RANBP2

RAN binding protein 2

PDB rendering based on 1rrp.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1RRP, 1XKE, 1Z5S, 3UIN, 3UIO, 3UIP, 4GA0, 4I9Y, 4L6E, 4LQW

Identifiers

Symbols

RANBP2 ; ADANE; ANE1; IIAE3; NUP358; TRP1; TRP2

External IDs

OMIM: 601181 MGI: 894323 HomoloGene: 136803 GeneCards: RANBP2 Gene

EC number

5.2.1.8

Gene ontology
Molecular function	• RNA binding • peptidyl-prolyl cis-trans isomerase activity • protein binding • zinc ion binding • Ran GTPase binding • ligase activity
Cellular component	• nuclear pore • mitochondrion • cytosol • membrane • nuclear membrane • nuclear inclusion body • nuclear pore nuclear basket
Biological process	• mitotic cell cycle • protein peptidyl-prolyl isomerization • carbohydrate metabolic process • protein folding • protein import into nucleus • mitotic nuclear envelope disassembly • hexose transport • regulation of glucose transport • glucose transport • viral process • protein sumoylation • cytokine-mediated signaling pathway • negative regulation of glucokinase activity • small molecule metabolic process • mRNA transport • transmembrane transport • regulation of gluconeogenesis involved in cellular glucose homeostasis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
109.34 – 109.4 Mb

Chr 10:
58.45 – 58.49 Mb

PubMed search

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

↑ Beddow AL, Richards SA, Orem NR, Macara IG (April 1995). "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. doi:10.1073/pnas.92.8.3328. PMC 42159. PMID 7724562.
↑ "Entrez Gene: RANBP2 RAN binding protein 2".
↑ Yaseen, N R; Blobel G (September 1999). "GTP hydrolysis links initiation and termination of nuclear import on the nucleoporin nup358". J. Biol. Chem. (UNITED STATES) 274 (37): 26493–502. doi:10.1074/jbc.274.37.26493. ISSN 0021-9258. PMID 10473610.
↑ Delphin, C; Guan T; Melchior F; Gerace L (Dec 1997). "RanGTP Targets p97 to RanBP2, a Filamentous Protein Localized at the Cytoplasmic Periphery of the Nuclear Pore Complex". Mol. Biol. Cell (UNITED STATES) 8 (12): 2379–90. doi:10.1091/mbc.8.12.2379. ISSN 1059-1524. PMC 25714. PMID 9398662.
↑ Ben-Efraim, I; Gerace L (January 2001). "Gradient of Increasing Affinity of Importin β for Nucleoporins along the Pathway of Nuclear Import". J. Cell Biol. (United States) 152 (2): 411–7. doi:10.1083/jcb.152.2.411. ISSN 0021-9525. PMC 2199621. PMID 11266456.
↑ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
↑ Zhang, Hong; Saitoh Hisato; Matunis Michael J (September 2002). "Enzymes of the SUMO Modification Pathway Localize to Filaments of the Nuclear Pore Complex". Mol. Cell. Biol. (United States) 22 (18): 6498–508. doi:10.1128/MCB.22.18.6498-6508.2002. ISSN 0270-7306. PMC 135644. PMID 12192048.

Ferreira PA, Hom JT, Pak WL (1995). "Retina-specifically expressed novel subtypes of bovine cyclophilin". J. Biol. Chem. 270 (39): 23179–88. doi:10.1074/jbc.270.39.23179. PMID 7559465.
Yokoyama N; Hayashi N; Seki T et al. (1995). "A giant nucleopore protein that binds Ran/TC4". Nature 376 (6536): 184–8. doi:10.1038/376184a0. PMID 7603572.
Beddow AL, Richards SA, Orem NR, Macara IG (1995). "The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif". Proc. Natl. Acad. Sci. U.S.A. 92 (8): 3328–32. doi:10.1073/pnas.92.8.3328. PMC 42159. PMID 7724562.
Wu J; Matunis MJ; Kraemer D et al. (1995). "Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region". J. Biol. Chem. 270 (23): 14209–13. doi:10.1074/jbc.270.23.14209. PMID 7775481.
Bischoff FR; Krebber H; Smirnova E et al. (1995). "Co-activation of RanGTPase and inhibition of GTP dissociation by Ran-GTP binding protein RanBP1". EMBO J. 14 (4): 705–15. PMC 398135. PMID 7882974.
Ferreira PA, Nakayama TA, Pak WL, Travis GH (1996). "Cyclophilin-related protein RanBP2 acts as chaperone for red/green opsin". Nature 383 (6601): 637–40. doi:10.1038/383637a0. PMID 8857542.
Mahajan R; Delphin C; Guan T et al. (1997). "A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2". Cell 88 (1): 97–107. doi:10.1016/S0092-8674(00)81862-0. PMID 9019411.
Ferreira PA, Nakayama TA, Travis GH (1997). "Interconversion of red opsin isoforms by the cyclophilin-related chaperone protein Ran-binding protein 2". Proc. Natl. Acad. Sci. U.S.A. 94 (4): 1556–61. doi:10.1073/pnas.94.4.1556. PMC 19830. PMID 9037092.
Yaseen NR, Blobel G (1997). "Cloning and characterization of human karyopherin β3". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4451–6. doi:10.1073/pnas.94.9.4451. PMC 20743. PMID 9114010.
Bonifaci N, Moroianu J, Radu A, Blobel G (1997). "Karyopherin β2 mediates nuclear import of a mRNA binding protein". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 5055–60. doi:10.1073/pnas.94.10.5055. PMC 24630. PMID 9144189.
Krebber H; Bastians H; Hoheisel J et al. (1997). "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. doi:10.1006/geno.1997.4777. PMID 9244446.
Delphin C, Guan T, Melchior F, Gerace L (2000). "RanGTP Targets p97 to RanBP2, a Filamentous Protein Localized at the Cytoplasmic Periphery of the Nuclear Pore Complex". Mol. Biol. Cell 8 (12): 2379–90. doi:10.1091/mbc.8.12.2379. PMC 25714. PMID 9398662.
Nothwang HG; Rensing C; Kübler M et al. (1998). "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. doi:10.1006/geno.1997.5119. PMID 9480752.
Ferreira PA, Yunfei C, Schick D, Roepman R (1998). "The cyclophilin-like domain mediates the association of Ran-binding protein 2 with subunits of the 19 S regulatory complex of the proteasome". J. Biol. Chem. 273 (38): 24676–82. doi:10.1074/jbc.273.38.24676. PMID 9733766.
Vetter IR; Nowak C; Nishimoto T et al. (1999). "Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport". Nature 398 (6722): 39–46. doi:10.1038/17969. PMID 10078529.
Yaseen NR, Blobel G (1999). "Two distinct classes of Ran-binding sites on the nucleoporin Nup-358". Proc. Natl. Acad. Sci. U.S.A. 96 (10): 5516–21. doi:10.1073/pnas.96.10.5516. PMC 21891. PMID 10318915.
Yaseen NR, Blobel G (1999). "GTP hydrolysis links initiation and termination of nuclear import on the nucleoporin nup358". J. Biol. Chem. 274 (37): 26493–502. doi:10.1074/jbc.274.37.26493. PMID 10473610.
Singh BB; Patel HH; Roepman R et al. (2000). "The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1". J. Biol. Chem. 274 (52): 37370–8. doi:10.1074/jbc.274.52.37370. PMID 10601307.
Ben-Efraim I, Gerace L (2001). "Gradient of Increasing Affinity of Importin β for Nucleoporins along the Pathway of Nuclear Import". J. Cell Biol. 152 (2): 411–7. doi:10.1083/jcb.152.2.411. PMC 2199621. PMID 11266456.
Fauser S, Aslanukov A, Roepman R, Ferreira PA (2001). "Genomic organization, expression, and localization of murine Ran-binding protein 2 (RanBP2) gene". Mamm. Genome 12 (6): 406–15. doi:10.1007/s003350010291. PMID 11353387.
Mavlyutov TA, Cai Y, Ferreira PA (2002). "Identification of RanBP2- and kinesin-mediated transport pathways with restricted neuronal and subcellular localization". Traffic. 3 (9): 630–40. doi:10.1034/j.1600-0854.2002.30905.x. PMID 12191015.
Aslanukov A, Bhowmick R, Guruju M, Oswald J, Raz D, Bush RA, Sieving PA, Lu X, Bock CB, Ferreira PA. (2006). "RanBP2 Modulates Cox11 and Hexokinase I Activities and Haploinsufficiency of RanBP2 Causes Deficits in Glucose Metabolism". PLoS Genet. 2 (10): e177. doi:10.1371/journal.pgen.0020177. PMC 1626108. PMID 17069463.
Cho KI, Cai Y, Yi H, Yeh A, Aslanukov A, Ferreira PA (2007). "Association of the Kinesin-Binding Domain of RanBP2 to KIF5B and KIF5C Determines Mitochondria Localization and Function". Traffic 8 (12): 1722–1735. doi:10.1111/j.1600-0854.2007.00647.x. PMID 17887960.
Yi H, Friedman J, Ferreira PA. (2007). "The cyclophilin-like domain of Ran-binding protein-2 modulates selectively the activity of the ubiquitin-proteasome system and protein biogenesis". J Biol Chem. 282 (48): 34770–8. doi:10.1074/jbc.M706903200. PMID 17911097.
Dawlaty MM, Malureanu L, Jeganathan KB, Kao E, Sustmann C, Tahk S, Shuai K, Grosschedl R, van Deursen JM. (2008). "Resolution of Sister Centromeres Requires RanBP2-Mediated SUMOylation of Topoisomerase IIα". Cell. 133 (1): 103–15. doi:10.1016/j.cell.2008.01.045. PMC 2693193. PMID 18394993.
Cho KI, Yi H, Yeh A, Tserentsoodol N, Cuadrado L, Searle K, Hao Y, Ferreira PA. (2008). "Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons". Cell Death Differ 16 (2): 287–97. doi:10.1038/cdd.2008.153. PMC 2626153. PMID 18949001.
Cho KI, Yi H, Desai R, Hand AR, Haas AL, Ferreira PA. (2009). "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. doi:10.1038/embor.2009.29. PMC 2680871. PMID 19305391.

PDB gallery

1rrp: STRUCTURE OF THE RAN-GPPNHP-RANBD1 COMPLEX

1xke: Solution structure of the second Ran-binding domain from human RanBP2

1z5s: Crystal structure of a complex between UBC9, SUMO-1, RANGAP1 and NUP358/RANBP2

RANBP2

Function

Clinical significance

Interactions

References

Further reading