PRS57_HUMAN
ID PRS57_HUMAN Reviewed; 283 AA.
AC Q6UWY2; B2RNW8;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Serine protease 57;
DE EC=3.4.21.- {ECO:0000269|PubMed:22474388, ECO:0000269|PubMed:23904161, ECO:0000269|PubMed:25156428};
DE AltName: Full=Neutrophil serine protease 4 {ECO:0000303|PubMed:22474388, ECO:0000303|PubMed:25156428};
DE Short=NSP4 {ECO:0000303|PubMed:22474388, ECO:0000303|PubMed:23904161, ECO:0000303|PubMed:25156428};
DE AltName: Full=Serine protease 1-like protein 1;
DE Flags: Precursor;
GN Name=PRSS57; Synonyms=PRSSL1; ORFNames=UNQ782/PRO1599;
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 MRNA], AND VARIANT LEU-143.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-143.
RC TISSUE=Testis;
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 [4]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP SIGNAL SEQUENCE, PROTEOLYTIC CLEAVAGE, AND TISSUE SPECIFICITY.
RX PubMed=22474388; DOI=10.1073/pnas.1200470109;
RA Perera N.C., Schilling O., Kittel H., Back W., Kremmer E., Jenne D.E.;
RT "NSP4, an elastase-related protease in human neutrophils with arginine
RT specificity.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:6229-6234(2012).
RN [5]
RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE BY
RP CTSC, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=23904161; DOI=10.4049/jimmunol.1301293;
RA Perera N.C., Wiesmueller K.H., Larsen M.T., Schacher B., Eickholz P.,
RA Borregaard N., Jenne D.E.;
RT "NSP4 is stored in azurophil granules and released by activated neutrophils
RT as active endoprotease with restricted specificity.";
RL J. Immunol. 191:2700-2707(2013).
RN [6] {ECO:0007744|PDB:4Q7X, ECO:0007744|PDB:4Q7Y, ECO:0007744|PDB:4Q7Z, ECO:0007744|PDB:4Q80}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 34-283 IN COMPLEX WITH SUBSTRATE
RP ANALOG, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, GLYCOSYLATION AT ASN-129
RP AND ASN-189, DISULFIDE BONDS, HEPARIN-BINDING, AND MUTAGENESIS OF PHE-213;
RP SER-215 AND SER-235.
RX PubMed=25156428; DOI=10.1016/j.str.2014.07.008;
RA Lin S.J., Dong K.C., Eigenbrot C., van Lookeren Campagne M., Kirchhofer D.;
RT "Structures of neutrophil serine protease 4 reveal an unusual mechanism of
RT substrate recognition by a trypsin-fold protease.";
RL Structure 22:1333-1340(2014).
CC -!- FUNCTION: Serine protease that cleaves preferentially after Arg
CC residues (PubMed:22474388, PubMed:23904161, PubMed:25156428). Can also
CC cleave after citrulline (deimidated arginine) and methylarginine
CC residues (PubMed:25156428). {ECO:0000269|PubMed:22474388,
CC ECO:0000269|PubMed:23904161, ECO:0000269|PubMed:25156428}.
CC -!- ACTIVITY REGULATION: Inhibited by SERPINA1, SERPINC1 and SERPING1.
CC {ECO:0000269|PubMed:22474388}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule lumen
CC {ECO:0000269|PubMed:22474388, ECO:0000269|PubMed:23904161}. Secreted
CC {ECO:0000269|PubMed:22474388, ECO:0000269|PubMed:23904161}. Note=Stored
CC in cytoplasmic granules and secreted as active enzyme in response to
CC stimulation of neutrophils. {ECO:0000269|PubMed:22474388}.
CC -!- TISSUE SPECIFICITY: Detected in peripheral blood neutrophil
CC granulocytes, but not in other types of leukocytes. Detected in
CC neutrophils and neutrophil precursors in bone marrow (at protein level)
CC (PubMed:22474388, PubMed:23904161). Detected in myeloblasts and
CC promyelocytes in bone marrow (PubMed:23904161).
CC {ECO:0000269|PubMed:22474388, ECO:0000269|PubMed:23904161}.
CC -!- PTM: After cleavage of the signal peptide, the N-terminus is probably
CC further processed by CTSC (PubMed:22474388, PubMed:23904161).
CC Processing by CTSC is probably required for accumulation in cytoplasmic
CC granules; in the absence of CTSC the protein does not accumulate
CC (PubMed:23904161). {ECO:0000269|PubMed:23904161,
CC ECO:0000305|PubMed:22474388}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:23904161}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AY358594; AAQ88957.1; -; mRNA.
DR EMBL; AC004156; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC112708; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137161; AAI37162.1; -; mRNA.
DR CCDS; CCDS12041.1; -.
DR RefSeq; NP_999875.1; NM_214710.4.
DR PDB; 4Q7X; X-ray; 2.55 A; A/B=34-283.
DR PDB; 4Q7Y; X-ray; 2.70 A; A=34-283.
DR PDB; 4Q7Z; X-ray; 1.40 A; A=34-283.
DR PDB; 4Q80; X-ray; 3.07 A; A/B=34-283.
DR PDBsum; 4Q7X; -.
DR PDBsum; 4Q7Y; -.
DR PDBsum; 4Q7Z; -.
DR PDBsum; 4Q80; -.
DR AlphaFoldDB; Q6UWY2; -.
DR SMR; Q6UWY2; -.
DR STRING; 9606.ENSP00000482358; -.
DR MEROPS; S01.319; -.
DR GlyGen; Q6UWY2; 2 sites.
DR BioMuta; PRSS57; -.
DR DMDM; 296452873; -.
DR EPD; Q6UWY2; -.
DR MassIVE; Q6UWY2; -.
DR PaxDb; Q6UWY2; -.
DR PeptideAtlas; Q6UWY2; -.
DR PRIDE; Q6UWY2; -.
DR ProteomicsDB; 67537; -.
DR Antibodypedia; 1455; 56 antibodies from 16 providers.
DR DNASU; 400668; -.
DR Ensembl; ENST00000613411.4; ENSP00000482358.1; ENSG00000185198.12.
DR GeneID; 400668; -.
DR KEGG; hsa:400668; -.
DR UCSC; uc002lpl.2; human.
DR CTD; 400668; -.
DR DisGeNET; 400668; -.
DR GeneCards; PRSS57; -.
DR HGNC; HGNC:31397; PRSS57.
DR HPA; ENSG00000185198; Tissue enriched (bone).
DR neXtProt; NX_Q6UWY2; -.
DR OpenTargets; ENSG00000185198; -.
DR PharmGKB; PA166049004; -.
DR VEuPathDB; HostDB:ENSG00000185198; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000162457; -.
DR HOGENOM; CLU_006842_1_0_1; -.
DR InParanoid; Q6UWY2; -.
DR OMA; VCNSSWR; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q6UWY2; -.
DR TreeFam; TF333630; -.
DR PathwayCommons; Q6UWY2; -.
DR SABIO-RK; Q6UWY2; -.
DR BioGRID-ORCS; 400668; 13 hits in 1069 CRISPR screens.
DR GenomeRNAi; 400668; -.
DR Pharos; Q6UWY2; Tbio.
DR PRO; PR:Q6UWY2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q6UWY2; protein.
DR Bgee; ENSG00000185198; Expressed in bone marrow and 34 other tissues.
DR ExpressionAtlas; Q6UWY2; baseline and differential.
DR GO; GO:0035578; C:azurophil granule lumen; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 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 Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Heparin-binding; Hydrolase;
KW Protease; Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000269|PubMed:22474388"
FT CHAIN 32..283
FT /note="Serine protease 57"
FT /id="PRO_0000295853"
FT DOMAIN 34..263
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 74
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:25156428"
FT ACT_SITE 122
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:25156428"
FT ACT_SITE 218
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:25156428"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:4Q7X, ECO:0007744|PDB:4Q7Y,
FT ECO:0007744|PDB:4Q7Z, ECO:0007744|PDB:4Q80"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:4Q7Y, ECO:0007744|PDB:4Q7Z,
FT ECO:0007744|PDB:4Q80"
FT DISULFID 59..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0007744|PDB:4Q7X, ECO:0007744|PDB:4Q7Y,
FT ECO:0007744|PDB:4Q7Z, ECO:0007744|PDB:4Q80"
FT DISULFID 157..224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0007744|PDB:4Q7X, ECO:0007744|PDB:4Q7Y,
FT ECO:0007744|PDB:4Q7Z, ECO:0007744|PDB:4Q80"
FT DISULFID 188..202
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0007744|PDB:4Q7X, ECO:0007744|PDB:4Q7Y,
FT ECO:0007744|PDB:4Q7Z, ECO:0007744|PDB:4Q80"
FT DISULFID 214..239
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0007744|PDB:4Q7X, ECO:0007744|PDB:4Q7Y,
FT ECO:0007744|PDB:4Q7Z, ECO:0007744|PDB:4Q80"
FT VARIANT 143
FT /note="P -> L (in dbSNP:rs8102982)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_051839"
FT MUTAGEN 213
FT /note="F->A: Decreases enzyme activity tenfold."
FT /evidence="ECO:0000269|PubMed:25156428"
FT MUTAGEN 215
FT /note="S->A: Decreases enzyme activity tenfold. Decreases
FT enzyme activity twentyfold; when associated with G-236."
FT /evidence="ECO:0000269|PubMed:25156428"
FT MUTAGEN 235
FT /note="S->G: Decreases enzyme activity tenfold. Decreases
FT enzyme activity twentyfold; when associated with A-215."
FT /evidence="ECO:0000269|PubMed:25156428"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 56..65
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 105..110
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:4Q7X"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:4Q7X"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 176..183
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT HELIX 185..191
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 206..209
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:4Q7Z"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:4Q7Z"
SQ SEQUENCE 283 AA; 30334 MW; 62A09B03C20CBDDA CRC64;
MGLGLRGWGR PLLTVATALM LPVKPPAGSW GAQIIGGHEV TPHSRPYMAS VRFGGQHHCG
GFLLRARWVV SAAHCFSHRD LRTGLVVLGA HVLSTAEPTQ QVFGIDALTT HPDYHPMTHA
NDICLLRLNG SAVLGPAVGL LRPPGRRARP PTAGTRCRVA GWGFVSDFEE LPPGLMEAKV
RVLDPDVCNS SWKGHLTLTM LCTRSGDSHR RGFCSADSGG PLVCRNRAHG LVSFSGLWCG
DPKTPDVYTQ VSAFVAWIWD VVRRSSPQPG PLPGTTRPPG EAA
