TMPRSS2

From Wikipedia the free encyclopedia

TMPRSS2
Identifiers
AliasesTMPRSS2, PP9284, PRSS10, transmembrane protease, serine 2, transmembrane serine protease 2
External IDsOMIM: 602060 MGI: 1354381 HomoloGene: 4136 GeneCards: TMPRSS2
Gene location (Human)
Chromosome 21 (human)
Chr.Chromosome 21 (human)[1]
Chromosome 21 (human)
Genomic location for TMPRSS2
Genomic location for TMPRSS2
Band21q22.3Start41,464,305 bp[1]
End41,531,116 bp[1]
RNA expression pattern
PBB GE TMPRSS2 211689 s at fs.png

PBB GE TMPRSS2 205102 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001135099
NM_005656
NM_001382720

NM_015775

RefSeq (protein)

NP_001128571
NP_005647
NP_001369649

NP_056590

Location (UCSC)Chr 21: 41.46 – 41.53 MbChr 16: 97.56 – 97.61 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene.[5][6]

Function[edit]

This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. The biological function of this gene is unknown.[6]

ERG gene fusion[edit]

TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. ERG overexpression contributes to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling.[7]

Relation to coronaviruses[edit]

Some coronaviruses, e.g. both the SARS coronavirus of 2003 and the SARS-CoV-2 are activated by TMPRSS2 and can thus be inhibited by TMPRSS2 inhibitors.[8] "SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming[9]. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option."[8] One experimental candidate as a TMPRSS2 inhibitor for potential use against both influenza and coronavirus infections in general, including those prior to the advent of COVID-19, is the OTC (in most countries) mucolytic cough medicine bromhexine,[10] which is also being investigated as a possible treatment for COVID-19 itself as well.[11]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000184012 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000385 - 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. ^ Paoloni-Giacobino A, Chen H, Peitsch MC, Rossier C, Antonarakis SE (September 1997). "Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3". Genomics. 44 (3): 309–20. doi:10.1006/geno.1997.4845. PMID 9325052.
  6. ^ a b "Entrez Gene: TMPRSS2 transmembrane protease, serine 2".
  7. ^ Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, et al. (May 2010). "An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression". Cancer Cell. 17 (5): 443–54. doi:10.1016/j.ccr.2010.03.018. PMC 2874722. PMID 20478527.
  8. ^ a b Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. (March 2020). "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor". Cell. 181 (2): 271–280.e8. doi:10.1016/j.cell.2020.02.052. PMC 7102627. PMID 32142651. Lay summaryDeutsches Primatenzentrum GmbH.
  9. ^ Rahman N, Basharat Z, Yousuf M, Castaldo G, Rastrelli L, Khan H (May 2020). "Virtual screening of natural products against type II transmembrane serine protease (TMPRSS2), the priming agent of Coronavirus 2 (SARS-CoV-2)". Molecules. 25 (10): 2271. doi:10.3390/molecules25102271. PMC 7287752. PMID 32408547.
  10. ^ Shen, Li Wen; Mao, Hui Juan; Wu, Yan Ling; Tanaka, Yoshimasa; Zhang, Wen (November 2017). "TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections". Biochimie. 142: 1–10. doi:10.1016/j.biochi.2017.07.016. PMC 7116903. PMID 28778717.
  11. ^ Depfenhart, Markus; de Villiers, Danielle; Lemperle, Gottfried; Meyer, Markus; Di Somma, Salvatore (August 2020). "Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?". Internal and Emergency Medicine. 15 (5): 801–812. doi:10.1007/s11739-020-02383-3. PMC 7249615. PMID 32458206.

Further reading[edit]