ID   TRY6_HUMAN              Reviewed;         247 AA.
AC   Q8NHM4;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   19-FEB-2014, sequence version 2.
DT   24-JAN-2024, entry version 121.
DE   RecName: Full=Putative trypsin-6;
DE            EC=3.4.21.4;
DE   AltName: Full=Serine protease 3 pseudogene 2;
DE   AltName: Full=Trypsinogen C;
DE   Flags: Precursor;
GN   Name=PRSS3P2; Synonyms=T6, TRY6;
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 [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   [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   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=15313892; DOI=10.1158/0008-5472.can-04-2004;
RA   Diederichs S., Bulk E., Steffen B., Ji P., Tickenbrock L., Lang K.,
RA   Zanker K.S., Metzger R., Schneider P.M., Gerke V., Thomas M., Berdel W.E.,
RA   Serve H., Muller-Tidow C.;
RT   "S100 family members and trypsinogens are predictors of distant metastasis
RT   and survival in early-stage non-small cell lung cancer.";
RL   Cancer Res. 64:5564-5569(2004).
CC   -!- FUNCTION: May regulate cell migration. {ECO:0000269|PubMed:15313892}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.; EC=3.4.21.4;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Overexpressed in metastasing in non small cell lung
CC       tumors, leading to an enhanced cell migration.
CC       {ECO:0000269|PubMed:15313892}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Tryptase subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC   -!- CAUTION: Could be the product of a pseudogene. However, some data
CC       suggest that it could be a protein-coding gene (PubMed:15313892).
CC       {ECO:0000305|PubMed:15313892}.
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; AC231380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; L36092; AAC80208.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q8NHM4; -.
DR   SMR; Q8NHM4; -.
DR   IntAct; Q8NHM4; 3.
DR   MEROPS; S01.298; -.
DR   iPTMnet; Q8NHM4; -.
DR   PhosphoSitePlus; Q8NHM4; -.
DR   BioMuta; HGNC:43788; -.
DR   DMDM; 74760358; -.
DR   jPOST; Q8NHM4; -.
DR   MassIVE; Q8NHM4; -.
DR   PeptideAtlas; Q8NHM4; -.
DR   ProteomicsDB; 73722; -.
DR   Pumba; Q8NHM4; -.
DR   AGR; HGNC:43788; -.
DR   GeneCards; PRSS3P2; -.
DR   HGNC; HGNC:43788; PRSS3P2.
DR   neXtProt; NX_Q8NHM4; -.
DR   InParanoid; Q8NHM4; -.
DR   PathwayCommons; Q8NHM4; -.
DR   SignaLink; Q8NHM4; -.
DR   Pharos; Q8NHM4; Tdark.
DR   Proteomes; UP000005640; Unplaced.
DR   RNAct; Q8NHM4; Protein.
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:0043542; P:endothelial cell migration; IMP:UniProtKB.
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:SF64; TRYPSIN-6-RELATED; 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   5: Uncertain;
KW   Calcium; Disulfide bond; Hydrolase; Metal-binding; Protease;
KW   Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT   SIGNAL          1..15
FT                   /evidence="ECO:0000255"
FT   CHAIN           16..247
FT                   /note="Putative trypsin-6"
FT                   /id="PRO_0000337059"
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   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   CONFLICT        103
FT                   /note="I -> T (in Ref. 2; AAC80208)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        182
FT                   /note="N -> K (in Ref. 2; AAC80208)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   247 AA;  26537 MW;  4F93CA1C93803264 CRC64;
     MNPLLILAFV GAAVAVPFDD DDKIVGGYTC EENSVPYQVS LNSGSHFCGG SLISEQWVVS
     AGHCYKPHIQ VRLGEHNIEV LEGNEQFINA AKIIRHPKYN RIILNNDIML IKLSTPAVIN
     AHVSTISLPT APPAAGTECL ISGWGNTLSS GADYPDELQC LDAPVLTQAK CKASYPLKIT
     SNMFCVGFLE GGKDSCQGDS GGPVVCNGQL QGIVSWGYGC AQKRRPGVYT KVYNYVDWIK
     DTIAANS
//