HPN (gene)

Hepsin-SRCR

extracellular domain of human hepsin
Identifiers
Symbol Hepsin-SRCR
Pfam PF09272
InterPro IPR015352
SCOP 1p57
SUPERFAMILY 1p57
Hepsin

PDB rendering based on 1o5e.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HPN ; TMPRSS1
External IDs OMIM: 142440 MGI: 1196620 HomoloGene: 20498 GeneCards: HPN Gene
EC number 3.4.21.106
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 3249 15451
Ensembl ENSG00000105707 ENSMUSG00000001249
UniProt P05981 O35453
RefSeq (mRNA) NM_002151 NM_001110252
RefSeq (protein) NP_002142 NP_001103722
Location (UCSC) Chr 19:
35.04 – 35.07 Mb		 Chr 7:
31.1 – 31.12 Mb
PubMed search

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. 1 2 "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

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