Exportin-1 (XPO1)

The protein contains 1071 amino acids for an estimated molecular weight of 123386 Da.

 

Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). 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, 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. 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. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap.', '(Microbial infection) Mediates the export of unspliced or incompletely spliced RNAs out of the nucleus from different viruses including HIV-1, HTLV-1 and influenza A. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization. (updated: July 18, 2018)

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. 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.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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_MODELLER-9.18

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The reference OMIM entry for this protein is 602559

Exportin 1; xpo1
Required for chromosome region maintenance; crm1

CLONING

Human CRM1, or XPO1, is the homolog of yeast crm1 (named for 'required for chromosome region maintenance'), a nuclear protein essential for proliferation and chromosome region maintenance. Fornerod et al. (1997) used the oncogenic nucleoporin CAN (114350) to coprecipitate human CRM1. The complete cDNA encodes a predicted protein of 1,071 amino acids with a predicted molecular mass of 123 kD. The CRM1 protein migrates at 112 kD. Human CRM1 has 47% identity with S. cerevisiae crm1 and 52% identity with S. pombe crm1+. The N terminus of human CRM1 shares significant homology with the N terminus of importin-beta. Fornerod et al. (1997) identified a group of largely uncharacterized yeast and vertebrate proteins of similar size (110 to 120 kD) that share this homology domain, which they proposed to call the CRIME domain (for 'CRM1, importin-beta, etc.'). Kudo et al. (1997) cloned human CRM1 cDNA using sequence information from EST databases and a PCR-based strategy based on the sequence of S. pombe crm1+. Northern blot analysis using the C-terminal region of human CRM1 cDNA as a probe revealed a major transcript of 5.6 kb expressed in all tissues tested except kidney.

GENE FUNCTION

Kudo et al. (1997) found that Human CRM1 weakly complemented the cold-sensitive mutation of S. pombe crm1-809. Overproduction of human CRM1 suppressed cell proliferation in wildtype S. pombe in an expression level-dependent manner. Overexpression of native S. pombe crm1+ had the same effect. Northern blot analysis with RNAs isolated from synchronized mammalian cells showed that the expression of mammalian CRM1 was initiated in the late G1 phase and reached a peak at G2/M, although the protein level did not change during the cell cycle. Human CRM1 fused to green fluorescent protein (GFP) and transiently expressed in NIH 3T3 cells showed that human CRM1 was localized preferentially in the nuclear envelope, but was also detectable in the nucleoplasm and the cytoplasm. A crm1 mutation of S. pombe caused nuclear import of a GFP fusion protein containing a nuclear export signal (NES) but no change in the distribution of a GFP fusion protein containing a nuclear localization signal (NLS). These data suggested to Kudo et al. (1997) that CRM1 is a novel cell cycle-regulated gene that is essential for the NES-dependent nuclear export of proteins. CRM1 protein binds CAN and NUP88 (602552), and its association with the nuclear pore is dynamic (Fornerod et al., 1997). To test whether CRM1 could be a nuclear export receptor, Fornerod et al. (1997) used Xenopus oocytes incubated in leptomycin B, a cytotoxin which blocks Rev export and Rev-mediated RNA export in tissue culture cells. Leptomycin B interacted directly with CRM1, as shown by gel shift assays, and blocked export of Rev and U snRNAs from Xenopus oocyte nucleus. Overexpression of CRM1 stimulated Rev and U snRNA export from the nucleus. Fornerod et al. (1997) found that an NES/CRM1/Ran complex forms in the presence of RanGTP. Leptomycin B blocks formation of this complex. Fornerod et al. (1997) concluded that CRM1 is an export receptor for leucine-rich NESs. Noting that CRM1 is a member of a family of proteins related to importin-beta, Fornerod et al. (1997) suggested the descriptive name 'exportins' for those family members involved in nuclear export. Stade et al. (1997) characterized CRM1 as an essential nuclear export factor in S. cerevisiae and proposed that CRM1 be renamed 'exportin-1,' ... 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. 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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602559 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

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