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FLASH GENE
Symbol KPNB1 contributors: mct/npt - updated : 28-12-2016
HGNC name karyopherin (importin) beta 1
HGNC id 6400
DNA
TYPE functioning gene
STRUCTURE 33.73 kb     22 Exon(s)
10 Kb 5' upstream gene genomic sequence study
motif repetitive sequence   ALU   long interspersed repetitive elements
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 4205 97 876 - 2015 26319354
20 - 3951 - 731 - 2015 26319354
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
blood / hematopoieticspleen   highly
Cardiovascularheart   highly
Digestiveliver   highly
Endocrinepancreas   highly
Nervousbrain   highly
Reproductivemale systemprostate  highly
Respiratorylung   highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Epithelialsecretoryglandularendocrine 
Epithelialsecretoryglandularexocrine 
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an importin N-terminal domain
  • eight HEAT repeats, forming a rod-like helical structure, functioning as protein-protein interaction surface and involved in intracellular processus
  • a central region (harboring nucleoporin-binding sites) that regulates microtubule dynamic functions and interaction with kinetochores
  • C-terminal region (which binds importin-alpha) inhibits mitotic spindle pole formation
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Kpnb1
    homolog to drosophila Fs(2)Ket
    homolog to C.elegans imb-1
    Homologene
    FAMILY
  • importin beta family
  • CATEGORY receptor nuclear , transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nuclear envelope,pore
    basic FUNCTION
  • docking the complex at the cytoplasmic side of the nuclear pore complex
  • binds cargo molecules either directly or via two types of adapter molecules, importin alpha, for import of proteins with a classical nuclear localization signal (NLS), or snurportin 1, for import of m3G-capped U snRNPs (Paraskeva 1999)
  • involved in nucleo-cytoplasmic trafficking and critical for protein and RNA subcellular localization
  • serving as a receptor for nuclear localization signals containing proteins (Van der Watt 2009)
  • regulating nucleocytoplasmic transport velocities and therefore potentially the speed of cargo traffic across the nuclear envelope (Yang 2006)
  • main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown
  • regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells
  • having functions at kinetochores exerted via RANBP2 and opposed by XPO1
  • localized translation of KPNB1 mRNA enables separation of cytoplasmic and nuclear transport functions of importins and is required for efficient retrograde signaling in injured axons
  • major nuclear import receptor, playing an integral role in importing transcription factors, cell signaling proteins, cell cycle proteins, and so forth, into the nucleus, thus playing a crucial role in maintaining normal cell homeostasis
  • involved in nuclear-cytoplasmic trafficking and is crucial for protein and RNA subcellular localization
  • is one of the soluble nuclear transport receptors, reported to act as an important role in the occurrence and development of tumor, such as cervical cancer, head and neck and lung cancer
  • is required for timely nuclear import of PER1/CRY1 in the negative feedback regulation of the circadian clock
  • transports nuclear factor RELA from the cytoplasm to the nucleus to increase pro-inflammatory genes expression
  • may play a key role in the inflammation process of rheumatoid arthritis via STAT3 signal transduction pathway
  • nuclear transport receptors KPNB1 and XPO1 play essential roles in localising the RANBP2-SUMO-RANGAP1 complex away from, or at kinetochores, respectively
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text nucleocytoplasmic transport, nuclear import of ribosomal proteins
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • component of the NLS import receptor which is a heterodimer of importin alpha and beta subunits
  • forms a high-molecular-weight complex with both AHCTF1 and the NUP107-160 complex in cytosol
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • binding to RAN importin alpha
  • binding specifically to the GTPbound form of RAN
  • critical function of RANBP2 is to capture recycling RANGTP-KPNB1 complexes at cytoplasmic fibrils to allow for adequate classical nuclear localization signal-mediated cargo import
  • TP53BP1 is imported to the nucleus through the NUP153-KPNB1 interplay
  • interacts through its central region with NUP358/RANBP2, which in turn binds SUMO-conjugated RANGAP1 in nuclear pores
  • nuclear import of RELA mainly relies on the canonical KPNA2/KPNB1 pathway
  • EI24 can bind specifically to KPNA2/KPNB1 to impede their normal role in nuclear import, shedding new light on the cellular functions of EI24 and its tumor suppressor role
  • SNAI1 C2H2-type zinc-finger (ZF) domain functions both as a nuclear localization signal which binds to KPNB1 directly and as a DNA-binding domain
  • mediates the translocation of NFKB1 into the nuclei of myeloma cells, thereby regulating proliferation and blocking apoptosis
  • KPNB1 and NUP153 interact at the nuclear pore complex (NPC) nuclear face to form a Ran-regulated mesh that modulates NPC permeability
  • allosteric coupling between a structured domain of a channel nucleoporin (NUP58) and its neighboring disordered domain in interaction with another channel nucleoporin (NUP54) and a transport factor (KPNB1)
  • nuclear translocation of IGFBP3 by KPNB1 is a prerequisite for IGFBP3-induced apoptosis
  • KPNB1 interacts mainly with PER proteins and directs PER1/CRY1 nuclear transport in a circadian fashion
  • cell & other
    REGULATION
    Other intracellular calcium levels can regulate KPNB1/KPNA-dependent nuclear import
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in cervical cancer and are critical for cancer cell survival and proliferation (van der Watt 2009)
    tumoral       gain of function
    in hepatocellular carcinoma (HCC) tissue samples and increasing HCC cells growth and the KPNB1 expression was associated with poor survival
    tumoral     --over  
    in cervical cancer, critical for cervical cancer cell survival and proliferation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • promising candidate as both biomarker in cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    therapeutic target for HCC
    cancer  
    potential anticancer therapeutic target
    cancerhemopathy 
    target for myeloma therapies
    cancerreproductiveuterus
    blocking KPNB1 has potential as an anticancer therapeutic approach
    ANIMAL & CELL MODELS