NETR_RAT
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 03-AUG-2022, entry version 67.
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 GlyGen; G3V801; 3 sites.
DR PaxDb; G3V801; -.
DR PRIDE; G3V801; -.
DR Ensembl; ENSRNOT00000021116; ENSRNOP00000021116; ENSRNOG00000015353.
DR GeneID; 85266; -.
DR KEGG; rno:85266; -.
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; KQDIGKH; -.
DR OrthoDB; 158600at2759; -.
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 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:0005044; F:scavenger receptor activity; IEA:InterPro.
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; 2.40.10.10; -; 1.
DR Gene3D; 2.40.20.10; -; 1.
DR Gene3D; 3.10.250.10; -; 3.
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 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; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56487; SSF56487; 3.
DR SUPFAM; SSF57440; SSF57440; 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
