UniProtKB - P05981 (HEPS_HUMAN)
Serine protease hepsin
HPN
Functioni
Serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL (PubMed:21875933, PubMed:15839837).
Plays a role in cell growth and maintenance of cell morphology (PubMed:8346233, PubMed:21875933).
Plays a role in the proteolytic processing of ACE2 (PubMed:24227843).
Mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (PubMed:26673890).
5 PublicationsCatalytic activityi
- Cleavage after basic amino-acid residues, with Arg strongly preferred to Lys.1 Publication2 Publications EC:3.4.21.106
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 203 | Charge relay system2 Publications | 1 | |
Active sitei | 257 | Charge relay system2 Publications | 1 | |
Active sitei | 353 | Charge relay system2 Publications | 1 |
GO - Molecular functioni
- peptidase activity Source: UniProtKB
- serine-type endopeptidase activity Source: UniProtKB
- serine-type exopeptidase activity Source: InterPro
- serine-type peptidase activity Source: UniProtKB
GO - Biological processi
- basement membrane disassembly Source: UniProtKB
- cochlea morphogenesis Source: UniProtKB
- detection of mechanical stimulus involved in sensory perception of sound Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of epithelial cell proliferation Source: UniProtKB
- negative regulation of epithelial to mesenchymal transition Source: UniProtKB
- pilomotor reflex Source: UniProtKB
- positive regulation by host of viral transcription Source: UniProtKB
- positive regulation of cell growth Source: UniProtKB
- positive regulation of gene expression Source: UniProtKB
- positive regulation of hepatocyte proliferation Source: UniProtKB
- positive regulation of plasminogen activation Source: UniProtKB
- positive regulation of thyroid hormone generation Source: UniProtKB
- potassium ion transmembrane transport Source: UniProtKB
- proteolysis Source: UniProtKB
- regulation of cell shape Source: UniProtKB
- response to thyroid hormone Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Enzyme and pathway databases
BRENDAi | 3.4.21.106, 2681 |
PathwayCommonsi | P05981 |
Reactomei | R-HSA-6806942, MET Receptor Activation R-HSA-8852405, Signaling by MST1 |
SignaLinki | P05981 |
SIGNORi | P05981 |
Protein family/group databases
MEROPSi | S01.224 |
TCDBi | 8.A.131.1.12, the transmembrane protease serine 3 (tmprss3) family |
Names & Taxonomyi
Protein namesi | Recommended name: Serine protease hepsin (EC:3.4.21.1061 Publication2 Publications)Alternative name(s): Transmembrane protease serine 1 Cleaved into the following 2 chains: |
Gene namesi | Name:HPN Synonyms:TMPRSS1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5155, HPN |
MIMi | 142440, gene |
neXtProti | NX_P05981 |
VEuPathDBi | HostDB:ENSG00000105707 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication
- Apical cell membrane 1 Publication; Single-pass type II membrane protein Curated
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB-SubCell
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cell surface Source: UniProtKB
- cell-cell junction Source: UniProtKB
- integral component of membrane Source: UniProtKB
- neuronal cell body Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 23 | CytoplasmicSequence analysisAdd BLAST | 23 | |
Transmembranei | 24 – 44 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 45 – 417 | ExtracellularSequence analysisAdd BLAST | 373 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 3249 |
OpenTargetsi | ENSG00000105707 |
PharmGKBi | PA29425 |
Miscellaneous databases
Pharosi | P05981, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2079849 |
DrugBanki | DB03865, 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine DB00522, Bentiromide DB03297, Benzylsulfonic acid DB03643, CRA_1144 |
DrugCentrali | P05981 |
Genetic variation databases
BioMutai | HPN |
DMDMi | 123057 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000027841 | 1 – 162 | Serine protease hepsin non-catalytic chainSequence analysisAdd BLAST | 162 | |
ChainiPRO_0000027842 | 163 – 417 | Serine protease hepsin catalytic chainSequence analysisAdd BLAST | 255 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 77 ↔ 140 | PROSITE-ProRule annotationCombined sources2 Publications | ||
Disulfide bondi | 90 ↔ 150 | PROSITE-ProRule annotationCombined sources2 Publications | ||
Glycosylationi | 112 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 119 ↔ 138 | PROSITE-ProRule annotationCombined sources2 Publications | ||
Disulfide bondi | 153 ↔ 277 | Interchain (between non-catalytic and catalytic chains)PROSITE-ProRule annotationCombined sources2 Publications | ||
Disulfide bondi | 188 ↔ 204 | PROSITE-ProRule annotationCombined sources2 Publications | ||
Disulfide bondi | 291 ↔ 359 | PROSITE-ProRule annotationCombined sources2 Publications | ||
Disulfide bondi | 322 ↔ 338 | PROSITE-ProRule annotationCombined sources2 Publications | ||
Disulfide bondi | 349 ↔ 381 | PROSITE-ProRule annotationCombined sources2 Publications |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | P05981 |
jPOSTi | P05981 |
MassIVEi | P05981 |
MaxQBi | P05981 |
PaxDbi | P05981 |
PeptideAtlasi | P05981 |
PRIDEi | P05981 |
ProteomicsDBi | 51865 |
PTM databases
GlyGeni | P05981, 1 site |
iPTMneti | P05981 |
PhosphoSitePlusi | P05981 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000105707, Expressed in right lobe of liver and 142 other tissues |
ExpressionAtlasi | P05981, baseline and differential |
Genevisiblei | P05981, HS |
Organism-specific databases
HPAi | ENSG00000105707, Tissue enhanced (kidney, liver, pancreas) |
Interactioni
Binary interactionsi
P05981
With | #Exp. | IntAct |
---|---|---|
BNIP3 [Q12983] | 3 | EBI-12816745,EBI-749464 |
SFTPC [P11686] | 3 | EBI-12816745,EBI-10197617 |
UPK2 [O00526] | 3 | EBI-12816745,EBI-10179682 |
Protein-protein interaction databases
BioGRIDi | 109486, 116 interactors |
IntActi | P05981, 3 interactors |
STRINGi | 9606.ENSP00000262626 |
Chemistry databases
BindingDBi | P05981 |
Miscellaneous databases
RNActi | P05981, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P05981 |
SMRi | P05981 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P05981 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 54 – 151 | SRCRAdd BLAST | 98 | |
Domaini | 163 – 405 | Peptidase S1PROSITE-ProRule annotationAdd BLAST | 243 |
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00940000159697 |
HOGENOMi | CLU_006842_19_2_1 |
InParanoidi | P05981 |
OMAi | GQTVPCC |
OrthoDBi | 1314811at2759 |
PhylomeDBi | P05981 |
TreeFami | TF351678 |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 1 hit 3.10.250.10, 1 hit |
InterProi | View protein in InterPro IPR038957, Hepsin IPR015352, Hepsin-SRCR_dom IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR017448, SRCR-like_dom IPR036772, SRCR-like_dom_sf IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
PANTHERi | PTHR24253:SF38, PTHR24253:SF38, 1 hit |
Pfami | View protein in Pfam PF09272, Hepsin-SRCR, 1 hit PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00202, SR, 1 hit SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF56487, SSF56487, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MAQKEGGRTV PCCSRPKVAA LTAGTLLLLT AIGAASWAIV AVLLRSDQEP
60 70 80 90 100
LYPVQVSSAD ARLMVFDKTE GTWRLLCSSR SNARVAGLSC EEMGFLRALT
110 120 130 140 150
HSELDVRTAG ANGTSGFFCV DEGRLPHTQR LLEVISVCDC PRGRFLAAIC
160 170 180 190 200
QDCGRRKLPV DRIVGGRDTS LGRWPWQVSL RYDGAHLCGG SLLSGDWVLT
210 220 230 240 250
AAHCFPERNR VLSRWRVFAG AVAQASPHGL QLGVQAVVYH GGYLPFRDPN
260 270 280 290 300
SEENSNDIAL VHLSSPLPLT EYIQPVCLPA AGQALVDGKI CTVTGWGNTQ
310 320 330 340 350
YYGQQAGVLQ EARVPIISND VCNGADFYGN QIKPKMFCAG YPEGGIDACQ
360 370 380 390 400
GDSGGPFVCE DSISRTPRWR LCGIVSWGTG CALAQKPGVY TKVSDFREWI
410
FQAIKTHSEA SGMVTQL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0R244 | M0R244_HUMAN | Serine protease hepsin | HPN | 80 | Annotation score: | ||
M0QZ63 | M0QZ63_HUMAN | Serine protease hepsin | HPN | 259 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M18930 mRNA Translation: AAA36013.1 X07732 mRNA Translation: CAA30558.1 X07002 mRNA Translation: CAA30058.1 AK315655 mRNA Translation: BAG38021.1 BC025716 mRNA Translation: AAH25716.1 |
CCDSi | CCDS32993.1 |
PIRi | S00845 |
RefSeqi | NP_002142.1, NM_002151.2 NP_892028.1, NM_182983.2 XP_005258895.2, XM_005258838.4 XP_006723244.2, XM_006723181.3 XP_016882220.1, XM_017026731.1 |
Genome annotation databases
Ensembli | ENST00000262626.6; ENSP00000262626.2; ENSG00000105707.15 ENST00000392226.5; ENSP00000376060.1; ENSG00000105707.15 ENST00000672452.2; ENSP00000500664.1; ENSG00000105707.15 ENST00000673426.1; ENSP00000500909.1; ENSG00000105707.15 |
GeneIDi | 3249 |
KEGGi | hsa:3249 |
MANE-Selecti | ENST00000672452.2; ENSP00000500664.1; NM_001384133.1; NP_001371062.1 |
UCSCi | uc002nxq.3, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M18930 mRNA Translation: AAA36013.1 X07732 mRNA Translation: CAA30558.1 X07002 mRNA Translation: CAA30058.1 AK315655 mRNA Translation: BAG38021.1 BC025716 mRNA Translation: AAH25716.1 |
CCDSi | CCDS32993.1 |
PIRi | S00845 |
RefSeqi | NP_002142.1, NM_002151.2 NP_892028.1, NM_182983.2 XP_005258895.2, XM_005258838.4 XP_006723244.2, XM_006723181.3 XP_016882220.1, XM_017026731.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1O5E | X-ray | 1.75 | H | 163-417 | [»] | |
L | 46-159 | [»] | ||||
1O5F | X-ray | 1.78 | H | 163-417 | [»] | |
L | 46-159 | [»] | ||||
1P57 | X-ray | 1.75 | A | 46-159 | [»] | |
B | 163-417 | [»] | ||||
1Z8G | X-ray | 1.55 | A | 46-417 | [»] | |
3T2N | X-ray | 2.55 | A/B | 46-417 | [»] | |
5CE1 | X-ray | 2.50 | A | 46-417 | [»] | |
AlphaFoldDBi | P05981 | |||||
SMRi | P05981 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109486, 116 interactors |
IntActi | P05981, 3 interactors |
STRINGi | 9606.ENSP00000262626 |
Chemistry databases
BindingDBi | P05981 |
ChEMBLi | CHEMBL2079849 |
DrugBanki | DB03865, 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine DB00522, Bentiromide DB03297, Benzylsulfonic acid DB03643, CRA_1144 |
DrugCentrali | P05981 |
Protein family/group databases
MEROPSi | S01.224 |
TCDBi | 8.A.131.1.12, the transmembrane protease serine 3 (tmprss3) family |
PTM databases
GlyGeni | P05981, 1 site |
iPTMneti | P05981 |
PhosphoSitePlusi | P05981 |
Genetic variation databases
BioMutai | HPN |
DMDMi | 123057 |
Proteomic databases
EPDi | P05981 |
jPOSTi | P05981 |
MassIVEi | P05981 |
MaxQBi | P05981 |
PaxDbi | P05981 |
PeptideAtlasi | P05981 |
PRIDEi | P05981 |
ProteomicsDBi | 51865 |
Protocols and materials databases
ABCDi | P05981, 2 sequenced antibodies |
Antibodypediai | 1718, 201 antibodies from 33 providers |
DNASUi | 3249 |
Genome annotation databases
Ensembli | ENST00000262626.6; ENSP00000262626.2; ENSG00000105707.15 ENST00000392226.5; ENSP00000376060.1; ENSG00000105707.15 ENST00000672452.2; ENSP00000500664.1; ENSG00000105707.15 ENST00000673426.1; ENSP00000500909.1; ENSG00000105707.15 |
GeneIDi | 3249 |
KEGGi | hsa:3249 |
MANE-Selecti | ENST00000672452.2; ENSP00000500664.1; NM_001384133.1; NP_001371062.1 |
UCSCi | uc002nxq.3, human |
Organism-specific databases
CTDi | 3249 |
DisGeNETi | 3249 |
GeneCardsi | HPN |
HGNCi | HGNC:5155, HPN |
HPAi | ENSG00000105707, Tissue enhanced (kidney, liver, pancreas) |
MIMi | 142440, gene |
neXtProti | NX_P05981 |
OpenTargetsi | ENSG00000105707 |
PharmGKBi | PA29425 |
VEuPathDBi | HostDB:ENSG00000105707 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00940000159697 |
HOGENOMi | CLU_006842_19_2_1 |
InParanoidi | P05981 |
OMAi | GQTVPCC |
OrthoDBi | 1314811at2759 |
PhylomeDBi | P05981 |
TreeFami | TF351678 |
Enzyme and pathway databases
BRENDAi | 3.4.21.106, 2681 |
PathwayCommonsi | P05981 |
Reactomei | R-HSA-6806942, MET Receptor Activation R-HSA-8852405, Signaling by MST1 |
SignaLinki | P05981 |
SIGNORi | P05981 |
Miscellaneous databases
BioGRID-ORCSi | 3249, 18 hits in 1079 CRISPR screens |
ChiTaRSi | HPN, human |
EvolutionaryTracei | P05981 |
GeneWikii | HPN_(gene) |
GenomeRNAii | 3249 |
Pharosi | P05981, Tchem |
PROi | PR:P05981 |
RNActi | P05981, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000105707, Expressed in right lobe of liver and 142 other tissues |
ExpressionAtlasi | P05981, baseline and differential |
Genevisiblei | P05981, HS |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 1 hit 3.10.250.10, 1 hit |
InterProi | View protein in InterPro IPR038957, Hepsin IPR015352, Hepsin-SRCR_dom IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR017448, SRCR-like_dom IPR036772, SRCR-like_dom_sf IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
PANTHERi | PTHR24253:SF38, PTHR24253:SF38, 1 hit |
Pfami | View protein in Pfam PF09272, Hepsin-SRCR, 1 hit PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00202, SR, 1 hit SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF56487, SSF56487, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HEPS_HUMAN | |
Accessioni | P05981Primary (citable) accession number: P05981 Secondary accession number(s): B2RDS4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1988 |
Last sequence update: | November 1, 1988 | |
Last modified: | May 25, 2022 | |
This is version 201 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families