Human Gene XPO1 (ENST00000401558.7) from GENCODE V44
Description: Homo sapiens exportin 1 (XPO1), mRNA. (from RefSeq NM_003400) RefSeq Summary (NM_003400): This cell-cycle-regulated gene encodes a protein that mediates leucine-rich nuclear export signal (NES)-dependent protein transport. The protein specifically inhibits 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, MPAK, and MAPKAP kinase 2. This protein also regulates NFAT and AP-1. [provided by RefSeq, Jan 2015]. Gencode Transcript: ENST00000401558.7 Gencode Gene: ENSG00000082898.19 Transcript (Including UTRs) Position: hg38 chr2:61,477,849-61,538,356 Size: 60,508 Total Exon Count: 25 Strand: - Coding Region Position: hg38 chr2:61,478,820-61,533,897 Size: 55,078 Coding Exon Count: 24
ID:XPO1_HUMAN DESCRIPTION: RecName: Full=Exportin-1; Short=Exp1; AltName: Full=Chromosome region maintenance 1 protein homolog; FUNCTION: 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 an 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. Several viruses, among them HIV-1, HTLV-1 and influenza A use it to export their unspliced or incompletely spliced RNAs out of the nucleus. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization. SUBUNIT: Found in a U snRNA export complex with RNUXA/PHAX, NCBP1, NCBP2, RAN, XPO1 and m7G-capped RNA (By similarity). Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1. Found in a trimeric export complex with SNUPN, RAN and XPO1. Found in a nuclear export complex with RANBP3 and RAN. Found in a 60S ribosomal subunit export complex with NMD3, RAN, XPO1. Interacts with DDX3X, NMD3, NUPL2, NUP88, NUP214, RANBP3 and TERT. Also found in complex with several viral proteins involved in RNAs' nuclear export like HIV-1 Rev and HTLV-1 Rex. Interacts presumably with influenza A nucleoprotein. Interacts with Epstein- Barr virus BMLF1. Interacts with NEMF (via its N-terminus). Interacts with the monomeric form of BIRC5/survivin deacetylated at 'Lys-129'. INTERACTION: P04626:ERBB2; NbExp=2; IntAct=EBI-355867, EBI-641062; P35232:PHB; NbExp=2; IntAct=EBI-355867, EBI-354213; SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleoplasm. Nucleus, Cajal body. Nucleus, nucleolus. Note=Located in the nucleoplasm, Cajal bodies and nucleoli. Shuttles between the nucleus/nucleolus and the cytoplasm. TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. Not expressed in the kidney. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. MISCELLANEOUS: Cellular target of leptomycin B (LMB), a XPO1/CRM1 nuclear export inhibitor. SIMILARITY: Belongs to the exportin family. SIMILARITY: Contains 10 HEAT repeats. SIMILARITY: Contains 1 importin N-terminal domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14980
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000054 ribosomal subunit export from nucleus GO:0000055 ribosomal large subunit export from nucleus GO:0000056 ribosomal small subunit export from nucleus GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006611 protein export from nucleus GO:0006886 intracellular protein transport GO:0006913 nucleocytoplasmic transport GO:0010824 regulation of centrosome duplication GO:0015031 protein transport GO:0016032 viral process GO:0034504 protein localization to nucleus GO:0042176 regulation of protein catabolic process GO:0042254 ribosome biogenesis GO:0042493 response to drug GO:0043488 regulation of mRNA stability GO:0046825 regulation of protein export from nucleus GO:0051028 mRNA transport GO:0075733 intracellular transport of virus
KJ892390 - Synthetic construct Homo sapiens clone ccsbBroadEn_01784 XPO1 gene, encodes complete protein. Y08614 - Homo sapiens mRNA for CRM1 protein. AL833550 - Homo sapiens mRNA; cDNA DKFZp686O173 (from clone DKFZp686O173). CR749840 - Homo sapiens mRNA; cDNA DKFZp686B1823 (from clone DKFZp686B1823). AK124769 - Homo sapiens cDNA FLJ42779 fis, clone BRAWH3005300, highly similar to Exportin-1. BX647758 - Homo sapiens mRNA; cDNA DKFZp686K0731 (from clone DKFZp686K0731). D89729 - Homo sapiens mRNA for CRM1 protein, complete cds. JD039310 - Sequence 20334 from Patent EP1572962. JD088324 - Sequence 69348 from Patent EP1572962. JD024153 - Sequence 5177 from Patent EP1572962. JD027872 - Sequence 8896 from Patent EP1572962. JD262950 - Sequence 243974 from Patent EP1572962. JD019077 - Sequence 101 from Patent EP1572962. JD028261 - Sequence 9285 from Patent EP1572962. AK289920 - Homo sapiens cDNA FLJ78427 complete cds, highly similar to Homo sapiens exportin 1 (CRM1 homolog, yeast) (XPO1), mRNA. JD287822 - Sequence 268846 from Patent EP1572962. JD556053 - Sequence 537077 from Patent EP1572962. JD301012 - Sequence 282036 from Patent EP1572962. BC032847 - Homo sapiens exportin 1 (CRM1 homolog, yeast), mRNA (cDNA clone MGC:33022 IMAGE:5267242), complete cds. AK299039 - Homo sapiens cDNA FLJ55480 complete cds, highly similar to Exportin-1. AK316481 - Homo sapiens cDNA, FLJ79380 complete cds, highly similar to Exportin-1. AK312426 - Homo sapiens cDNA, FLJ92769. DQ891271 - Synthetic construct clone IMAGE:100003901; FLH170613.01X; RZPDo839H0598D exportin 1 (CRM1 homolog, yeast) (XPO1) gene, encodes complete protein. AB463037 - Synthetic construct DNA, clone: pF1KB0170, Homo sapiens XPO1 gene for exportin 1, without stop codon, in Flexi system. AK094339 - Homo sapiens cDNA FLJ37020 fis, clone BRACE2010684, highly similar to Rattus norvegicus mRNA for CRM1 protein. AK098297 - Homo sapiens cDNA FLJ40978 fis, clone UTERU2014223. KX404982 - Homo sapiens isolate XPO1_exon_exclusion_F circular RNA circRNA, complete sequence. JD073862 - Sequence 54886 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ptc1Pathway - Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle h_cremPathway - Regulation of Spermatogenesis by CREM
Reactome (by CSHL, EBI, and GO)
Protein O14980 (Reactome details) participates in the following event(s):
R-HSA-168857 Binding of vRNP:M1:NEP complex to CRM1 export receptor R-HSA-180885 Rev multimer-bound HIV mRNA associates with Crm1 R-HSA-450387 HuR binds the CRM1 nuclear export machinery R-HSA-2167924 SMAD7:SMURF1 complex binds XPO1 (CRM1) R-NUL-2169012 Smad7:SMURF1 complex binds XPO1 (CRM1) R-HSA-3769391 XPO1 binds the beta-catenin:CBY complex R-HSA-165028 Release of the HIV mRNA and Crm1 from Rev in the cytoplasm R-HSA-178215 SMAD7:SMURF1 complex is exported to the cytosol R-NUL-2169016 Smad7:SMURF1 complex translocates to the cytosol R-HSA-165034 Rev multimer-bound HIV mRNA:CRM1 complex associates with Ran:GTP R-HSA-168880 vRNP Export through the nuclear pore R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-165043 Rev multimer-bound HIV mRNA:Crm1:Ran:GTP complex associates with the NPC R-HSA-180739 Association of RanBP1 with Ran-GTP:CRM1:Rev:mRNA complex R-HSA-165047 Translocation of nuclear RNA transport complex to cytoplasm R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-165055 Hydrolysis of Ran:GTP to Ran:GDP R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery R-HSA-165054 Rev-mediated nuclear export of HIV RNA R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA R-HSA-2173788 Downregulation of TGF-beta receptor signaling R-HSA-3769402 Deactivation of the beta-catenin transactivating complex R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus R-HSA-162599 Late Phase of HIV Life Cycle R-HSA-177243 Interactions of Rev with host cellular proteins R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-2173789 TGF-beta receptor signaling activates SMADs R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-168255 Influenza Life Cycle R-HSA-162587 HIV Life Cycle R-HSA-162909 Host Interactions of HIV factors R-HSA-8953854 Metabolism of RNA R-HSA-170834 Signaling by TGF-beta Receptor Complex R-HSA-195721 Signaling by WNT R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-168254 Influenza Infection R-HSA-162906 HIV Infection R-HSA-9006936 Signaling by TGF-beta family members R-HSA-162582 Signal Transduction R-HSA-68882 Mitotic Anaphase R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-5663205 Infectious disease R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle R-HSA-1643685 Disease
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