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P05981 (HEPS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine protease hepsin

EC=3.4.21.106
Alternative name(s):
Transmembrane protease serine 1
Gene names
Name:HPN
Synonyms:TMPRSS1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length417 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Ref.7 Ref.8

Catalytic activity

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

Subcellular location

Membrane; Single-pass type II membrane protein.

Tissue specificity

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

Sequence similarities

Belongs to the peptidase S1 family.

Contains 1 peptidase S1 domain.

Contains 1 SRCR domain.

Ontologies

Keywords
   Cellular componentMembrane
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbasement membrane disassembly

Inferred from direct assay PubMed 16908524. Source: UniProtKB

cochlea morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

detection of mechanical stimulus involved in sensory perception of sound

Inferred from sequence or structural similarity. Source: UniProtKB

epithelium development

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from direct assay PubMed 15614436. Source: UniProtKB

negative regulation of epithelial cell proliferation

Inferred from direct assay PubMed 19843851. Source: UniProtKB

negative regulation of epithelial to mesenchymal transition

Inferred from direct assay PubMed 19843851. Source: UniProtKB

pilomotor reflex

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation by host of viral transcription

Inferred from direct assay PubMed 15614436. Source: UniProtKB

positive regulation of cell growth

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of hepatocyte proliferation

Inferred from direct assay PubMed 15614436. Source: UniProtKB

positive regulation of plasminogen activation

Inferred from direct assay PubMed 16908524. Source: UniProtKB

positive regulation of thyroid hormone generation

Inferred from sequence or structural similarity. Source: UniProtKB

potassium ion transmembrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

proteolysis

Inferred from direct assay PubMed 16908524PubMed 19843851PubMed 19911255. Source: UniProtKB

regulation of cell shape

Inferred from mutant phenotype Ref.5. Source: UniProtKB

response to thyroid hormone

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell surface

Inferred from direct assay PubMed 16908524Ref.5. Source: UniProtKB

cell-cell junction

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from direct assay PubMed 17918732. Source: UniProtKB

integral component of membrane

Inferred from direct assay PubMed 19843851. Source: UniProtKB

integral component of plasma membrane

Inferred from direct assay Ref.4. Source: UniProtKB

neuronal cell body

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functioncalcium-activated potassium channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

peptidase activity

Inferred from direct assay PubMed 16908524PubMed 19843851. Source: UniProtKB

scavenger receptor activity

Inferred from electronic annotation. Source: InterPro

serine-type endopeptidase activity

Inferred from direct assay PubMed 16908524. Source: UniProtKB

serine-type exopeptidase activity

Inferred from electronic annotation. Source: InterPro

serine-type peptidase activity

Inferred from direct assay PubMed 19911255. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 162162Serine protease hepsin non-catalytic chain Potential
PRO_0000027841
Chain163 – 417255Serine protease hepsin catalytic chain Potential
PRO_0000027842

Regions

Topological domain1 – 2323Cytoplasmic Potential
Transmembrane24 – 4421Helical; Signal-anchor for type II membrane protein; Potential
Topological domain45 – 417373Extracellular Potential
Domain54 – 15198SRCR
Domain163 – 405243Peptidase S1

Sites

Active site2031Charge relay system By similarity
Active site2571Charge relay system By similarity
Active site3531Charge relay system By similarity

Amino acid modifications

Glycosylation1121N-linked (GlcNAc...) Ref.6
Disulfide bond77 ↔ 140 Ref.8
Disulfide bond90 ↔ 150 Ref.8
Disulfide bond119 ↔ 138 Ref.8
Disulfide bond153 ↔ 277Interchain (between non-catalytic and catalytic chains) By similarity
Disulfide bond188 ↔ 204 Ref.8
Disulfide bond291 ↔ 359 Ref.8
Disulfide bond322 ↔ 338 Ref.8
Disulfide bond349 ↔ 381 Ref.8

Secondary structure

.................................................................. 417
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05981 [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: B2086FF661E551D7

FASTA41745,011
        10         20         30         40         50         60 
MAQKEGGRTV PCCSRPKVAA LTAGTLLLLT AIGAASWAIV AVLLRSDQEP LYPVQVSSAD 

        70         80         90        100        110        120 
ARLMVFDKTE GTWRLLCSSR SNARVAGLSC EEMGFLRALT HSELDVRTAG ANGTSGFFCV 

       130        140        150        160        170        180 
DEGRLPHTQR LLEVISVCDC PRGRFLAAIC QDCGRRKLPV DRIVGGRDTS LGRWPWQVSL 

       190        200        210        220        230        240 
RYDGAHLCGG SLLSGDWVLT AAHCFPERNR VLSRWRVFAG AVAQASPHGL QLGVQAVVYH 

       250        260        270        280        290        300 
GGYLPFRDPN SEENSNDIAL VHLSSPLPLT EYIQPVCLPA AGQALVDGKI CTVTGWGNTQ 

       310        320        330        340        350        360 
YYGQQAGVLQ EARVPIISND VCNGADFYGN QIKPKMFCAG YPEGGIDACQ GDSGGPFVCE 

       370        380        390        400        410 
DSISRTPRWR LCGIVSWGTG CALAQKPGVY TKVSDFREWI FQAIKTHSEA SGMVTQL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Proteolytic activation of pro-macrophage-stimulating protein by hepsin."
Ganesan R., Kolumam G.A., Lin S.J., Xie M.H., Santell L., Wu T.D., Lazarus R.A., Chaudhuri A., Kirchhofer D.
Mol. Cancer Res. 9:1175-1186(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS00845.
RefSeqNP_002142.1. NM_002151.2.
NP_892028.1. NM_182983.2.
UniGeneHs.182385.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP05981.
SMRP05981. Positions 49-417.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109486. 1 interaction.
STRING9606.ENSP00000262626.

Chemistry

BindingDBP05981.
ChEMBLCHEMBL2079849.
DrugBankDB00036. Coagulation factor VIIa.

Protein family/group databases

MEROPSS01.224.

PTM databases

PhosphoSiteP05981.

Polymorphism databases

DMDM123057.

Proteomic databases

PaxDbP05981.
PeptideAtlasP05981.
PRIDEP05981.

Protocols and materials databases

DNASU3249.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262626; ENSP00000262626; ENSG00000105707.
ENST00000392226; ENSP00000376060; ENSG00000105707.
GeneID3249.
KEGGhsa:3249.
UCSCuc002nxq.2. human.

Organism-specific databases

CTD3249.
GeneCardsGC19P035531.
H-InvDBHIX0137465.
HGNCHGNC:5155. HPN.
HPAHPA006804.
MIM142440. gene.
neXtProtNX_P05981.
PharmGKBPA29425.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251822.
HOVERGENHBG013304.
InParanoidP05981.
KOK08665.
OrthoDBEOG75B84T.
PhylomeDBP05981.
TreeFamTF351678.

Enzyme and pathway databases

BRENDA3.4.21.106. 2681.

Gene expression databases

ArrayExpressP05981.
BgeeP05981.
CleanExHS_HPN.
GenevestigatorP05981.

Family and domain databases

Gene3D3.10.250.10. 1 hit.
InterProIPR015352. Hepsin-SRCR_dom.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR017448. SRCR-like_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF09272. Hepsin-SRCR. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
ProDomPD021735. Hepsin-SRCR. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF56487. SSF56487. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP05981.
GeneWikiHPN_(gene).
GenomeRNAi3249.
NextBio12917.
PMAP-CutDBP05981.
PROP05981.
SOURCESearch...

Entry information

Entry nameHEPS_HUMAN
AccessionPrimary (citable) accession number: P05981
Secondary accession number(s): B2RDS4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: April 16, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM