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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox protein family
{{PBB_Controls
| Symbol = Hepsin-SRCR
| update_page = yes
| Name = Hepsin-SRCR
| require_manual_inspection = no
| image = PDB 1p57 EBI.jpg
| update_protein_box = yes
| width =
| update_summary = yes
| caption = extracellular domain of human hepsin
| update_citations = yes
| Pfam = PF09272
| Pfam_clan = 
| InterPro = IPR015352
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 1p57
| TCDB =  
| OPM family =  
| OPM protein =  
| CAZy =  
| CDD =  
}}
}}
{{Infobox_gene}}
'''Serine protease hepsin''' is an [[enzyme]] that in humans is encoded by the ''HPN'' [[gene]].<ref name="pmid2835076">{{cite journal | vauthors = Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW | title = A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells | journal = Biochemistry | volume = 27 | issue = 3 | pages = 1067–74 | date = Feb 1988 | pmid = 2835076 | pmc =  | doi = 10.1021/bi00403a032 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HPN hepsin (transmembrane protease, serine 1)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3249| accessdate = }}</ref>


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
 
| image = PBB_Protein_HPN_image.jpg
Hepsin is a cell surface serine protease.<ref name="entrez">{{cite web | title = Entrez Gene: HPN hepsin (transmembrane protease, serine 1)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3249| accessdate = }}</ref>
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1o5e.
 
| PDB = {{PDB2|1o5e}}, {{PDB2|1o5f}}, {{PDB2|1p57}}, {{PDB2|1z8g}}
Hepson contains a [[peptidase]] S1 domain and an SRCR domain. The SRCR domain is located in the [[extracellular]] part of the [[protein]], it is formed primarily by three elements of regular [[secondary structure]]: a 12-residue [[alpha helix]], a twisted five-stranded [[Antiparallel (biochemistry)|antiparallel]] beta sheet, and a second, two-stranded, antiparallel sheet. The two [[beta-sheet]]s lie at roughly right angles to each other, with the [[helix]] nestled between the two, adopting an SRCR [[protein folding|fold]]. The exact function of this domain has not been identified, though it probably may serve to orient the [[protease]] domain or place it in the vicinity of its [[Enzyme substrate|substrate]].<ref name="pmid12962630">{{cite journal | vauthors = Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA | title = The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain | journal = Structure | volume = 11 | issue = 9 | pages = 1123–31 | date = Sep 2003 | pmid = 12962630 | doi = 10.1016/S0969-2126(03)00148-5 }}</ref>
| Name = Hepsin (transmembrane protease, serine 1)
 
| HGNCid = 5155
== Clinical significance ==
| Symbol = HPN
 
| AltSymbols =; TMPRSS1
Hepsin expression is unregulated in [[prostate cancer]] and correlates with disease progression.<ref name="pmid17569629">{{cite journal | vauthors = Wu Q, Parry G | title = Hepsin and prostate cancer | journal = Frontiers in Bioscience | volume = 12 | issue = | pages = 5052–9 | year = 2007 | pmid = 17569629 | doi = 10.2741/2447 }}</ref>
| OMIM = 142440
| ECnumber =
| Homologene = 20498
| MGIid = 1196620
| GeneAtlas_image1 = PBB_GE_HPN_204934_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004252 |text = serine-type endopeptidase activity}} {{GNF_GO|id=GO:0005044 |text = scavenger receptor activity}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}}
| Process = {{GNF_GO|id=GO:0006508 |text = proteolysis}}  
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3249
    | Hs_Ensembl = ENSG00000105707
    | Hs_RefseqProtein = NP_002142
    | Hs_RefseqmRNA = NM_002151
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 40223250
    | Hs_GenLoc_end = 40249315
    | Hs_Uniprot = P05981
    | Mm_EntrezGene = 15451
    | Mm_Ensembl = ENSMUSG00000001249
    | Mm_RefseqmRNA = NM_008281
    | Mm_RefseqProtein = NP_032307
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 30807485
    | Mm_GenLoc_end = 30819662
    | Mm_Uniprot = Q3U0U6
  }}
}}
'''Hepsin (transmembrane protease, serine 1)''', also known as '''HPN''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HPN hepsin (transmembrane protease, serine 1)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3249| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== References ==
{{PBB_Summary
{{reflist}}
| section_title =  
| summary_text = Hepsin is a cell surface serine protease.[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: HPN hepsin (transmembrane protease, serine 1)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3249| accessdate = }}</ref>
}}


==References==
== Further reading ==
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Wu Q | title = Gene targeting in hemostasis. Hepsin | journal = Frontiers in Bioscience | volume = 6 | issue =  | pages = D192-200 | date = Feb 2001 | pmid = 11171558 | doi =  }}
| citations =
* {{cite journal | vauthors = Tsuji A, Torres-Rosado A, Arai T, Le Beau MM, Lemons RS, Chou SH, Kurachi K | title = Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization | journal = The Journal of Biological Chemistry | volume = 266 | issue = 25 | pages = 16948–53 | date = Sep 1991 | pmid = 1885621 | doi =  }}
*{{cite journal | author=Wu Q |title=Gene targeting in hemostasis. Hepsin. |journal=Front. Biosci. |volume=6 |issue=  |pages= D192-200 |year= 2001 |pmid= 11171558 |doi=  }}
* {{cite journal | vauthors = Kazama Y, Hamamoto T, Foster DC, Kisiel W | title = Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation | journal = The Journal of Biological Chemistry | volume = 270 | issue = 1 | pages = 66–72 | date = Jan 1995 | pmid = 7814421 | doi = 10.1074/jbc.270.1.66 }}
*{{cite journal | author=Tsuji A, Torres-Rosado A, Arai T, ''et al.'' |title=Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization. |journal=J. Biol. Chem. |volume=266 |issue= 25 |pages= 16948-53 |year= 1991 |pmid= 1885621 |doi=  }}
* {{cite journal | vauthors = Torres-Rosado A, O'Shea KS, Tsuji A, Chou SH, Kurachi K | title = Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 15 | pages = 7181–5 | date = Aug 1993 | pmid = 8346233 | pmc = 47100 | doi = 10.1073/pnas.90.15.7181 }}
*{{cite journal | author=Leytus SP, Loeb KR, Hagen FS, ''et al.'' |title=A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells. |journal=Biochemistry |volume=27 |issue= 3 |pages= 1067-74 |year= 1988 |pmid= 2835076 |doi=  }}
* {{cite journal | vauthors = Chen Z, Fan Z, McNeal JE, Nolley R, Caldwell MC, Mahadevappa M, Zhang Z, Warrington JA, Stamey TA | title = Hepsin and maspin are inversely expressed in laser capture microdissectioned prostate cancer | journal = The Journal of Urology | volume = 169 | issue = 4 | pages = 1316–9 | date = Apr 2003 | pmid = 12629351 | doi = 10.1097/01.ju.0000050648.40164.0d }}
*{{cite journal  | author=Kazama Y, Hamamoto T, Foster DC, Kisiel W |title=Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation. |journal=J. Biol. Chem. |volume=270 |issue= 1 |pages= 66-72 |year= 1995 |pmid= 7814421 |doi= }}
* {{cite journal | vauthors = Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA | title = The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain | journal = Structure | volume = 11 | issue = 9 | pages = 1123–31 | date = Sep 2003 | pmid = 12962630 | doi = 10.1016/S0969-2126(03)00148-5 }}
*{{cite journal | author=Torres-Rosado A, O'Shea KS, Tsuji A, ''et al.'' |title=Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 15 |pages= 7181-5 |year= 1993 |pmid= 8346233 |doi= }}
* {{cite journal | vauthors = Kirchhofer D, Peek M, Lipari MT, Billeci K, Fan B, Moran P | title = Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2 | journal = FEBS Letters | volume = 579 | issue = 9 | pages = 1945–50 | date = Mar 2005 | pmid = 15792801 | doi = 10.1016/j.febslet.2005.01.085 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Pal P, Xi H, Kaushal R, Sun G, Jin CH, Jin L, Suarez BK, Catalona WJ, Deka R | title = Variants in the HEPSIN gene are associated with prostate cancer in men of European origin | journal = Human Genetics | volume = 120 | issue = 2 | pages = 187–92 | date = Sep 2006 | pmid = 16783571 | doi = 10.1007/s00439-006-0204-3 }}
*{{cite journal | author=Chen Z, Fan Z, McNeal JE, ''et al.'' |title=Hepsin and maspin are inversely expressed in laser capture microdissectioned prostate cancer. |journal=J. Urol. |volume=169 |issue= 4 |pages= 1316-9 |year= 2003 |pmid= 12629351 |doi= 10.1097/01.ju.0000050648.40164.0d }}
* {{cite journal | vauthors = Moran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D | title = Pro-urokinase-type plasminogen activator is a substrate for hepsin | journal = The Journal of Biological Chemistry | volume = 281 | issue = 41 | pages = 30439–46 | date = Oct 2006 | pmid = 16908524 | doi = 10.1074/jbc.M605440200 }}
*{{cite journal | author=Somoza JR, Ho JD, Luong C, ''et al.'' |title=The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain. |journal=Structure |volume=11 |issue= 9 |pages= 1123-31 |year= 2004 |pmid= 12962630 |doi=  }}
* {{cite journal | vauthors = Betsunoh H, Mukai S, Akiyama Y, Fukushima T, Minamiguchi N, Hasui Y, Osada Y, Kataoka H | title = Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma | journal = Cancer Science | volume = 98 | issue = 4 | pages = 491–8 | date = Apr 2007 | pmid = 17309599 | doi = 10.1111/j.1349-7006.2007.00412.x }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal | author=Kirchhofer D, Peek M, Lipari MT, ''et al.'' |title=Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2. |journal=FEBS Lett. |volume=579 |issue= 9 |pages= 1945-50 |year= 2005 |pmid= 15792801 |doi= 10.1016/j.febslet.2005.01.085 }}
*{{cite journal | author=Pal P, Xi H, Kaushal R, ''et al.'' |title=Variants in the HEPSIN gene are associated with prostate cancer in men of European origin. |journal=Hum. Genet. |volume=120 |issue= 2 |pages= 187-92 |year= 2007 |pmid= 16783571 |doi= 10.1007/s00439-006-0204-3 }}
*{{cite journal | author=Moran P, Li W, Fan B, ''et al.'' |title=Pro-urokinase-type plasminogen activator is a substrate for hepsin. |journal=J. Biol. Chem. |volume=281 |issue= 41 |pages= 30439-46 |year= 2006 |pmid= 16908524 |doi= 10.1074/jbc.M605440200 }}
*{{cite journal | author=Betsunoh H, Mukai S, Akiyama Y, ''et al.'' |title=Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma. |journal=Cancer Sci. |volume=98 |issue= 4 |pages= 491-8 |year= 2007 |pmid= 17309599 |doi= 10.1111/j.1349-7006.2007.00412.x }}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=3249}}
{{InterPro content|IPR015352}}
{{gene-19-stub}}


{{protein-stub}}
[[Category:Protein domains]]
{{WikiDoc Sources}}

Latest revision as of 02:29, 27 October 2017

Hepsin-SRCR
File:PDB 1p57 EBI.jpg
extracellular domain of human hepsin
Identifiers
SymbolHepsin-SRCR
PfamPF09272
InterProIPR015352
SCOP1p57
SUPERFAMILY1p57
VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Serine protease hepsin is an enzyme that in humans is encoded by the HPN gene.[1][2]

Function

Hepsin is a cell surface serine protease.[2]

Hepson contains a peptidase S1 domain and an SRCR domain. The SRCR domain is located in the extracellular part of the protein, it is formed primarily by three elements of regular secondary structure: a 12-residue alpha helix, a twisted five-stranded antiparallel beta sheet, and a second, two-stranded, antiparallel sheet. The two beta-sheets lie at roughly right angles to each other, with the helix nestled between the two, adopting an SRCR fold. The exact function of this domain has not been identified, though it probably may serve to orient the protease domain or place it in the vicinity of its substrate.[3]

Clinical significance

Hepsin expression is unregulated in prostate cancer and correlates with disease progression.[4]

References

  1. ↑ Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW (Feb 1988). "A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells". Biochemistry. 27 (3): 1067–74. doi:10.1021/bi00403a032. PMID 2835076.
  2. ↑ 2.0 2.1 "Entrez Gene: HPN hepsin (transmembrane protease, serine 1)".
  3. ↑ Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA (Sep 2003). "The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain". Structure. 11 (9): 1123–31. doi:10.1016/S0969-2126(03)00148-5. PMID 12962630.
  4. ↑ Wu Q, Parry G (2007). "Hepsin and prostate cancer". Frontiers in Bioscience. 12: 5052–9. doi:10.2741/2447. PMID 17569629.

Further reading

  • Wu Q (Feb 2001). "Gene targeting in hemostasis. Hepsin". Frontiers in Bioscience. 6: D192–200. PMID 11171558.
  • Tsuji A, Torres-Rosado A, Arai T, Le Beau MM, Lemons RS, Chou SH, Kurachi K (Sep 1991). "Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization". The Journal of Biological Chemistry. 266 (25): 16948–53. PMID 1885621.
  • Kazama Y, Hamamoto T, Foster DC, Kisiel W (Jan 1995). "Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation". The Journal of Biological Chemistry. 270 (1): 66–72. doi:10.1074/jbc.270.1.66. PMID 7814421.
  • Torres-Rosado A, O'Shea KS, Tsuji A, Chou SH, Kurachi K (Aug 1993). "Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth". Proceedings of the National Academy of Sciences of the United States of America. 90 (15): 7181–5. doi:10.1073/pnas.90.15.7181. PMC 47100. PMID 8346233.
  • Chen Z, Fan Z, McNeal JE, Nolley R, Caldwell MC, Mahadevappa M, Zhang Z, Warrington JA, Stamey TA (Apr 2003). "Hepsin and maspin are inversely expressed in laser capture microdissectioned prostate cancer". The Journal of Urology. 169 (4): 1316–9. doi:10.1097/01.ju.0000050648.40164.0d. PMID 12629351.
  • Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA (Sep 2003). "The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain". Structure. 11 (9): 1123–31. doi:10.1016/S0969-2126(03)00148-5. PMID 12962630.
  • Kirchhofer D, Peek M, Lipari MT, Billeci K, Fan B, Moran P (Mar 2005). "Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2". FEBS Letters. 579 (9): 1945–50. doi:10.1016/j.febslet.2005.01.085. PMID 15792801.
  • Pal P, Xi H, Kaushal R, Sun G, Jin CH, Jin L, Suarez BK, Catalona WJ, Deka R (Sep 2006). "Variants in the HEPSIN gene are associated with prostate cancer in men of European origin". Human Genetics. 120 (2): 187–92. doi:10.1007/s00439-006-0204-3. PMID 16783571.
  • Moran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D (Oct 2006). "Pro-urokinase-type plasminogen activator is a substrate for hepsin". The Journal of Biological Chemistry. 281 (41): 30439–46. doi:10.1074/jbc.M605440200. PMID 16908524.
  • Betsunoh H, Mukai S, Akiyama Y, Fukushima T, Minamiguchi N, Hasui Y, Osada Y, Kataoka H (Apr 2007). "Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma". Cancer Science. 98 (4): 491–8. doi:10.1111/j.1349-7006.2007.00412.x. PMID 17309599.
This article incorporates text from the public domain Pfam and InterPro: IPR015352
Retrieved from "https://www.wikidoc.org/index.php?title=HPN_(gene)&oldid=1418996"