DB03251; RWJ-51084. DR DrugBank; DB02812; RWJ-56423. DR DrugBank; DB03876; Thieno[2,3-B]Pyridine-2-Carboxamidine. DR DrugBank; DB04008; Zinc;[amino-[2-[[5-[amino(azaniumylidene)methyl]benzimidazol-1-id-2-yl]methyl]benzimidazol-1-id-5-yl]methylidene]azanium. DR DrugBank; DB04432; ZK-805623. DR DrugBank; DB02112; Zk-806450. DR DrugBank; DB03373; ZK-806711. DR DrugCentral; P07477; -. DR GuidetoPHARMACOLOGY; 2397; -. DR MEROPS; S01.127; -. DR GlyGen; P07477; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P07477; -. DR PhosphoSitePlus; P07477; -. DR BioMuta; PRSS1; -. DR DMDM; 136408; -. DR EPD; P07477; -. DR jPOST; P07477; -. DR MassIVE; P07477; -. DR PaxDb; 9606-ENSP00000308720; -. DR PeptideAtlas; P07477; -. DR ProteomicsDB; 52006; -. DR Antibodypedia; 18375; 576 antibodies from 37 providers. DR DNASU; 5644; -. DR Ensembl; ENST00000311737.12; ENSP00000308720.7; ENSG00000204983.15. DR Ensembl; ENST00000616256.4; ENSP00000479217.1; ENSG00000274247.4. DR GeneID; 5644; -. DR KEGG; hsa:5644; -. DR MANE-Select; ENST00000311737.12; ENSP00000308720.7; NM_002769.5; NP_002760.1. DR UCSC; uc003wak.3; human. DR AGR; HGNC:9475; -. DR CTD; 5644; -. DR DisGeNET; 5644; -. DR GeneCards; PRSS1; -. DR GeneReviews; PRSS1; -. DR HGNC; HGNC:9475; PRSS1. DR HPA; ENSG00000204983; Tissue enriched (pancreas). 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 Orphanet; 64740; NON RARE IN EUROPE: Recurrent acute pancreatitis. DR PharmGKB; PA33828; -. DR VEuPathDB; HostDB:ENSG00000204983; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT01050000244883; -. DR InParanoid; P07477; -. DR OrthoDB; 4629979at2759; -. DR PhylomeDB; P07477; -. DR TreeFam; TF331065; -. DR PathwayCommons; P07477; -. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-HSA-9758881; Uptake of dietary cobalamins into enterocytes. DR SignaLink; P07477; -. DR SIGNOR; P07477; -. DR BioGRID-ORCS; 5644; 12 hits in 1126 CRISPR screens. DR ChiTaRS; PRSS1; human. DR EvolutionaryTrace; P07477; -. DR GeneWiki; Trypsin_1; -. DR GenomeRNAi; 5644; -. DR Pharos; P07477; Tclin. DR PRO; PR:P07477; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P07477; Protein. DR Bgee; ENSG00000204983; Expressed in body of pancreas and 92 other cell types or tissues. DR ExpressionAtlas; P07477; baseline and differential. 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: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 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:SF71; SERINE PROTEASE 1; 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; P07477; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Digestion; Direct protein sequencing; KW Disease variant; Disulfide bond; Hydrolase; Metal-binding; Protease; KW Reference proteome; Secreted; Serine protease; Signal; Sulfation; Zymogen. FT SIGNAL 1..15 FT /evidence="ECO:0000269|PubMed:2598466, FT ECO:0000269|PubMed:7945238" FT PROPEP 16..23 FT /note="Activation peptide" FT /id="PRO_0000028197" FT CHAIN 24..247 FT /note="Serine protease 1" FT /id="PRO_0000028198" FT CHAIN 24..122 FT /note="Alpha-trypsin chain 1" FT /id="PRO_0000313570" FT CHAIN 123..247 FT /note="Alpha-trypsin chain 2" FT /id="PRO_0000313571" 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 ACT_SITE 107 FT /note="Charge relay system" FT ACT_SITE 200 FT /note="Charge relay system" FT BINDING 75 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 77 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 80 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 85 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" 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 DISULFID 48..64 FT DISULFID 139..206 FT DISULFID 171..185 FT DISULFID 196..220 FT VARIANT 16 FT /note="A -> V (in PCTT; disrupts signal sequence cleavage FT site; dbSNP:rs202003805)" FT /evidence="ECO:0000269|PubMed:10381903" FT /id="VAR_011693" FT VARIANT 22 FT /note="D -> G (in PCTT; increased rate of activation; FT dbSNP:rs397507442)" FT /evidence="ECO:0000269|PubMed:10930381" FT /id="VAR_011652" FT VARIANT 23 FT /note="K -> R (in PCTT; increased rate of activation; FT dbSNP:rs111033567)" FT /evidence="ECO:0000269|PubMed:10204851" FT /id="VAR_011653" FT VARIANT 29 FT /note="N -> I (in PCTT; dbSNP:rs111033566)" FT /evidence="ECO:0000269|PubMed:11866271, FT ECO:0000269|PubMed:15776435, ECO:0000269|PubMed:9322498, FT ECO:0000269|PubMed:9633818" FT /id="VAR_006720" FT VARIANT 29 FT /note="N -> T (in PCTT; dbSNP:rs111033566)" FT /evidence="ECO:0000269|PubMed:11788572" FT /id="VAR_012712" FT VARIANT 54 FT /note="N -> S (in PCTT; associated with Ile-29; the double FT mutant shows increased autocatalytic activation which is FT solely due to the Ile-29 mutation; dbSNP:rs144422014)" FT /evidence="ECO:0000269|PubMed:15776435" FT /id="VAR_037908" FT VARIANT 79 FT /note="E -> K (in PCTT; Lys-79 trypsin activates anionic FT trypsinogen PRSS2 2-fold while the common FT pancreatitis-associated mutants His-122 or Ile-29 have no FT such effect; dbSNP:rs111033564)" FT /evidence="ECO:0000269|PubMed:14695529" FT /id="VAR_037909" FT VARIANT 104 FT /note="L -> P (in PCTT; dbSNP:rs1554499091)" FT /evidence="ECO:0000269|PubMed:11866271" FT /id="VAR_011654" FT VARIANT 116 FT /note="R -> C (in PCTT; dbSNP:rs387906698)" FT /evidence="ECO:0000269|PubMed:11866271" FT /id="VAR_011655" FT VARIANT 122 FT /note="R -> C (in PCTT; suppresses an autocleavage site; FT dbSNP:rs111033568)" FT /evidence="ECO:0000269|PubMed:11788572" FT /id="VAR_012713" FT VARIANT 122 FT /note="R -> H (in PCTT; suppresses an autocleavage site FT which is probably part of a fail-safe mechanism by which FT trypsin, which is activated within the pancreas, may be FT inactivated; loss of this cleavage site would permit FT autodigestion resulting in pancreatitis; FT dbSNP:rs267606982)" FT /evidence="ECO:0000269|PubMed:10381903, FT ECO:0000269|PubMed:11073545, ECO:0000269|PubMed:11866271, FT ECO:0000269|PubMed:8841182, ECO:0000269|PubMed:9322498" FT /id="VAR_006721" FT VARIANT 137 FT /note="T -> M (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs117497341)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036299" FT VARIANT 139 FT /note="C -> F (in PCTT)" FT /evidence="ECO:0000269|PubMed:11866271" FT /id="VAR_011656" FT MUTAGEN 154 FT /note="Y->F: Lack of sulfation." FT /evidence="ECO:0000269|PubMed:17087724" FT CONFLICT 4 FT /note="L -> F (in Ref. 7; AAI28227)" FT /evidence="ECO:0000305" FT STRAND 38..54 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 57..60 FT /evidence="ECO:0007829|PDB:2RA3" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 70..74 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 76..80 FT /evidence="ECO:0007829|PDB:7QE9" FT STRAND 86..95 FT /evidence="ECO:0007829|PDB:2RA3" FT TURN 101..103 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 109..115 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 120..122 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 138..144 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 159..165 FT /evidence="ECO:0007829|PDB:2RA3" FT HELIX 168..174 FT /evidence="ECO:0007829|PDB:2RA3" FT TURN 176..178 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 183..187 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 192..194 FT /evidence="ECO:0007829|PDB:1TRN" FT STRAND 203..206 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 209..216 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 218..222 FT /evidence="ECO:0007829|PDB:2RA3" FT STRAND 227..231 FT /evidence="ECO:0007829|PDB:2RA3" FT HELIX 232..235 FT /evidence="ECO:0007829|PDB:2RA3" FT HELIX 236..245 FT /evidence="ECO:0007829|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 //