HPN (gene)

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; OMA:HPN - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q13.11 Start 35,040,506 bp [1] End 35,066,573 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 B1 Start 30,798,150 bp [2] End 30,814,715 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver body of pancreas kidney tubule body of stomach gastrocnemius muscle left lobe of thyroid gland human kidney muscle of thigh right lobe of thyroid gland pancreatic ductal cell Top expressed in right kidney left lobe of liver proximal tubule human kidney yolk sac renal pelvis medullary collecting duct blastocyst vestibular sensory epithelium epithelium of stomach More reference expression data BioGPS More reference expression data
Gene ontology Molecular function serine-type exopeptidase activity calcium-activated potassium channel activity peptidase activity protein binding serine-type peptidase activity hydrolase activity serine-type endopeptidase activity Cellular component integral component of membrane nuclear membrane endoplasmic reticulum membrane membrane cell-cell junction integral component of plasma membrane cell surface soma apical plasma membrane extracellular exosome plasma 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: 30.8 – 30.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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) A604: 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. doi: 10.1016/S0021-9258(18)55395-3 . 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. Bibcode:1993PNAS...90.7181T. 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. PMC   11160002 . PMID   17309599. S2CID   26220332.

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