PRSS8_HUMAN
ID PRSS8_HUMAN Reviewed; 343 AA.
AC Q16651; B4DWP2; Q9UCA3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Prostasin;
DE EC=3.4.21.-;
DE AltName: Full=Channel-activating protease 1;
DE Short=CAP1;
DE AltName: Full=Serine protease 8;
DE Contains:
DE RecName: Full=Prostasin light chain;
DE Contains:
DE RecName: Full=Prostasin heavy chain;
DE Flags: Precursor;
GN Name=PRSS8;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND PARTIAL PROTEIN
RP SEQUENCE.
RC TISSUE=Prostate;
RX PubMed=7768952; DOI=10.1074/jbc.270.22.13483;
RA Yu J.X., Chao L., Chao J.;
RT "Molecular cloning, tissue-specific expression, and cellular localization
RT of human prostasin mRNA.";
RL J. Biol. Chem. 270:13483-13489(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [5]
RP PROTEIN SEQUENCE OF 45-64.
RC TISSUE=Semen;
RX PubMed=8034638; DOI=10.1016/s0021-9258(17)32244-5;
RA Yu J.X., Chao L., Chao J.;
RT "Prostasin is a novel human serine proteinase from seminal fluid.
RT Purification, tissue distribution, and localization in prostate gland.";
RL J. Biol. Chem. 269:18843-18848(1994).
RN [6]
RP FUNCTION IN SODIUM CHANNELS ACTIVATION.
RX PubMed=15246975; DOI=10.1152/ajplung.00160.2004;
RA Tong Z., Illek B., Bhagwandin V.J., Verghese G.M., Caughey G.H.;
RT "Prostasin, a membrane-anchored serine peptidase, regulates sodium currents
RT in JME/CF15 cells, a cystic fibrosis airway epithelial cell line.";
RL Am. J. Physiol. 287:L928-L935(2004).
RN [7]
RP FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=15474520; DOI=10.1016/j.bbrc.2004.09.123;
RA Shipway A., Danahay H., Williams J.A., Tully D.C., Backes B.J.,
RA Harris J.L.;
RT "Biochemical characterization of prostasin, a channel activating
RT protease.";
RL Biochem. Biophys. Res. Commun. 324:953-963(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 45-305 IN COMPLEX WITH INHIBITOR,
RP AND DISULFIDE BONDS.
RX PubMed=19388054; DOI=10.1002/pro.118;
RA Spraggon G., Hornsby M., Shipway A., Tully D.C., Bursulaya B., Danahay H.,
RA Harris J.L., Lesley S.A.;
RT "Active site conformational changes of prostasin provide a new mechanism of
RT protease regulation by divalent cations.";
RL Protein Sci. 18:1081-1094(2009).
CC -!- FUNCTION: Possesses a trypsin-like cleavage specificity with a
CC preference for poly-basic substrates. Stimulates epithelial sodium
CC channel (ENaC) activity through activating cleavage of the gamma
CC subunits (SCNN1G). {ECO:0000269|PubMed:15246975,
CC ECO:0000269|PubMed:15474520}.
CC -!- SUBUNIT: Heterodimer of two chains, light and heavy, held by a
CC disulfide bond. {ECO:0000269|PubMed:19388054}.
CC -!- SUBCELLULAR LOCATION: [Prostasin]: Cell membrane; Single-pass membrane
CC protein.
CC -!- SUBCELLULAR LOCATION: [Prostasin light chain]: Secreted, extracellular
CC space. Note=Found in the seminal fluid. Secreted after cleavage of its
CC C-terminus.
CC -!- SUBCELLULAR LOCATION: [Prostasin heavy chain]: Secreted, extracellular
CC space. Note=Found in the seminal fluid. Secreted after cleavage of its
CC C-terminus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16651-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16651-2; Sequence=VSP_056632;
CC -!- TISSUE SPECIFICITY: Found in prostate, liver, salivary gland, kidney,
CC lung, pancreas, colon, bronchus and renal proximal tubular cells. In
CC the prostate gland it may be synthesized in epithelial cells, secreted
CC into the ducts, and excreted into the seminal fluid.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRSS8ID41880ch16p11.html";
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DR EMBL; L41351; AAC41759.1; -; mRNA.
DR EMBL; U33446; AAB19071.1; -; Genomic_DNA.
DR EMBL; AK301619; BAG63104.1; -; mRNA.
DR EMBL; AC009088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001462; AAH01462.1; -; mRNA.
DR CCDS; CCDS45469.1; -. [Q16651-1]
DR PIR; A57014; A57014.
DR RefSeq; NP_002764.1; NM_002773.4. [Q16651-1]
DR PDB; 3DFJ; X-ray; 1.45 A; A=45-289.
DR PDB; 3DFL; X-ray; 2.00 A; A=45-289.
DR PDB; 3E0N; X-ray; 1.70 A; B=45-305.
DR PDB; 3E0P; X-ray; 1.70 A; B=45-305.
DR PDB; 3E16; X-ray; 1.60 A; B=45-305.
DR PDB; 3E1X; X-ray; 1.70 A; B=45-305.
DR PDB; 3FVF; X-ray; 1.60 A; B=45-305.
DR PDB; 3GYL; X-ray; 1.30 A; B=45-305.
DR PDB; 3GYM; X-ray; 2.80 A; A/B=45-305.
DR PDBsum; 3DFJ; -.
DR PDBsum; 3DFL; -.
DR PDBsum; 3E0N; -.
DR PDBsum; 3E0P; -.
DR PDBsum; 3E16; -.
DR PDBsum; 3E1X; -.
DR PDBsum; 3FVF; -.
DR PDBsum; 3GYL; -.
DR PDBsum; 3GYM; -.
DR AlphaFoldDB; Q16651; -.
DR SMR; Q16651; -.
DR BioGRID; 111633; 143.
DR IntAct; Q16651; 4.
DR MINT; Q16651; -.
DR STRING; 9606.ENSP00000319730; -.
DR BindingDB; Q16651; -.
DR ChEMBL; CHEMBL5610; -.
DR DrugBank; DB06900; 1-[4-(hydroxymethyl)phenyl]guanidine.
DR GuidetoPHARMACOLOGY; 2400; -.
DR MEROPS; S01.159; -.
DR GlyGen; Q16651; 2 sites, 1 O-linked glycan (1 site).
DR PhosphoSitePlus; Q16651; -.
DR BioMuta; PRSS8; -.
DR DMDM; 2833277; -.
DR EPD; Q16651; -.
DR jPOST; Q16651; -.
DR MassIVE; Q16651; -.
DR MaxQB; Q16651; -.
DR PaxDb; Q16651; -.
DR PeptideAtlas; Q16651; -.
DR PRIDE; Q16651; -.
DR ProteomicsDB; 5365; -.
DR ProteomicsDB; 61002; -. [Q16651-1]
DR Antibodypedia; 27665; 329 antibodies from 32 providers.
DR DNASU; 5652; -.
DR Ensembl; ENST00000317508.11; ENSP00000319730.6; ENSG00000052344.16. [Q16651-1]
DR Ensembl; ENST00000568261.5; ENSP00000457750.1; ENSG00000052344.16. [Q16651-2]
DR GeneID; 5652; -.
DR KEGG; hsa:5652; -.
DR MANE-Select; ENST00000317508.11; ENSP00000319730.6; NM_002773.5; NP_002764.1.
DR UCSC; uc002ebc.5; human. [Q16651-1]
DR CTD; 5652; -.
DR DisGeNET; 5652; -.
DR GeneCards; PRSS8; -.
DR HGNC; HGNC:9491; PRSS8.
DR HPA; ENSG00000052344; Tissue enhanced (salivary).
DR MIM; 600823; gene.
DR neXtProt; NX_Q16651; -.
DR OpenTargets; ENSG00000052344; -.
DR PharmGKB; PA33840; -.
DR VEuPathDB; HostDB:ENSG00000052344; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000154999; -.
DR HOGENOM; CLU_006842_0_4_1; -.
DR InParanoid; Q16651; -.
DR OMA; YNGVHVC; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q16651; -.
DR TreeFam; TF351676; -.
DR BRENDA; 3.4.21.B6; 2681.
DR PathwayCommons; Q16651; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q16651; -.
DR BioGRID-ORCS; 5652; 16 hits in 1074 CRISPR screens.
DR ChiTaRS; PRSS8; human.
DR EvolutionaryTrace; Q16651; -.
DR GeneWiki; PRSS8; -.
DR GenomeRNAi; 5652; -.
DR Pharos; Q16651; Tchem.
DR PRO; PR:Q16651; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q16651; protein.
DR Bgee; ENSG00000052344; Expressed in mucosa of transverse colon and 129 other tissues.
DR ExpressionAtlas; Q16651; baseline and differential.
DR Genevisible; Q16651; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0017080; F:sodium channel regulator activity; IBA:GO_Central.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 InterPro; IPR033116; TRYPSIN_SER.
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.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Protease; Reference proteome; Secreted; Serine protease; Signal;
KW Transmembrane; Transmembrane helix; Zymogen.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..32
FT /note="Activation peptide"
FT /id="PRO_0000028027"
FT CHAIN 33..343
FT /note="Prostasin"
FT /id="PRO_0000240511"
FT CHAIN 33..44
FT /note="Prostasin light chain"
FT /id="PRO_0000028028"
FT CHAIN 45..322
FT /note="Prostasin heavy chain"
FT /id="PRO_0000028029"
FT PROPEP 323..343
FT /id="PRO_0000028030"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 45..286
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 85
FT /note="Charge relay system"
FT ACT_SITE 134
FT /note="Charge relay system"
FT ACT_SITE 238
FT /note="Charge relay system"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..154
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 70..86
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:19388054"
FT DISULFID 168..244
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:19388054"
FT DISULFID 201..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:19388054"
FT DISULFID 234..262
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:19388054"
FT VAR_SEQ 60..113
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056632"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:3GYL"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:3GYL"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 96..101
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:3GYL"
FT HELIX 124..128
FT /evidence="ECO:0007829|PDB:3E0P"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:3GYM"
FT STRAND 136..142
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:3DFJ"
FT STRAND 167..174
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 189..196
FT /evidence="ECO:0007829|PDB:3GYL"
FT HELIX 198..205
FT /evidence="ECO:0007829|PDB:3GYL"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:3GYL"
FT TURN 218..220
FT /evidence="ECO:0007829|PDB:3E0N"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:3GYL"
FT TURN 235..239
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 249..256
FT /evidence="ECO:0007829|PDB:3GYL"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:3GYM"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:3GYL"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:3GYL"
FT HELIX 278..288
FT /evidence="ECO:0007829|PDB:3GYL"
SQ SEQUENCE 343 AA; 36431 MW; 98DD6447F5A8C1B2 CRC64;
MAQKGVLGPG QLGAVAILLY LGLLRSGTGA EGAEAPCGVA PQARITGGSS AVAGQWPWQV
SITYEGVHVC GGSLVSEQWV LSAAHCFPSE HHKEAYEVKL GAHQLDSYSE DAKVSTLKDI
IPHPSYLQEG SQGDIALLQL SRPITFSRYI RPICLPAANA SFPNGLHCTV TGWGHVAPSV
SLLTPKPLQQ LEVPLISRET CNCLYNIDAK PEEPHFVQED MVCAGYVEGG KDACQGDSGG
PLSCPVEGLW YLTGIVSWGD ACGARNRPGV YTLASSYASW IQSKVTELQP RVVPQTQESQ
PDSNLCGSHL AFSSAPAQGL LRPILFLPLG LALGLLSPWL SEH
