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EXPORTIN 4; XPO4

EXPORTIN 4; XPO4

Alternative titles; symbolsEXP4KIAA1721HGNC Approved Gene Symbol: XPO4Cytogenetic location: 13q12.11 Genomic coordinates (GRCh38): 13:20,777,328-20,902,773 (...

Alternative titles; symbols

  • EXP4
  • KIAA1721

HGNC Approved Gene Symbol: XPO4

Cytogenetic location: 13q12.11 Genomic coordinates (GRCh38): 13:20,777,328-20,902,773 (from NCBI)

▼ Description
XPO4 belongs to a large family of karyopherins (see 602738) that mediate the transport of proteins and other cargo between the nuclear and cytoplasmic compartments (Lipowsky et al., 2000).

▼ Cloning and Expression
By sequencing clones obtained from a size-fractionated human adult hippocampus cDNA library, Nagase et al. (2000) cloned XPO4, which they designated KIAA1721. The 3-prime UTR contains a repetitive sequence, and the 1,150-amino acid protein shares 99% amino acid identity with mouse Xpo4. RT-PCR ELISA detected high to moderate expression in all human tissues and specific brain regions examined.

Using affinity chromatography on immobilized RanGTP (see RANGAP1; 602362) to identify novel RanGTP-binding proteins in HeLa cell extract, followed by database analysis and 3-prime and 5-prime RACE, Lipowsky et al. (2000) cloned mouse Xpo4, which they called Exp4. The deduced 1,170-amino acid mouse protein has a calculated molecular mass of 129.9 kD. Xpo4 shares similarity over the N-terminal RanGTP-binding motif with importin-beta family members, with highest similarity to exportin-1 (XPO1; 602559) and tRNA export receptor exportin-t (XPOT; 603180).

▼ Gene Function
Using recombinant Xpo4 expressed in E. coli and HeLa cell extract components, Lipowsky et al. (2000) showed that RanGTP-bound Xpo4 bound EIF5A (600187) and thymidylate synthase (TYMS; 188350). Immunoblotting assay of recombinant EIF5A and bound Xpo4 showed that EIF5A forms a EIF5A-Xpo4-RanGTP complex with Xpo4 specifically and that the Xpo4-EIF5A interaction was enhanced in the presence of RanGTP. Nuclear export assays in permeabilized cells demonstrated that Xpo4 mediates specific nuclear export of EIF5A. By mutation and posttranslational modification analyses, Lipowsky et al. (2000) concluded that Xpo4-EIF5A interaction is complex and requires large parts of the EIF5A molecule and hypusine modification of EIF5A.

Using a protein-protein interaction screen, Kurisaki et al. (2006) showed that human XPO4 interacted with Smad3 (603109) via the Smad3 MH2 domain. RNAi knockdown of XPO4 blocked Smad3 export, as did addition of competing short peptides representing the Smad3-XPO4 interaction domain. In vivo and in vitro assays showed that XPO4 mediated nuclear export of Smad3 in a RanGTPase-dependent manner.

▼ Mapping
The International Radiation Hybrid Mapping Consortium mapped the XPO4 gene to chromosome 13 (RH91537).

Tags: 13q12.11