Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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RanBD Ran-binding domain

SMART accession number:	SM00160
Description:	Domain of apporximately 150 residues that stabilises the GTP-bound form of Ran (the Ras-like nuclear small GTPase).
Interpro abstract (IPR000156):	Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran Binding Protein 1 (RanBP1) has guanine nucleotide dissociation inhibitory activity, specific for the GTP form of Ran and also functions to stimulate Ran GTPase activating protein(GAP)-mediated GTP hydrolysis by Ran. RanBP1 contributes to maintaining the gradient of RanGTP across the nuclear envelope high (GDI activity) or the cytoplasmic levels of RanGTP low (GAP cofactor) [(PUBMED:12019565)]. All RanBP1 proteins contain an approx 150 amino acid residue Ran binding domain. Ran BP1 binds directly to RanGTP with high affinity. There are four sites of contact between Ran and the Ran binding domain. One of these involves binding of the C-terminal segment of Ran to a groove on the Ran binding domain that is analogous to the surface utilised in the EVH1-peptide interaction [(PUBMED:10404224)]. Nup358 contains four Ran binding domains. The structure of the first of these is known [(PUBMED:10078529)].
GO process:	intracellular transport (GO:0046907)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 939 RanBD domains in 767 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a RanBD domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with RanBD domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Binding / catalysis: protein-binding, RanGTP-binding

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Callebaut I, Cossart P, Dehoux P
  • EVH1/WH1 domains of VASP and WASP proteins belong to a large family including Ran-binding domains of the RanBP1 family.
  • FEBS Lett. 1998; 441: 181-5
  • Display abstract

  • The two cytoskeletal proteins VASP and WASP and the protein Homer share a conserved domain, currently designated the WHI domain (WASP homology domain 1) or EVH1 domain (ENA/VASP homology domain 1), which could play an important role in various cellular events such as transport, folding of proteins, and signal transduction. We report here additional occurrences of this domain in Ran-binding proteins of the RanBP1 family and various others proteins, or putative proteins of eukaryotic organisms, suggesting that the EVH1/WH1 domain may be more widely used than originally thought.

  • 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.
  • Proc Natl Acad Sci U S A. 1995; 92: 3328-32
  • Display abstract

  • Ran/TC4 is an essential, nuclear GTPase implicated in the initiation of DNA replication, entry into and exit from mitosis, and in nuclear RNA and protein transport through the nuclear pore complex. This diversity of functions suggests that Ran interacts with a large number of down-stream targets. Using an overlay assay, we detected a family of putative target proteins that associate with GTP-bound Ran. The sequence of only one such protein, HTF9a/RanBP1, is known. We have now cloned two additional Ran-binding proteins, allowing identification of a distinctive, highly conserved sequence motif of approximately 150 residues. This motif represents a minimal Ran-binding domain that stabilizes the GTP-bound state of Ran. The isolated domain also functions as a coactivator of Ran-GTPase-activating protein. Mutation of a conserved residue within the Ran-binding domain of HTF9a protein drastically reduced Ran binding. Ran-binding proteins coimmunoprecipitated with epitope-tagged Ran from cell lysates, suggesting that these proteins may associate in vivo. A previously uncharacterized Caenorhabditis elegans gene could encode a protein (96 kDa) possessing two Ran-binding domains. This open reading frame also contains similarities to nucleoporins, suggesting a functional link between Ran and nuclear pore complexes.

  • Dingwall C, Kandels-Lewis S, Seraphin B
  • A family of Ran binding proteins that includes nucleoporins.
  • Proc Natl Acad Sci U S A. 1995; 92: 7525-9
  • Display abstract

  • Ran, a small nuclear GTP binding protein, is essential for the translocation of nuclear proteins through the nuclear pore complex. We show that several proteins, including the Saccharomyces cerevisiae Nup2p and Caenorhabditis elegans F59A2.1 nucleoporins, contain domains similar to the previously characterized murine Ran binding protein (RBP, termed RBP1). To test the significance of this similarity, we have used the corresponding domains of Nup2p and a putative S. cerevisiae RBP in Ran binding assays and the yeast two-hybrid system. Both proteins bind S. cerevisiae Ran, but only the putative S. cerevisiae RBP binds human Ran. Two-hybrid analysis revealed Ran-Ran interactions and that yeast and human Rans can interact. These data identify Nup2p as a target for Ran in the nuclear pore complex, suggesting a direct role for it in nuclear-cytoplasmic transport. We discuss the possibility that proteins harboring Ran binding domains link the Ran GTPase cycle to specific functions in the nucleus.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 100.00 map04810 Regulation of actin cytoskeleton This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with RanBD domain which could be assigned to a KEGG orthologous group, and not all proteins containing RanBD domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of RanBD domains in PDB

  PDB code	Main view	Title
  1evh		Evh1 domain from murine enabled in complex with acta peptide
  1k5d		Crystal structure of ran-gppnhp-ranbp1-rangap complex
  1k5g		Crystal structure of ran-gdp-alfx-ranbp1-rangap complex
  1rrp		Structure of the ran-gppnhp-ranbd1 complex
  1xke		Solution structure of the second ran-binding domain from human ranbp2
  2crf		Solution structure of the ran_bp1 domain of ran-binding protein-3
  2ec1		Solution structure of the ranbd1 domain from human nucleoporin 50 kda
  2iyb		Structure of complex between the 3rd lim domain of tes and the evh1 domain of mena

• Links (links to other resources describing this domain)

• INTERPRO	IPR000156

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