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XPO1
Available structures PDB Ortholog search: C9JV99 PDBe C9JV99 RCSB List of PDB id codes 1W9C, 2L1L, 3GB8, 4BSM, 4BSN, 5DIS
Identifiers
Aliases	XPO1, CRM1, emb, exp1, exportin 1, CRM-1
External IDs	OMIM: 602559; MGI: 2144013; HomoloGene: 2554; GeneCards: XPO1; OMA:XPO1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2p15 Start 61,476,032 bp End 61,538,741 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 A3.2 Start 23,206,041 bp End 23,248,249 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia ventricular zone germinal epithelium epithelium of nasopharynx parietal pleura visceral pleura embryo skin of hip trabecular bone palpebral conjunctiva Top expressed in tail of embryo primitive streak genital tubercle Gonadal ridge dermis abdominal wall epiblast human fetus mandibular prominence medullary collecting duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein domain specific binding transporter activity protein binding RNA binding structural constituent of nuclear pore nuclear export signal receptor activity Cellular component cytoplasm Cajal body nuclear membrane membrane intracellular membrane-bounded organelle nuclear envelope nucleoplasm lamellae anulatae nucleus kinetochore nucleolus cytosol host cell protein-containing complex ribonucleoprotein complex intracellular anatomical structure Biological process ribosomal small subunit export from nucleus intracellular transport of virus regulation of centrosome duplication mRNA transport regulation of mRNA stability negative regulation of transcription by RNA polymerase II protein export from nucleus regulation of protein catabolic process protein localization to nucleus protein transport ribosomal large subunit export from nucleus intracellular protein transport viral process sister chromatid cohesion ribosomal subunit export from nucleus regulation of protein export from nucleus ribosome biogenesis transport nucleocytoplasmic transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7514 103573 Ensembl ENSG00000082898 ENSMUSG00000020290 UniProt O14980 Q6P5F9 RefSeq (mRNA) NM_003400 NM_001035226 NM_134014 RefSeq (protein) NP_003391 NP_001030303 NP_598775 Location (UCSC) Chr 2: 61.48 – 61.54 Mb Chr 11: 23.21 – 23.25 Mb PubMed search
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Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs.

History

XPO1 (CRM1) originally was identified in the fission yeast Schizosaccharomyces pombe in a genetic screen, and investigators determined that it was involved in control of the chromosome structure. It was later shown to be the nuclear transport receptor for cargos with leucine-rich nuclear export signals (NES). The structural details of the interaction of XPO1 with its cargos were revealed two decades after the gene was identified.

Function

XPO1 mediates NES-dependent protein transport. It exports several hundreds of different proteins from the nucleus. XPO1 is involved in the nuclear export of ribosomal subunits. XPO1 plays a role in export of various RNAs including U snRNAs, rRNAs (as a part of ribosomal subunits), and some mRNAs.

Medical relevance

XPO1 is involved in various viral infections. For example, it is required for the nuclear export of HIV-1 RNA in complex with the viral protein Rev, an event that is a crucial part of the infection cycle. XPO1 is affected in some cancer types and is therefore viewed as a target for development of anti-cancer drugs. Selinexor, a drug specifically targeting XPO1, was approved by the FDA for treatment of multiple myeloma.

Interactions

XPO1 has been shown to interact with:

• APC,
• CDKN1B,
• CIITA,
• NMD3,
• Nucleoporin 62,
• RANBP1,
• RANBP3,
• Ran,
• SMARCB1, and
• p53.

See also

• Karyopherin
• Importin
• Nuclear transport
• Nuclear export signal

References

1. ^ GRCh38: Ensembl release 89: ENSG00000082898 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000020290 – Ensembl, May 2017
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4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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6. Fornerod M, Ohno M, Yoshida M, Mattaj IW (1997-09-19). "CRM1 is an export receptor for leucine-rich nuclear export signals". Cell. 90 (6): 1051–1060. doi:10.1016/s0092-8674(00)80371-2. ISSN 0092-8674. PMID 9323133.
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17. Ho JH, Kallstrom G, Johnson AW (2000-11-27). "Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit". The Journal of Cell Biology. 151 (5): 1057–1066. doi:10.1083/jcb.151.5.1057. ISSN 0021-9525. PMC 2174350. PMID 11086007.
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21. Sloan KE, Gleizes PE, Bohnsack MT (2016-05-22). "Nucleocytoplasmic Transport of RNAs and RNA–Protein Complexes". Journal of Molecular Biology. 428 (10): 2040–2059. doi:10.1016/j.jmb.2015.09.023. ISSN 0022-2836. PMID 26434509.
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23. Taylor J, Sendino M, Gorelick AN, Pastore A, Chang MT, Penson AV, Gavrila EI, Stewart C, Melnik EM, Herrejon Chavez F, Bitner L (October 2019). "Altered Nuclear Export Signal Recognition as a Driver of Oncogenesis". Cancer Discovery. 9 (10): 1452–1467. doi:10.1158/2159-8290.CD-19-0298. ISSN 2159-8290. PMC 6774834. PMID 31285298.
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Further reading

• Görlich D, Kutay U (1999). "Transport between the cell nucleus and the cytoplasm". Annu. Rev. Cell Dev. Biol. 15 (1): 607–60. doi:10.1146/annurev.cellbio.15.1.607. PMID 10611974.
• Budhu AS, Wang XW (2007). "Loading and unloading: orchestrating centrosome duplication and spindle assembly by Ran/Crm1". Cell Cycle. 4 (11): 1510–4. doi:10.4161/cc.4.11.2187. PMC 1402358. PMID 16294017.
• Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–34. doi:10.1038/sj.cr.7290370. PMID 16354571.
• Stauber RH, Mann W, Knauer SK (2007). "Nuclear and cytoplasmic survivin: molecular mechanism, prognostic, and therapeutic potential". Cancer Res. 67 (13): 5999–6002. doi:10.1158/0008-5472.CAN-07-0494. PMID 17616652.
• Mathew C, Ghildyal R (2017). "CRM1 inhibitors for antiviral therapy". Frontiers in Microbiology. 8: 1171. doi:10.3389/fmicb.2017.01171. PMC 5487384. PMID 28702009.

External links

• 3D electron microscopy structures of CRM1 from the EM Data Bank(EMDB)

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