JMJD6 explained

Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 is an enzyme that in humans is encoded by the JMJD6 gene.^{[1] [2]}

Function

This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins belong to the alpha-ketoglutarate-dependent hydroxylase superfamily. They are predicted to function as protein hydroxylases or histone demethylases. This protein was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells. Subsequent studies suggest that the protein may cross-react with a monoclonal antibody that recognizes the phosphatidylserine receptor and does not directly function in the clearance of apoptotic cells. Multiple transcript variants encoding different isoforms have been found for this gene. On a physiological level JMJD6 has a role in angiogenesis, the process of vessel formation, whereas further roles of JMJD6 in pathophysiological processes were implicated, such as mammary tumorigenesis.^[3] Here, elevated JMJD6 level were found in breast cancer associated with aggressiveness and metastasis in mice.^[4]

Further reading

• Boeckel JN, Guarani V, Koyanagi M, Roexe T, Lengeling A, Schermuly RT, Gellert P, Braun T, Zeiher A, Dimmeler S . Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1 . Proceedings of the National Academy of Sciences of the United States of America . 108 . 8 . 3276–81 . February 2011 . 21300889 . 10.1073/pnas.1008098108 . 3044381. 2011PNAS..108.3276B . free .
• Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Böttger A . Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing . Science . 325 . 5936 . 90–3 . July 2009 . 19574390 . 10.1126/science.1175865 . 2009Sci...325...90W . 10033/78493 . 38938528 . free .
• Zakharova L, Dadsetan S, Fomina AF . Endogenous Jmjd6 gene product is expressed at the cell surface and regulates phagocytosis in immature monocyte-like activated THP-1 cells . Journal of Cellular Physiology . 221 . 1 . 84–91 . October 2009 . 19492415 . 10.1002/jcp.21829 . 12228555 .
• Hahn P, Böse J, Edler S, Lengeling A . Genomic structure and expression of Jmjd6 and evolutionary analysis in the context of related JmjC domain containing proteins . BMC Genomics . 9 . 293 . 2008 . 18564434 . 2453528 . 10.1186/1471-2164-9-293 . free .
• Chang B, Chen Y, Zhao Y, Bruick RK . JMJD6 is a histone arginine demethylase . Science . 318 . 5849 . 444–7 . October 2007 . 17947579 . 10.1126/science.1145801 . 2007Sci...318..444C . 35792729 .
• Klose RJ, Kallin EM, Zhang Y . JmjC-domain-containing proteins and histone demethylation . Nature Reviews Genetics . 7 . 9 . 715–27 . September 2006 . 16983801 . 10.1038/nrg1945 . 30005607 .
• Williamson P, Schlegel RA . Hide and seek: the secret identity of the phosphatidylserine receptor . Journal of Biology . 3 . 4 . 14 . 2005 . 15453906 . 549716 . 10.1186/jbiol14 . free .
• Böse J, Gruber AD, Helming L, Schiebe S, Wegener I, Hafner M, Beales M, Köntgen F, Lengeling A . The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal . Journal of Biology . 3 . 4 . 15 . 2005 . 15345036 . 549712 . 10.1186/jbiol10 . free .
• Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro . DNA Research . 5 . 1 . 31–9 . February 1998 . 9628581 . 10.1093/dnares/5.1.31 . free .
• Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM . A receptor for phosphatidylserine-specific clearance of apoptotic cells . Nature . 405 . 6782 . 85–90 . May 2000 . 10811223 . 10.1038/35011084 . 2000Natur.405...85F . 205006217 .
• Ajmone-Cat MA, De Simone R, Nicolini A, Minghetti L . Effects of phosphatidylserine on p38 mitogen activated protein kinase, cyclic AMP responding element binding protein and nuclear factor-kappaB activation in resting and activated microglial cells . Journal of Neurochemistry . 84 . 2 . 413–6 . January 2003 . 12559004 . 10.1046/j.1471-4159.2003.01562.x . 29957905 .
• Chan A, Seguin R, Magnus T, Papadimitriou C, Toyka KV, Antel JP, Gold R . Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: termination of CNS autoimmune inflammation and modulation by interferon-beta . Glia . 43 . 3 . 231–42 . September 2003 . 12898702 . 10.1002/glia.10258 . 9085775 . free .
• Wang X, Wu YC, Fadok VA, Lee MC, Gengyo-Ando K, Cheng LC, Ledwich D, Hsu PK, Chen JY, Chou BK, Henson P, Mitani S, Xue D . Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12 . Science . 302 . 5650 . 1563–6 . November 2003 . 14645848 . 10.1126/science.1087641 . 2003Sci...302.1563W . 25672278 .
• Cui P, Qin B, Liu N, Pan G, Pei D . Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals . Experimental Cell Research . 293 . 1 . 154–63 . February 2004 . 14729065 . 10.1016/j.yexcr.2003.09.023 .
• Cao WM, Murao K, Imachi H, Hiramine C, Abe H, Yu X, Dobashi H, Wong NC, Takahara J, Ishida T . Phosphatidylserine receptor cooperates with high-density lipoprotein receptor in recognition of apoptotic cells by thymic nurse cells . Journal of Molecular Endocrinology . 32 . 2 . 497–505 . April 2004 . 15072554 . 10.1677/jme.0.0320497 . free .
• Cikala M, Alexandrova O, David CN, Pröschel M, Stiening B, Cramer P, Böttger A . The phosphatidylserine receptor from Hydra is a nuclear protein with potential Fe(II) dependent oxygenase activity . BMC Cell Biology . 5 . 26 . June 2004 . 15193161 . 442123 . 10.1186/1471-2121-5-26 . free .
• Hong JR, Lin GH, Lin CJ, Wang WP, Lee CC, Lin TL, Wu JL . Phosphatidylserine receptor is required for the engulfment of dead apoptotic cells and for normal embryonic development in zebrafish . Development . 131 . 21 . 5417–27 . November 2004 . 15469976 . 10.1242/dev.01409 . 11188261 .
• Köninger J, Balaz P, Wagner M, Shi X, Cima I, Zimmermann A, di Sebastiano P, Büchler MW, Friess H . Phosphatidylserine receptor in chronic pancreatitis: evidence for a macrophage independent role . Annals of Surgery . 241 . 1 . 144–51 . January 2005 . 15622002 . 1356857 . 10.1097/01.sla.0000149304.89456.5a .

Notes and References

1. Vandivier RW, Fadok VA, Hoffmann PR, Bratton DL, Penvari C, Brown KK, Brain JD, Accurso FJ, Henson PM . Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis . The Journal of Clinical Investigation . 109 . 5 . 661–70 . March 2002 . 11877474 . 150889 . 10.1172/JCI13572 .
2. Web site: Entrez Gene: JMJD6 jumonji domain containing 6.
3. Boeckel JN, Guarani V, Koyanagi M, Roexe T, Lengeling A, Schermuly RT, Gellert P, Braun T, Zeiher A, Dimmeler S . Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1 . Proceedings of the National Academy of Sciences of the United States of America . 108 . 8 . 3276–81 . February 2011 . 21300889 . 3044381 . 10.1073/pnas.1008098108 . 2011PNAS..108.3276B . free .
4. Aprelikova O, Chen K, El Touny LH, Brignatz-Guittard C, Han J, Qiu T, Yang HH, Lee MP, Zhu M, Green JE . The epigenetic modifier JMJD6 is amplified in mammary tumors and cooperates with c-Myc to enhance cellular transformation, tumor progression, and metastasis . Clin Epigenetics . 8 . 38 . 14 Apr 2016 . 38 . 10.1186/s13148-016-0205-6 . 4831179 . 27081402 . free .