TMPRSS2
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| Transmembrane protease, serine 2 | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | TMPRSS2; PP9284; PRSS10 | ||||||||||||
| External IDs | OMIM: 602060 MGI: 1354381 HomoloGene: 4136 ChEMBL: 1795140 GeneCards: TMPRSS2 Gene | ||||||||||||
| EC number | 3.4.21.- | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| More reference expression data | |||||||||||||
| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 7113 | 50528 | |||||||||||
| Ensembl | ENSG00000184012 | ENSMUSG00000000385 | |||||||||||
| UniProt | O15393 | Q9JIQ8 | |||||||||||
| RefSeq (mRNA) | NM_001135099 | NM_015775 | |||||||||||
| RefSeq (protein) | NP_001128571 | NP_056590 | |||||||||||
| Location (UCSC) | Chr 21: 42.84 – 42.9 Mb | Chr 16: 97.56 – 97.61 Mb | |||||||||||
| PubMed search | |||||||||||||
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene.[1][2]
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.[2]
ERG gene fusion
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.[3]
References
- ↑ Paoloni-Giacobino A, Chen H, Peitsch MC, Rossier C, Antonarakis SE (Nov 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.
- ↑ 2.0 2.1 "Entrez Gene: TMPRSS2 transmembrane protease, serine 2".
- ↑ Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM. (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.
Further reading
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Lin B, Ferguson C, White JT et al. (1999). "Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2". Cancer Res. 59 (17): 4180–4. PMID 10485450.
- Hattori M, Fujiyama A, Taylor TD et al. (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
- Vaarala MH, Porvari KS, Kellokumpu S et al. (2001). "Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues". J. Pathol. 193 (1): 134–40. doi:10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T. PMID 11169526.
- Afar DE, Vivanco I, Hubert RS et al. (2001). "Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia". Cancer Res. 61 (4): 1686–92. PMID 11245484.
- Jacquinet E, Rao NV, Rao GV et al. (2001). "Cloning and characterization of the cDNA and gene for human epitheliasin". Eur. J. Biochem. 268 (9): 2687–99. doi:10.1046/j.1432-1327.2001.02165.x. PMID 11322890.
- Teng DH, Chen Y, Lian L et al. (2001). "Mutation analyses of 268 candidate genes in human tumor cell lines". Genomics 74 (3): 352–64. doi:10.1006/geno.2001.6551. PMID 11414763.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Wilson S, Greer B, Hooper J et al. (2005). "The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells". Biochem. J. 388 (Pt 3): 967–72. doi:10.1042/BJ20041066. PMC 1183478. PMID 15537383.
- Soller MJ, Isaksson M, Elfving P et al. (2006). "Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer". Genes Chromosomes Cancer 45 (7): 717–9. doi:10.1002/gcc.20329. PMID 16575875.
- Tomlins SA, Mehra R, Rhodes DR et al. (2006). "TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer". Cancer Res. 66 (7): 3396–400. doi:10.1158/0008-5472.CAN-06-0168. PMID 16585160.
- Yoshimoto M, Joshua AM, Chilton-Macneill S et al. (2006). "Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement". Neoplasia 8 (6): 465–9. doi:10.1593/neo.06283. PMC 1601467. PMID 16820092.
- Böttcher E, Matrosovich T, Beyerle M et al. (2006). "Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium". J. Virol. 80 (19): 9896–8. doi:10.1128/JVI.01118-06. PMC 1617224. PMID 16973594.
- Cerveira N, Ribeiro FR, Peixoto A et al. (2006). "TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions". Neoplasia 8 (10): 826–32. doi:10.1593/neo.06427. PMC 1715930. PMID 17032499.
- Yoo NJ, Lee JW, Lee SH (2007). "Absence of fusion of TMPRSS2 and ETS transcription factor genes in gastric and colorectal carcinomas". APMIS 115 (3): 252–3. doi:10.1111/j.1600-0463.2007.apm_652.x. PMID 17367471.
- Winnes M, Lissbrant E, Damber JE, Stenman G (2007). "Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer". Oncol. Rep. 17 (5): 1033–6. PMID 17390040.
- Tu JJ, Rohan S, Kao J et al. (2007). "Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues". Mod. Pathol. 20 (9): 921–8. doi:10.1038/modpathol.3800903. PMID 17632455.
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