Biology:RANBP2

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

RAN binding protein 2 (RANBP2) is protein which in humans is encoded by the RANBP2 gene. 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).

Interactions

RANBP2 has been shown to interact with KPNB1 and UBE2I.

Further reading

• "Nup358 interacts with APC and plays a role in cell polarization". Journal of Cell Science 122 (Pt 17): 3113–22. Sep 2009. doi:10.1242/jcs.037523. PMID 19654215. 
• "Retina-specifically expressed novel subtypes of bovine cyclophilin". The Journal of Biological Chemistry 270 (39): 23179–88. Sep 1995. doi:10.1074/jbc.270.39.23179. PMID 7559465. 
• "A giant nucleopore protein that binds Ran/TC4". Nature 376 (6536): 184–8. Jul 1995. doi:10.1038/376184a0. PMID 7603572. Bibcode: 1995Natur.376..184Y. 
• "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. doi:10.1073/pnas.92.8.3328. PMID 7724562. Bibcode: 1995PNAS...92.3328B. 
• "Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region". The Journal of Biological Chemistry 270 (23): 14209–13. Jun 1995. doi:10.1074/jbc.270.23.14209. PMID 7775481. 
• "Co-activation of RanGTPase and inhibition of GTP dissociation by Ran-GTP binding protein RanBP1". The EMBO Journal 14 (4): 705–15. Feb 1995. doi:10.1002/j.1460-2075.1995.tb07049.x. PMID 7882974. 
• "Cyclophilin-related protein RanBP2 acts as chaperone for red/green opsin". Nature 383 (6601): 637–40. Oct 1996. doi:10.1038/383637a0. PMID 8857542. Bibcode: 1996Natur.383..637F. 
• "A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2". Cell 88 (1): 97–107. Jan 1997. doi:10.1016/S0092-8674(00)81862-0. PMID 9019411. 
• "Interconversion of red opsin isoforms by the cyclophilin-related chaperone protein Ran-binding protein 2". Proceedings of the National Academy of Sciences of the United States of America 94 (4): 1556–61. Feb 1997. doi:10.1073/pnas.94.4.1556. PMID 9037092. Bibcode: 1997PNAS...94.1556F. 
• "Cloning and characterization of human karyopherin beta3". Proceedings of the National Academy of Sciences of the United States of America 94 (9): 4451–6. Apr 1997. doi:10.1073/pnas.94.9.4451. PMID 9114010. Bibcode: 1997PNAS...94.4451Y. 
• "Karyopherin beta2 mediates nuclear import of a mRNA binding protein". Proceedings of the National Academy of Sciences of the United States of America 94 (10): 5055–60. May 1997. doi:10.1073/pnas.94.10.5055. PMID 9144189. Bibcode: 1997PNAS...94.5055B. 
• "Localization of the gene encoding the Ran-binding protein RanBP2 to human chromosome 2q11-q13 by fluorescence in situ hybridization". Genomics 43 (2): 247–8. Jul 1997. doi:10.1006/geno.1997.4777. PMID 9244446. 
• "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. doi:10.1091/mbc.8.12.2379. PMID 9398662. 
• "Identification of a novel Ran binding protein 2 related gene (RANBP2L1) and detection of a gene cluster on human chromosome 2q11-q12". Genomics 47 (3): 383–92. Feb 1998. doi:10.1006/geno.1997.5119. PMID 9480752. 
• "The cyclophilin-like domain mediates the association of Ran-binding protein 2 with subunits of the 19 S regulatory complex of the proteasome". The Journal of Biological Chemistry 273 (38): 24676–82. Sep 1998. doi:10.1074/jbc.273.38.24676. PMID 9733766. 
• "Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport". Nature 398 (6722): 39–46. Mar 1999. doi:10.1038/17969. PMID 10078529. Bibcode: 1999Natur.398...39V. 
• "Two distinct classes of Ran-binding sites on the nucleoporin Nup-358". Proceedings of the National Academy of Sciences of the United States of America 96 (10): 5516–21. May 1999. doi:10.1073/pnas.96.10.5516. PMID 10318915. Bibcode: 1999PNAS...96.5516Y. 
• "GTP hydrolysis links initiation and termination of nuclear import on the nucleoporin nup358". The Journal of Biological Chemistry 274 (37): 26493–502. Sep 1999. doi:10.1074/jbc.274.37.26493. PMID 10473610. 
• "The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1". The Journal of Biological Chemistry 274 (52): 37370–8. Dec 1999. doi:10.1074/jbc.274.52.37370. PMID 10601307. 
• "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. doi:10.1083/jcb.152.2.411. PMID 11266456. 
• "Genomic organization, expression, and localization of murine Ran-binding protein 2 (RanBP2) gene". Mammalian Genome 12 (6): 406–15. Jun 2001. doi:10.1007/s003350010291. PMID 11353387. 
• "Identification of RanBP2- and kinesin-mediated transport pathways with restricted neuronal and subcellular localization". Traffic 3 (9): 630–40. Sep 2002. doi:10.1034/j.1600-0854.2002.30905.x. PMID 12191015. 
• "RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism". PLOS Genetics 2 (10): e177. Oct 2006. doi:10.1371/journal.pgen.0020177. PMID 17069463. 
• "Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function". Traffic 8 (12): 1722–35. Dec 2007. doi:10.1111/j.1600-0854.2007.00647.x. PMID 17887960. 
• "The cyclophilin-like domain of Ran-binding protein-2 modulates selectively the activity of the ubiquitin-proteasome system and protein biogenesis". The Journal of Biological Chemistry 282 (48): 34770–8. Nov 2007. doi:10.1074/jbc.M706903200. PMID 17911097. 
• "Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha". Cell 133 (1): 103–15. Apr 2008. doi:10.1016/j.cell.2008.01.045. PMID 18394993. 
• "Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons". Cell Death and Differentiation 16 (2): 287–97. Feb 2009. doi:10.1038/cdd.2008.153. PMID 18949001. 
• "RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system". EMBO Reports 10 (5): 480–6. May 2009. doi:10.1038/embor.2009.29. PMID 19305391.