RHBDF2 explained

Inactive rhomboid protein 2 is a protein that in humans is encoded by the RHBDF2 gene.^{[1] [2]} The alternative name iRhom2 has been proposed, in order to clarify that it is a catalytically inactive member of the rhomboid family of intramembrane serine proteases.^{[3] [4]}

The RHBDF2 gene is located on the long arm of chromosome 17 (17q25.1) on the Crick (minus) strand. It is 30.534 kilobases in length and encodes a protein of 856 amino acids with a predicted molecular weight of 96.686 kilodaltons.

The RHBDF2 protein plays an important role in the secretion of tumor necrosis factor alpha,^{[5] [6] [7]} and has also been implicated in familial esophageal cancer.^[8]

It is involved in the regulation of the secretion of several ligands of the epidermal growth factor receptor.^[9]

Further reading

• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . Sep 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Puente XS, López-Otín C . A genomic analysis of rat proteases and protease inhibitors . Genome Research . 14 . 4 . 609–22 . Apr 2004 . 15060002 . 383305 . 10.1101/gr.1946304 .
• Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags . Proceedings of the National Academy of Sciences of the United States of America . 97 . 7 . 3491–6 . Mar 2000 . 10737800 . 16267 . 10.1073/pnas.97.7.3491 . 2000PNAS...97.3491D . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .

Notes and References

1. Puente XS, Sánchez LM, Overall CM, López-Otín C . Human and mouse proteases: a comparative genomic approach . Nature Reviews Genetics . 4 . 7 . 544–58 . Jul 2003 . 12838346 . 10.1038/nrg1111 . 2856065 .
2. Web site: Entrez Gene: RHBDF2 rhomboid 5 homolog 2 (Drosophila).
3. Lemberg MK, Freeman M . Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases . Genome Research . 17 . 11 . Nov 2007 . 17938163 . 10.1101/gr.6425307 . 2045146 . 1634–46.
4. Zettl M, Adrain C, Strisovsky K, Lastun V, Freeman M . Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling . Cell . 145 . 1 . Apr 2011 . 21439629 . 10.1016/j.cell.2011.02.047 . 3149277 . 79–91.
5. Siggs OM, Xiao N, Wang Y, Shi H, Tomisato W, Li X, Xia Y, Beutler B . iRhom2 is required for the secretion of mouse TNFα . Blood . 119 . 24 . Jun 2012 . 22550345 . 10.1182/blood-2012-03-417949 . 5769–71 . 3382936.
6. Adrain C, Zettl M, Christova Y, Taylor N, Freeman M . Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE . Science . 335 . 6065 . Jan 2012 . 22246777 . 10.1126/science.1214400 . 225–8 . 3272371. 2012Sci...335..225A .
7. McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Häussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW . iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS . Science . 335 . 6065 . Jan 2012 . 22246778 . 10.1126/science.1214448 . 229–32 . 4250273. 2012Sci...335..229M .
8. Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ, Carroll R, Plagnol V, McRonald FE, Stevens HP, Spurr NK, Bishop DT, Ellis A, Jankowski J, Field JK, Leigh IM, South AP, Kelsell DP . RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome . American Journal of Human Genetics . 90 . 2 . Feb 2012 . 22265016 . 10.1016/j.ajhg.2011.12.008 . 340–6 . 3276661.
9. Siggs OM, Grieve A, Xu H, Bambrough P, Christova Y, Freeman M . Genetic interaction implicates iRhom2 in the regulation of EGF receptor signalling in mice . Biol Open . 3 . 12 . 1151–7 . November 2014 . 25395669 . 4265752 . 10.1242/bio.201410116 .