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FLASH GENE
Symbol XPO1 contributors: mct/pgu - updated : 04-02-2019
HGNC name exportin 1 (CRM1 homolog, yeast)
HGNC id 12825
Location 2p15      Physical location : 61.705.069 - 61.765.418
Synonym name
  • exportin-1 required for chromosome region maintenance
  • chromosome region maintenance 1 protein homolog
  • CRM1, yeast, homolog
  • Synonym symbol(s) CRM1, DKFZp686B1823, Exp1
    DNA
    TYPE functioning gene
    STRUCTURE 60.35 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC130839 2p16.1 hypothetical gene LOC130839 BCL11A 2p15 B-cell CLL/lymphoma 11A (zinc finger protein) LOC130865 2p16.1 similar to 60S RIBOSOMAL PROTEIN L26 ATP1B3P1 2p13-p15 ATPase, Na+/K+ transporting, beta 3 pseudogene PAPOLG 2p15 poly(A) polymerase gamma REL 2p12 v-rel reticuloendotheliosis viral oncogene homolog (avian) LOC344423 2p16.1 similar to ribosomal protein S12 FLJ32312 2p16.1 hypothetical protein FLJ32312 PEX13 2p16-p14 peroxisome biogenesis factor 13 KIAA1841 2q14 KIAA1841 protein LOC339804 2p16.1 hypothetical gene supported by AK075484; BC014578 AHSA2 2p16.1-p15 AHA1, activator of heat shock 90kDa protein ATPase homolog 2 (yeast) USP34 2p14 ubiquitin specific protease 34 XPO1 2p16 exportin 1 (CRM1 homolog, yeast) LOC391376 2 similar to 60S ribosomal protein L14 (CAG-ISL 7) FLJ13305 2p15 hypothetical protein FLJ13305 CCT4 2p13.3 chaperonin containing TCP1, subunit 4 (delta) C2orf5 2p15 chromosome 2 open reading frame 5 (MURR1) LOC388954 2 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) B3GNT1 2p14 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1 FLJ34583 KIAA0903 2p15 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1 OTX1 2p13 orthodenticle homolog 1 (Drosophila) LOC51057 2p15 hypothetical protein LOC51057 MDH1 2p16 malate dehydrogenase 1, NAD (soluble) LOC388955 2 similar to Px19-like protein (25 kDa protein of relevant evolutionary and lymphoid interest) (PRELI) (CGI-106) (SBBI12) LOC391377 2 similar to ribosomal protein S4 LOC391378 2 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed) UGP2 2p14-p13 UDP-glucose pyrophosphorylase 2 VPS54 2p13-p14 vacuolar protein sorting 54 (yeast)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 4830 123.2 1071 - 2000 1108016
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     stomach    
    Lymphoid/Immunespleen    
     thymus    
    Reproductivefemale systemuteruscervix highly
     male systemtestis   
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal importin beta domain
  • a coiled-coil domain
  • 20 HEAT repeats (HEAT repeat generally contains two antiparallel helices A and B, each lining the convex and concave side of the protein)
  • C-terminal helix is a major determinant restricting the conformational flexibility and thus shifting the population more toward the extended conformation
  • secondary structure
  • in the free state can adopt a compact, ring-like structure, and an extended, superhelical structure
  • HOMOLOGY
    Homologene
    FAMILY
  • exportin family
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,kinetochore
    intracellular,nucleus,nucleolus
    intracellular,nuclear envelope,pore
    text located at centrosomes through its N-terminal CRIME domain interacting with RanGTP
    basic FUNCTION
  • essential mediator of the leucine-rich NES-dependent nuclear export of proteins in a process requiring the GTP bound form of RanGTPase
  • mediates nuclear export of numerous unrelated cargoes, which may carry a short leucine-rich nuclear export signal or export signatures that include folded domains
  • implicated in the centrosomal association of NPM1
  • maintaining centrosome integrity, disrupted by hepatitis B viral protein X
  • mediating nuclear export of HDAC7A independently of HDAC7A phosphorylation and its association with SFN
  • with ILKAP, are pivotal modulators of ILK subcellular distribution and activity in the keratinocytes
  • might interact with pericentrin and regulate the localization and function of pericentrin at centrosomes
  • critical involvement of the XPO1 transport receptor in dendritic cells maturation, most likely by enabling efficient nucleo-cytoplasmic translocation of specific mRNAs
  • exhibits large overall structural dynamics, in line with other transport receptors such as KPNB1, XPOT, and CSE1L
  • karyopherin that mediates nuclear export of proteins and ribonucleoproteins bearing a leucine-rich nuclear export signal (NES)
  • controls the composition of nucleoplasmic pre-snoRNA complexes to licence them for nucleolar transport
  • plays a key role in normal cell functioning, mediating the nucleo-cytoplasmic transport of cargo proteins
  • XPO1, BARD1 and AURKA promote the targeting and function of BRCA1 at centrosomes
  • IPO7 and XPO1 link MYC and TP53 to regulation of ribosomal biogenesis
  • is essential for nuclear depletion of numerous structurally and functionally unrelated protein and ribonucleoprotein cargoes
  • adopt a toroidal structure in several functional transport complexes and was thought to maintain this conformation throughout the entire nucleocytoplasmic transport cycle
  • is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components
  • mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure
  • nuclear pores are essential for spatial genome organization and gene regulation and XPO1 (exportin 1/CRM1) is the key nuclear export protein
  • binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm
  • regulatory role of XPO1 in juxta-nuclear microtubule-dependent adenovirus transport
  • nuclear transport receptors KPNB1 and XPO1 play essential roles in localising the RANBP2-SUMO-RANGAP1 complex away from, or at kinetochores, respectively
  • XPO1 regulates the nuclear localization of many proteins including tumor suppressor proteins
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text needed for translocation across the nuclear pore complex
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of nuclear pore complex and nucleoplasm
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associating in a subcomplex with NUP214 and NUP88
  • forming a complex with EIF5A
  • exporting STAT1, SMURF1 from the nucleus
  • linked to CHC1 (RCC1) by RANBP3
  • STRADA facilitates nuclear export of STK11 by serving as an adaptor between STK11 and exportins XPO1 and XPO7
  • XPO1-mediated nuclear export may be required for the proper execution of ubiquitin-proteasome-dependent degradation of SERTAD2
  • binds SNUPN in a bipartite manner by means of an amino-terminal LR-NES (leucine-rich nuclear export signal) and its nucleotide-binding domain
  • NUP98 functions as a novel shuttling cofactor for XPO1-mediated nuclear export in conjunction with RANBP3
  • interaction with AVEN (regulation of the ATM-activator protein AVEN by XPO1-dependent nuclear export)
  • RANBP3 acts as a XPO1 cofactor, enhancing NES export by stabilizing the export complex in the nucleus
  • competitive binding mechanism between SKP1 and exportin 1 (XPO1) controls the localization of a subset of F-box proteins
  • binds to specific amino acid motifs termed NESs (nuclear export sequences)
  • binds to undimerized BRCA1 and is displaced by BARD1
  • interacting with BACH1 (BACH1 is predominantly exported to the cytoplasm in a XPO1-dependent manner)
  • KPNB1 having functions at kinetochores exerted via RANBP2 and opposed by XPO1
  • XPO1 and EIF4E seem to play an important role in the nucleocytoplasmic export of human NOS2 mRNA
  • AKT3 is likely a regulator of mitochondrial dynamics in the vasculature via regulation of XPO1-dependent nuclear export
  • a binding interaction between the exportin XPO1 and the unstructured carboxylic tail of TPR, suggesting that this interaction is vital to the functions of XPO1
  • mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure
  • RANGAP1 is actively transported between the nuclear and cytoplasmic compartments, and the cytoplasmic and nuclear pore complex (NPC) localization of RANGAP1 is dependent on XPO1-mediated nuclear export
  • highly selective targeting of NUP98-fusion proteins to HOX cluster regions via prebound XPO1 induces the formation of higher order chromatin structures that causes aberrant HOX gene regulation
  • nuclear exporting of TNS4 is a XPO1-dependent process
  • cell & other
    REGULATION
    inhibited by inhibited by HIV1 viral protein Rev
    Other cell-cycle regulated gene
    its transcription is inhibited by DNA damage and the mechanism of inhibition involves TP53 interfering with NFY function
    XPO1-mediated export is regulated by RANBP3, a Ran-interacting nuclear protein
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   translocation   protein chimeric
    -
    tumoral     --over  
    in cervical cancer and critical for cancer cell survival and proliferation
    tumoral     --over  
    overexpressed in cancer
    tumoral somatic mutation      
    in primary mediastinal diffuse large B cell lymphoma and classical Hodgkin lymphoma
    tumoral     --over  
    in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells
    Susceptibility to autism spectrum disorders (ASD)
    Variant & Polymorphism SNP
  • rs6735330 was associated with were associated with ASD
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    promising candidate as both biomarker and potential anticancer therapeutic target
    cancerreproductiveprostate
    XPO1 inhibition could be a novel promising agent used in combination with conventional chemotherapeutics and AR-targeted therapy for the better treatment of PCa, especially castrate-resistant prostate cancer (CRPC)
    cancer  
    therapeutic targeting of XPO1 has emerged as a novel cancer treatment strategy
    ANIMAL & CELL MODELS