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O35453

- HEPS_MOUSE

UniProt

O35453 - HEPS_MOUSE

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Protein

Serine protease hepsin

Gene

Hpn

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

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

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei222 – 2221Charge relay systemBy similarity
Active sitei276 – 2761Charge relay systemBy similarity
Active sitei372 – 3721Charge relay systemBy similarity

GO - Molecular functioni

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

GO - Biological processi

  1. basement membrane disassembly Source: UniProtKB
  2. cholesterol homeostasis Source: MGI
  3. cochlea morphogenesis Source: UniProtKB
  4. detection of mechanical stimulus involved in sensory perception of sound Source: UniProtKB
  5. epithelium development Source: UniProtKB
  6. negative regulation of alkaline phosphatase activity Source: MGI
  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
  21. sensory perception of sound Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Protein family/group databases

MEROPSiS01.224.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease hepsin (EC:3.4.21.106)
Cleaved into the following 2 chains:
Gene namesi
Name:Hpn
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1196620. Hpn.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3838CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei39 – 5921Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini60 – 436377ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 181181Serine protease hepsin non-catalytic chainSequence AnalysisPRO_0000027843Add
BLAST
Chaini182 – 436255Serine protease hepsin catalytic chainSequence AnalysisPRO_0000027844Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi96 ↔ 159PROSITE-ProRule annotation
Disulfide bondi109 ↔ 169PROSITE-ProRule annotation
Glycosylationi131 – 1311N-linked (GlcNAc...)Sequence Analysis
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

PaxDbiO35453.
PRIDEiO35453.

PTM databases

PhosphoSiteiO35453.

Expressioni

Gene expression databases

BgeeiO35453.
CleanExiMM_HPN.
ExpressionAtlasiO35453. baseline and differential.
GenevestigatoriO35453.

Structurei

3D structure databases

ProteinModelPortaliO35453.
SMRiO35453. Positions 68-435.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini73 – 17098SRCRAdd
BLAST
Domaini182 – 424243Peptidase 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.
InParanoidiO35453.
KOiK08665.
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]
SMARTiSM00202. SR. 1 hit.
SM00020. 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]

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. Align

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

Sequence cautioni

The sequence BAB22289.2 differs from that shown. Reason: Frameshift at positions 155, 191 and 233. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti85 – 851F → L in AAB84221. (PubMed:9395459)Curated
Sequence conflicti204 – 2041T → Y in BAB22289. (PubMed:16141072)Curated
Sequence conflicti214 – 2141G → R in BAB22289. (PubMed:16141072)Curated
Sequence conflicti228 – 2292NR → ET in BAB22289. (PubMed:16141072)Curated
Sequence conflicti264 – 2641P → L in BAB22289. (PubMed:16141072)Curated
Sequence conflicti281 – 2811H → N in BAB22289. (PubMed:16141072)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei25 – 4420Missing in isoform 2. 2 PublicationsVSP_007232Add
BLAST

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.
XP_006539624.1. XM_006539561.1. [O35453-1]
UniGeneiMm.19182.

Genome annotation databases

EnsembliENSMUST00000108102; ENSMUSP00000103737; ENSMUSG00000001249. [O35453-1]
GeneIDi15451.
KEGGimmu:15451.
UCSCiuc009gid.2. mouse. [O35453-1]

Keywords - Coding sequence diversityi

Alternative splicing

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 .
CCDSi CCDS52188.1. [O35453-1 ]
RefSeqi NP_001103722.1. NM_001110252.2. [O35453-1 ]
NP_001263198.1. NM_001276269.1.
NP_032307.2. NM_008281.4.
XP_006539624.1. XM_006539561.1. [O35453-1 ]
UniGenei Mm.19182.

3D structure databases

ProteinModelPortali O35453.
SMRi O35453. Positions 68-435.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

MEROPSi S01.224.

PTM databases

PhosphoSitei O35453.

Proteomic databases

PaxDbi O35453.
PRIDEi O35453.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000108102 ; ENSMUSP00000103737 ; ENSMUSG00000001249 . [O35453-1 ]
GeneIDi 15451.
KEGGi mmu:15451.
UCSCi uc009gid.2. mouse. [O35453-1 ]

Organism-specific databases

CTDi 3249.
MGIi MGI:1196620. Hpn.

Phylogenomic databases

eggNOGi COG5640.
GeneTreei ENSGT00760000118962.
HOGENOMi HOG000251822.
HOVERGENi HBG013304.
InParanoidi O35453.
KOi K08665.
TreeFami TF351678.

Miscellaneous databases

NextBioi 288256.
PROi O35453.
SOURCEi Search...

Gene expression databases

Bgeei O35453.
CleanExi MM_HPN.
ExpressionAtlasi O35453. baseline and differential.
Genevestigatori O35453.

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 SM00202. SR. 1 hit.
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. "Identification and cloning of the membrane-associated serine protease, hepsin, from mouse preimplantation embryos."
    Vu T.-K.H., Liu R.W., Haaksma C., Tomasek J.J., Howard E.W.
    J. Biol. Chem. 272:31315-31320(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Liver.
  2. "Complete nucleotide sequence, origin of isoform and functional characterization of the mouse hepsin gene."
    Kawamura S., Kurachi S., Deyashiki Y., Kurachi K.
    Eur. J. Biochem. 262:755-764(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Kidney.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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] (ISOFORM 1).
    Tissue: Lung.

Entry informationi

Entry nameiHEPS_MOUSE
AccessioniPrimary (citable) accession number: O35453
Secondary accession number(s): B2RSC4, Q9CW97
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 124 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3