ID   HEPS_RAT                Reviewed;         416 AA.
AC   Q05511;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   25-MAY-2022, entry version 137.
DE   RecName: Full=Serine protease hepsin;
DE            EC=3.4.21.106 {ECO:0000250|UniProtKB:P05981};
DE   Contains:
DE     RecName: Full=Serine protease hepsin non-catalytic chain;
DE   Contains:
DE     RecName: Full=Serine protease hepsin catalytic chain;
GN   Name=Hpn;
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].
RC   TISSUE=Liver;
RX   PubMed=8318546; DOI=10.1016/0167-4781(93)90137-3;
RA   Farley D., Reymond F., Nick H.;
RT   "Cloning and sequence analysis of rat hepsin, a cell surface serine
RT   proteinase.";
RL   Biochim. Biophys. Acta 1173:350-352(1993).
RN   [2]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=17918732; DOI=10.1002/humu.20617;
RA   Guipponi M., Toh M.-Y., Tan J., Park D., Hanson K., Ballana E., Kwong D.,
RA   Cannon P.Z.F., Wu Q., Gout A., Delorenzi M., Speed T.P., Smith R.J.H.,
RA   Dahl H.-H.M., Petersen M., Teasdale R.D., Estivill X., Park W.J.,
RA   Scott H.S.;
RT   "An integrated genetic and functional analysis of the role of type II
RT   transmembrane serine proteases (TMPRSSs) in hearing loss.";
RL   Hum. Mutat. 29:130-141(2008).
CC   -!- FUNCTION: Serine protease that cleaves extracellular substrates, and
CC       contributes to the proteolytic processing of growth factors, such as
CC       HGF and MST1/HGFL. Plays a role in cell growth and maintenance of cell
CC       morphology. Plays a role in the proteolytic processing of ACE2.
CC       Mediates the proteolytic cleavage of urinary UMOD that is required for
CC       UMOD polymerization. {ECO:0000250|UniProtKB:P05981}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Cleavage after basic amino-acid residues, with Arg strongly
CC         preferred to Lys.; EC=3.4.21.106;
CC         Evidence={ECO:0000250|UniProtKB:P05981};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P05981};
CC       Single-pass type II membrane protein {ECO:0000250|UniProtKB:P05981}.
CC       Apical cell membrane {ECO:0000250|UniProtKB:P05981}; Single-pass type
CC       II membrane protein {ECO:0000250|UniProtKB:P05981}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. Present in brain, heart, kidney,
CC       liver, stomach, muscle, lung, testis, skin and eye. Not expressed in
CC       ovary and thynus. In inner ear tissues, expressed in stria vascularis,
CC       modiolus, organ of Corti and spiral ganglion.
CC       {ECO:0000269|PubMed:17918732}.
CC   -!- DEVELOPMENTAL STAGE: Expressed during development in embryonic stages
CC       E8.5, E9.5, E12.5 and E19. {ECO:0000269|PubMed:17918732}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00274}.
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DR   EMBL; X70900; CAA50256.1; -; mRNA.
DR   PIR; S33777; S33777.
DR   RefSeq; NP_058808.1; NM_017112.1.
DR   AlphaFoldDB; Q05511; -.
DR   SMR; Q05511; -.
DR   STRING; 10116.ENSRNOP00000028644; -.
DR   MEROPS; S01.224; -.
DR   GlyGen; Q05511; 1 site.
DR   PaxDb; Q05511; -.
DR   GeneID; 29135; -.
DR   KEGG; rno:29135; -.
DR   UCSC; RGD:61982; rat.
DR   CTD; 3249; -.
DR   RGD; 61982; Hpn.
DR   eggNOG; KOG3627; Eukaryota.
DR   InParanoid; Q05511; -.
DR   OrthoDB; 1314811at2759; -.
DR   PhylomeDB; Q05511; -.
DR   Reactome; R-RNO-6806942; MET Receptor Activation.
DR   Reactome; R-RNO-8852405; Signaling by MST1.
DR   PRO; PR:Q05511; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR   GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR   GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISO:RGD.
DR   GO; GO:0070008; F:serine-type exopeptidase activity; IEA:InterPro.
DR   GO; GO:0008236; F:serine-type peptidase activity; ISS:UniProtKB.
DR   GO; GO:0034769; P:basement membrane disassembly; ISS:UniProtKB.
DR   GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR   GO; GO:0090103; P:cochlea morphogenesis; ISS:UniProtKB.
DR   GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; ISS:UniProtKB.
DR   GO; GO:0060429; P:epithelium development; ISO:RGD.
DR   GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISS:UniProtKB.
DR   GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR   GO; GO:0097195; P:pilomotor reflex; ISS:UniProtKB.
DR   GO; GO:0043923; P:positive regulation by host of viral transcription; ISS:UniProtKB.
DR   GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR   GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISS:UniProtKB.
DR   GO; GO:0010756; P:positive regulation of plasminogen activation; ISS:UniProtKB.
DR   GO; GO:2000611; P:positive regulation of thyroid hormone generation; ISS:UniProtKB.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR   GO; GO:0097066; P:response to thyroid hormone; ISS:UniProtKB.
DR   GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.40.10.10; -; 2.
DR   Gene3D; 3.10.250.10; -; 1.
DR   InterPro; IPR038957; Hepsin.
DR   InterPro; IPR015352; Hepsin-SRCR_dom.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
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; PTHR24253:SF38; PTHR24253:SF38; 1.
DR   Pfam; PF09272; Hepsin-SRCR; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00202; SR; 1.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF56487; SSF56487; 1.
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   Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Protease;
KW   Reference proteome; Serine protease; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..161
FT                   /note="Serine protease hepsin non-catalytic chain"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000027845"
FT   CHAIN           162..416
FT                   /note="Serine protease hepsin catalytic chain"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000027846"
FT   TOPO_DOM        1..18
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        19..39
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        40..416
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          53..150
FT                   /note="SRCR"
FT   DOMAIN          162..404
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        202
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:P05981"
FT   ACT_SITE        256
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:P05981"
FT   ACT_SITE        352
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:O35453"
FT   CARBOHYD        111
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        76..139
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        89..149
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        118..137
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        152..276
FT                   /note="Interchain (between non-catalytic and catalytic
FT                   chains)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        187..203
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        290..358
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        321..337
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        348..380
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ   SEQUENCE   416 AA;  44926 MW;  E5A9F8FA9550E180 CRC64;
     MAKEGGRTAP CCSRPKVAAL TVGTLLFLTG IGAASWAIVT ILLRSDQEPL YQVQLSPGDS
     RLLVLDKTEG TWRLLCSSRS NARVAGLGCE EMGFLRALAH SELDVRTAGA NGTSGFFCVD
     EGGLPLAQRL LDVISVCDCP RGRFLTATCQ DCGRRKLPVD RIVGGQDSSL GRWPWQVSLR
     YDGTHLCGGS LLSGDWVLTA AHCFPERNRV LSRWRVFAGA VARTSPHAVQ LGVQAVIYHG
     GYLPFRDPTI DENSNDIALV HLSSSLPLTE YIQPVCLPAA GQALVDGKVC TVTGWGNTQF
     YGQQAVVLQE ARVPIISNEV CNSPDFYGNQ IKPKMFCAGY PEGGIDACQG DSGGHFVCED
     RISGTSRWRL CGIVSWGTGC ALARKPGVYT KVIDFREWIF QAIKTHSEAT GMVTQP