Exportin-5 (XPO5)

The protein contains 1204 amino acids for an estimated molecular weight of 136311 Da.

 

Mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos). XPO5 in the nucleus binds cooperatively to the RNA and to the GTPase Ran in its active GTP-bound form. Proteins containing dsRBDs can associate with this trimeric complex through the RNA. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause disassembly of the complex and 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 transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi). Mediates nuclear export of isoform 5 of ADAR/ADAR1 in a RanGTP-dependent manner.', "Mediates the nuclear export of micro-RNA precursors, which form short hairpins (PubMed:14681208, PubMed:14631048, PubMed:15613540). Also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference. In some circumstances can also mediate the nuclear export of deacylated and aminoacylated tRNAs. Specifically recognizes dsRNAs that lack a 5'-overhang in a sequenc (updated: Dec. 20, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 100
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs34324334
dbSNP:rs12173786
Found in a patient with nephrotic syndrome

The reference OMIM entry for this protein is 607845

Exportin 5; xpo5
Kiaa1291

DESCRIPTION

Exportin-5 belongs to a large family of karyopherins (see 602738) that mediate the transport of proteins and other cargo between the nuclear and cytoplasmic compartments.

CLONING

By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (1999) cloned an XPO5 cDNA, which they designated KIAA1291. RT-PCR ELISA detected low to moderate expression in all tissues and specific brain regions examined. Brownawell and Macara (2002) determined that KIAA1291 shares significant homology with the general nucleoporin export receptor, CRM1 (XPO1; 602559). They obtained a full-length XPO5 cDNA by 5-prime RACE of a brain cDNA library. The deduced 1,205-amino acid protein has a calculated molecular mass of about 136 kD. XPO5 and XPO1 share 25% amino acid identity. Northern blot analysis detected transcripts of about 3.6 and 5.0 kb in all tissues examined.

GENE FUNCTION

Using various criteria, Brownawell and Macara (2002) determined that XPO5 shares several characteristics with other karyopherins. XPO5 bound RAN (601179) in the GTP-bound conformation, and binding required the N-terminal domain of XPO5. XPO5 bound the nucleoporins NUP214 (114350) and NUP153 (603948) in a RAN-GTP-independent manner and bound a cargo protein, ILF3 (603182), in a RAN-GTP-dependent manner. XPO5 bound ILF3 at its double-stranded RNA-binding domain (dsRBD) and also bound the dsRBDs of other proteins. Using a heterokaryon fusion assay, Brownawell and Macara (2002) demonstrated that XPO5 shuttles between the nuclear and cytoplasmic compartments. They concluded that XPO5 regulates the translocation of dsRBD proteins to the cytoplasm, where they interact with target mRNAs. By microinjection in Xenopus oocytes, Gwizdek et al. (2003) found that XPO5 mediated the nuclear export of adenovirus VA1 RNA. XPO5 directly interacted with VA1 RNA in a RAN-GTP-dependent manner. In vivo and in vitro competition experiments with various VA1, artificial, and cellular RNAs led the authors to conclude that XPO5 preferentially recognizes and transports RNAs containing a minihelix motif, which is a double-stranded stem structure. Lund et al. (2004) demonstrated that exportin-5 mediates efficient nuclear export of short microRNA (miRNA) precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. XPO5 binds correctly processed pre-miRNAs directly and specifically, in a RAN-GTP-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer (606241) in vitro. Thus, Lund et al. (2004) concluded that XPO5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.

BIOCHEMICAL FEATURES

- Crystal Structure Okada et al. (2009) presented the 2.9-angstrom structure of the pre-miRNA nuclear export machinery formed by pre-miRNA complexed with Exp5 and a GTP-bound form of the small nuclear GTPase Ran (RANGAP1; 602362). The x-ray structure showed that Exp5:RanGTP recognizes the 2-nucleotide 3-prime overhang structure and the double-stranded stem of the pre-miRNA. Exp5:RanGTP shields the pre-miRNA stem from degradation in a baseball mitt-like structure where it is held by broadly distributed weak interactions, whereas a tunnel-like structure of Exp5 interacts strongly with the 2-nucleotide 3-prime overhang through hydrogen bonds and ionic interactions. RNA recognition by Exp5:RanGTP does not depend ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607845 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed