Serine protease hepsin

Details

Name
Serine protease hepsin
Synonyms
  • 3.4.21.106
  • TMPRSS1
  • Transmembrane protease serine 1
Gene Name
HPN
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016689|Serine protease hepsin
MAQKEGGRTVPCCSRPKVAALTAGTLLLLTAIGAASWAIVAVLLRSDQEPLYPVQVSSAD
ARLMVFDKTEGTWRLLCSSRSNARVAGLSCEEMGFLRALTHSELDVRTAGANGTSGFFCV
DEGRLPHTQRLLEVISVCDCPRGRFLAAICQDCGRRKLPVDRIVGGRDTSLGRWPWQVSL
RYDGAHLCGGSLLSGDWVLTAAHCFPERNRVLSRWRVFAGAVAQASPHGLQLGVQAVVYH
GGYLPFRDPNSEENSNDIALVHLSSPLPLTEYIQPVCLPAAGQALVDGKICTVTGWGNTQ
YYGQQAGVLQEARVPIISNDVCNGADFYGNQIKPKMFCAGYPEGGIDACQGDSGGPFVCE
DSISRTPRWRLCGIVSWGTGCALAQKPGVYTKVSDFREWIFQAIKTHSEASGMVTQL
Number of residues
417
Molecular Weight
45011.01
Theoretical pI
7.66
GO Classification
Functions
calcium-activated potassium channel activity / peptidase activity / serine-type endopeptidase activity / serine-type exopeptidase activity / serine-type peptidase activity
Processes
basement membrane disassembly / cholesterol homeostasis / cochlea morphogenesis / detection of mechanical stimulus involved in sensory perception of sound / negative regulation of alkaline phosphatase activity / negative regulation of apoptotic process / negative regulation of epithelial cell proliferation / negative regulation of epithelial to mesenchymal transition / pilomotor reflex / positive regulation by host of viral transcription / positive regulation of cell growth / positive regulation of gene expression / positive regulation of hepatocyte proliferation / positive regulation of plasminogen activation / positive regulation of thyroid hormone generation / potassium ion transmembrane transport / proteolysis / regulation of cell shape / response to thyroid hormone
Components
anchored component of plasma membrane / cell surface / cell-cell junction / endoplasmic reticulum membrane / extracellular exosome / integral component of membrane / integral component of plasma membrane / neuronal cell body / plasma membrane
General Function
Serine-type peptidase activity
Specific Function
Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Plays a role in the proteolytic processing of ACE2.
Pfam Domain Function
Transmembrane Regions
24-44
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0016690|Serine protease hepsin (HPN)
ATGGCGCAGAAGGAGGGTGGCCGGACTGTGCCATGCTGCTCCAGACCCAAGGTGGCAGCT
CTCACTGCGGGGACCCTGCTACTTCTGACAGCCATCGGGGCGGCATCCTGGGCCATTGTG
GCTGTTCTCCTCAGGAGTGACCAGGAGCCGCTGTACCCAGTGCAGGTCAGCTCTGCGGAC
GCTCGGCTCATGGTCTTTGACAAGACGGAAGGGACGTGGCGGCTGCTGTGCTCCTCGCGC
TCCAACGCCAGGGTAGCCGGACTCAGCTGCGAGGAGATGGGCTTCCTCAGGGCACTGACC
CACTCCGAGCTGGACGTGCGAACGGCGGGCGCCAATGGCACGTCGGGCTTCTTCTGTGTG
GACGAGGGGAGGCTGCCCCACACCCAGAGGCTGCTGGAGGTCATCTCCGTGTGTGATTGC
CCCAGAGGCCGTTTCTTGGCCGCCATCTGCCAAGACTGTGGCCGCAGGAAGCTGCCCGTG
GACCGCATCGTGGGAGGCCGGGACACCAGCTTGGGCCGGTGGCCGTGGCAAGTCAGCCTT
CGCTATGATGGAGCACACCTCTGTGGGGGATCCCTGCTCTCCGGGGACTGGGTGCTGACA
GCCGCCCACTGCTTCCCGGAGCGGAACCGGGTCCTGTCCCGATGGCGAGTGTTTGCCGGT
GCCGTGGCCCAGGCCTCTCCCCACGGTCTGCAGCTGGGGGTGCAGGCTGTGGTCTACCAC
GGGGGCTATCTTCCCTTTCGGGACCCCAACAGCGAGGAGAACAGCAACGATATTGCCCTG
GTCCACCTCTCCAGTCCCCTGCCCCTCACAGAATACATCCAGCCTGTGTGCCTCCCAGCT
GCCGGCCAGGCCCTGGTGGATGGCAAGATCTGTACCGTGACGGGCTGGGGCAACACGCAG
TACTATGGCCAACAGGCCGGGGTACTCCAGGAGGCTCGAGTCCCCATAATCAGCAATGAT
GTCTGCAATGGCGCTGACTTCTATGGAAACCAGATCAAGCCCAAGATGTTCTGTGCTGGC
TACCCCGAGGGTGGCATTGATGCCTGCCAGGGCGACAGCGGTGGTCCCTTTGTGTGTGAG
GACAGCATCTCTCGGACGCCACGTTGGCGGCTGTGTGGCATTGTGAGTTGGGGCACTGGC
TGTGCCCTGGCCCAGAAGCCAGGCGTCTACACCAAAGTCAGTGACTTCCGGGAGTGGATC
TTCCAGGCCATAAAGACTCACTCCGAAGCCAGCGGCATGGTGACCCAGCTCTGA
Chromosome Location
19
Locus
19q11-q13.2
External Identifiers
ResourceLink
UniProtKB IDP05981
UniProtKB Entry NameHEPS_HUMAN
GenBank Protein ID306886
GenBank Gene IDM18930
GenAtlas IDHPN
HGNC IDHGNC:5155
General References
  1. Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW: A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells. Biochemistry. 1988 Feb 9;27(3):1067-74. [PubMed:2835076]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Tsuji A, Torres-Rosado A, Arai T, Le Beau MM, Lemons RS, Chou SH, Kurachi K: Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization. J Biol Chem. 1991 Sep 5;266(25):16948-53. [PubMed:1885621]
  5. Torres-Rosado A, O'Shea KS, Tsuji A, Chou SH, Kurachi K: Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7181-5. [PubMed:8346233]
  6. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  7. Ganesan R, Kolumam GA, Lin SJ, Xie MH, Santell L, Wu TD, Lazarus RA, Chaudhuri A, Kirchhofer D: Proteolytic activation of pro-macrophage-stimulating protein by hepsin. Mol Cancer Res. 2011 Sep;9(9):1175-86. doi: 10.1158/1541-7786.MCR-11-0004. Epub 2011 Aug 29. [PubMed:21875933]
  8. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  9. Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pohlmann S: TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014 Jan;88(2):1293-307. doi: 10.1128/JVI.02202-13. Epub 2013 Nov 13. [PubMed:24227843]
  10. Herter S, Piper DE, Aaron W, Gabriele T, Cutler G, Cao P, Bhatt AS, Choe Y, Craik CS, Walker N, Meininger D, Hoey T, Austin RJ: Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers. Biochem J. 2005 Aug 15;390(Pt 1):125-36. [PubMed:15839837]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00036Coagulation factor VIIa Recombinant HumanapprovedunknownDetails
DB03297Benzylsulfinic AcidexperimentalunknownDetails
DB00522Bentiromideinvestigational, withdrawnyesligandDetails
DB038656-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-CarboxamidineexperimentalunknownDetails
DB03643CRA_1144experimentalunknownDetails