Human Gene XPO1 (ENST00000406957.5) Description and Page Index
  Description: 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. (from UniProt O14980)
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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660809.249384.1, BX647758.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000401558.7/ ENSP00000384863.2 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Gencode Transcript: ENST00000406957.5
Gencode Gene: ENSG00000082898.17
Transcript (Including UTRs)
   Position: hg38 chr2:61,478,700-61,538,248 Size: 59,549 Total Exon Count: 26 Strand: -
Coding Region
   Position: hg38 chr2:61,478,820-61,533,897 Size: 55,078 Coding Exon Count: 24 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:61,478,700-61,538,248)mRNA (may differ from genome)Protein (1071 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
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Wikipedia

-  Comments and Description Text from UniProtKB
  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.

-  MalaCards Disease Associations
  MalaCards Gene Search: XPO1
Diseases sorted by gene-association score: influenza (22), mixed malaria (11), tooth ankylosis (11), chromosome 2p16.1-p15 deletion syndrome (9), breast abscess (9), human t-cell leukemia virus type 1 (7), mediastinal malignant lymphoma (7), mediastinal gray zone lymphoma (6), hiv-1 (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C016403 2,4-dinitrotoluene
  • C023514 2,6-dinitrotoluene
  • C049584 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • C016583 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • C035207 4-amino-2,6-dinitrotoluene
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • D000082 Acetaminophen
  • D016604 Aflatoxin B1
  • D000643 Ammonium Chloride
  • D019256 Cadmium Chloride
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 42.95 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 798.08 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -52.20143-0.365 Picture PostScript Text
3' UTR -32.20120-0.268 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011989 - ARM-like
IPR016024 - ARM-type_fold
IPR014877 - CRM1_C_dom
IPR013598 - Exportin-1/Importin-b-like
IPR001494 - Importin-beta_N

Pfam Domains:
PF08767 - CRM1 C terminal
PF03810 - Importin-beta N-terminal domain
PF08389 - Exportin 1-like protein

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1W9C
- X-ray MuPIT

2L1L
- NMR MuPIT

3GB8
- X-ray MuPIT


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologGenome Browser
Gene Details    Gene Details
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MGIRGDEnsemblEnsembl SGD
Protein SequenceProtein Sequence Protein Sequence Protein Sequence
AlignmentAlignment Alignment Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0005049 nuclear export signal receptor activity
GO:0005215 transporter activity
GO:0005515 protein binding
GO:0008536 Ran GTPase binding
GO:0008565 protein transporter activity
GO:0019904 protein domain specific binding

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

Cellular Component:
GO:0000776 kinetochore
GO:0005634 nucleus
GO:0005635 nuclear envelope
GO:0005642 annulate lamellae
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0015030 Cajal body
GO:0016020 membrane
GO:0031965 nuclear membrane
GO:0032991 macromolecular complex
GO:0043231 intracellular membrane-bounded organelle
GO:0043657 host cell
GO:1990904 ribonucleoprotein complex


-  Descriptions from all associated GenBank mRNAs
  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.
AK289920 - Homo sapiens cDNA FLJ78427 complete cds, highly similar to Homo sapiens exportin 1 (CRM1 homolog, yeast) (XPO1), mRNA.
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

-  Other Names for This Gene
  Alternate Gene Symbols: A6NL14, A8K1K5, CR749840, CRM1, D6W5E2, O14980, Q63HP8, Q68CP3, Q99433, uc061job.1, XPO1_HUMAN
UCSC ID: uc061job.1
RefSeq Accession: NM_003400
Protein: O14980 (aka XPO1_HUMAN)
CCDS: CCDS33205.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.