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Protein

Serine protease hepsin

Gene

HPN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 Publications

Catalytic activityi

Cleavage after basic amino-acid residues, with Arg strongly preferred to Lys.1 Publication2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei203Charge relay system2 Publications1
Active sitei257Charge relay system2 Publications1
Active sitei353Charge relay system2 Publications1

GO - Molecular functioni

  • calcium-activated potassium channel activity Source: UniProtKB
  • 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
  • hepatocyte growth factor receptor signaling pathway Source: Reactome
  • 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 functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.106 2681
ReactomeiR-HSA-6806942 MET Receptor Activation
R-HSA-8852405 Signaling by MST1

Protein family/group databases

MEROPSiS01.224

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105707.13
HGNCiHGNC:5155 HPN
MIMi142440 gene
neXtProtiNX_P05981

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 23CytoplasmicSequence analysisAdd BLAST23
Transmembranei24 – 44Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini45 – 417ExtracellularSequence analysisAdd BLAST373

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3249
OpenTargetsiENSG00000105707
PharmGKBiPA29425

Chemistry databases

ChEMBLiCHEMBL2079849
DrugBankiDB03865 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine
DB00522 Bentiromide
DB03297 Benzylsulfinic Acid
DB00036 Coagulation factor VIIa Recombinant Human
DB03643 CRA_1144

Polymorphism and mutation databases

BioMutaiHPN
DMDMi123057

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000278411 – 162Serine protease hepsin non-catalytic chainSequence analysisAdd BLAST162
ChainiPRO_0000027842163 – 417Serine protease hepsin catalytic chainSequence analysisAdd BLAST255

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi77 ↔ 140PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi90 ↔ 150PROSITE-ProRule annotationCombined sources2 Publications
Glycosylationi112N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi119 ↔ 138PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi153 ↔ 277Interchain (between non-catalytic and catalytic chains)PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi188 ↔ 204PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi291 ↔ 359PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi322 ↔ 338PROSITE-ProRule annotationCombined sources2 Publications
Disulfide bondi349 ↔ 381PROSITE-ProRule annotationCombined sources2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP05981
MaxQBiP05981
PaxDbiP05981
PeptideAtlasiP05981
PRIDEiP05981

PTM databases

iPTMnetiP05981
PhosphoSitePlusiP05981

Miscellaneous databases

PMAP-CutDBiP05981

Expressioni

Tissue specificityi

Detected in liver and kidney.1 Publication

Gene expression databases

BgeeiENSG00000105707
CleanExiHS_HPN
ExpressionAtlasiP05981 baseline and differential
GenevisibleiP05981 HS

Organism-specific databases

HPAiHPA006804

Interactioni

Protein-protein interaction databases

BioGridi109486, 1 interactor
IntActiP05981, 3 interactors
STRINGi9606.ENSP00000262626

Chemistry databases

BindingDBiP05981

Structurei

Secondary structure

1417
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi53 – 56Combined sources4
Turni58 – 60Combined sources3
Beta strandi62 – 67Combined sources6
Turni68 – 71Combined sources4
Beta strandi72 – 77Combined sources6
Helixi82 – 93Combined sources12
Beta strandi98 – 105Combined sources8
Helixi106 – 109Combined sources4
Beta strandi116 – 120Combined sources5
Turni122 – 124Combined sources3
Helixi125 – 127Combined sources3
Helixi131 – 134Combined sources4
Beta strandi135 – 138Combined sources4
Beta strandi144 – 150Combined sources7
Beta strandi177 – 182Combined sources6
Beta strandi185 – 200Combined sources16
Helixi202 – 204Combined sources3
Helixi207 – 209Combined sources3
Helixi212 – 214Combined sources3
Beta strandi215 – 220Combined sources6
Beta strandi229 – 232Combined sources4
Beta strandi234 – 240Combined sources7
Helixi244 – 246Combined sources3
Beta strandi259 – 265Combined sources7
Beta strandi290 – 300Combined sources11
Beta strandi310 – 317Combined sources8
Helixi319 – 322Combined sources4
Turni325 – 330Combined sources6
Beta strandi336 – 340Combined sources5
Beta strandi345 – 347Combined sources3
Turni350 – 354Combined sources5
Beta strandi356 – 361Combined sources6
Beta strandi368 – 382Combined sources15
Beta strandi388 – 392Combined sources5
Helixi393 – 396Combined sources4
Helixi397 – 406Combined sources10
Turni407 – 409Combined sources3
Beta strandi412 – 416Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1O5EX-ray1.75H163-417[»]
L46-159[»]
1O5FX-ray1.78H163-417[»]
L46-159[»]
1P57X-ray1.75A46-159[»]
B163-417[»]
1Z8GX-ray1.55A46-417[»]
3T2NX-ray2.55A/B46-417[»]
5CE1X-ray2.50A46-417[»]
ProteinModelPortaliP05981
SMRiP05981
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05981

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 151SRCRAdd BLAST98
Domaini163 – 405Peptidase S1PROSITE-ProRule annotationAdd BLAST243

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118962
HOGENOMiHOG000251822
HOVERGENiHBG013304
InParanoidiP05981
KOiK08665
OMAiRWRQVCS
OrthoDBiEOG091G0AH5
PhylomeDBiP05981
TreeFamiTF351678

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di3.10.250.10, 1 hit
InterProiView protein in InterPro
IPR015352 Hepsin-SRCR_dom
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF09272 Hepsin-SRCR, 1 hit
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
ProDomiView protein in ProDom or Entries sharing at least one domain
PD021735 Hepsin-SRCR, 1 hit
SMARTiView protein in SMART
SM00202 SR, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF56487 SSF56487, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P05981-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:417
Mass (Da):45,011
Last modified:November 1, 1988 - v1
Checksum:iB2086FF661E551D7
GO

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
CCDSiCCDS32993.1
PIRiS00845
RefSeqiNP_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
UniGeneiHs.182385

Genome annotation databases

EnsembliENST00000262626; ENSP00000262626; ENSG00000105707
ENST00000392226; ENSP00000376060; ENSG00000105707
GeneIDi3249
KEGGihsa:3249
UCSCiuc002nxq.3 human

Similar proteinsi

Entry informationi

Entry nameiHEPS_HUMAN
AccessioniPrimary (citable) accession number: P05981
Secondary accession number(s): B2RDS4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: March 28, 2018
This is version 176 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health