ID TRY4_MOUSE Reviewed; 246 AA. AC Q9R0T7; DT 03-MAY-2023, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 29-MAY-2024, entry version 179. DE RecName: Full=Trypsin-4 {ECO:0000312|MGI:MGI:102757}; DE EC=3.4.21.4 {ECO:0000269|PubMed:23814066}; DE Flags: Precursor; GN Name=Try4 {ECO:0000312|MGI:MGI:102757}; GN Synonyms=T8 {ECO:0000303|PubMed:23814066}, GN Td {ECO:0000303|PubMed:10506205}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090 {ECO:0000312|Proteomes:UP000000589}; RN [1] {ECO:0000312|EMBL:BAA74761.1} RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RC STRAIN=129/SvJ {ECO:0000312|EMBL:BAA74761.1}; RX PubMed=10506205; DOI=10.1074/jbc.274.41.29426; RA Ohmura K., Kohno N., Kobayashi Y., Yamagata K., Sato S., Kashiwabara S., RA Baba T.; RT "A homologue of pancreatic trypsin is localized in the acrosome of RT mammalian sperm and is released during acrosome reaction."; RL J. Biol. Chem. 274:29426-29432(1999). RN [2] {ECO:0000312|EMBL:AAB69056.1} RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11160223; DOI=10.4049/jimmunol.166.3.1771; RA Chen F., Rowen L., Hood L., Rothenberg E.V.; RT "Differential transcriptional regulation of individual TCR V beta segments RT before gene rearrangement."; RL J. Immunol. 166:1771-1780(2001). RN [3] {ECO:0000312|EMBL:BAB22542.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB22542.1}; RC TISSUE=Spleen {ECO:0000312|EMBL:BAB22542.1}, and RC Stomach {ECO:0000312|EMBL:BAB25821.1}; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] {ECO:0000312|Proteomes:UP000000589} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589}; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] {ECO:0000312|EMBL:AAH61135.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver {ECO:0000312|EMBL:AAH61135.1}; 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 [6] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, CLEAVAGE BY RP AUTOCATALYSIS, AND MUTAGENESIS OF ARG-122. RX PubMed=23814066; DOI=10.1074/jbc.m113.478800; RA Nemeth B.C., Wartmann T., Halangk W., Sahin-Toth M.; RT "Autoactivation of mouse trypsinogens is regulated by chymotrypsin C via RT cleavage of the autolysis loop."; RL J. Biol. Chem. 288:24049-24062(2013). CC -!- FUNCTION: Serine protease capable of autoactivation. CC {ECO:0000269|PubMed:23814066}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.; EC=3.4.21.4; CC Evidence={ECO:0000269|PubMed:23814066}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:P35030}; CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:P35030}; CC -!- ACTIVITY REGULATION: Activated by autocatalytic cleavage CC (PubMed:23814066). Cleavage by CTRC inhibits autoactivation CC (PubMed:23814066). {ECO:0000269|PubMed:23814066}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Expressed in the pancreas, lung and kidney. CC {ECO:0000269|PubMed:10506205}. CC -!- PTM: Proteolytically cleaved and activated by an autocatalytic CC mechanism (PubMed:23814066). Cleavage by CTRC inhibits autoactivation CC (PubMed:23814066). {ECO:0000269|PubMed:23814066}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. 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; AB017032; BAA74761.1; -; Genomic_DNA. DR EMBL; AE000664; AAB69056.1; -; Genomic_DNA. DR EMBL; AK003064; BAB22542.1; -; mRNA. DR EMBL; AK008667; BAB25821.1; -; mRNA. DR EMBL; BC061135; AAH61135.1; -; mRNA. DR CCDS; CCDS20044.1; -. DR RefSeq; NP_035776.1; NM_011646.5. DR AlphaFoldDB; Q9R0T7; -. DR SMR; Q9R0T7; -. DR STRING; 10090.ENSMUSP00000031913; -. DR MEROPS; S01.057; -. DR MaxQB; Q9R0T7; -. DR PaxDb; 10090-ENSMUSP00000031913; -. DR DNASU; 22074; -. DR Ensembl; ENSMUST00000031913.5; ENSMUSP00000031913.5; ENSMUSG00000054106.8. DR GeneID; 22074; -. DR KEGG; mmu:22074; -. DR UCSC; uc009bos.1; mouse. DR AGR; MGI:102757; -. DR CTD; 22074; -. DR MGI; MGI:102757; Try4. DR VEuPathDB; HostDB:ENSMUSG00000054106; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT01050000244883; -. DR HOGENOM; CLU_006842_7_0_1; -. DR InParanoid; Q9R0T7; -. DR OMA; QCEAAYP; -. DR OrthoDB; 1314811at2759; -. DR TreeFam; TF331065; -. DR Reactome; R-MMU-1442490; Collagen degradation. DR Reactome; R-MMU-1462054; Alpha-defensins. DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR Reactome; R-MMU-6803157; Antimicrobial peptides. DR BioGRID-ORCS; 22074; 5 hits in 46 CRISPR screens. DR ChiTaRS; Try4; mouse. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q9R0T7; Protein. DR Bgee; ENSMUSG00000054106; Expressed in pancreas and 22 other cell types or tissues. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. 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; IDA:MGI. 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:SF57; TRYPSIN-2; 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. PE 1: Evidence at protein level; KW Autocatalytic cleavage; Calcium; Disulfide bond; Hydrolase; Metal-binding; KW Protease; Reference proteome; Secreted; Serine protease; Signal; Zymogen. FT SIGNAL 1..15 FT /evidence="ECO:0000255" FT PROPEP 16..23 FT /note="Activation peptide" FT /evidence="ECO:0000305" FT /id="PRO_0000457719" FT CHAIN 24..246 FT /note="Trypsin-4" FT /evidence="ECO:0000255" FT /id="PRO_5015099944" 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:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 107 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 200 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT BINDING 75 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P35030" FT BINDING 77 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P35030" FT BINDING 80 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P35030" FT BINDING 82 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P35030" FT BINDING 85 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P35030" FT SITE 81..82 FT /note="Cleavage; by CTRC" FT /evidence="ECO:0000269|PubMed:23814066" FT SITE 122..123 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:23814066" FT SITE 150..151 FT /note="Cleavage; by CTRC" FT /evidence="ECO:0000269|PubMed:23814066" FT SITE 193..194 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:23814066" FT DISULFID 48..64 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 139..206 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 MUTAGEN 122 FT /note="R->H: Slightly increases autoactivation." FT /evidence="ECO:0000269|PubMed:23814066" SQ SEQUENCE 246 AA; 26274 MW; B6A9F4C99079633F CRC64; MRALLFLALV GAAVAFPVDD DDKIVGGYTC RENSVPYQVS LNSGYHFCGG SLINDQWVVS AAHCYKSRIQ VRLGEHNINV LEGNEQFVNS AKIIKHPNFN SRTLNNDIML IKLASPVTLN ARVATVALPS SCAPAGTQCL ISGWGNTLSF GVNNPDLLQC LDAPLLPQAD CEASYPGKIT NNMICVGFLE GGKDSCQGDS GGPVVCNGQL QGIVSWGYGC ALKDNPGVYT KVCNYVDWIQ NTIAAN //