5kho

Structural highlights

Function

[RAIN_HUMAN] Required for the proper formation of vascular structures that develop via both vasculogenesis and angiogenesis. Acts as a critical and vascular-specific regulator of GTPase signaling, cell architecture, and adhesion, which is essential for endothelial cell morphogenesis and blood vessel tubulogenesis. Regulates the activity of Rho GTPases in part by recruiting ARHGAP29 and suppressing RhoA signaling and dampening ROCK and MYH9 activities in endothelial cells (By similarity). May act as effector for Golgi-bound HRAS and other Ras-like proteins. May promote HRAS-mediated transformation. Negative regulator of amino acid starvation-induced autophagy.^{[1] [2]} [RAP1B_HUMAN] GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction.^{[3] [4]}

References

1. ↑ Mitin NY, Ramocki MB, Zullo AJ, Der CJ, Konieczny SF, Taparowsky EJ. Identification and characterization of rain, a novel Ras-interacting protein with a unique subcellular localization. J Biol Chem. 2004 May 21;279(21):22353-61. Epub 2004 Mar 18. PMID:15031288 doi:http://dx.doi.org/10.1074/jbc.M312867200
2. ↑ McKnight NC, Jefferies HB, Alemu EA, Saunders RE, Howell M, Johansen T, Tooze SA. Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. EMBO J. 2012 Apr 18;31(8):1931-46. doi: 10.1038/emboj.2012.36. Epub 2012 Feb 21. PMID:22354037 doi:10.1038/emboj.2012.36
3. ↑ Lampugnani MG, Orsenigo F, Rudini N, Maddaluno L, Boulday G, Chapon F, Dejana E. CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci. 2010 Apr 1;123(Pt 7):1073-80. doi: 10.1242/jcs.059329. PMID:20332120 doi:10.1242/jcs.059329
4. ↑ Rehmann H, Arias-Palomo E, Hadders MA, Schwede F, Llorca O, Bos JL. Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B. Nature. 2008 Sep 4;455(7209):124-7. Epub 2008 Jul 27. PMID:18660803 doi:http://dx.doi.org/10.1038/nature07187