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P05981

- HEPS_HUMAN

UniProt

P05981 - HEPS_HUMAN

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Protein

Serine protease hepsin

Gene

HPN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Plays a role in the proteolytic processing of ACE2.3 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei203 – 2031Charge relay systemBy similarity
Active sitei257 – 2571Charge relay systemBy similarity
Active sitei353 – 3531Charge relay systemBy similarity

GO - Molecular functioni

  1. calcium-activated potassium channel activity Source: UniProtKB
  2. peptidase activity Source: UniProtKB
  3. serine-type endopeptidase activity Source: UniProtKB
  4. serine-type exopeptidase activity Source: InterPro
  5. serine-type peptidase activity Source: UniProtKB

GO - Biological processi

  1. basement membrane disassembly Source: UniProtKB
  2. cholesterol homeostasis Source: Ensembl
  3. cochlea morphogenesis Source: UniProtKB
  4. detection of mechanical stimulus involved in sensory perception of sound Source: UniProtKB
  5. epithelium development Source: Ensembl
  6. negative regulation of alkaline phosphatase activity Source: Ensembl
  7. negative regulation of apoptotic process Source: UniProtKB
  8. negative regulation of epithelial cell proliferation Source: UniProtKB
  9. negative regulation of epithelial to mesenchymal transition Source: UniProtKB
  10. pilomotor reflex Source: UniProtKB
  11. positive regulation by host of viral transcription Source: UniProtKB
  12. positive regulation of cell growth Source: UniProtKB
  13. positive regulation of gene expression Source: UniProtKB
  14. positive regulation of hepatocyte proliferation Source: UniProtKB
  15. positive regulation of plasminogen activation Source: UniProtKB
  16. positive regulation of thyroid hormone generation Source: UniProtKB
  17. potassium ion transmembrane transport Source: UniProtKB
  18. proteolysis Source: UniProtKB
  19. regulation of cell shape Source: UniProtKB
  20. response to thyroid hormone Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.106. 2681.

Protein family/group databases

MEROPSiS01.224.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease hepsin (EC:3.4.21.106)
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
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:5155. HPN.

Subcellular locationi

GO - Cellular componenti

  1. cell-cell junction Source: UniProtKB
  2. cell surface Source: UniProtKB
  3. endoplasmic reticulum membrane Source: UniProtKB
  4. extracellular vesicular exosome Source: UniProtKB
  5. integral component of membrane Source: UniProtKB
  6. integral component of plasma membrane Source: UniProtKB
  7. neuronal cell body Source: UniProtKB
  8. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29425.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 162162Serine protease hepsin non-catalytic chainSequence AnalysisPRO_0000027841Add
BLAST
Chaini163 – 417255Serine protease hepsin catalytic chainSequence AnalysisPRO_0000027842Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi77 ↔ 1401 PublicationPROSITE-ProRule annotation
Disulfide bondi90 ↔ 1501 PublicationPROSITE-ProRule annotation
Glycosylationi112 – 1121N-linked (GlcNAc...)1 Publication
Disulfide bondi119 ↔ 1381 PublicationPROSITE-ProRule annotation
Disulfide bondi153 ↔ 277Interchain (between non-catalytic and catalytic chains)PROSITE-ProRule annotation
Disulfide bondi188 ↔ 2041 PublicationPROSITE-ProRule annotation
Disulfide bondi291 ↔ 3591 PublicationPROSITE-ProRule annotation
Disulfide bondi322 ↔ 3381 PublicationPROSITE-ProRule annotation
Disulfide bondi349 ↔ 3811 PublicationPROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP05981.
PaxDbiP05981.
PeptideAtlasiP05981.
PRIDEiP05981.

PTM databases

PhosphoSiteiP05981.

Miscellaneous databases

PMAP-CutDBP05981.

Expressioni

Tissue specificityi

Present in most tissues, with the highest level in liver.

Gene expression databases

BgeeiP05981.
CleanExiHS_HPN.
ExpressionAtlasiP05981. baseline and differential.
GenevestigatoriP05981.

Organism-specific databases

HPAiHPA006804.

Interactioni

Protein-protein interaction databases

BioGridi109486. 2 interactions.
STRINGi9606.ENSP00000262626.

Structurei

Secondary structure

1
417
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi53 – 564
Turni58 – 603
Beta strandi62 – 676
Turni68 – 714
Beta strandi72 – 776
Helixi82 – 9312
Beta strandi98 – 1058
Helixi106 – 1094
Beta strandi116 – 1205
Turni122 – 1243
Helixi125 – 1273
Helixi131 – 1344
Beta strandi135 – 1384
Beta strandi144 – 1507
Beta strandi177 – 1826
Beta strandi185 – 20016
Helixi202 – 2043
Helixi207 – 2093
Helixi212 – 2143
Beta strandi215 – 2206
Beta strandi229 – 2324
Beta strandi234 – 2407
Helixi244 – 2463
Beta strandi259 – 2657
Beta strandi290 – 30011
Beta strandi310 – 3178
Helixi319 – 3224
Turni325 – 3306
Beta strandi336 – 3405
Beta strandi345 – 3473
Beta strandi356 – 3616
Beta strandi368 – 38215
Beta strandi388 – 3925
Helixi393 – 3964
Helixi397 – 40610
Turni407 – 4093
Beta strandi412 – 4165

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP05981.
SMRiP05981. Positions 49-417.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05981.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2323CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini45 – 417373ExtracellularSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei24 – 4421Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 15198SRCRAdd
BLAST
Domaini163 – 405243Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation
Contains 1 SRCR domain.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00760000118962.
HOGENOMiHOG000251822.
HOVERGENiHBG013304.
InParanoidiP05981.
KOiK08665.
OMAiLTCVLTP.
OrthoDBiEOG75B84T.
PhylomeDBiP05981.
TreeFamiTF351678.

Family and domain databases

Gene3Di3.10.250.10. 1 hit.
InterProiIPR015352. Hepsin-SRCR_dom.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR017448. SRCR-like_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF09272. Hepsin-SRCR. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
ProDomiPD021735. Hepsin-SRCR. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF56487. SSF56487. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

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:
EMBL
GenBank
DDBJ
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.
UniGeneiHs.182385.

Genome annotation databases

EnsembliENST00000262626; ENSP00000262626; ENSG00000105707.
ENST00000392226; ENSP00000376060; ENSG00000105707.
GeneIDi3249.
KEGGihsa:3249.
UCSCiuc002nxq.2. human.

Polymorphism databases

DMDMi123057.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Hs.182385.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali P05981.
SMRi P05981. Positions 49-417.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109486. 2 interactions.
STRINGi 9606.ENSP00000262626.

Chemistry

BindingDBi P05981.
ChEMBLi CHEMBL2079849.
DrugBanki DB00036. Coagulation factor VIIa.

Protein family/group databases

MEROPSi S01.224.

PTM databases

PhosphoSitei P05981.

Polymorphism databases

DMDMi 123057.

Proteomic databases

MaxQBi P05981.
PaxDbi P05981.
PeptideAtlasi P05981.
PRIDEi P05981.

Protocols and materials databases

DNASUi 3249.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262626 ; ENSP00000262626 ; ENSG00000105707 .
ENST00000392226 ; ENSP00000376060 ; ENSG00000105707 .
GeneIDi 3249.
KEGGi hsa:3249.
UCSCi uc002nxq.2. human.

Organism-specific databases

CTDi 3249.
GeneCardsi GC19P035531.
H-InvDB HIX0137465.
HGNCi HGNC:5155. HPN.
HPAi HPA006804.
MIMi 142440. gene.
neXtProti NX_P05981.
PharmGKBi PA29425.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5640.
GeneTreei ENSGT00760000118962.
HOGENOMi HOG000251822.
HOVERGENi HBG013304.
InParanoidi P05981.
KOi K08665.
OMAi LTCVLTP.
OrthoDBi EOG75B84T.
PhylomeDBi P05981.
TreeFami TF351678.

Enzyme and pathway databases

BRENDAi 3.4.21.106. 2681.

Miscellaneous databases

EvolutionaryTracei P05981.
GeneWikii HPN_(gene).
GenomeRNAii 3249.
NextBioi 12917.
PMAP-CutDB P05981.
PROi P05981.
SOURCEi Search...

Gene expression databases

Bgeei P05981.
CleanExi HS_HPN.
ExpressionAtlasi P05981. baseline and differential.
Genevestigatori P05981.

Family and domain databases

Gene3Di 3.10.250.10. 1 hit.
InterProi IPR015352. Hepsin-SRCR_dom.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR017448. SRCR-like_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF09272. Hepsin-SRCR. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view ]
PRINTSi PR00722. CHYMOTRYPSIN.
ProDomi PD021735. Hepsin-SRCR. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
SMARTi SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
SSF56487. SSF56487. 1 hit.
PROSITEi PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells."
    Leytus S.P., Loeb K.R., Hagen F.S., Kurachi K., Davie E.W.
    Biochemistry 27:1067-1074(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Mammary gland.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pancreas and Spleen.
  4. "Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization."
    Tsuji A., Torres-Rosado A., Arai T., le Beau M.M., Lemons R.S., Chou S.H., Kurachi K.
    J. Biol. Chem. 266:16948-16953(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  5. "Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth."
    Torres-Rosado A., O'Shea K.S., Tsuji A., Chou S.-H., Kurachi K.
    Proc. Natl. Acad. Sci. U.S.A. 90:7181-7185(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  6. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-112.
    Tissue: Liver.
  7. Cited for: FUNCTION.
  8. "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein."
    Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O., Poehlmann S.
    J. Virol. 88:1293-1307(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers."
    Herter S., Piper D.E., Aaron W., Gabriele T., Cutler G., Cao P., Bhatt A.S., Choe Y., Craik C.S., Walker N., Meininger D., Hoey T., Austin R.J.
    Biochem. J. 390:125-136(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 46-417, DISULFIDE BONDS, FUNCTION.

Entry informationi

Entry nameiHEPS_HUMAN
AccessioniPrimary (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: October 29, 2014
This is version 148 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3