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exportin-5 (Exp5, Ran-binding protein 21, XPO5, KIAA1291, RANBP21)
Function:
1) mediates the nuclear export of proteins bearing a double-stranded RNA binding domain & double-stranded RNAs (cargo)
- XPO5 in the nucleus binds cooperatively to RNA & to the GTPase Ran in its active GTP-bound form (trimeric complex)
- proteins containing double-stranded RNA binding domains can associate with this trimeric complex through RNA
- docking of this complex to the nuclear pore complex is mediated through binding to nucleoporins
- upon transit of a nuclear export complex into cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 & RANGAP1, respectively) cause disassembly of the complex & release of the cargo from the export receptor
- XPO5 then returns to the nuclear compartment by diffusion through the nuclear pore complex, to mediate another round of transpor
- directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- & GDP-bound forms of Ran between cytoplasm & nucleus
2) overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi).
3) mediates nuclear export of micro-RNA precursors, which form short hairpins
- also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference
- mediates nuclear export of deacylated & aminoacylated tRNAs
- recognizes dsRNAs that lack a 5' overhang (sequence- independent), have only a short 3' overhang, & that have a double-stranded length of at least 15 base-pairs (Ran-GTP-dependent)
4) component of nuclear export receptor complexes
- XPO5, Ran, dsRNA-binding proteins & dsRNA
- XPO5, Ran, EEF1A1, & aminoacylated tRNA
- XPO5, Ran, ILF3 & dsRNA
- XPO5, Ran & pre-miRNA
- XPO5, Ran, ILF3 & minihelix VA1 dsRNA
- XPO5, RAN, ILF3, ZNF346 & dsRNA
5) interacts with EEF1A1, ILF3, NUP153, NUP214 & ZNF346
6) interacts with Ran & cargo proteins (GTP-dependent)
Structure:
- belongs to the exportin family
Compartment:
- nucleus, cytoplasm
- shuttles between nucleus & the cytoplasm
Alternative splicing: named isoforms=2
Expression:
- expressed in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas
Pathology:
- mediates the nuclear export of adenovirus VA1 dsRNA
General
exportin
Properties
SIZE: MW = 136 kD
entity length = 1204 aa
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: Ran interaction {1-108}
ILF3 interaction {533-640}
Database Correlations
OMIM 607845
UniProt Q9HAV4
Pfam PF08389
References
UniProt :accession Q9HAV4