* 601179

RAS-RELATED NUCLEAR PROTEIN; RAN


HGNC Approved Gene Symbol: RAN

Cytogenetic location: 12q24.33     Genomic coordinates (GRCh38): 12:130,872,066-130,877,678 (from NCBI)


TEXT

Cloning and Expression

RAN (Ras-related nuclear protein) is a small GTP-binding protein belonging to the RAS superfamily (see 190020) that is essential for the translocation of RNA and proteins through the nuclear pore complex (Ren et al., 1993). The RAN protein is also involved in control of DNA synthesis and of cell cycle progression. By screening a human teratocarcinoma cDNA library with a mixed-oligonucleotide probe corresponding to a domain conserved among RAS-like proteins, Drivas et al. (1990) identified a cDNA, TC4, identical to RAN. Ren et al. (1993) showed that nuclear localization of RAN requires the presence of RCC1 (179710) and that mutations in RAN expected to disrupt GTP hydrolysis led to a disruption of DNA synthesis. Because of its many functions, it is likely that RAN interacts with several other proteins (see 601180 and 601181).

Coutavas et al. (1994) showed that 2 distinct, but closely related, Ran transcripts from separate loci are present in the mouse, 1 of which is specific to the testis.


Biochemical Features

Crystal Structure

Seewald et al. (2002) presented the 3-dimensional structure of a Ran-RanBP1-RanGAP ternary complex in the ground state and in a transition-state mimic. The structure and biochemical experiments showed that RanGAP does not act through an arginine finger, that the basic machinery for fast GTP hydrolysis is provided exclusively by Ran, and that correct positioning of the catalytic glutamine is essential for catalysis.

To provide a basis for understanding the crucial cargo-release step of nuclear import, Lee et al. (2005) presented the crystal structure of full-length yeast importin-beta (Kap95; see 602738) complexed with RanGTP. They identified a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95. This interaction produced a change in helicoidal pitch that locks Kap95 in a conformation that cannot bind importin-alpha (see 600685) or cargo. Lee et al. (2005) suggested an allosteric mechanism for nuclear import complex disassembly by RanGTP.

Monecke et al. (2009) presented the crystal structure of the snurportin-1 (SPN1; 607902)-CRM1 (602559)-RanGTP export complex at 2.5-angstrom resolution. SPN1 is a nuclear import adaptor for cytoplasmically assembled, m3G (5-prime-2,2,7-terminal trimethylguanosine)-capped spliceosomal U snRNPs. The structure showed how CRM1 can specifically return the cargo-free form of SPN1 to the cytoplasm. The extensive contact area includes 5 hydrophobic residues at the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as well as numerous hydrophilic contacts of CRM1 to m3G cap-binding domain and carboxyl-terminal residues of SPN1. Monecke et al. (2009) concluded that RanGTP promotes cargo binding to CRM1 solely through long-range conformational changes in the exportin.


Gene Function

Ohba et al. (1999) demonstrated that the nucleotide exchange activity of RCC1, the only known nucleotide exchange factor for RAN, was required for microtubule aster formation with or without demembranated sperm in Xenopus egg extracts arrested in meiosis II. In the RCC1-depleted egg extracts, RanGTP (see RANGAP1, 602362), but not RanGDP, induced self-organization of microtubule asters, and the process required the activity of dynein (see 603297). Thus, RAN was shown to regulate formation of the microtubule network. The egg extracts used in the experiments by Ohba et al. (1999) were prepared from unfertilized eggs arrested in metaphase, and therefore no nuclear membrane was formed during the experiments. Thus, RAN affects microtubule organization independently of its role in the nucleus-cytosol exchange of macromolecules. RANGAP1 is localized in the mitotic spindles. Wilde and Zheng (1999) demonstrated that RanGTP, but not RanGDP, stimulated polymerization of astral microtubules from centrosomes assembled on Xenopus sperm. Moreover, a RAN allele with a mutation in the effector domain (RanL43E) induced the formation of microtubule asters and spindle assembly in the absence of sperm nuclei in a gamma-tubulin ring complex and Xenopus microtubule-associated protein-dependent manner. The authors suggested that RAN could be a key signaling molecule regulating microtubule polymerization during mitosis.

Adding chromatin beads to Xenopus egg extracts causes nucleation of microtubules, which eventually reorganize into a bipolar spindle. Using this assay, Carazo-Salas et al. (1999) demonstrated that the activity of chromosome-associated RCC1 protein is required for spindle formation. When in the GTP-bound state (RanGTP), Ran itself induces microtubule nucleation and spindle-like structures in M-phase extract. Carazo-Salas et al. (1999) proposed that RCC1 generates a high local concentration of RAN-GTP around chromatin which, in turn, induces the local nucleation of microtubules.

The guanosine triphosphatase Ran stimulates assembly of microtubule asters and spindles in mitotic Xenopus egg extracts. A carboxy-terminal region of the nuclear mitotic apparatus protein (NUMA; 164009), a nuclear protein required for organizing mitotic spindle poles, mimics Ran's ability to induce asters. This NUMA fragment also specifically interacted with the nuclear transport factor, importin-beta. Wiese et al. (2001) showed that importin-beta is an inhibitor of microtubule aster assembly in Xenopus egg extracts and that Ran regulates the interaction between importin-beta and NUMA. Importin-beta therefore links NUMA to regulation by Ran. Wiese et al. (2001) concluded that this suggests that similar mechanisms regulate nuclear import during interphase and spindle assembly during mitosis.

RAN-GTP becomes depleted from the nucleus bound to transport factors and adaptors during the export of macromolecular cargo. Using an in vitro model of nuclear import, Ribbeck et al. (1998) found evidence that restoration of nuclear RAN concentration is not driven by a concentration gradient across the nuclear pore, but requires interaction between RAN-GDP with nuclear transport factor-2 (NTF2; 605813). By mutation analysis and biochemical studies, they determined that nuclear reaccumulation of RAN is mediated by direct interaction between the 2 proteins, and that RAN-GDP is the species bound and transported by NTF2.

Using combined experimental and computational analysis, Smith et al. (2002) predicted that RAN transport is regulated primarily by RCC1 rather than the flux capacity of the nuclear pore complex (NPC). The model estimated that the robust transport system allows a flux of 520 molecules per NPC per second in vivo.

Kalab et al. (2002) used fluorescence resonance energy transfer to visualize gradients of RAN-GTP and liberated cargoes around chromosomes in mitotic Xenopus egg extracts. During interphase, RAN-GTP was highly enriched in the nucleoplasm, and a steep concentration difference between nuclear and cytoplasmic RAN-GTP was established. The authors suggested that a RAN-GTP gradient surrounds chromosomes throughout the cell cycle.

Caudron et al. (2005) reported that the spatial cues necessary for microtubules to reproducibly self-organize during cell division are provided by chromosome-mediated interaction gradients between the small guanosine triphosphatase (GTPase) Ran and importin-beta (602738). This produces activity gradients that determine the spatial distribution of microtubule nucleation and stabilization around chromosomes and that are essential for the self-organization of microtubules into a bipolar spindle.

Using Xenopus egg extracts, Walther et al. (2003) showed that RanGTP triggers distinct steps in nuclear pore complex assembly.

Kalab et al. (2006) examined the Ran-importin-beta system in cells by conventional and fluorescence lifetime microscopy using a biosensor, termed Rango, that increases its fluorescence resonance energy transfer signal when released from importin-beta by RanGTP. Rango is predominantly free in mitotic cells, but is further liberated around mitotic chromatin. In vitro experiments and modeling showed that this localized increase of free cargoes corresponds to changes in RanGTP concentration sufficient to stabilize microtubules in extracts. In cells, the Ran-importin-beta-cargo gradient kinetically promotes spindle formation but is largely dispensable once the spindle has been established. Kalab et al. (2006) observed that the Ran system also affects spindle pole formation and chromosome congression in vivo. Kalab et al. (2006) concluded that conserved Ran-regulated pathways are involved in multiple, parallel processes required for spindle function, but that their relative contribution differs in chromatin- versus centrosome/kinetochore-driven spindle assembly systems.


REFERENCES

  1. Carazo-Salas, R. E., Guarguaglini, G., Gruss, O. J., Segref, A., Karsenti, E., Mattaj, I. W. Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature 400: 178-181, 1999. [PubMed: 10408446, related citations] [Full Text]

  2. Caudron, M., Bunt, G., Bastiaens, P., Karsenti, E. Spatial coordination of spindle assembly by chromosome-mediated signaling gradients. Science 309: 1373-1376, 2005. [PubMed: 16123300, related citations] [Full Text]

  3. Coutavas, E. E., Hsieh, C. M., Ren, M., Drivas, G. T., Rush, M. G., D'Eustachio, P. Tissue-specific expression of Ran isoforms in the mouse. Mammalian Genome 5: 623-628, 1994. [PubMed: 7849398, related citations] [Full Text]

  4. Drivas, G. T., Shih, A., Coutavas, E., Rush, M. G., D'Eustachio, P. Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Molec. Cell. Biol. 10: 1793-1797, 1990. [PubMed: 2108320, related citations] [Full Text]

  5. Kalab, P., Pralle, A., Isacoff, E. Y., Heald, R., Weis, K. Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440: 697-701, 2006. [PubMed: 16572176, related citations] [Full Text]

  6. Kalab, P., Weis, K., Heald, R. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295: 2452-2456, 2002. [PubMed: 11923538, related citations] [Full Text]

  7. Lee, S. J., Matsuura, Y., Liu, S. M., Stewart, M. Structural basis for nuclear import complex dissociation by RanGTP. (Letter) Nature 435: 693-696, 2005. [PubMed: 15864302, related citations] [Full Text]

  8. Monecke, T., Guttler, T., Neumann, P., Dickmanns, A., Gorlich, D., Ficner, R. Crystal structure of the nuclear export receptor CRM1 in complex with snurportin 1 and RanGTP. Science 324: 1087-1091, 2009. [PubMed: 19389996, related citations] [Full Text]

  9. Ohba, T., Nakamura, M., Nishitani, H., Nishimoto, T. Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. Science 284: 1356-1358, 1999. [PubMed: 10334990, related citations] [Full Text]

  10. Ren, M., Drivas, G., D'Eustachio, P., Rush, M. G. Ran/TC4: a small nuclear GTP-binding protein that regulates DNA synthesis. J. Cell Biol. 120: 313-323, 1993. [PubMed: 8421051, related citations] [Full Text]

  11. Ribbeck, K., Lipowsky, G., Kent, H. M., Stewart, M., Gorlich, D. NTF2 mediates nuclear import of Ran. EMBO J. 17: 6587-6598, 1998. [PubMed: 9822603, related citations] [Full Text]

  12. Seewald, M. J., Korner, C., Wittinghofer, A., Vetter, I. R. RanGAP mediates GTP hydrolysis without an arginine finger. Nature 415: 662-666, 2002. [PubMed: 11832950, related citations] [Full Text]

  13. Smith, A. E., Slepchenko, B. M., Schaff, J. C., Loew, L. M., Macara, I. G. Systems analysis of Ran transport. Science 295: 488-491, 2002. [PubMed: 11799242, related citations] [Full Text]

  14. Walther, T. C., Askjaer, P., Gentzel, M., Habermann, A., Griffiths, G., Wilm, M., Mattaj, I. W., Hetzer, M. RanGTP mediates nuclear pore complex assembly. Nature 424: 689-694, 2003. [PubMed: 12894213, related citations] [Full Text]

  15. Wiese, C., Wilde, A., Moore, M. S., Adam, S. A., Merdes, A., Zheng, Y. Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. Science 291: 653-656, 2001. [PubMed: 11229403, related citations] [Full Text]

  16. Wilde, A., Zheng, Y. Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. Science 284: 1359-1362, 1999. [PubMed: 10334991, related citations] [Full Text]


Ada Hamosh - updated : 6/17/2009
Ada Hamosh - updated : 5/26/2006
Patricia A. Hartz - updated : 1/26/2006
Ada Hamosh - updated : 10/10/2005
Ada Hamosh - updated : 6/15/2005
Ada Hamosh - updated : 12/29/2004
Patricia A. Hartz - updated : 4/26/2002
Paul J. Converse - updated : 4/3/2002
Ada Hamosh - updated : 2/4/2002
Paul J. Converse - updated : 1/18/2002
Ada Hamosh - updated : 4/5/2001
Ada Hamosh - updated : 8/25/1999
Ada Hamosh - updated : 5/20/1999
Creation Date:
Alan F. Scott : 4/4/1996
alopez : 09/30/2019
alopez : 06/23/2009
alopez : 6/23/2009
terry : 6/17/2009
alopez : 6/6/2006
terry : 5/26/2006
mgross : 2/2/2006
terry : 1/26/2006
alopez : 10/12/2005
terry : 10/10/2005
alopez : 6/16/2005
terry : 6/15/2005
alopez : 12/30/2004
terry : 12/29/2004
carol : 4/29/2002
terry : 4/26/2002
mgross : 4/3/2002
alopez : 2/7/2002
terry : 2/4/2002
mgross : 1/18/2002
alopez : 4/19/2001
alopez : 4/6/2001
terry : 4/5/2001
alopez : 8/25/1999
alopez : 5/20/1999
terry : 5/20/1999
mark : 4/5/1996
terry : 4/4/1996
mark : 4/4/1996

* 601179

RAS-RELATED NUCLEAR PROTEIN; RAN


HGNC Approved Gene Symbol: RAN

Cytogenetic location: 12q24.33     Genomic coordinates (GRCh38): 12:130,872,066-130,877,678 (from NCBI)


TEXT

Cloning and Expression

RAN (Ras-related nuclear protein) is a small GTP-binding protein belonging to the RAS superfamily (see 190020) that is essential for the translocation of RNA and proteins through the nuclear pore complex (Ren et al., 1993). The RAN protein is also involved in control of DNA synthesis and of cell cycle progression. By screening a human teratocarcinoma cDNA library with a mixed-oligonucleotide probe corresponding to a domain conserved among RAS-like proteins, Drivas et al. (1990) identified a cDNA, TC4, identical to RAN. Ren et al. (1993) showed that nuclear localization of RAN requires the presence of RCC1 (179710) and that mutations in RAN expected to disrupt GTP hydrolysis led to a disruption of DNA synthesis. Because of its many functions, it is likely that RAN interacts with several other proteins (see 601180 and 601181).

Coutavas et al. (1994) showed that 2 distinct, but closely related, Ran transcripts from separate loci are present in the mouse, 1 of which is specific to the testis.


Biochemical Features

Crystal Structure

Seewald et al. (2002) presented the 3-dimensional structure of a Ran-RanBP1-RanGAP ternary complex in the ground state and in a transition-state mimic. The structure and biochemical experiments showed that RanGAP does not act through an arginine finger, that the basic machinery for fast GTP hydrolysis is provided exclusively by Ran, and that correct positioning of the catalytic glutamine is essential for catalysis.

To provide a basis for understanding the crucial cargo-release step of nuclear import, Lee et al. (2005) presented the crystal structure of full-length yeast importin-beta (Kap95; see 602738) complexed with RanGTP. They identified a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95. This interaction produced a change in helicoidal pitch that locks Kap95 in a conformation that cannot bind importin-alpha (see 600685) or cargo. Lee et al. (2005) suggested an allosteric mechanism for nuclear import complex disassembly by RanGTP.

Monecke et al. (2009) presented the crystal structure of the snurportin-1 (SPN1; 607902)-CRM1 (602559)-RanGTP export complex at 2.5-angstrom resolution. SPN1 is a nuclear import adaptor for cytoplasmically assembled, m3G (5-prime-2,2,7-terminal trimethylguanosine)-capped spliceosomal U snRNPs. The structure showed how CRM1 can specifically return the cargo-free form of SPN1 to the cytoplasm. The extensive contact area includes 5 hydrophobic residues at the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as well as numerous hydrophilic contacts of CRM1 to m3G cap-binding domain and carboxyl-terminal residues of SPN1. Monecke et al. (2009) concluded that RanGTP promotes cargo binding to CRM1 solely through long-range conformational changes in the exportin.


Gene Function

Ohba et al. (1999) demonstrated that the nucleotide exchange activity of RCC1, the only known nucleotide exchange factor for RAN, was required for microtubule aster formation with or without demembranated sperm in Xenopus egg extracts arrested in meiosis II. In the RCC1-depleted egg extracts, RanGTP (see RANGAP1, 602362), but not RanGDP, induced self-organization of microtubule asters, and the process required the activity of dynein (see 603297). Thus, RAN was shown to regulate formation of the microtubule network. The egg extracts used in the experiments by Ohba et al. (1999) were prepared from unfertilized eggs arrested in metaphase, and therefore no nuclear membrane was formed during the experiments. Thus, RAN affects microtubule organization independently of its role in the nucleus-cytosol exchange of macromolecules. RANGAP1 is localized in the mitotic spindles. Wilde and Zheng (1999) demonstrated that RanGTP, but not RanGDP, stimulated polymerization of astral microtubules from centrosomes assembled on Xenopus sperm. Moreover, a RAN allele with a mutation in the effector domain (RanL43E) induced the formation of microtubule asters and spindle assembly in the absence of sperm nuclei in a gamma-tubulin ring complex and Xenopus microtubule-associated protein-dependent manner. The authors suggested that RAN could be a key signaling molecule regulating microtubule polymerization during mitosis.

Adding chromatin beads to Xenopus egg extracts causes nucleation of microtubules, which eventually reorganize into a bipolar spindle. Using this assay, Carazo-Salas et al. (1999) demonstrated that the activity of chromosome-associated RCC1 protein is required for spindle formation. When in the GTP-bound state (RanGTP), Ran itself induces microtubule nucleation and spindle-like structures in M-phase extract. Carazo-Salas et al. (1999) proposed that RCC1 generates a high local concentration of RAN-GTP around chromatin which, in turn, induces the local nucleation of microtubules.

The guanosine triphosphatase Ran stimulates assembly of microtubule asters and spindles in mitotic Xenopus egg extracts. A carboxy-terminal region of the nuclear mitotic apparatus protein (NUMA; 164009), a nuclear protein required for organizing mitotic spindle poles, mimics Ran's ability to induce asters. This NUMA fragment also specifically interacted with the nuclear transport factor, importin-beta. Wiese et al. (2001) showed that importin-beta is an inhibitor of microtubule aster assembly in Xenopus egg extracts and that Ran regulates the interaction between importin-beta and NUMA. Importin-beta therefore links NUMA to regulation by Ran. Wiese et al. (2001) concluded that this suggests that similar mechanisms regulate nuclear import during interphase and spindle assembly during mitosis.

RAN-GTP becomes depleted from the nucleus bound to transport factors and adaptors during the export of macromolecular cargo. Using an in vitro model of nuclear import, Ribbeck et al. (1998) found evidence that restoration of nuclear RAN concentration is not driven by a concentration gradient across the nuclear pore, but requires interaction between RAN-GDP with nuclear transport factor-2 (NTF2; 605813). By mutation analysis and biochemical studies, they determined that nuclear reaccumulation of RAN is mediated by direct interaction between the 2 proteins, and that RAN-GDP is the species bound and transported by NTF2.

Using combined experimental and computational analysis, Smith et al. (2002) predicted that RAN transport is regulated primarily by RCC1 rather than the flux capacity of the nuclear pore complex (NPC). The model estimated that the robust transport system allows a flux of 520 molecules per NPC per second in vivo.

Kalab et al. (2002) used fluorescence resonance energy transfer to visualize gradients of RAN-GTP and liberated cargoes around chromosomes in mitotic Xenopus egg extracts. During interphase, RAN-GTP was highly enriched in the nucleoplasm, and a steep concentration difference between nuclear and cytoplasmic RAN-GTP was established. The authors suggested that a RAN-GTP gradient surrounds chromosomes throughout the cell cycle.

Caudron et al. (2005) reported that the spatial cues necessary for microtubules to reproducibly self-organize during cell division are provided by chromosome-mediated interaction gradients between the small guanosine triphosphatase (GTPase) Ran and importin-beta (602738). This produces activity gradients that determine the spatial distribution of microtubule nucleation and stabilization around chromosomes and that are essential for the self-organization of microtubules into a bipolar spindle.

Using Xenopus egg extracts, Walther et al. (2003) showed that RanGTP triggers distinct steps in nuclear pore complex assembly.

Kalab et al. (2006) examined the Ran-importin-beta system in cells by conventional and fluorescence lifetime microscopy using a biosensor, termed Rango, that increases its fluorescence resonance energy transfer signal when released from importin-beta by RanGTP. Rango is predominantly free in mitotic cells, but is further liberated around mitotic chromatin. In vitro experiments and modeling showed that this localized increase of free cargoes corresponds to changes in RanGTP concentration sufficient to stabilize microtubules in extracts. In cells, the Ran-importin-beta-cargo gradient kinetically promotes spindle formation but is largely dispensable once the spindle has been established. Kalab et al. (2006) observed that the Ran system also affects spindle pole formation and chromosome congression in vivo. Kalab et al. (2006) concluded that conserved Ran-regulated pathways are involved in multiple, parallel processes required for spindle function, but that their relative contribution differs in chromatin- versus centrosome/kinetochore-driven spindle assembly systems.


REFERENCES

  1. Carazo-Salas, R. E., Guarguaglini, G., Gruss, O. J., Segref, A., Karsenti, E., Mattaj, I. W. Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature 400: 178-181, 1999. [PubMed: 10408446] [Full Text: https://doi.org/10.1038/22133]

  2. Caudron, M., Bunt, G., Bastiaens, P., Karsenti, E. Spatial coordination of spindle assembly by chromosome-mediated signaling gradients. Science 309: 1373-1376, 2005. [PubMed: 16123300] [Full Text: https://doi.org/10.1126/science.1115964]

  3. Coutavas, E. E., Hsieh, C. M., Ren, M., Drivas, G. T., Rush, M. G., D'Eustachio, P. Tissue-specific expression of Ran isoforms in the mouse. Mammalian Genome 5: 623-628, 1994. [PubMed: 7849398] [Full Text: https://doi.org/10.1007/BF00411457]

  4. Drivas, G. T., Shih, A., Coutavas, E., Rush, M. G., D'Eustachio, P. Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Molec. Cell. Biol. 10: 1793-1797, 1990. [PubMed: 2108320] [Full Text: https://doi.org/10.1128/mcb.10.4.1793-1798.1990]

  5. Kalab, P., Pralle, A., Isacoff, E. Y., Heald, R., Weis, K. Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440: 697-701, 2006. [PubMed: 16572176] [Full Text: https://doi.org/10.1038/nature04589]

  6. Kalab, P., Weis, K., Heald, R. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295: 2452-2456, 2002. [PubMed: 11923538] [Full Text: https://doi.org/10.1126/science.1068798]

  7. Lee, S. J., Matsuura, Y., Liu, S. M., Stewart, M. Structural basis for nuclear import complex dissociation by RanGTP. (Letter) Nature 435: 693-696, 2005. [PubMed: 15864302] [Full Text: https://doi.org/10.1038/nature03578]

  8. Monecke, T., Guttler, T., Neumann, P., Dickmanns, A., Gorlich, D., Ficner, R. Crystal structure of the nuclear export receptor CRM1 in complex with snurportin 1 and RanGTP. Science 324: 1087-1091, 2009. [PubMed: 19389996] [Full Text: https://doi.org/10.1126/science.1173388]

  9. Ohba, T., Nakamura, M., Nishitani, H., Nishimoto, T. Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. Science 284: 1356-1358, 1999. [PubMed: 10334990] [Full Text: https://doi.org/10.1126/science.284.5418.1356]

  10. Ren, M., Drivas, G., D'Eustachio, P., Rush, M. G. Ran/TC4: a small nuclear GTP-binding protein that regulates DNA synthesis. J. Cell Biol. 120: 313-323, 1993. [PubMed: 8421051] [Full Text: https://doi.org/10.1083/jcb.120.2.313]

  11. Ribbeck, K., Lipowsky, G., Kent, H. M., Stewart, M., Gorlich, D. NTF2 mediates nuclear import of Ran. EMBO J. 17: 6587-6598, 1998. [PubMed: 9822603] [Full Text: https://doi.org/10.1093/emboj/17.22.6587]

  12. Seewald, M. J., Korner, C., Wittinghofer, A., Vetter, I. R. RanGAP mediates GTP hydrolysis without an arginine finger. Nature 415: 662-666, 2002. [PubMed: 11832950] [Full Text: https://doi.org/10.1038/415662a]

  13. Smith, A. E., Slepchenko, B. M., Schaff, J. C., Loew, L. M., Macara, I. G. Systems analysis of Ran transport. Science 295: 488-491, 2002. [PubMed: 11799242] [Full Text: https://doi.org/10.1126/science.1064732]

  14. Walther, T. C., Askjaer, P., Gentzel, M., Habermann, A., Griffiths, G., Wilm, M., Mattaj, I. W., Hetzer, M. RanGTP mediates nuclear pore complex assembly. Nature 424: 689-694, 2003. [PubMed: 12894213] [Full Text: https://doi.org/10.1038/nature01898]

  15. Wiese, C., Wilde, A., Moore, M. S., Adam, S. A., Merdes, A., Zheng, Y. Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. Science 291: 653-656, 2001. [PubMed: 11229403] [Full Text: https://doi.org/10.1126/science.1057661]

  16. Wilde, A., Zheng, Y. Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. Science 284: 1359-1362, 1999. [PubMed: 10334991] [Full Text: https://doi.org/10.1126/science.284.5418.1359]


Contributors:
Ada Hamosh - updated : 6/17/2009
Ada Hamosh - updated : 5/26/2006
Patricia A. Hartz - updated : 1/26/2006
Ada Hamosh - updated : 10/10/2005
Ada Hamosh - updated : 6/15/2005
Ada Hamosh - updated : 12/29/2004
Patricia A. Hartz - updated : 4/26/2002
Paul J. Converse - updated : 4/3/2002
Ada Hamosh - updated : 2/4/2002
Paul J. Converse - updated : 1/18/2002
Ada Hamosh - updated : 4/5/2001
Ada Hamosh - updated : 8/25/1999
Ada Hamosh - updated : 5/20/1999

Creation Date:
Alan F. Scott : 4/4/1996

Edit History:
alopez : 09/30/2019
alopez : 06/23/2009
alopez : 6/23/2009
terry : 6/17/2009
alopez : 6/6/2006
terry : 5/26/2006
mgross : 2/2/2006
terry : 1/26/2006
alopez : 10/12/2005
terry : 10/10/2005
alopez : 6/16/2005
terry : 6/15/2005
alopez : 12/30/2004
terry : 12/29/2004
carol : 4/29/2002
terry : 4/26/2002
mgross : 4/3/2002
alopez : 2/7/2002
terry : 2/4/2002
mgross : 1/18/2002
alopez : 4/19/2001
alopez : 4/6/2001
terry : 4/5/2001
alopez : 8/25/1999
alopez : 5/20/1999
terry : 5/20/1999
mark : 4/5/1996
terry : 4/4/1996
mark : 4/4/1996