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Protein

Serine protease hepsin

Gene

Hpn

Organism
Mus musculus (Mouse)
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. Plays a role in cell growth and maintenance of cell morphology. Plays a role in the proteolytic processing of ACE2 (By similarity). Mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (PubMed:26673890).By similarity1 Publication

Catalytic activityi

Cleavage after basic amino-acid residues, with Arg strongly preferred to Lys.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei222Charge relay systemBy similarity1
Active sitei276Charge relay systemBy similarity1
Active sitei372Charge relay system1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

ReactomeiR-MMU-6806942 MET Receptor Activation

Protein family/group databases

MEROPSiS01.224

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease hepsin (EC:3.4.21.1062 Publications)
Cleaved into the following 2 chains:
Gene namesi
Name:Hpn
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1196620 Hpn

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 – 38CytoplasmicSequence analysisAdd BLAST38
Transmembranei39 – 59Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini60 – 436ExtracellularSequence analysisAdd BLAST377

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice are viable and fertile (PubMed:9435303, PubMed:11127869). They present no defect in blood coagulation (PubMed:9435303). Likewise, they present no defect in liver regeneration after liver resection (PubMed:11127869). Mice have severely impaired hearing, with abnormal morphology of the tectorial membrane in the cochlea, but no visible defects of the organ of Corti and no loss of inner or outer hair cells. Mutant mice have reduced levels of thyroid hormone. This may play a role in their hearing deficit, since adequate levels of thyroid hormone are required for normal development of the auditory system (PubMed:17620368). Urine from mutant mice lacks normally processed Umod; contrary to wild-type, urinary Umod from mutant mice does not polymerize into long fibers (PubMed:26673890).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi372S → A: Abolishes catalytic activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000278431 – 181Serine protease hepsin non-catalytic chainSequence analysisAdd BLAST181
ChainiPRO_0000027844182 – 436Serine protease hepsin catalytic chainSequence analysisAdd BLAST255

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi96 ↔ 159PROSITE-ProRule annotation
Disulfide bondi109 ↔ 169PROSITE-ProRule annotation
Glycosylationi131N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi138 ↔ 157PROSITE-ProRule annotation
Disulfide bondi172 ↔ 296Interchain (between non-catalytic and catalytic chains)PROSITE-ProRule annotation
Disulfide bondi207 ↔ 223PROSITE-ProRule annotation
Disulfide bondi310 ↔ 378PROSITE-ProRule annotation
Disulfide bondi341 ↔ 357PROSITE-ProRule annotation
Disulfide bondi368 ↔ 400PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO35453
PaxDbiO35453
PRIDEiO35453

PTM databases

iPTMnetiO35453
PhosphoSitePlusiO35453
SwissPalmiO35453

Expressioni

Tissue specificityi

Detected in kidney, in thick ascending tubule epithelial cells (at protein level) (PubMed:26673890). Detected in kidney and liver (PubMed:9395459, PubMed:9435303).2 Publications

Gene expression databases

BgeeiENSMUSG00000001249 Expressed in 209 organ(s), highest expression level in kidney
CleanExiMM_HPN
ExpressionAtlasiO35453 baseline and differential
GenevisibleiO35453 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000103737

Structurei

3D structure databases

ProteinModelPortaliO35453
SMRiO35453
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini73 – 170SRCRAdd BLAST98
Domaini182 – 424Peptidase 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
InParanoidiO35453
KOiK08665
TreeFamiTF351678

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di3.10.250.10, 1 hit
InterProiView protein in InterPro
IPR038957 Hepsin
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
PANTHERiPTHR45072 PTHR45072, 1 hit
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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O35453-1) [UniParc]FASTAAdd to basket
Also known as: 1a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAKEDEEPGA HRGGSTCSRP QPGKGGRTAA CCSRPKVAAL IVGTLLFLTG
60 70 80 90 100
IGAASWAIVT ILLQSDQEPL YQVQLSPGDS RLAVFDKTEG TWRLLCSSRS
110 120 130 140 150
NARVAGLGCE EMGFLRALAH SELDVRTAGA NGTSGFFCVD EGGLPLAQRL
160 170 180 190 200
LDVISVCDCP RGRFLTATCQ DCGRRKLPVD RIVGGQDSSL GRWPWQVSLR
210 220 230 240 250
YDGTHLCGGS LLSGDWVLTA AHCFPERNRV LSRWRVFAGA VARTSPHAVQ
260 270 280 290 300
LGVQAVIYHG GYLPFRDPTI DENSNDIALV HLSSSLPLTE YIQPVCLPAA
310 320 330 340 350
GQALVDGKVC TVTGWGNTQF YGQQAMVLQE ARVPIISNEV CNSPDFYGNQ
360 370 380 390 400
IKPKMFCAGY PEGGIDACQG DSGGPFVCED SISGTSRWRL CGIVSWGTGC
410 420 430
ALARKPGVYT KVTDFREWIF KAIKTHSEAS GMVTQP
Note: Minor isoform.
Length:436
Mass (Da):46,821
Last modified:July 27, 2011 - v3
Checksum:iC0C71FFFF4D016F0
GO
Isoform 2 (identifier: O35453-2) [UniParc]FASTAAdd to basket
Also known as: 2a

The sequence of this isoform differs from the canonical sequence as follows:
     25-44: Missing.

Note: Major isoform.
Show »
Length:416
Mass (Da):44,908
Checksum:i3689A7277E186CF6
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9Q5P0E9Q5P0_MOUSE
Serine protease hepsin
Hpn
445Annotation score:
G3UWE8G3UWE8_MOUSE
Hepsin, isoform CRA_c
Hpn mCG_20361
416Annotation score:
A0A0U1RNM3A0A0U1RNM3_MOUSE
Serine protease hepsin
Hpn
137Annotation score:
F6W6S4F6W6S4_MOUSE
Serine protease hepsin
Hpn
179Annotation score:
F7C9T6F7C9T6_MOUSE
Serine protease hepsin
Hpn
32Annotation score:
E9Q3X9E9Q3X9_MOUSE
Serine protease hepsin
Hpn
82Annotation score:

Sequence cautioni

The sequence BAB22289 differs from that shown. Reason: Frameshift at positions 155, 191 and 233.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti85F → L in AAB84221 (PubMed:9395459).Curated1
Sequence conflicti204T → Y in BAB22289 (PubMed:16141072).Curated1
Sequence conflicti214G → R in BAB22289 (PubMed:16141072).Curated1
Sequence conflicti228 – 229NR → ET in BAB22289 (PubMed:16141072).Curated2
Sequence conflicti264P → L in BAB22289 (PubMed:16141072).Curated1
Sequence conflicti281H → N in BAB22289 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00723225 – 44Missing in isoform 2. 2 PublicationsAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030065 mRNA Translation: AAB84221.1
AK002694 mRNA Translation: BAB22289.2 Frameshift.
CH466593 Genomic DNA Translation: EDL23952.1
BC138809 mRNA Translation: AAI38810.1
BC145413 mRNA Translation: AAI45414.1
CCDSiCCDS52188.1 [O35453-1]
RefSeqiNP_001103722.1, NM_001110252.2 [O35453-1]
NP_001263198.1, NM_001276269.1
NP_032307.2, NM_008281.4
UniGeneiMm.19182

Genome annotation databases

EnsembliENSMUST00000108102; ENSMUSP00000103737; ENSMUSG00000001249 [O35453-1]
GeneIDi15451
KEGGimmu:15451
UCSCiuc009gid.3 mouse [O35453-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030065 mRNA Translation: AAB84221.1
AK002694 mRNA Translation: BAB22289.2 Frameshift.
CH466593 Genomic DNA Translation: EDL23952.1
BC138809 mRNA Translation: AAI38810.1
BC145413 mRNA Translation: AAI45414.1
CCDSiCCDS52188.1 [O35453-1]
RefSeqiNP_001103722.1, NM_001110252.2 [O35453-1]
NP_001263198.1, NM_001276269.1
NP_032307.2, NM_008281.4
UniGeneiMm.19182

3D structure databases

ProteinModelPortaliO35453
SMRiO35453
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000103737

Protein family/group databases

MEROPSiS01.224

PTM databases

iPTMnetiO35453
PhosphoSitePlusiO35453
SwissPalmiO35453

Proteomic databases

MaxQBiO35453
PaxDbiO35453
PRIDEiO35453

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000108102; ENSMUSP00000103737; ENSMUSG00000001249 [O35453-1]
GeneIDi15451
KEGGimmu:15451
UCSCiuc009gid.3 mouse [O35453-1]

Organism-specific databases

CTDi3249
MGIiMGI:1196620 Hpn

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118962
HOGENOMiHOG000251822
HOVERGENiHBG013304
InParanoidiO35453
KOiK08665
TreeFamiTF351678

Enzyme and pathway databases

ReactomeiR-MMU-6806942 MET Receptor Activation

Miscellaneous databases

PROiPR:O35453
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000001249 Expressed in 209 organ(s), highest expression level in kidney
CleanExiMM_HPN
ExpressionAtlasiO35453 baseline and differential
GenevisibleiO35453 MM

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di3.10.250.10, 1 hit
InterProiView protein in InterPro
IPR038957 Hepsin
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
PANTHERiPTHR45072 PTHR45072, 1 hit
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
ProtoNetiSearch...

Entry informationi

Entry nameiHEPS_MOUSE
AccessioniPrimary (citable) accession number: O35453
Secondary accession number(s): B2RSC4, Q9CW97
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 149 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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