HPN (gene)

Serine protease hepsin is an enzyme that in humans is encoded by the HPN gene.[5][6]

Hepsin-SRCR
extracellular domain of human hepsin
Identifiers
Symbol	Hepsin-SRCR
Pfam	PF09272
InterPro	IPR015352
SCOP2	1p57 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

HPN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1O5E, 1O5F, 1P57, 1Z8G, 3T2N, 5CE1
Identifiers
Aliases	HPN, TMPRSS1, hepsin
External IDs	OMIM: 142440 MGI: 1196620 HomoloGene: 20498 GeneCards: HPN
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.11 Start 35,040,506 bp[1] End 35,066,571 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B1 Start 31,098,725 bp[2] End 31,115,290 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • serine-type exopeptidase activity • calcium-activated potassium channel activity • peptidase activity • GO:0001948 protein binding • serine-type peptidase activity • hydrolase activity • serine-type endopeptidase activity Cellular component • integral component of membrane • not the membrane • endoplasmic reticulum membrane • membrane • intercellular junction • integral component of plasma membrane • cell surface • neuronal cell body • apical plasma membrane • extracellular exosome • cell membrane Biological process • positive regulation of hepatocyte proliferation • positive regulation of plasminogen activation • response to thyroid hormone • negative regulation of apoptotic process • proteolysis • detection of mechanical stimulus involved in sensory perception of sound • positive regulation of thyroid hormone generation • positive regulation of cell growth • positive regulation of gene expression • pilomotor reflex • cochlea morphogenesis • potassium ion transmembrane transport • regulation of cell shape • negative regulation of epithelial cell proliferation • basement membrane disassembly • negative regulation of epithelial to mesenchymal transition • hepatocyte growth factor receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3249	15451
Ensembl	ENSG00000105707	ENSMUSG00000001249
UniProt	P05981	O35453
RefSeq (mRNA)	NM_002151 NM_182983 NM_001375441 NM_001384133	NM_001110252 NM_001276269 NM_008281
RefSeq (protein)	NP_002142 NP_892028 NP_001362370 NP_001371062	NP_001103722 NP_001263198 NP_032307
Location (UCSC)	Chr 19: 35.04 – 35.07 Mb	Chr 7: 31.1 – 31.12 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Hepsin is a cell surface serine protease.[6]

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.[7]

Clinical significance

Hepsin expression is unregulated in prostate cancer and correlates with disease progression.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000105707 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001249 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: HPN hepsin (transmembrane protease, serine 1)".
7. 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.
8. Wu Q, Parry G (2007). "Hepsin and prostate cancer". Frontiers in Bioscience. 12 (12): 5052–9. doi:10.2741/2447. PMID 17569629.

Further reading

• Wu Q (Feb 2001). "Gene targeting in hemostasis. Hepsin". Frontiers in Bioscience. 6 (3): D192-200. doi:10.2741/a604. 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. S2CID 46441979.
• 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. S2CID 13411333.
• 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. S2CID 26220332.

This article incorporates text from the public domain Pfam and InterPro: IPR015352