XPO1

Exportin 1 (XPO1), also known as chromosomal maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of proteins, rRNA, snRNA, and some mRNA.[5][6][7][8]

XPO1
Available structures PDB Ortholog search: PDBe 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
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p15 Start 61,477,849 bp[1] End 61,538,626 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A3.2 Start 23,256,041 bp[2] End 23,298,249 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein domain specific binding • transporter activity • Ran GTPase binding • GO:0001948 protein binding • RNA binding • GO:0005487 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 • annulate lamellae • cell nucleus • kinetochore • nucleolus • cytosol • host cell • macromolecular complex • ribonucleoprotein • intracellular • cell Biological process • ribosomal small subunit export from nucleus • GO:0046795 intracellular transport of virus • regulation of centrosome duplication • mRNA transport • regulation of mRNA stability • negative regulation of transcription from RNA polymerase II promoter • protein export from nucleus • regulation of protein catabolic process • protein localization to nucleus • protein transport • ribosomal large subunit export from nucleus • intracellular protein transport • GO:0022415 viral process • response to drug • 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: 23.26 – 23.3 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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[9]

Function

Exportin 1 mediates leucine-rich nuclear export signal (NES)-dependent protein transport. Exportin 1 specifically mediates the nuclear export of Rev and U snRNAs. It is involved in the control of several cellular processes by controlling the localization of cyclin B, MAPK, and MAPKAP kinase 2. This protein also regulates NFAT and AP-1.[10]

Interactions

XPO1 has been shown to interact with:

• APC,[11]
• CDKN1B,[12][13]
• CIITA,[14][15]
• NMD3,[16]
• Nucleoporin 62,[17][18]
• RANBP1,[19][20]
• RANBP3,[17][21]
• Ran,[11][19][22]
• SMARCB1,[23] and
• p53.[24][25]

See also

• Karyopherin
• Selinexor

References

1. GRCh38: Ensembl release 89: ENSG00000082898 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020290 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Fornerod M, Ohno M, Yoshida M, Mattaj IW (September 1997). "CRM1 is an export receptor for leucine-rich nuclear export signals". Cell. 90 (6): 1051–60. doi:10.1016/S0092-8674(00)80371-2. PMID 9323133.
6. Kudo N, Khochbin S, Nishi K, Kitano K, Yanagida M, Yoshida M, Horinouchi S (Dec 1997). "Molecular cloning and cell cycle-dependent expression of mammalian CRM1, a protein involved in nuclear export of proteins". J Biol Chem. 272 (47): 29742–51. doi:10.1074/jbc.272.47.29742. PMID 9368044.
7. Köhler, Alwin; Hurt, Ed (October 2007). "Exporting RNA from the nucleus to the cytoplasm". Nature Reviews Molecular Cell Biology. 8 (10): 761–773. doi:10.1038/nrm2255. PMID 17786152.
8. Lu C, Figueroa JA, Liu Z, Konala V, Aulakh A, Verma R, Cobos E, Chiriva-Internati M, Gao W (September 2015). "Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection". Current Cancer Drug Targets. 15 (7): 575–592. doi:10.2174/156800961507150828223554. PMID 26324128.
9. Noske A, Weichert W, Niesporek S, Röske A, Buckendahl AC, Koch I, Sehouli J, Dietel M, Denkert C (Apr 2008). "Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer". Cancer. 112 (8): 1733–43. doi:10.1002/cncr.23354. PMID 18306389.
10. "Entrez Gene: XPO1 exportin 1 (CRM1 homolog, yeast)".
11. Tickenbrock L, Cramer J, Vetter IR, Muller O (August 2002). "The coiled coil region (amino acids 129-250) of the tumor suppressor protein adenomatous polyposis coli (APC). Its structure and its interaction with chromosome maintenance region 1 (Crm-1)". J. Biol. Chem. 277 (35): 32332–8. doi:10.1074/jbc.M203990200. PMID 12070164.
12. Ishida N, Hara T, Kamura T, Yoshida M, Nakayama K, Nakayama KI (April 2002). "Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export". J. Biol. Chem. 277 (17): 14355–8. doi:10.1074/jbc.C100762200. PMID 11889117.
13. Connor MK, Kotchetkov R, Cariou S, Resch A, Lupetti R, Beniston RG, Melchior F, Hengst L, Slingerland JM (January 2003). "CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis". Mol. Biol. Cell. 14 (1): 201–13. doi:10.1091/mbc.E02-06-0319. PMC 140238. PMID 12529437.
14. Raval A, Weissman JD, Howcroft TK, Singer DS (January 2003). "The GTP-binding domain of class II transactivator regulates its nuclear export". J. Immunol. 170 (2): 922–30. doi:10.4049/jimmunol.170.2.922. PMID 12517958.
15. Voong LN, Slater AR, Kratovac S, Cressman DE (April 2008). "Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator". J. Biol. Chem. 283 (14): 9031–9. doi:10.1074/jbc.M706487200. PMC 2431044. PMID 18245089.
16. Thomas F, Kutay U (June 2003). "Biogenesis and nuclear export of ribosomal subunits in higher eukaryotes depend on the CRM1 export pathway". J. Cell Sci. 116 (Pt 12): 2409–19. doi:10.1242/jcs.00464. PMID 12724356.
17. Lindsay ME, Holaska JM, Welch K, Paschal BM, Macara IG (June 2001). "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export". J. Cell Biol. 153 (7): 1391–402. doi:10.1083/jcb.153.7.1391. PMC 2150735. PMID 11425870.
18. Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T, Gerace L (May 1999). "A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export". J. Cell Biol. 145 (4): 645–57. doi:10.1083/jcb.145.4.645. PMC 2133185. PMID 10330396.
19. Plafker K, Macara IG (May 2000). "Facilitated nucleocytoplasmic shuttling of the Ran binding protein RanBP1". Mol. Cell. Biol. 20 (10): 3510–21. doi:10.1128/mcb.20.10.3510-3521.2000. PMC 85643. PMID 10779340.
20. Singh BB, Patel HH, Roepman R, Schick D, Ferreira PA (Dec 1999). "The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1". J. Biol. Chem. 274 (52): 37370–8. doi:10.1074/jbc.274.52.37370. PMID 10601307.
21. Lindsay ME, Plafker K, Smith AE, Clurman BE, Macara IG (August 2002). "Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import". Cell. 110 (3): 349–60. doi:10.1016/s0092-8674(02)00836-x. PMID 12176322.
22. Fornerod M, Ohno M, Yoshida M, Mattaj IW (September 1997). "CRM1 is an export receptor for leucine-rich nuclear export signals". Cell. 90 (6): 1051–60. doi:10.1016/s0092-8674(00)80371-2. PMID 9323133.
23. Craig E, Zhang ZK, Davies KP, Kalpana GV (January 2002). "A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis". EMBO J. 21 (1–2): 31–42. doi:10.1093/emboj/21.1.31. PMC 125819. PMID 11782423.
24. Kanai M, Hanashiro K, Kim SH, Hanai S, Boulares AH, Miwa M, Fukasawa K (September 2007). "Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation". Nat. Cell Biol. 9 (10): 1175–83. doi:10.1038/ncb1638. PMID 17891139.
25. Shao C, Lu C, Chen L, Koty PP, Cobos E, Gao W (August 2010). "p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma". Cancer Chemother. Pharmacol. 67 (6): 1369–80. doi:10.1007/s00280-010-1434-6. PMID 20803015.

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)