ID   NETR_RAT                Reviewed;         761 AA.
AC   G3V801; Q99JC8;
DT   18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT   16-NOV-2011, sequence version 1.
DT   24-JAN-2024, entry version 73.
DE   RecName: Full=Neurotrypsin;
DE            EC=3.4.21.-;
DE   AltName: Full=Serine protease 12;
DE   Flags: Precursor;
GN   Name=Prss12;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Hintsch G., Sonderegger P.;
RT   "Cloning and sequencing of the cDNA encoding rat neurotrypsin.";
RL   Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   STRUCTURE BY NMR OF 84-160, PARTIAL PROTEIN SEQUENCE, DISULFIDE BOND, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=18956887; DOI=10.1021/bi800555z;
RA   Ozhogina O.A., Grishaev A., Bominaar E.L., Patthy L., Trexler M.,
RA   Llinas M.;
RT   "NMR solution structure of the neurotrypsin Kringle domain.";
RL   Biochemistry 47:12290-12298(2008).
CC   -!- FUNCTION: Plays a role in neuronal plasticity and the proteolytic
CC       action may subserve structural reorganizations associated with learning
CC       and memory operations. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00274}.
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DR   EMBL; AJ311671; CAC35028.2; -; mRNA.
DR   EMBL; CH473952; EDL82129.1; -; Genomic_DNA.
DR   RefSeq; NP_445956.1; NM_053504.1.
DR   PDB; 2K4R; NMR; -; A=84-160.
DR   PDB; 2K51; NMR; -; A=84-160.
DR   PDBsum; 2K4R; -.
DR   PDBsum; 2K51; -.
DR   AlphaFoldDB; G3V801; -.
DR   BMRB; G3V801; -.
DR   SMR; G3V801; -.
DR   STRING; 10116.ENSRNOP00000021116; -.
DR   MEROPS; S01.237; -.
DR   GlyCosmos; G3V801; 3 sites, No reported glycans.
DR   GlyGen; G3V801; 3 sites.
DR   PhosphoSitePlus; G3V801; -.
DR   PaxDb; 10116-ENSRNOP00000021116; -.
DR   Ensembl; ENSRNOT00000021116.4; ENSRNOP00000021116.3; ENSRNOG00000015353.4.
DR   GeneID; 85266; -.
DR   KEGG; rno:85266; -.
DR   AGR; RGD:69238; -.
DR   CTD; 8492; -.
DR   RGD; 69238; Prss12.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT00940000158131; -.
DR   HOGENOM; CLU_013656_0_0_1; -.
DR   InParanoid; G3V801; -.
DR   OMA; GPIHADN; -.
DR   OrthoDB; 3035117at2759; -.
DR   PhylomeDB; G3V801; -.
DR   TreeFam; TF329295; -.
DR   PRO; PR:G3V801; -.
DR   Proteomes; UP000002494; Chromosome 2.
DR   Proteomes; UP000234681; Chromosome 2.
DR   Bgee; ENSRNOG00000015353; Expressed in kidney and 15 other cell types or tissues.
DR   GO; GO:0030424; C:axon; ISS:UniProtKB.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR   GO; GO:0030425; C:dendrite; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; ISO:RGD.
DR   GO; GO:0043083; C:synaptic cleft; ISO:RGD.
DR   GO; GO:0043195; C:terminal bouton; ISO:RGD.
DR   GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISO:RGD.
DR   GO; GO:0006887; P:exocytosis; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; ISO:RGD.
DR   GO; GO:0031638; P:zymogen activation; ISO:RGD.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.40.20.10; Plasminogen Kringle 4; 1.
DR   Gene3D; 3.10.250.10; SRCR-like domain; 3.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR   InterPro; IPR000001; Kringle.
DR   InterPro; IPR013806; Kringle-like.
DR   InterPro; IPR018056; Kringle_CS.
DR   InterPro; IPR038178; Kringle_sf.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001190; SRCR.
DR   InterPro; IPR017448; SRCR-like_dom.
DR   InterPro; IPR036772; SRCR-like_dom_sf.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR48071:SF5; NEUROTRYPSIN; 1.
DR   PANTHER; PTHR48071; SRCR DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF00530; SRCR; 3.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   PRINTS; PR00258; SPERACTRCPTR.
DR   SMART; SM00130; KR; 1.
DR   SMART; SM00202; SR; 3.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF57440; Kringle-like; 1.
DR   SUPFAM; SSF56487; SRCR-like; 3.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS00021; KRINGLE_1; 1.
DR   PROSITE; PS50070; KRINGLE_2; 1.
DR   PROSITE; PS00420; SRCR_1; 3.
DR   PROSITE; PS50287; SRCR_2; 3.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Hydrolase; Kringle; Protease; Reference proteome; Repeat; Secreted;
KW   Serine protease; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..761
FT                   /note="Neurotrypsin"
FT                   /id="PRO_0000416843"
FT   DOMAIN          85..157
FT                   /note="Kringle"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT   DOMAIN          166..267
FT                   /note="SRCR 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT   DOMAIN          273..373
FT                   /note="SRCR 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT   DOMAIN          386..487
FT                   /note="SRCR 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT   DOMAIN          517..760
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   REGION          26..89
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          505..516
FT                   /note="Zymogen activation region"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        51..65
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        562
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        612
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        711
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   SITE            516..517
FT                   /note="Reactive bond homolog"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        93
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        521
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        569
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        85..157
FT                   /evidence="ECO:0000269|PubMed:18956887"
FT   DISULFID        101..141
FT                   /evidence="ECO:0000269|PubMed:18956887"
FT   DISULFID        130..155
FT                   /evidence="ECO:0000269|PubMed:18956887"
FT   DISULFID        191..255
FT                   /evidence="ECO:0000250"
FT   DISULFID        204..265
FT                   /evidence="ECO:0000250"
FT   DISULFID        235..245
FT                   /evidence="ECO:0000250"
FT   DISULFID        298..361
FT                   /evidence="ECO:0000250"
FT   DISULFID        311..371
FT                   /evidence="ECO:0000250"
FT   DISULFID        341..351
FT                   /evidence="ECO:0000250"
FT   DISULFID        411..475
FT                   /evidence="ECO:0000250"
FT   DISULFID        424..485
FT                   /evidence="ECO:0000250"
FT   DISULFID        455..465
FT                   /evidence="ECO:0000250"
FT   DISULFID        505..636
FT                   /evidence="ECO:0000255"
FT   DISULFID        547..563
FT                   /evidence="ECO:0000250"
FT   DISULFID        651..717
FT                   /evidence="ECO:0000250"
FT   DISULFID        680..694
FT                   /evidence="ECO:0000250"
FT   DISULFID        707..736
FT                   /evidence="ECO:0000250"
FT   CONFLICT        134
FT                   /note="G -> D (in Ref. 1; CAC35028)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        404
FT                   /note="S -> N (in Ref. 1; CAC35028)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        515
FT                   /note="K -> T (in Ref. 1; CAC35028)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        565
FT                   /note="K -> T (in Ref. 1; CAC35028)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        588
FT                   /note="E -> G (in Ref. 1; CAC35028)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        592
FT                   /note="E -> D (in Ref. 1; CAC35028)"
FT                   /evidence="ECO:0000305"
FT   STRAND          92..95
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   STRAND          98..101
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   HELIX           104..106
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   HELIX           119..121
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   STRAND          131..134
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   TURN            135..137
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   STRAND          138..144
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   STRAND          150..154
FT                   /evidence="ECO:0007829|PDB:2K4R"
FT   STRAND          156..158
FT                   /evidence="ECO:0007829|PDB:2K4R"
SQ   SEQUENCE   761 AA;  84220 MW;  215EE73A3CE468EA CRC64;
     MALARCVLAV ILGVLSEVAR ADPVLHSPLH RPHPSPPRSQ HAHYLPSSRR PPRTPRFPLP
     PRAPAAQRPQ LLSTRHTPPT ISRRCGAGEP WGNATNLGVP CLHWDEVPPF LERSPPASWA
     ELRGQPHNFC RSPGGAGRPW CFYRNAQGKV DWGYCDCGQG PALPVIRLVG GKSGHEGRVE
     LYHAGQWGTI CDDQWDDADA EVICRQLGLS GIAKAWHQAH FGEGSGPILL DEVRCTGNEL
     SIEQCPKSSW GEHNCGHKED AGVSCAPLTD GVIRLSGGKS VHEGRLEVYY RGQWGTVCDD
     GWTEMNTYVA CRLLGFKYGK QSSVNHFEGS SRPIWLDDVS CSGKEASFIQ CSRRQWGRHD
     CSHREDVGLT CYPDSDGHRL SPGFPIRLMD GENKREGRVE VFVSGQWGTI CDDGWTDKHA
     AVICRQLGYK GPARARTMAY FGEGKGPIHM DNVKCTGNEK ALADCVKQDI GRHNCRHSED
     AGVICDYYEK KTSGHGNKET LSSGCGLRLL HRRQKRIIGG NNSLRGAWPW QASLRLKSTH
     GDGRLLCGAT LLSSCWVLTA AHCFKRYGNN SRSYAVRVGD YHTLVPEEFE QEIGVQQIVI
     HRNYRPDSSD YDIALVRLQG SGEQCARLST HVLPACLPLW RERPQKTASN CHITGWGDTG
     RAYSRTLQQA AVPLLPKRFC KERYKGLFTG RMLCAGNLQE DNRVDSCQGD SGGPLMCEKP
     DETWVVYGVT SWGYGCGIKD TPGVYTRVPA FVPWIKSVTS L
//