Entry created on 1 July 2019 (Revision 1.0) Annotator: Rita Pancsa
Basic protein information
Accession P52948
Common name NUP98
Gene NUP98
Organism Homo sapiens
Uniprot name Nuclear pore complex protein Nup98-Nup96
Basic LLPS information
Organelle nuclear pore central transport channel; selective hydrogel-like meshwork formed by FG-nucleoporins in nuclear pore central channel
Type of experimental evidence
Protein region(s) mediating LLPS
1
-
500
FG-rich repeats
Based on the experimental results of the following publication: 25562883
Molecular features viewer
PDB structures
View on PDBe
Extended LLPS information
Functional description
The permeability barrier of nuclear pore complexes (NPCs) controls the exchange between nucleus and cytoplasm. It suppresses the flux of inert macromolecules >30 kDa but allows rapid passage of even very large cargoes, provided these are bound to appropriate nuclear transport receptors (facilitated translocation). FG-rich nucleoporin repeats constitute the permeability barrier (PMID:17082456). Nup98 FG domains of mammals, lancelets, insects, nematodes, fungi, plants, amoebas, ciliates, and excavates spontaneously and rapidly phase-separate from dilute (submicromolar) aqueous solutions into characteristic ‘FG particles’ (PMID:25562883). Nup98 FG domain also formed characteristic intra-cellular foci in HeLa cells (PMID:23427268).
Literature supporting the LLPS: 25562883, 27198189, 23427268
Functional class of membraneless organelle: biomolecular filter/selectivity barrier
Binding partners (at biological protein concentrations)
N/A
Type of RNA(s) required/used for the LLPS at biological protein concentrations
RNA not required.
Molecular interaction types contributing to LLPS
gelation (PMID:17082456) π-π (pi-pi) interactions (PMID:17082456)
Determinants of phase separation and droplet properties
1) protein concentration of Nup98
Membrane cluster No
Partner-dependent No
RNA-dependent No
PTM required No
Domain-motif interactions No
Discrete oligomerization No
Regulation and disease
Post-translational modifications affecting LLPS
Position Residue PTM Effect Reference Modifying enzyme Notes
Isoforms known to affect LLPS
Isoform Effect Reference
All known isoforms containing sequence changes in the LLPS region(s)
Position type Isoform names from UniProt
Disease mutations affecting LLPS
Mutation dbSNP Disease OMIM Effect Reference Notes
Experimental information
Experimental techniques applied to prove/investigate LLPS
Overexpression of GFP-fused Nup98 FG domain in HeLa cells in vivo resulted in characteristic intra-cellular foci (particle size and count) (PMID:23427268). Recombinantly expressed, purified, and immobilized Nup98 domains of diverse species, including human, bound to (physical interaction) human Importin β specifically in vitro. They have also self-assembled into highly selective FG particles. Strikingly, Nup98 FG particles from all ten tested Nup98 FG domains efficiently excluded not only the rather large MBP-mCherry fusion protein (≈75 kDa) but also rejected the far smaller mCherry (≈25 kDa) (other change in phenotype/functional readout). At the same time, these FG phases allowed a high or very high accumulation of NTF2 (other change in phenotype/functional readout, co-localization). In each case, the partition coefficient of NTF2 was at least 1000 times higher than that of mCherry (PMID:25562883).
Experimental observations supporting the liquid material state of the condensate
sensitivity to 1,6-hexanediol (PMID:25562883) other: FG NUPs form hydrogels rather than liquids through phase separation (PMID:17082456, PMID:25562883)