NETR_HUMAN
ID NETR_HUMAN Reviewed; 875 AA.
AC P56730; Q9UP16;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Neurotrypsin;
DE EC=3.4.21.-;
DE AltName: Full=Leydin;
DE AltName: Full=Motopsin;
DE AltName: Full=Serine protease 12;
DE Flags: Precursor;
GN Name=PRSS12;
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].
RC TISSUE=Brain;
RX PubMed=9540828; DOI=10.1016/s0167-4781(97)00205-4;
RA Proba K., Gschwend T.P., Sonderegger P.;
RT "Cloning and sequencing of the cDNA encoding human neurotrypsin.";
RL Biochim. Biophys. Acta 1396:143-147(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 615-875.
RC TISSUE=Testis;
RX PubMed=10103056; DOI=10.1046/j.1432-1327.1999.00266.x;
RA Poorafshar M., Hellman L.;
RT "Cloning and structural analysis of leydin, a novel human serine protease
RT expressed by the Leydig cells of the testis.";
RL Eur. J. Biochem. 261:244-250(1999).
RN [4]
RP INVOLVEMENT IN MRT1.
RX PubMed=12459588; DOI=10.1126/science.1076521;
RA Molinari F., Rio M., Meskenaite V., Encha-Razavi F., Auge J., Bacq D.,
RA Briault S., Vekemans M., Munnich A., Attie-Bitach T., Sonderegger P.,
RA Colleaux L.;
RT "Truncating neurotrypsin mutation in autosomal recessive nonsyndromic
RT mental retardation.";
RL Science 298:1779-1781(2002).
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.
CC -!- TISSUE SPECIFICITY: Brain and Leydig cells of the testis.
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 1
CC (MRT1) [MIM:249500]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:12459588}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AJ001531; CAA04816.1; -; mRNA.
DR EMBL; AC096762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF077298; AAD25919.1; -; mRNA.
DR CCDS; CCDS3709.1; -.
DR RefSeq; NP_003610.2; NM_003619.3.
DR AlphaFoldDB; P56730; -.
DR SMR; P56730; -.
DR BioGRID; 114064; 19.
DR IntAct; P56730; 5.
DR STRING; 9606.ENSP00000296498; -.
DR ChEMBL; CHEMBL4523246; -.
DR MEROPS; S01.237; -.
DR GlyGen; P56730; 2 sites.
DR iPTMnet; P56730; -.
DR PhosphoSitePlus; P56730; -.
DR BioMuta; PRSS12; -.
DR DMDM; 259016287; -.
DR MassIVE; P56730; -.
DR PaxDb; P56730; -.
DR PeptideAtlas; P56730; -.
DR PRIDE; P56730; -.
DR ProteomicsDB; 56941; -.
DR Antibodypedia; 26601; 135 antibodies from 25 providers.
DR DNASU; 8492; -.
DR Ensembl; ENST00000296498.3; ENSP00000296498.3; ENSG00000164099.3.
DR GeneID; 8492; -.
DR KEGG; hsa:8492; -.
DR MANE-Select; ENST00000296498.3; ENSP00000296498.3; NM_003619.4; NP_003610.2.
DR UCSC; uc003ica.3; human.
DR CTD; 8492; -.
DR DisGeNET; 8492; -.
DR GeneCards; PRSS12; -.
DR HGNC; HGNC:9477; PRSS12.
DR HPA; ENSG00000164099; Low tissue specificity.
DR MalaCards; PRSS12; -.
DR MIM; 249500; phenotype.
DR MIM; 606709; gene.
DR neXtProt; NX_P56730; -.
DR OpenTargets; ENSG00000164099; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA33830; -.
DR VEuPathDB; HostDB:ENSG00000164099; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000158131; -.
DR HOGENOM; CLU_013656_0_0_1; -.
DR InParanoid; P56730; -.
DR OMA; KQDIGKH; -.
DR OrthoDB; 158600at2759; -.
DR PhylomeDB; P56730; -.
DR TreeFam; TF329295; -.
DR PathwayCommons; P56730; -.
DR SignaLink; P56730; -.
DR BioGRID-ORCS; 8492; 8 hits in 1068 CRISPR screens.
DR ChiTaRS; PRSS12; human.
DR GenomeRNAi; 8492; -.
DR Pharos; P56730; Tchem.
DR PRO; PR:P56730; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P56730; protein.
DR Bgee; ENSG00000164099; Expressed in bronchial epithelial cell and 134 other tissues.
DR Genevisible; P56730; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043083; C:synaptic cleft; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0006887; P:exocytosis; ISS:UniProtKB.
DR GO; GO:0031638; P:zymogen activation; IBA:GO_Central.
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; -; 4.
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; PF00051; Kringle; 1.
DR Pfam; PF00530; SRCR; 4.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00258; SPERACTRCPTR.
DR SMART; SM00130; KR; 1.
DR SMART; SM00202; SR; 4.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56487; SSF56487; 4.
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; 4.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Hydrolase; Intellectual disability; Kringle;
KW Protease; Reference proteome; Repeat; Secreted; Serine protease; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..875
FT /note="Neurotrypsin"
FT /id="PRO_0000027663"
FT DOMAIN 93..165
FT /note="Kringle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 170..271
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 280..381
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 387..487
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 500..601
FT /note="SRCR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 631..874
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 29..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 619..630
FT /note="Zymogen activation region"
FT COMPBIAS 41..73
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 676
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 726
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 825
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 630..631
FT /note="Reactive bond homolog"
FT /evidence="ECO:0000255"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 683
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 93..165
FT /evidence="ECO:0000250"
FT DISULFID 109..149
FT /evidence="ECO:0000250"
FT DISULFID 138..163
FT /evidence="ECO:0000250"
FT DISULFID 195..259
FT /evidence="ECO:0000250"
FT DISULFID 208..269
FT /evidence="ECO:0000250"
FT DISULFID 239..249
FT /evidence="ECO:0000250"
FT DISULFID 305..369
FT /evidence="ECO:0000250"
FT DISULFID 318..379
FT /evidence="ECO:0000250"
FT DISULFID 349..359
FT /evidence="ECO:0000250"
FT DISULFID 412..475
FT /evidence="ECO:0000250"
FT DISULFID 425..485
FT /evidence="ECO:0000250"
FT DISULFID 455..465
FT /evidence="ECO:0000250"
FT DISULFID 525..589
FT /evidence="ECO:0000250"
FT DISULFID 538..599
FT /evidence="ECO:0000250"
FT DISULFID 569..579
FT /evidence="ECO:0000250"
FT DISULFID 619..750
FT /evidence="ECO:0000255"
FT DISULFID 661..677
FT /evidence="ECO:0000250"
FT DISULFID 765..831
FT /evidence="ECO:0000250"
FT DISULFID 794..808
FT /evidence="ECO:0000250"
FT DISULFID 821..850
FT /evidence="ECO:0000250"
FT VARIANT 606
FT /note="A -> S (in dbSNP:rs28661939)"
FT /id="VAR_051835"
FT VARIANT 833
FT /note="R -> Q (in dbSNP:rs17594503)"
FT /id="VAR_051836"
FT CONFLICT 55
FT /note="R -> T (in Ref. 1; CAA04816)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="A -> V (in Ref. 3; AAD25919)"
FT /evidence="ECO:0000305"
FT CONFLICT 701
FT /note="E -> V (in Ref. 3; AAD25919)"
FT /evidence="ECO:0000305"
FT CONFLICT 839..841
FT /note="VVY -> AAL (in Ref. 3; AAD25919)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 875 AA; 97067 MW; EB357047C39371BC CRC64;
MTLARFVLAL MLGALPEVVG FDSVLNDSLH HSHRHSPPAG PHYPYYLPTQ QRPPRTRPPP
PLPRFPRPPR ALPAQRPHAL QAGHTPRPHP WGCPAGEPWV SVTDFGAPCL RWAEVPPFLE
RSPPASWAQL RGQRHNFCRS PDGAGRPWCF YGDARGKVDW GYCDCRHGSV RLRGGKNEFE
GTVEVYASGV WGTVCSSHWD DSDASVICHQ LQLGGKGIAK QTPFSGLGLI PIYWSNVRCR
GDEENILLCE KDIWQGGVCP QKMAAAVTCS FSHGPTFPII RLAGGSSVHE GRVELYHAGQ
WGTVCDDQWD DADAEVICRQ LGLSGIAKAW HQAYFGEGSG PVMLDEVRCT GNELSIEQCP
KSSWGEHNCG HKEDAGVSCT PLTDGVIRLA GGKGSHEGRL EVYYRGQWGT VCDDGWTELN
TYVVCRQLGF KYGKQASANH FEESTGPIWL DDVSCSGKET RFLQCSRRQW GRHDCSHRED
VSIACYPGGE GHRLSLGFPV RLMDGENKKE GRVEVFINGQ WGTICDDGWT DKDAAVICRQ
LGYKGPARAR TMAYFGEGKG PIHVDNVKCT GNERSLADCI KQDIGRHNCR HSEDAGVICD
YFGKKASGNS NKESLSSVCG LRLLHRRQKR IIGGKNSLRG GWPWQVSLRL KSSHGDGRLL
CGATLLSSCW VLTAAHCFKR YGNSTRSYAV RVGDYHTLVP EEFEEEIGVQ QIVIHREYRP
DRSDYDIALV RLQGPEEQCA RFSSHVLPAC LPLWRERPQK TASNCYITGW GDTGRAYSRT
LQQAAIPLLP KRFCEERYKG RFTGRMLCAG NLHEHKRVDS CQGDSGGPLM CERPGESWVV
YGVTSWGYGC GVKDSPGVYT KVSAFVPWIK SVTKL
