REPS2 explained

RalBP1-associated Eps domain-containing protein 2 is a protein that in humans is encoded by the REPS2 gene.^{[1] [2] [3]}

Function

The product of this gene is part of a protein complex that regulates the endocytosis of growth factor receptors. The encoded protein directly interacts with a GTPase activating protein that functions downstream of the small G protein Ral. Its expression can negatively affect receptor internalization and inhibit growth factor signaling. Multiple transcript variants encoding different isoforms have been found for this gene.

Interactions

REPS2 has been shown to interact with EPN1,^[4] EPS15^[5] and RALBP1.

Further reading

• Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K, Iwamatsu A, Kishida S, Kikuchi A . Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors . EMBO J. . 18 . 13 . 3629–42 . 1999 . 10393179 . 1171441 . 10.1093/emboj/18.13.3629 .
• Morinaka K, Koyama S, Nakashima S, Hinoi T, Okawa K, Iwamatsu A, Kikuchi A . Epsin binds to the EH domain of POB1 and regulates receptor-mediated endocytosis . Oncogene . 18 . 43 . 5915–22 . 1999 . 10557078 . 10.1038/sj.onc.1202974 . 23390428 .
• Matsuzaki T, Hanai S, Kishi H, Liu Z, Bao Y, Kikuchi A, Tsuchida K, Sugino H . Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway . J. Biol. Chem. . 277 . 21 . 19008–18 . 2002 . 11882656 . 10.1074/jbc.M112472200 . free .
• Oshiro T, Koyama S, Sugiyama S, Kondo A, Onodera Y, Asahara T, Sabe H, Kikuchi A . Interaction of POB1, a downstream molecule of small G protein Ral, with PAG2, a paxillin-binding protein, is involved in cell migration . J. Biol. Chem. . 277 . 41 . 38618–26 . 2002 . 12149250 . 10.1074/jbc.M203453200 . free .
• Oosterhoff JK, Penninkhof F, Brinkmann AO, Anton Grootegoed J, Blok LJ . REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells . Oncogene . 22 . 19 . 2920–5 . 2003 . 12771942 . 10.1038/sj.onc.1206397 . 22877286 .
• Rossé C, L'Hoste S, Offner N, Picard A, Camonis J . RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis . J. Biol. Chem. . 278 . 33 . 30597–604 . 2003 . 12775724 . 10.1074/jbc.M302191200 . free .
• Penninkhof F, Grootegoed JA, Blok LJ . Identification of REPS2 as a putative modulator of NF-kappaB activity in prostate cancer cells . Oncogene . 23 . 33 . 5607–15 . 2004 . 15184881 . 10.1038/sj.onc.1207750 . free .
• Oosterhoff JK, Kühne LC, Grootegoed JA, Blok LJ . EGF signalling in prostate cancer cell lines is inhibited by a high expression level of the endocytosis protein REPS2 . Int. J. Cancer . 113 . 4 . 561–7 . 2005 . 15455380 . 10.1002/ijc.20612 . 6956264 .
• Yadav S, Zajac E, Singhal SS, Singhal J, Drake K, Awasthi YC, Awasthi S . POB1 over-expression inhibits RLIP76-mediated transport of glutathione-conjugates, drugs and promotes apoptosis . Biochem. Biophys. Res. Commun. . 328 . 4 . 1003–9 . 2005 . 15707977 . 10.1016/j.bbrc.2005.01.055 .

Notes and References

1. Ikeda M, Ishida O, Hinoi T, Kishida S, Kikuchi A . Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral . J Biol Chem . 273 . 2 . 814–21 . Feb 1998 . 9422736 . 10.1074/jbc.273.2.814 . free .
2. Koshiba S, Kigawa T, Iwahara J, Kikuchi A, Yokoyama S . Solution structure of the Eps15 homology domain of a human POB1 (partner of RalBP1) . FEBS Lett . 442 . 2–3 . 138–42 . Feb 1999 . 9928989 . 10.1016/S0014-5793(98)01644-5 . free .
3. Web site: Entrez Gene: REPS2 RALBP1 associated Eps domain containing 2.
4. Morinaka K, Koyama S, Nakashima S, Hinoi T, Okawa K, Iwamatsu A, Kikuchi A . Epsin binds to the EH domain of POB1 and regulates receptor-mediated endocytosis . Oncogene . 18 . 43 . 5915–22 . Oct 1999 . 10557078 . 10.1038/sj.onc.1202974 . 23390428 .
5. Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K, Iwamatsu A, Kishida S, Kikuchi A . Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors . EMBO J. . 18 . 13 . 3629–42 . Jul 1999 . 10393179 . 1171441 . 10.1093/emboj/18.13.3629 .