PROFILBARU.COM

XPO5
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3A6P
Identifiers
Aliases	XPO5, exp5, exportin 5
External IDs	OMIM: 607845; MGI: 1913789; HomoloGene: 69316; GeneCards: XPO5; OMA:XPO5 - orthologs
Gene location (Human)
Chr.	Chromosome 6 (human)
End	43,576,038 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	46,554,524 bp
RNA expression pattern
	Top expressed in
	gonad; ; skin of arm; ; testicle; ; left testis; ; right testis; ; body of pancreas; ; ganglionic eminence; ; ventricular zone; ; bone marrow cells; ; skin of leg;
	Top expressed in
	gallbladder; ; superior surface of tongue; ; tail of embryo; ; epiblast; ; mandibular prominence; ; maxillary prominence; ; interventricular septum; ; genital tubercle; ; ventricular zone; ; spermatocyte;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	tRNA binding; mRNA binding; protein binding; RNA binding; nuclear export signal receptor activity; pre-miRNA binding;
Cellular component	cytoplasm; RNA nuclear export complex; nucleus; nucleoplasm; cytosol; nuclear RNA export factor complex;
Biological process	protein export from nucleus; positive regulation of RNA interference; protein transport; intracellular protein transport; miRNA metabolic process; gene silencing; regulation of protein export from nucleus; pre-miRNA export from nucleus; transport; nuclear export;
	Sources:Amigo / QuickGO
Orthologs
	57510
	72322
	ENSG00000124571
	ENSMUSG00000067150
	Q9HAV4
	Q924C1
	NM_020750
	NM_028198
	NP_065801
	NP_082474
	Wikidata
View/Edit Human	View/Edit Mouse

Exportin-5 (XPO5) is a protein that, in humans, is encoded by the XPO5 gene.^[5]^[6]^[7] In eukaryotic cells, the primary purpose of XPO5 is to export pre-microRNA (also known as pre-miRNA) out of the nucleus and into the cytoplasm, for further processing by the Dicer enzyme.^[8]^[9]^[10]^[11] Once in the cytoplasm, the microRNA (also known as miRNA) can act as a gene silencer by regulating translation of mRNA. Although XPO5 is primarily involved in the transport of pre-miRNA, it has also been reported to transport tRNA.^[12]

Much research on XPO5 is ongoing. miRNA is a prominent research topic due to its potential use as a therapeutic, with several miRNA-based drugs already in use.^[13]

Mechanism

Binding to pre-miRNA

After RanGTP binds to XPO5, the XPO5-RanGTP complex forms a U-like structure to hold the pre-miRNA. The XPO5-RanGTP complex recognizes pre-miRNA by its two-nucleotide 3’ overhang—a sequence consisting of two bases at the 3’ end of the pre-miRNA that are not paired with other bases. This motif is unique to pre-miRNA, and by recognizing it XPO5 ensures specificity for transporting only pre-miRNA. On its own, pre-miRNA is in a “closed” conformation, with the 3’ overhang flipped up toward the RNA minor groove. However, upon binding to XPO5, the 3’ overhang is flipped downwards away from the rest of the pre-miRNA molecule into an “open” conformation. This helps the backbone phosphates of these two nucleotides form hydrogen bonds with many XPO5 residues, allowing XPO5 to recognize the RNA as pre-miRNA. Because these interactions involve only the RNA phosphate backbone, they are nonspecific and allow XPO5 to recognize and transport any pre-miRNA. The rest of the pre-miRNA stem binds to XPO5 via interactions between the negatively-charged phosphate backbone and several positively-charged interior XPO5 residues.^[15]

XPO5 Ternary Complex Transport Mechanism

The combined structure of XPO5, RanGTP, and pre-miRNA is known as the ternary complex. Once the ternary complex is formed, it diffuses through a nuclear pore complex into the cytoplasm, transporting pre-miRNA into the cytoplasm in the process. Once in the cytoplasm, RanGAP hydrolyzes GTP to GDP, causing a conformational change that releases the pre-miRNA into the cytoplasm.^[15]

Export out of the Nucleus

It has been suggested, through evidence provided by contour maps of water density, that the interior of XPO5 is hydrophilic, while the exterior of XPO5 is hydrophobic.^[15] Therefore, this enhances the binding capabilities of XPO5 to the nuclear pore complex, allowing for transport of the ternary complex out of the nucleus.^[15]

Additional interactions

XPO5 has been shown to interact with ILF3^[5] and Ran.^[5]

Potential oncogenic role

Recent evidence has shown higher levels of XPO5 in prostate cancer cell lines in-vitro, suggesting that altered XPO5 expression levels may have a role in cancer development. Suppressing XPO5 has also been found to be therapeutic in-vitro.^[16] It has also been shown to function as an oncogene in colorectal cancer.^[17]