Transmembrane protease serine 2

Details

Name
Transmembrane protease serine 2
Synonyms
  • 3.4.21.-
  • PRSS10
  • Serine protease 10
Gene Name
TMPRSS2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052395|Transmembrane protease serine 2
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG
Number of residues
492
Molecular Weight
53858.845
Theoretical pI
Not Available
GO Classification
Functions
scavenger receptor activity / serine-type endopeptidase activity / serine-type peptidase activity
Processes
positive regulation of viral entry into host cell / protein autoprocessing / proteolysis
Components
extracellular exosome / integral component of plasma membrane / plasma membrane
General Function
Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity).
Specific Function
Scavenger receptor activity
Pfam Domain Function
Transmembrane Regions
85-105
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0052396|Transmembrane protease serine 2 (TMPRSS2)
ATGGCTTTGAACTCAGGGTCACCACCAGCTATTGGACCTTACTATGAAAACCATGGATAC
CAACCGGAAAACCCCTATCCCGCACAGCCCACTGTGGTCCCCACTGTCTACGAGGTGCAT
CCGGCTCAGTACTACCCGTCCCCCGTGCCCCAGTACGCCCCGAGGGTCCTGACGCAGGCT
TCCAACCCCGTCGTCTGCACGCAGCCCAAATCCCCATCCGGGACAGTGTGCACCTCAAAG
ACTAAGAAAGCACTGTGCATCACCTTGACCCTGGGGACCTTCCTCGTGGGAGCTGCGCTG
GCCGCTGGCCTACTCTGGAAGTTCATGGGCAGCAAGTGCTCCAACTCTGGGATAGAGTGC
GACTCCTCAGGTACCTGCATCAACCCCTCTAACTGGTGTGATGGCGTGTCACACTGCCCC
GGCGGGGAGGACGAGAATCGGTGTGTTCGCCTCTACGGACCAAACTTCATCCTTCAGGTG
TACTCATCTCAGAGGAAGTCCTGGCACCCTGTGTGCCAAGACGACTGGAACGAGAACTAC
GGGCGGGCGGCCTGCAGGGACATGGGCTATAAGAATAATTTTTACTCTAGCCAAGGAATA
GTGGATGACAGCGGATCCACCAGCTTTATGAAACTGAACACAAGTGCCGGCAATGTCGAT
ATCTATAAAAAACTGTACCACAGTGATGCCTGTTCTTCAAAAGCAGTGGTTTCTTTACGC
TGTATAGCCTGCGGGGTCAACTTGAACTCAAGCCGCCAGAGCAGGATTGTGGGCGGCGAG
AGCGCGCTCCCGGGGGCCTGGCCCTGGCAGGTCAGCCTGCACGTCCAGAACGTCCACGTG
TGCGGAGGCTCCATCATCACCCCCGAGTGGATCGTGACAGCCGCCCACTGCGTGGAAAAA
CCTCTTAACAATCCATGGCATTGGACGGCATTTGCGGGGATTTTGAGACAATCTTTCATG
TTCTATGGAGCCGGATACCAAGTAGAAAAAGTGATTTCTCATCCAAATTATGACTCCAAG
ACCAAGAACAATGACATTGCGCTGATGAAGCTGCAGAAGCCTCTGACTTTCAACGACCTA
GTGAAACCAGTGTGTCTGCCCAACCCAGGCATGATGCTGCAGCCAGAACAGCTCTGCTGG
ATTTCCGGGTGGGGGGCCACCGAGGAGAAAGGGAAGACCTCAGAAGTGCTGAACGCTGCC
AAGGTGCTTCTCATTGAGACACAGAGATGCAACAGCAGATATGTCTATGACAACCTGATC
ACACCAGCCATGATCTGTGCCGGCTTCCTGCAGGGGAACGTCGATTCTTGCCAGGGTGAC
AGTGGAGGGCCTCTGGTCACTTCGAAGAACAATATCTGGTGGCTGATAGGGGATACAAGC
TGGGGTTCTGGCTGTGCCAAAGCTTACAGACCAGGAGTGTACGGGAATGTGATGGTATTC
ACGGACTGGATTTATCGACAAATGAGGGCAGACGGCTAA
Chromosome Location
21
Locus
21q22.3
External Identifiers
ResourceLink
UniProtKB IDO15393
UniProtKB Entry NameTMPS2_HUMAN
HGNC IDHGNC:11876
General References
  1. Paoloni-Giacobino A, Chen H, Peitsch MC, Rossier C, Antonarakis SE: Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3. Genomics. 1997 Sep 15;44(3):309-20. doi: 10.1006/geno.1997.4845. [Article]
  2. Teng DH, Chen Y, Lian L, Ha PC, Tavtigian SV, Wong AK: Mutation analyses of 268 candidate genes in human tumor cell lines. Genomics. 2001 Jun 15;74(3):352-64. [Article]
  3. Afar DE, Vivanco I, Hubert RS, Kuo J, Chen E, Saffran DC, Raitano AB, Jakobovits A: Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res. 2001 Feb 15;61(4):1686-92. [Article]
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  7. Vaarala MH, Porvari KS, Kellokumpu S, Kyllonen AP, Vihko PT: Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues. J Pathol. 2001 Jan;193(1):134-40. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T. [Article]
  8. Wilson S, Greer B, Hooper J, Zijlstra A, Walker B, Quigley J, Hawthorne S: The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. Biochem J. 2005 Jun 15;388(Pt 3):967-72. doi: 10.1042/BJ20041066. [Article]
  9. Chen YW, Lee MS, Lucht A, Chou FP, Huang W, Havighurst TC, Kim K, Wang JK, Antalis TM, Johnson MD, Lin CY: TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells. Am J Pathol. 2010 Jun;176(6):2986-96. doi: 10.2353/ajpath.2010.090665. Epub 2010 Apr 9. [Article]
  10. Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T: A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol. 2011 Jan;85(2):873-82. doi: 10.1128/JVI.02062-10. Epub 2010 Nov 10. [Article]
  11. Glowacka I, Bertram S, Muller MA, Allen P, Soilleux E, Pfefferle S, Steffen I, Tsegaye TS, He Y, Gnirss K, Niemeyer D, Schneider H, Drosten C, Pohlmann S: Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol. 2011 May;85(9):4122-34. doi: 10.1128/JVI.02232-10. Epub 2011 Feb 16. [Article]
  12. Bertram S, Dijkman R, Habjan M, Heurich A, Gierer S, Glowacka I, Welsch K, Winkler M, Schneider H, Hofmann-Winkler H, Thiel V, Pohlmann S: TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. J Virol. 2013 Jun;87(11):6150-60. doi: 10.1128/JVI.03372-12. Epub 2013 Mar 27. [Article]
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  14. Shirato K, Kawase M, Matsuyama S: Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2. J Virol. 2013 Dec;87(23):12552-61. doi: 10.1128/JVI.01890-13. Epub 2013 Sep 11. [Article]
  15. 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. [Article]
  16. Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, Morrissey C, Corey E, Montgomery B, Mostaghel E, Clegg N, Coleman I, Brown CM, Schneider EL, Craik C, Simon JA, Bedalov A, Nelson PS: The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov. 2014 Nov;4(11):1310-25. doi: 10.1158/2159-8290.CD-13-1010. Epub 2014 Aug 13. [Article]
  17. Ko CJ, Huang CC, Lin HY, Juan CP, Lan SW, Shyu HY, Wu SR, Hsiao PW, Huang HP, Shun CT, Lee MS: Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis. Cancer Res. 2015 Jul 15;75(14):2949-60. doi: 10.1158/0008-5472.CAN-14-3297. Epub 2015 May 27. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB13729CamostatexperimentalunknowninhibitorDetails
DB09019BromhexineapprovedunknownDetails