RANBP2 explained

RAN binding protein 2 (RANBP2) is protein which in humans is encoded by the RANBP2 gene.[1] It is also known as nucleoporin 358 (Nup358) since it is a member nucleoporin family that makes up the nuclear pore complex. RanBP2 has a mass of 358 kDa.

Function

RAN is a small GTP-binding protein of the RAS superfamily. Ran GTPase is a master regulatory switch, which among other functions, controls the shuttling of proteins between the nuclear and cytoplasm compartments of the cell. Ran GTPase controls a variety of cellular functions through its interactions with other proteins. The RanBP2 gene encodes a very large RAN-binding protein that localizes to cytoplasmic filaments emanating from the nuclear pore complex. RanBP2/Nup358 is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in controlling selective processes of the Ran-GTPase cycle. RanBP2 is composed of multiple domains. Each domain of RanBP2 selectively and directly interacts with distinct proteins such as Ran GTPase, importin-beta, exportin-1/CRM1, red opsin, subunits of the proteasome, cox11 and the kinesin-1 isoforms, KIF5B and KIF5C. Another partner of RanBP2 is the E2 enzyme UBC9. RanBP2 strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. Another target for SUMOylation is RanGAP which is the GTPase activating protein for Ran. SUMO-RanGAP interacts with a domain near the carboxyl terminus of RanBP2. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. The pleiotropic (multifunctional) role of RanBP2 reflects its interaction with multiple partners, each presenting distinct cellular or molecular functions. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on human chromosome 2q.

Clinical significance

Insufficiency of RanBP2 is directly linked to carcinogenesis, aneuploidy, and neuroprotection of photoreceptor neurons to light-elicited stress and aging. Human missense mutations in RanBP2 were identified in its leucine-rich domain and they cause autosomal dominant necrotizing encephalopathy (ADNE).[2]

Interactions

RANBP2 has been shown to interact with KPNB1[3] [4] [5] and UBE2I.[6] [7]

References

Further reading

Notes and References

  1. Beddow AL, Richards SA, Orem NR, Macara IG . The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif . Proceedings of the National Academy of Sciences of the United States of America . 92 . 8 . 3328–32 . Apr 1995 . 7724562 . 42159 . 10.1073/pnas.92.8.3328 . 1995PNAS...92.3328B . free .
  2. Web site: Entrez Gene: RANBP2 RAN binding protein 2.
  3. Yaseen NR, Blobel G . GTP hydrolysis links initiation and termination of nuclear import on the nucleoporin nup358 . The Journal of Biological Chemistry . 274 . 37 . 26493–502 . Sep 1999 . 10473610 . 10.1074/jbc.274.37.26493 . free .
  4. Delphin C, Guan T, Melchior F, Gerace L . RanGTP targets p97 to RanBP2, a filamentous protein localized at the cytoplasmic periphery of the nuclear pore complex . Molecular Biology of the Cell . 8 . 12 . 2379–90 . Dec 1997 . 9398662 . 25714 . 10.1091/mbc.8.12.2379 .
  5. Ben-Efraim I, Gerace L . Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import . The Journal of Cell Biology . 152 . 2 . 411–7 . Jan 2001 . 11266456 . 2199621 . 10.1083/jcb.152.2.411 .
  6. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
  7. Zhang H, Saitoh H, Matunis MJ . Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex . Molecular and Cellular Biology . 22 . 18 . 6498–508 . Sep 2002 . 12192048 . 135644 . 10.1128/MCB.22.18.6498-6508.2002 .

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