Exportin-4 (XPO4)
The protein contains 1151 amino acids for an estimated molecular weight of 130139 Da.
Mediates the nuclear export of proteins (cargos) with broad substrate specificity. In the nucleus binds cooperatively to its cargo and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. XPO4 then return to the nuclear compartment and 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. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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| Variant | Description |
|---|---|
| dbSNP:rs17320607 | |
| dbSNP:rs9552285 |
The reference OMIM entry for this protein is 611449
Exportin 4; xpo4 exp4
Kiaa1721
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
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 (TMAP RH91537). ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611449 was added.