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FLASH GENE
Symbol MAPK8IP3 contributors: mct/ - updated : 25-03-2019
HGNC name mitogen-activated protein kinase 8 interacting protein 3
HGNC id 6884
Corresponding disease
IDVBA intellectual disability with variable brain anomalies
Location 16p13.3      Physical location : 1.756.220 - 1.820.317
Synonym name
  • JNK/stress-activated protein kinase-associated protein 1
  • JNK interacting protein 3
  • homolog of Drosophila Sunday driver 2
  • C-jun-amino-terminal kinase interacting protein 3
  • c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1
  • homolog of Drosophila Sunday driver 2
  • Synonym symbol(s) FLJ00027, SYD2, KIAA1066, JSAP1, JIP3, JIP-3, syd
    DNA
    TYPE functioning gene
    STRUCTURE 64.10 kb     32 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
    31 - 5635 - 1330 - 2000 11024282
    also called variant 2 or JSAP1A
    - splicing - - - - 2000 11024282
    also called JSAP1B
    - splicing - - 1373 - 2000 11024282
    also called JSAP1C
    - splicing - - 1373 - 2000 11024282
    also called JSAP1D
    32 - 5653 - 1336 - 2000 11024282
    also called variant 1
    32 - 5693 - 1332 - 2000 11024282
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Mus musculusAdult
     nervecranial nerve  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text developing brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal JNB binding domain containing two coiled-coil region which mediate interactions with adapter proteins at the presynaptic active zone
  • a leucine zipper
  • a C terminal region containing a conserved hydrophobic core, myosin tail and three SAM domains in the C terminus, which bind proteins such as LAR receptor tyrosine phosphatase
  • HOMOLOGY
    interspecies homolog to murine Jna/Sapk associated protein 1
    ortholog to C.elegans UNC-16
    Homologene
    FAMILY
  • ezrin/radixin/moesin family
  • Liprin-alphafamily
  • family of scaffold factors for the mitogen-activated protein kinase
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nuclear envelope
    text growth cones of developing neurites
    basic FUNCTION
  • regulator of JNK-signaling pathway
  • mediating the axonal transport of at least I class of vesicles by interacting directly with kinesin light chain
  • involved in the neuronal apoptosis following cerebral ischemia and hypoxia(critical component of the stress -induced JNK signaling and neuronal apoptosis)
  • cooperative scaffold for activation of JNK and regulation of cell migration in response to fibronectin (FN) stimulation
  • functions as a scaffold protein for JNK cascade molecules to efficiently activate JNKs
  • having a KIF1A-dependent adaptor function that appears to connect the KIF1A motor to KIF1A1 cargoes that are carried on or within small transport vesicles
  • may be important for the differentiation of the mesodermal lineages, functioning as a positive factor for cardiomyocyte differentiation, and as an inhibitory factor for differentiation into other lineages
  • antagonizes the mitogenic effect of SHH on cerebellar granule cell precursors and promotes their exit from the cell cycle and differentiation, by modulating JNK activity
  • crucial for the regulation of neurite morphogenesis as a downstream effector of ARF6
  • positive regulator of kinesin activity and motility
  • role for MAPK8IP3-mediated NTRK2 anterograde axonal transport in recruiting more NTRK2 into distal axons and facilitating BDNF-induced retrograde signaling and synapse modulation
  • acts together with a GAP protein SPAG9 to promote presynaptic assembly
  • is necessary for the retrograde transport of two distinct cargos, active JNK and lysosomes
  • MAPK8IP3 promotes axon elongation in a kinesin- and JNK-dependent manner
  • MAPK8IP3 and SPAG9 are critical and functionally redundant in cytokinesis and control ARF6 localization to the midbody by forming a tripartite complex of MAPK8IP3/SPAG9, active ARF6, and kinesin-1
  • MAPK8IP3, SPAG9 are positive regulators of kinesin-1-dependent axonal transport, which prevents neuronal degeneration
  • MAPK8IP3 regulation of kinesin-1 motility is critical for axon elongation and regeneration
  • SPAG9 and MAPK8IP3 play critical roles in kinesin-1-dependent axonal transport, which prevents brain neuronal degeneration
  • important regulator of axonal lysosome transport and maturation
  • critical role of MAPK8IP3-dependent axonal lysosome transport in regulating amyloidogenic amyloid precursor protein processing
  • part of the axonal transport machinery, which is essential for the function and maintenance of neurons
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • MAZPK8IP3/PTK2 complex functions cooperatively as a scaffold for the JNK signaling pathway and regulator of cell migration on fibronectin, and is also associated with malignancy in brain tumors
  • ARF6/MAPK8IP3 signaling regulates neurite morphogenesis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MKK7
  • links vesicular axonal transport to injury signaling
  • binds directly to NTRK2, via a minimal 12 AA domain in the NTRK2 juxtamembrane region, and links NTRK2 to kinesin-1
  • MAPK8IP3, SPAG9 which might be paralogous to each other, are critical and functionally redundant in cytokinesis and control ARF6 localization to the midbody by forming a tripartite complex of MAPK8IP3/SPAG9, active ARF6, and kinesin-1
  • MAPK8IP3 binding to kinesin heavy chains (KHC), but not kinesin light chains (KLC), is essential for axon elongation in hippocampal neurons as well as axon regeneration in sensory neurons
  • MAPK8IP3 regulates cortical neuronal migration by mediating NTRK2 axonal anterograde transport during brain development
  • MAPK8IP1, MAPK8IP3 cooperate to mediate NTRK2 anterograde axonal transport
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IDVBA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    enhanced phosphorylation and kinase activation of JNK and reduced the inhibitory effect of cyclic MS (mechanical strain)
    constitutional     --over  
    in human hearts with hypertrophic cardiomyopathy (HCM)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascular  
    blockage of MAPK8IP3 could alleviate cardiac hypertrophy via inactivating JNK pathway, and thus might be a promising strategy to prevent pathological cardiac hypertrophy
    ANIMAL & CELL MODELS