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| Functional site class: | NES Nuclear Export Signal |
| Functional site description: | The Nuclear Export Signal (NES) is a linear motif involved in the regulated export of macromolecules from the nucleus via the nuclear pores. Import and export of macromolecules is the main way to communicate between cytosol and nucleus. Therefore, although many nuclear proteins do not need to be re-exported, a substantial number of nuclear proteins can shuttle between nucleus and cytoplasm. In such proteins, availability of the import and export signals needs to be regulated, or they will immediately be returned to the other compartment. Thus open and closed conformations of NES-bearing proteins are likely to be common features. |
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| ELMs: | TRG_NES_CRM1_1 |
| Description: | Accessible peptides matching the leucine-rich nuclear export signal (NES) bind to the CRM1 exportin protein. The fungicide Leptomycin B (LMB) specifically inhibits this export pathway. Since the NES has been reported as four conserved hydrophobic residues, it has presented a particular problem for experimental verification. Solving 3D structures of putative NES motif bearing proteins has often revealed that the apparent export signals are buried in the hydrophobic core of globular domains where they cannot function as linear motifs (e.g. Kadlec et al., 2004). While some of the reported NES peptides are unlikely to be true, more proteins will undoubtedly be found to return to the cytoplasm from the nucleus by this mechanism. The NES pattern in ELM was therefore derived exclusively from reported instances that were not buried in domain cores. The conserved motif is found to be longer and less hydrophobic than reported, with a negatively charged residue at each end. An educational structure to view is the MapKapK2 kinase (pdb:1KWP), where the NES is conditionally packed onto the kinase domain (Meng et al., 2002) but the negative residues are solvent exposed. There are indications that further negative charge may play a role (la Cour et al., 2004). Solved CRM1-NES complexes (Monecke et al., 2009; Dong et al., 2009) show that a number of complementary positively-charged residues are spaced around the NES-binding groove. The structures also show most of the NES peptide is helical when bound, indicating that proline cannot occur in some of the less conserved positions. |
| Pattern: | ([DEQ].{0,1}[LIM].{2,3}[LIVMF][^P]{2,3}[LMVF].[LMIV].{0,3}[DE])|([DE].{0,1}[LIM].{2,3}[LIVMF][^P]{2,3}[LMVF].[LMIV].{0,3}[DEQ]) (Probability: 0.0007626) |
| Present in taxons: |
 Eukaryota
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PDB Structure:  3GJX 
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| Interaction Domain: |
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See 18 Instances for TRG_NES_CRM1_1
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| The import-export protein traffic through the nuclear envelope is mediated by soluble transport receptors (carriers) termed importins and exportins that bind to specific signals present within their substrates. The best-characterized export carrier is CRM1 (also known as exportin1/Xpo1), an evolutionarily well-conserved protein. The CRM1-mediated export is inhibited by the fungicide leptomycin B (LMB), providing a unique experimental tool for studying nuclear localization and trafficking in eukaryotic cells. The NES signal was first identified in the HIV Rev protein and in the Protein Kinase A inhibitor (PKI-alpha). The majority of the export substrates of CRM1 contain a Leucine-rich Nuclear Export signal (NES) consisting of 4-5 hydrophobic residues in a region of ~ 10 amino acids. The NetNES 1.1 server (http://www.cbs.dtu.dk/services/NetNES/) predicts leucine-rich nuclear export signals (NES) in eukaryotic proteins using a combination of neural networks and hidden Markov models. |
12 selected references:
4 GO-Terms:
18 Instances for TRG_NES_CRM1_1
(click table headers for sorting)
Please cite: ELM - the database of eukaryotic linear motifs (PMID:22110040)
ELM data can be downloaded and distributed for non-commercial use according to the ELM Software License Agreement