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FLASH GENE
Symbol RAN contributors: mct - updated : 15-04-2017
HGNC name RAN, member RAS oncogene family
HGNC id 9846
Location 12q24.33      Physical location : 131.356.616 - 131.360.824
Synonym name
  • androgen receptor associated 24
  • ras-related nuclear protein
  • member RAS oncogene family
  • RanGTPase
  • guanosine triphosphatase Ran
  • Ras-like protein TC4
  • Synonym symbol(s) TC4, ARA24, CAT61, Gsp1, OK/SW-cl.81
    EC.number 3.6.5.1/3.6.5.2/3.6.5.3/ 3.6.5.4
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 4.21 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1087 24.3 216 - 2006 16481399
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   moderately
     salivary gland   moderately
    Lymphoid/Immunetonsils   moderately
    Urinarybladder   moderately
    cell lineage
    cell lines human teratocarcinoma cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    cell cycle     cell cycle, interphase
    Text placenta (mitochondria)
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a GTP binding site
  • a C terminus essential for defining the GDP-bound form of RAN
  • HOMOLOGY
    interspecies homolog to yeast
    homolog to Drosophila
    Homologene
    FAMILY
  • small GTPase superfamily
  • Ran family
  • CATEGORY regulatory , DNA associated , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    intracellular,nuclear envelope,pore
    text
  • shuttling between the nucleus and the cytoplasm
  • expressed in the placental mitochondria
  • basic FUNCTION
  • GTP binding protein coupling DNA assembly completion to mitosis
  • involved in nucleocytoplamsic transport and nuclear envelope assembly
  • involved in microtubule organization, in the alignment of chromosomes at the metaphase plate and is required for postmetaphase events, including chromosome segregation and the assembly of the microtubule midbody
  • nuclear Ras-like GTPase that is required for various nuclear events including the bi-directional transport of proteins and ribonucleoproteins through the nuclear pore complex, spindle formation, and reassembly of the nuclear envelope
  • plays a central role in nucleocytoplasmic transport
  • NUTF2 and RAN control nuclear import of the filamentous actin capping protein CAPG
  • NUTF2 and RAN control nuclear import of the filamentous actin capping protein CAPG
  • small GTPase, functioning as an AR coactivator
  • GTPase that regulates multiple processes, including mitotic spindle assembly, spindle pole formation and micotubules dynamics and is therefore essential to formation of a functional mitotic apparatus
  • maintains spindle Microtubules in anaphase through the local activation of SMARCA5 which is essential for proper chromosome segregation
  • has a global role in regulating cellular compartmentalization by controlling the shuttling of cytoplasmic proteins into nuclear and ciliary compartments
  • contribute to both nucleocytoplasmic transport and cell cycle progression
  • new function for RAN GTP in stimulating cilia formation, reinforcing the notion that RN GTP and the importins play key roles in ciliogenesis and ciliary protein transport
  • a finely-tuned balance of RAN GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis
  • regulates a variety of processes throughout the cell cycle, including interphase nucleocytoplasmic transport and mitotic spindle assembly
  • has important roles in nucleocytoplasmic transport
  • CELLULAR PROCESS cell cycle, progression
    nucleotide, replication
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text organization of microtubule network and regulating the centrosome through RANBP9
  • translocation of RNA and proteins through the nuclear pore complex,in and out
  • mitotic spindle assembly
  • PATHWAY
    metabolism
    signaling signal transduction
    Ran pathway having a role in spindle assembly
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GTP binding
  • protein
  • RAN binding protein, RAN GTPase RANGAP1
  • CHC1 generating RAS-GTP, required for nuclear localization and chromatin-induced mitotic spindle formation
  • binding to AR (androgen receptor)
  • binding to the importin site of karyopherins beta (KPNBx)
  • interacting with NUP153 Ran-binding zinc finger domain
  • mediates these mitotic events, in part, by facilitating the correct targeting of the kinase Aurora A and the kinesins to spindles
  • import cargo of NUTF2
  • increases AR transactivation by enhancing the AR interaction in the nucleus
  • RAN is a novel MAD2L2 binding protein (protein-protein interaction may play a role in the control over the spindle checkpoint during mitosis andin the regulation of nucleocytoplasmic trafficking during interphase (pMID: 19753112)
  • with RANBP2, anchor RAPGEF3 to the nuclear pore, permitting cAMP signals to activate RAP1A at the nuclear envelope)
  • interacts with the nuclear import protein importin-beta2 in a manner dependent on the CLS (ciliary localization signal) and inhibited by RAN
  • interacting with RCC1 (recruits RAN to nucleosomes and activates RAN nucleotide exchange activity)
  • interaction with XPO6 (reduction of its activity leads to actin accumulation via failure of RANGTP restoration and NUTF2 sequestration in the nuclei of senescent cells
  • connection between the hyper-activation of the small GTPase RAN and the matricellular protein SMOC2 that has important consequences for oncogenic transformation
  • MYC binds to the upstream sequence of RAN and transactivates RAN promoter activity
  • TACC3is also a target of the RAN GTPase system, and it may coordinate with RAN to regulate acentrosomal microtubules for kinetochore capture
  • BIRC5 is a potential RAN target gene (inhibition of BIRC5 reduced cell proliferation and induced apoptosis by down-regulating CCND1 and phospho-Rb and activating CASP3)
  • RAN is involved in the process of VHL nuclear-cytoplasmic trafficking following microtubule network alteration in hypoxic cardiomyocytes (CMs)
  • RAN-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons
  • EMD and RAN are direct binding partners of TMEM201, but RAN attenuates the interaction between EMD and TMEM201
  • VSMC proliferation can be modulated via an HSPD1 dependent, cytosol localized mechanism that in part involves a stimulation of nuclear protein import through an interaction with RAN
  • cell & other
  • interacts dynamically with chromatin, nuclear pore complexes and the mitotic spindle during the cell cycleand this interaction is dependent on the nucleotide-bound state of the protein
  • REGULATION
    activated by heregulin (heregulin-dependent activation of RAN requires MTOR and stimulates the capped RNA binding capability of the cap-binding complex in the nucleus, thus influencing gene expression at the level of mRNA processing)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    coactivation with longer poly-Q AR may contribute to partial androgen sensitivity during the development of Kennedy disease
    tumoral     --over  
    in the early stages of primary prostate cancer
    tumoral     --over  
    in high grade serous epithelial ovarian cancers, and its overexpression is associated with a poor prognosis
    constitutional     --low  
    significantly reduced in the replicative senescence
    tumoral     --over  
    in pancreatic cancer tissues highly correlated with the histological grade
    constitutional     --low  
    in Alzheimer disease
    tumoral     --low  
    in myeloma patients, compared with peripheral blood lymphocytes
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a novel biomarker and target molecule for the diagnosis of pancreatic cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    may be suitable as a therapeutic target
    cancerdigestivepancreas
    target molecule for the treatment of pancreatic cancer
    cancerlung 
    potential therapeutic target of MYC-driven cancer progression in lung cancers
    cancerreproductivebreast
    potential therapeutic target of MYC-driven cancer progression in breast cancers
    ANIMAL & CELL MODELS