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FLASH GENE
Symbol RANBP9 contributors: mct - updated : 06-12-2014
HGNC name RAN binding protein 9
HGNC id 13727
Location 6p23      Physical location : 13.621.730 - 13.711.796
Synonym name
  • RAN binding protein, centrosomal
  • Ran Binding Protein in the Microtubule-Organizing Center
  • novel centrosomal protein RanBPM
  • Synonym symbol(s) RANBPM, BPM-L, BPM90, RanBP7
    DNA
    TYPE functioning gene
    STRUCTURE 90.07 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 3132 90 729 - 2009 19251705
    also called RANBP9-IL
    - - - 90 - - Nishitani 11470507
  • also called isoform RANBP9-T
  • truncated
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Hearing/Equilibriumear   highly
    Lymphoid/Immunelymph node   highly
    Reproductivemale systemtestis  highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Reproductivespermatocyte
    Reproductivespermatogonia
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal PQ-rich region and half containing SPRY-LisH domains not only interacted with LRP but also with APP and BACE1 , involved in protein-protein interactions
  • a CRA domain
  • a CTLH motif (C-terminal to LisH), and the LISH/CTLH domain is involved in dimerization
  • protein-interaction motifs
  • the MOR domain corresponds to almost entire SPRY domain, necessary for binding of YPEL5
  • a cytoskeletal-binding domain
  • multiple canonical docking sites for signaling intermediates
  • conjugated PhosphoP
    HOMOLOGY
    Homologene
    FAMILY
  • Scorpin family
  • CATEGORY chaperone/stress , structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • region surrounding the centrosome
  • in the neurons, RANBP9 is localized mostly in the cytoplasm but also in the neurites and dendritic processes
  • basic FUNCTION
  • RAN stimulated microtubule assembly
  • RanGTP-binding protein required for correct nucleation of microtubules
  • acting as a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system
  • is a scaffolding protein implicated in a variety of functions through integration of cell surface receptors with intracellular signaling targets
  • crucial role for RANBP9 in mammalian gametogenesis in both genders
  • RANBP9 participates in gene transcription by binding to TRAF6
  • role of RANBP9 in integrin-dependent focal adhesion signaling and assembly
  • acts as a negative regulator of LTB4R2 signaling to attenuate LTB4R2-mediated cell motility
  • role for RANBP9 in the regulation of LT4BR2 should contribute to a better understanding of the regulatory mechanisms of LT4BR2-mediated cellular phenotypes, including chemotactic motility
  • retards the anterograde axonal transport of mitochondria in primary neurons and decreases synaptic mitochondrial activity in brain
  • multi-domain scaffolding protein known to integrate extracellular signaling with intracellular target
  • RANBP9 promotes aggresome formation through an association with HDAC6
  • modulates APP intracellular domain (AICD) localization and transcriptional activity via direct interaction with KAT5
  • dispensable for Sertoli cell development and functions, but critical for male germ cell development and male fertility
  • role of RANBP9 in regulating alternative splicing in spermatogenic cells, which is critical for normal spermatogenesis and male fertility
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of a large complex of more than 670kDa
  • complexing with MKLN1 (role for muskelin-RANBP9 complex in pathways that integrate cell morphology regulation and nucleocytoplasmic communication)
  • RANBP9/TP73 complex implicated in mitochondria-mediated apoptosis in addition to its role in enhancing APP generation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding RAN
  • associated with USP11 in the nucleus (is the enzymic substrate for USP11 and is deubiquitinated specifically)
  • interacting with the integrin LFA-1
  • interaction between SPAG8 and RANBP9 may be involved in the process of male germ cell differentiation
  • ADAP1 and RANBP9 were shown to be involved in dendritic differentiation and RANBP9 could potentially act as a modulator together with ADAP1 in synaptic plasticity
  • interacting with CDK11, Met protooncogene, HIPK2, RAF1
  • interaction with FMR1 in a CRA motif present in the RanBPM C terminus (modulation of the RNA-binding properties of FMR1)
  • interaction with MKLN1
  • interacting with MKLN1 (subcellular localization of MKLN1 is coregulated by its C terminus, which provides a cytoplasmic restraint and also controls the interaction of muskelin with RANBP9)
  • strongly increased BACE1 cleavage of APP and Abeta generation
  • RANBP9 may modulate NTRK2-mediated downstream signaling and biological functions
  • YPEL5-binding protein
  • RANBP9 and TP73 have cooperative roles in inducing cell death, and the RANBP9/TP73 complex is implicated in mitochondria-mediated apoptosis in addition to its role in enhancing APP generation
  • RANBP9 appears to control brain growth and development through signaling mechanisms involving MAPK3 and L1CAM receptor
  • COPS5 is a RANBP9-interacting protein that robustly increases APP generation
  • acts as a negative regulator of LTB4R2
  • RANBP9 was found to interact with HDAC6 and to inhibit its deacetylase activity
  • RANBP9-KAT5 interaction dramatically relocated RANBP9 from a widespread cellular distribution to nuclear speckles
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    its overexpression reduces dendritic arbor and spine density
    constitutional     --over  
    in brains of patients with Alzheimer disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target promising therapeutic target for Alzheimer disease (therapeutic strategy might be to reduce RanBP9 levels and/or specifically disrupt its interactions with APP, LRP, and/or BACE1)
    ANIMAL & CELL MODELS
  • most of Ran-/- mice die neonatally due to defects in the brain growth and development