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FLASH GENE
Symbol UNC119 contributors: mct/shn - updated : 31-08-2017
HGNC name unc-119 homolog (C. elegans)
HGNC id 12565
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • rich in glycine and proline and in its proximal part
  • C-terminal domain of UNC119 sharing significant sequence and structural homology with PDE6D
    • HOMOLOGY
    interspecies homolog to C.elegans Unc119
    ortholog to Unc119, Mus musculus
    ortholog to Unc119, Rattus norvegicus
    ortholog to UNC119, pan troglodytes
    intraspecies paralog to PDE6D
    Homologene
    FAMILY
  • PDE6D/UNC119 family
    • CATEGORY adaptor , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    text
  • expressed at high levels in photoreceptor ribbon synapses
  • CABP4 and UNC119 colocalized in the photoreceptor synapse of adult retina and during postnatal retinal development
  • localizes to the centrosome in interphase cells and begins to translocate from the spindle pole to the spindle midzone after the onset of mitosis
    • basic FUNCTION
  • receptor-associated activator of Src family tyrosine kinases
  • involved in the mechanism of photoreceptor neurotransmitter release through the synaptic vesicle cycle
  • role for UNC119 and CABP4 in neurotransmitter release and in the maintenance of the photoreceptor synapse
  • essential for vision and synaptic transmission at photoreceptor ribbon synapses
  • regulates myofibroblast differentiation through the activation of FYN and the MAPK14 pathway
  • orchestrates the recruitment of the actin-based motor protein, myosin 5B, and the organization of multiprotein complexes on endosomes
  • UNC119-regulated pathway is essential for immunological synapse formation and T cell activation
  • adaptor protein that is involved in the development of the vertebrate nervous system
  • role in clathrin- and caveolae-based endocytosis as well as macropinocytosis
  • regulates various endocytic pathways through dynamin and sets a threshold point for vesicular trafficking
  • playing an important role in fibrotic processes through myofibroblast differentiation
  • adapter signaling molecule, which regulates activation of tyrosine kinases in T cells, eosinophils and fibroblasts
  • activates the Src family and inhibits the Abl family of tyrosine kinases
  • essential for transducin transport in darkness
  • a G-alpha subunit cofactor essential for G protein trafficking in sensory cilia
  • may play conserved inhibitory role in regulation of GPCR-G protein signaling in non-visual tissues
  • in addition to transducin trafficking, may play important roles in regulation of vesicle and ciliary trafficking processes in photoreceptor cells
  • apart from its role as a cofactor of G-protein trafficking in ciliary sensory cells, may modulate signal transduction from GPCRs to G proteins in different cell types and tissues
  • UNC119/HRG4 is responsible for ciliary delivery of myristoylated cargo
  • promotes cell proliferation and growth through Wnt/CTNNB1 signaling
  • solubilising factor UNC119 sequesters myristoylated Src family protein tyrosine kinases (SFKs) to maintain its enrichment at the plasma membrane to enable signal transduction
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text
  • may play an important role in vision
    • PATHWAY
    metabolism
    signaling neurotransmission
    synaptic transmission
    a component
  • synaptic ribbon-associated component
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IL-5Ralpha and Src family tyrosine kinases
  • ADP-ribosylation factor-like protein 2, ARL2
  • interaction of CABP4 with UNC119
  • CTBP2-interacting protein at photoreceptor ribbon synapses (can be recruited to synaptic ribbons via its interaction with CTBP2)
  • interacts with dynamin, a key effector molecule of many endocytic processes (inhibits the GTPase activity of dynamin)
  • through inhibition of Abl kinases, dampens IFNG production
  • acylated G-alpha peptides, acylated Talpha N-terminal peptide, Talpha-GTP
  • interaction with transducin is dependent on the N-acylation, but does not require the GTP-bound form of GNAT1
  • bound the myristoylated N terminus of GNAT1 with much higher affinity than a prenylated substrate, and inhibit the GTPase activity of GNAT1
  • may inhibit GPCR-dependent activation of the Gi family G proteins
  • although ARL3 and ARL2 bind UNC119 with similar affinities, only ARL3 allosterically displaces cargo by accelerating its release by three orders of magnitude
  • as a dominant partner, GNAT1 may potentially modulate the function of other known UNC119-interacting proteins involved in photoreceptor ciliary trafficking and synaptic regulation, in a light-dependent manner
  • UNC119 interacts with a Src family kinase, FYN and is required for the activation of this kinase
  • plays a key role in the FYN signal transduction pathway, which regulates the completion of cytokinesis via RAB11A
  • in photoreceptors, ARL2 and ARL3 participate in the trafficking of lipidated membrane-associated proteins and colocalize in the inner segment with UNC119 and PDE6D
  • GNAT1, NPHP3, and PKD1 bind with high affinity to UNC119 whereas a peptide derived from a non-ciliary localizing protein (SRC) has low affinity
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD13
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    late onset cone rod dystrophy in a female heterozygous for a premature termination codon mutation
    constitutional     --other  
    enhanced in CD4 T cells from patients with asthma
    tumoral     --over  
    in hepatocellular carcinoma (HCC) tissues
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • a strong candidate gene for retinal diseases (
    • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • transgenic mice carrying a premature termination codon mutation developed age-dependent fundus lesions with electroretinographic changes consistent with defects in photoreceptor synaptic transmission , and retinal degeneration (
  • reduction in proteins associated with synaptic vesicles and a possible compensatory increase in proteins involved in docking-exocytosis and endocytosis were observed in both the outer and inner plexiform layers of the retina of the transgenic HRG4 mouse model (
  • deletion of UNC119 gene in both mouse and C. elegans led to G protein mislocalization (