Affinage

UNC119

Protein unc-119 homolog A · UniProt Q13432

Length
240 aa
Mass
27.0 kDa
Annotated
2026-04-28
48 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UNC119 is a myristoyl-binding chaperone with an immunoglobulin-like β-sandwich fold that sequesters acylated cargo proteins in a deep hydrophobic pocket, enabling their soluble transport between membrane compartments and regulated delivery to specific destinations including the primary cilium and plasma membrane (PMID:21642972, PMID:22085962, PMID:27481943). Cargo release is driven by ARL3-GTP, which allosterically widens the hydrophobic pocket to accelerate dissociation ~1000-fold; high-affinity ciliary cargoes (transducin Gαt1/Gαt2, NPHP3) are released exclusively by ARL3-GTP, while lower-affinity cargoes such as Src-family kinases can also be released by ARL2-GTP, thereby spatially sorting myristoylated proteins to cilia versus the plasma membrane (PMID:22960633, PMID:27481943, PMID:28740133). UNC119 additionally functions at photoreceptor ribbon synapses—interacting with RIBEYE and facilitating steady-state glutamate release—and in T cells, where it traffics LCK to the immunological synapse and activates Src-family kinases to promote TCR signaling (PMID:18664567, PMID:37175812, PMID:14757743, PMID:39814552). Heterozygous truncating mutations in UNC119 cause late-onset cone-rod dystrophy, and complete loss leads to progressive photoreceptor degeneration with mislocalization of both rod and cone transducin α-subunits (PMID:11006213, PMID:16565359, PMID:41107067).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 Medium

    Establishing UNC-119 as a novel neural gene: its identification in C. elegans revealed that a previously unknown protein is required pan-neuronally for locomotion, feeding, and chemosensation, posing the question of its molecular function.

    Evidence Genetic mapping, transgenic rescue, and lacZ reporter in C. elegans

    PMID:8582641

    Open questions at the time
    • Molecular function completely unknown
    • No vertebrate ortholog characterized
    • Subcellular localization unresolved
  2. 1998 Medium

    Localizing the vertebrate ortholog to photoreceptor synapses narrowed the functional question from generic neural role to a specific site of action in neurotransmission.

    Evidence Immunofluorescence and electron microscopic immunolocalization in human retina

    PMID:9538874

    Open questions at the time
    • No binding partner identified
    • Functional consequence of synaptic localization untested
  3. 2000 High

    Cross-species rescue and disease association established that UNC119 is functionally conserved across metazoans and that its disruption causes cone-rod dystrophy, linking molecular dysfunction to human retinal disease.

    Evidence Transgenic rescue of C. elegans unc-119 with human/Drosophila orthologs; human truncation mutation modeled in transgenic mice causing retinal degeneration with ERG defects

    PMID:10858820 PMID:11006213

    Open questions at the time
    • Mechanism of synaptic dysfunction unknown
    • Direct binding partners at the synapse unidentified
    • Whether the truncation acts as dominant-negative vs. haploinsufficiency unclear
  4. 2001 High

    Demonstrating cell-autonomous suppression of axon branching revealed a post-developmental role for UNC-119 in maintaining neuronal morphology, distinct from its synaptic function.

    Evidence Live imaging of growth cone dynamics and temporally controlled rescue in C. elegans motor neurons

    PMID:11641230

    Open questions at the time
    • Molecular pathway downstream of UNC-119 in axon stabilization unknown
    • Whether this function is conserved in vertebrates untested
  5. 2002 Medium

    Discovery of UNC119 as an activator of Src-family kinases via SH2/SH3 interactions opened a second functional axis—signal transduction—beyond photoreceptor biology.

    Evidence Yeast two-hybrid, co-immunoprecipitation, kinase activity assays with Lyn in eosinophils

    PMID:12496276

    Open questions at the time
    • Structural basis of SFK activation unknown
    • Whether UNC119-SFK interaction is direct in vivo vs. mediated by acylation unclear
  6. 2003 Medium

    Identification of ARL2 as a binding partner, combined with structural homology to PDEδ, first suggested that UNC119 functions as a lipid-binding protein regulated by ARL-family GTPases.

    Evidence Yeast two-hybrid, co-immunoprecipitation, direct binding analysis

    PMID:12527357

    Open questions at the time
    • No structural evidence for lipid binding
    • Functional consequence of ARL2 interaction unknown
    • Single-lab finding
  7. 2004 High

    Essential role in T cell activation was established: UNC119 associates with TCR complex components and is required for Lck/Fyn activation and IL-2 production, demonstrating immune system relevance.

    Evidence Co-IP with CD3/CD4, kinase assays, UNC119-deficient T cells with reconstitution

    PMID:14757743

    Open questions at the time
    • Mechanism of Lck/Fyn activation unresolved—direct kinase activation vs. membrane delivery unclear
    • In vivo immune phenotype not characterized
  8. 2006 High

    Pathogenic mechanism of truncated UNC119 was elucidated (enhanced ARL2 sequestration leading to mitochondrial dysfunction and apoptosis), while separately KO mice revealed a second function in photoreceptor inner/outer segments beyond the synapse.

    Evidence Saturation binding, mitochondrial/apoptotic readouts in transgenic mice; independent KO mouse with ERG and EM analysis

    PMID:16565359 PMID:17174953

    Open questions at the time
    • How UNC119 functions in outer segments mechanistically undefined
    • Whether ARL2 sequestration is the sole disease mechanism for the truncation mutant uncertain
  9. 2008 High

    RIBEYE was identified as a direct synaptic partner, localizing UNC119 to ribbon synapses through its PDEδ-homology domain, providing a molecular basis for its role in glutamate release.

    Evidence Five orthogonal binding assays including mutagenesis of RIBEYE; CaBP4 interaction confirmed separately

    PMID:18296658 PMID:18664567

    Open questions at the time
    • How UNC119-RIBEYE interaction modulates vesicle release unknown
    • Relative contribution of CaBP4 vs. RIBEYE interaction unclear
  10. 2009 Medium

    Two additional molecular activities were uncovered—inhibition of dynamin GTPase activity to regulate endocytosis, and inhibition of Abl kinases—expanding UNC119's role to membrane trafficking and pathogen defense.

    Evidence Co-IP, GTPase assays, endocytosis assays (transferrin/albumin uptake); Abl kinase assays plus in vivo Shigella infection model

    PMID:19381274 PMID:19781630

    Open questions at the time
    • Whether dynamin and Abl interactions occur through the hydrophobic pocket or distinct surfaces unknown
    • Physiological relevance of endocytosis regulation in vivo unestablished
    • Single-lab findings for each
  11. 2011 High

    The core molecular mechanism was solved: crystal structures revealed an immunoglobulin-like β-sandwich with a hydrophobic cavity that buries myristoyl chains, and UNC119 was shown to function as a myristoyl-dependent chaperone for transducin and ciliary G proteins, with ARL3-GTP releasing cargo for ciliary targeting.

    Evidence Crystal structures at 1.95–2.0 Å, ITC, KO mice and C. elegans; parallel identification of myristoylated NPHP3 as cargo released by ARL3-GTP using structure-guided mutagenesis

    PMID:21642972 PMID:21712387 PMID:22085962

    Open questions at the time
    • Full cargo repertoire unknown
    • How cargo specificity for ciliary vs. non-ciliary destinations is encoded at residue level unresolved
  12. 2012 High

    Structural comparison of ARL3-GTP vs. ARL2-GTP complexes with UNC119 explained the ~1000-fold selectivity for ARL3 in cargo release: ARL3's surface-bound amphipathic helix allosterically widens the myristoyl pocket, a mechanism distinct from PDEδ regulation.

    Evidence Crystal structures of ARL3-UNC119 and ARL2-UNC119 complexes plus dissociation kinetics

    PMID:22960633

    Open questions at the time
    • Whether ARL2 contributes to cargo release for low-affinity substrates in cells untested at this point
    • Structural basis for cargo discrimination not yet defined
  13. 2016 High

    A structural code for cargo sorting was defined: residues at +2/+3 positions of the myristoylated peptide determine binding affinity, and high-affinity ciliary cargoes are released exclusively by ARL3-GTP while low-affinity cargoes respond to both ARL2 and ARL3, establishing a biophysical basis for spatial sorting.

    Evidence Crystal structure of myristoylated NPHP3 peptide with UNC119a, ITC affinity measurements, cargo mutagenesis with cellular mislocalization assays

    PMID:27481943

    Open questions at the time
    • Whether additional factors besides affinity contribute to sorting in vivo
    • Complete set of high- vs. low-affinity cargoes not catalogued
  14. 2017 High

    The spatial cycle for non-ciliary cargo was visualized: UNC119 captures Src-family kinases from endomembranes, diffuses as a soluble complex, and delivers them to the plasma membrane via ARL2/3-dependent release at recycling endosomes, maintaining SFK enrichment at the cell surface.

    Evidence Live-cell imaging, FRAP, siRNA, quantitative fluorescence microscopy

    PMID:28740133

    Open questions at the time
    • Whether recycling endosome localization of ARL2/3 is regulated
    • Relative contribution of ARL2 vs. ARL3 at recycling endosomes unresolved
  15. 2023 Medium

    Electrophysiology in heterozygous and KO mice demonstrated that even partial UNC119 loss reduces steady-state glutamate release without affecting photocurrent or synaptic calcium channels, functionally separating its ribbon synapse role from transducin trafficking.

    Evidence Patch-clamp recordings from retinal slices in UNC119 heterozygous and KO mice

    PMID:37175812

    Open questions at the time
    • Molecular mechanism by which UNC119 facilitates vesicle release at the ribbon unresolved
    • Whether the effect is mediated by RIBEYE interaction or another partner untested
  16. 2025 High

    UNC119 was shown to traffic LCK to the immunological synapse (distinct from activating its kinase activity) and to be essential for cone transducin (Gnat2) outer-segment localization; UNC119 deficiency triggers retinal inflammation via JAK-STAT and NF-κB pathways.

    Evidence UNC119 inhibition with live-cell LCK imaging and TCR signaling in T cells; Unc119 KO mice with co-IP, RNA-seq, immunofluorescence, and curcumin rescue for cone degeneration

    PMID:39814552 PMID:41107067

    Open questions at the time
    • Whether inflammatory pathways are a direct consequence of transducin mislocalization or secondary to photoreceptor stress unknown
    • Whether UNC119 trafficking of LCK is mechanistically identical to its SFK plasma-membrane cycle unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the complete inventory of myristoylated UNC119 cargo, the structural basis for UNC119's interactions outside its hydrophobic pocket (dynamin, RIBEYE, KRAS-RASSF6 axis), and whether UNC119's synaptic and ciliary functions can be therapeutically uncoupled.
  • Full myristoylated cargo repertoire uncharacterized
  • No structural model for UNC119-RIBEYE or UNC119-dynamin interaction
  • In vivo immune phenotype of UNC119 deficiency not fully described

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0098772 molecular function regulator activity 5 GO:0044183 protein folding chaperone 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005929 cilium 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-9609507 Protein localization 5 R-HSA-9709957 Sensory Perception 4 R-HSA-112316 Neuronal System 3 R-HSA-168256 Immune System 2
Partners
ARL2ARL3FYNGNAT1GNAT2LCKNPHP3RIBEYE
Complex memberships
UNC119-ARL3-GTP cargo release complexUNC119-RIBEYE synaptic ribbon complexUNC119-transducin complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 unc-119 is expressed throughout the C. elegans nervous system and is required for locomotion, feeding behavior, and chemosensation; the UNC-119 protein is predicted to be a novel protein with no similarity to other known proteins at that time. Genetic mapping, transgenic rescue, reporter gene (unc-119/lacZ fusion), phenotypic characterization Genetics Medium 8582641
1998 HRG4 (UNC119) protein is localized specifically to the synaptic termini of rod and cone photoreceptors in the outer plexiform layer, on presynaptic membranes and cytoplasm, suggesting a function in photoreceptor neurotransmission. Immunofluorescence and electron microscopic immunolocalization, Western blot (retina-specific expression) Investigative ophthalmology & visual science Medium 9538874
2000 The conserved C-terminal domain of human HRG4/UNC119 is functionally required; expression of human or Drosophila UNC119 in C. elegans unc-119 mutants fully rescues the mutant phenotype, establishing functional conservation across metazoans. Transgenic rescue experiments in C. elegans with heterologous UNC119 constructs and domain deletions Journal of neurogenetics Medium 10858820
2000 A heterozygous premature termination mutation in HRG4 (UNC119) causes late-onset cone-rod dystrophy in a patient, and transgenic mice expressing the identical truncation mutation develop age-dependent retinal degeneration with defects consistent with photoreceptor synaptic transmission dysfunction (depressed b-wave, normal c-wave). Transgenic mouse model, ERG, funduscopy, histopathology Investigative ophthalmology & visual science High 11006213
2001 UNC-119 acts cell-autonomously in neurons to suppress axon branching; in unc-119 mutants, motor neuron commissures develop supernumerary branches after development is complete, with secondary growth cones sprouting from existing axons, and this defect can be suppressed by post-embryonic UNC-119 expression. Live imaging of growth cone dynamics, genetic rescue with temporal control, loss-of-function analysis Development (Cambridge, England) High 11641230
2002 UNC119 interacts with Src family tyrosine kinases (Lyn) via SH2 and SH3 domains and activates their catalytic activity; it also associates with the IL-5Rα receptor; UNC119 overexpression prolongs eosinophil survival by increasing Lyn activity. Yeast two-hybrid, co-immunoprecipitation, kinase activity assays, overexpression in eosinophils The Journal of biological chemistry Medium 12496276
2003 HRG4 (UNC119) interacts with ARL2 (ADP-ribosylation factor-like protein 2); the interaction was identified by yeast two-hybrid and confirmed by co-immunoprecipitation and direct binding analysis; residues in HRG4 homologous to those in PDEδ that form the hydrophobic pocket are conserved, suggesting a similar binding mechanism. Yeast two-hybrid, co-immunoprecipitation, direct binding analysis, immunofluorescence co-localization FEBS letters Medium 12527357
2004 UNC119 associates with CD3 and CD4 in T cells, activates Lck and Fyn kinases, and is essential for T cell activation; UNC119-deficient T cells have dramatically reduced Lck/Fyn activity, decreased IL-2 production, and impaired proliferation; reconstitution with UNC119 reverses these defects. Co-immunoprecipitation, kinase activity assays, UNC119-deficient T cells, reconstitution experiments The Journal of experimental medicine High 14757743
2006 The truncated HRG4 mutant protein exhibits approximately 3-fold greater affinity for ARL2 compared to wild-type HRG4, leading to sequestration of ARL2, reduced ANT-1 in photoreceptor synaptic mitochondria, mitochondrial dysfunction, cytochrome c release and caspase 3 activation within photoreceptor synapses, and ultimately apoptosis — establishing a novel synaptic degeneration pathway. Saturation binding analysis, Western blot, immunofluorescence, TUNEL, morphometric analysis in transgenic mouse model Investigative ophthalmology & visual science High 16565359
2006 Knockout of HRG4 (MRG4) in mice causes a slowly progressive retinal degeneration distinct from the transgenic truncation model, with early dysfunction in the distal photoreceptor (inner/outer segments), revealing a second function for UNC119 outside the synapse. Gene targeting/knockout mouse, ERG, Western blot, immunofluorescence, EM, TUNEL Experimental eye research High 17174953
2007 UNC119 activates Fyn kinase and is required for TGF-β/PDGF-induced Fyn phosphorylation; UNC119 overexpression stimulates p38 MAPK (but not JNK), and p38 pathway activity downstream of UNC119 is required for α-SMA induction and myofibroblast differentiation; this mechanism requires Fyn as demonstrated by reconstitution in SYF cells. Co-precipitation, co-localization, kinase activity assays, siRNA knockdown, overexpression in SYF cells and human lung fibroblasts, p38 inhibitor experiments Journal of immunology High 17579091
2008 Munc119/UNC119 is recruited to photoreceptor synaptic ribbons through direct interaction with the RIBEYE protein; the PrBP/delta homology domain of Munc119 is essential for binding to the NADH-binding region of the RIBEYE(B) domain; the RIBEYE-Munc119 interaction is independent of NADH binding. Five independent approaches: yeast two-hybrid, co-immunoprecipitation, direct binding assays, affinity chromatography, point mutant analysis (RE(B)E844Q) The Journal of biological chemistry High 18664567
2008 CaBP4 directly interacts with UNC119 at the photoreceptor synapse; reduction in UNC119 levels is observed in photoreceptor terminals of CaBP4-knockout mice, suggesting a functional relationship for neurotransmitter release. Affinity chromatography, yeast two-hybrid, co-immunoprecipitation, gel overlay assay, immunohistochemistry in CaBP4-KO mice Investigative ophthalmology & visual science Medium 18296658
2009 UNC119 interacts with dynamin and inhibits its GTPase activity; binding of UNC119 to dynamin decreases its association with amphiphysin; UNC119 overexpression inhibits clathrin- and caveolae-based endocytosis, while depletion increases endocytosis. Co-immunoprecipitation, GTPase activity assay, endocytosis assays (transferrin, FM4-64, albumin uptake), overexpression/knockdown Cellular signalling Medium 19781630
2009 UNC119 interacts with Abl family kinases and inhibits their kinase activity, thereby inhibiting Crk phosphorylation and reducing Shigella cell invasion; UNC119 co-localizes with Crk and Shigella in infected cells. Co-immunoprecipitation, kinase activity assays, siRNA knockdown, in vivo mouse model of shigellosis PloS one Medium 19381274
2011 UNC119 recognizes and tightly binds the acylated (myristoylated/lauroylated) N-terminus of the rod transducin α subunit (Gαt1) and C. elegans G proteins ODR-3 and GPA-13; the crystal structure of human UNC119 at 1.95 Å reveals an immunoglobulin-like β-sandwich fold with a hydrophobic cavity that buries the lipid chain; co-crystal structure with acylated Tα peptide at 2.0 Å shows the lipid buried deeply in the cavity; UNC119 binding to Tα-GTP inhibits GTPase activity, stabilizing a diffusible UNC119-Tα-GTP complex; UNC119 deletion causes G protein mislocalization in mouse and C. elegans. Crystal structure (1.95 Å and 2.0 Å co-crystal), isothermal titration calorimetry, pulldowns, UNC119 knockout mouse and C. elegans Nature neuroscience High 21642972
2011 Human UNC119 (HRG4) interaction with transducin (Gαt1) requires N-acylation but not the GTP-bound form; UNC119 binds myristoylated Gαt1 with much higher affinity than prenylated substrates; UNC119 can interact with Gαt1-GDP and heterotrimeric transducin, displacing Gβ1γ1 and facilitating solubilization of transducin from rod outer segment membranes; UNC119 inhibits rhodopsin-dependent Gt activation and inhibits Go activation by D2 dopamine receptor in cultured cells. Pulldown assays, GTPase activity assays, membrane solubilization assay, cell-based GPCR activation assay The Journal of biological chemistry High 21712387
2011 UNC119 (specifically UNC119b) functions as a chaperone for myristoylated NPHP3, binding NPHP3 via its N-terminal 200 residues in a myristoylation-dependent manner; ARL3-GTP releases myristoylated cargo from UNC119b; ARL3, UNC119b, and the ARL3 GAP RP2 are all required for NPHP3 ciliary targeting; UNC119b myristoyl-binding activity is required for this targeting; conserved phenylalanines in a hydrophobic β-sandwich are essential for myristate binding. Proteomic approach, co-immunoprecipitation, directed mutagenesis of predicted structural residues, UNC119b knockdown in IMCD3 cells, C. elegans genetics Genes & development High 22085962
2012 Crystal structures of Arl3 and Arl2 in complex with UNC119a show both bind with similar affinities, but only Arl3-GTP allosterically displaces myristoylated cargo by accelerating release by ~1000-fold; this is due to the N-terminal amphipathic helix of Arl3·GppNHp remaining surface-bound and inducing widening of the myristoyl binding pocket, opposite to the PDEδ mechanism. Crystal structures of Arl3/Arl2 complexes with UNC119a, dissociation kinetics, affinity measurements The EMBO journal High 22960633
2016 Myristoylated ciliary cargo peptides (GNAT1, NPHP3, Cystin1) bind UNC119a and UNC119b with subnanomolar affinities, while non-ciliary Src peptide has low affinity; high-affinity cargo is exclusively released by Arl3·GppNHp but not Arl2; low-affinity cargo is released by both; crystal structure of myristoylated NPHP3 peptide with UNC119a identifies residues at +2/+3 positions as determinants of binding affinity; swapping these residues reverses affinities and causes mislocalization. X-ray crystal structure, ITC/affinity measurements, mutagenesis of cargo peptides, cellular localization assays The Journal of biological chemistry High 27481943
2017 UNC119 sequesters myristoylated Src family kinases (SFKs) from the cytoplasm, forming a soluble complex that enables diffusion to the recycling endosome, where localized Arl2/3 activity releases SFKs; this spatial cycle maintains SFK enrichment at the plasma membrane; UNC119 knockdown disrupts SFK plasma membrane localization and signaling activity. Live-cell imaging, FRAP, siRNA knockdown, quantitative fluorescence microscopy, biochemical fractionation Nature communications High 28740133
2017 Squarunkin A, a small-molecule inhibitor, selectively inhibits UNC119A binding to a myristoylated Src N-terminal peptide with IC50 ~10 nM, binds UNC119 proteins in cell lysate, and interferes with Src kinase activation, demonstrating the druggability of the UNC119-cargo interaction. Biochemical binding assay (IC50 determination), cell lysate binding, Src kinase activity assay Angewandte Chemie (International ed. in English) Medium 28471079
2018 UNC119 (UNC119A) interacts with RASSF6 tumor suppressor, promotes RASSF6-MDM2 interaction, and stabilizes p53, inducing apoptosis; UNC119 depletion impairs DNA repair after damage and results in polyploid cell generation. Immunoprecipitation, RNAi knockdown, cell biology assays (apoptosis, DNA damage repair, ploidy) Cancer science Low 29931788
2019 UNC119a plays a role in cytokinesis; lipidated stapled peptides derived from the Gnat1 UNC119-binding region bind UNC119a and induce accumulation of cytokinetic and binucleated cells upon cell treatment. Hydrocarbon peptide-stapling, cell-based assays (cytokinesis phenotype), binding assays Chembiochem Low 31680402
2020 UNC119A interacts with the active form of KRAS (requiring C-terminal KRAS modification but not the hydrophobic pocket of UNC119A), promotes KRAS-RASSF6 interaction, enhances RASSF6-MDM2 binding, and induces apoptosis; UNC119A silencing promotes soft-agar colony formation, migration, and invasiveness in KRAS-mutated cancer cells. Immunoprecipitation, RNAi gene silencing, quantitative RT-PCR, soft-agar colony formation assay, migration/invasion assays The Journal of biological chemistry Low 32554467
2023 UNC119 deletion from even one allele reduces steady-state glutamate release at rod synapses (depolarizes bipolar cell membrane potential, decreases sensitivity, accelerates response decay), without affecting rod outer segment photocurrent or voltage dependence of synaptic Ca current; this effect persists after transducin translocation, implicating an interaction with RIBEYE or other synaptic proteins rather than CaBP4 or calcium channels. Patch-clamp recordings from retinal slices in UNC119 heterozygous and knockout mice, background light adaptation experiments International journal of molecular sciences Medium 37175812
2025 UNC119 traffics LCK to the immunological synapse in T cells; inhibiting UNC119 reduces LCK localization at the synapse without impairing LCK phosphorylation, thereby reducing TCR signal transduction; UNC119 is also required to sustain proliferation in T-ALL cells. UNC119 inhibition, live-cell imaging of LCK localization, TCR signaling assays, cytotoxicity assays, T-ALL cell proliferation assays Life science alliance Medium 39814552
2025 UNC119 interacts with Gnat2 (cone transducin α-subunit) in cone photoreceptors and is essential for Gnat2 translocation to the outer segment; UNC119 deficiency leads to activation of JAK-STAT and NF-κB inflammatory pathways in the retina; a human CRD-associated UNC119 mutant competitively inhibits UNC119 interaction with both GNAT1 and GNAT2; curcumin treatment targeting these inflammatory pathways suppresses cone degeneration in Unc119-KO mice. Unc119 knockout mouse, co-immunoprecipitation, RNA-seq, immunofluorescence for Gnat2 localization, curcumin treatment experiment The Journal of neuroscience High 41107067

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system. Genetics 388 8582641
2014 C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta neuropathologica 260 25120191
2011 An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes & development 188 22085962
2011 UNC119 is required for G protein trafficking in sensory neurons. Nature neuroscience 146 21642972
2000 HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model. Investigative ophthalmology & visual science 102 11006213
2012 Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119. The EMBO journal 92 22960633
2004 Unc119, a novel activator of Lck/Fyn, is essential for T cell activation. The Journal of experimental medicine 75 14757743
1996 Conservation of function and expression of unc-119 from two Caenorhabditis species despite divergence of non-coding DNA. Gene 65 8996090
2012 Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins. Vision research 57 23000199
2001 UNC-119 suppresses axon branching in C. elegans. Development (Cambridge, England) 55 11641230
2008 RIBEYE recruits Munc119, a mammalian ortholog of the Caenorhabditis elegans protein unc119, to synaptic ribbons of photoreceptor synapses. The Journal of biological chemistry 54 18664567
2002 Identification of UNC119 as a novel activator of SRC-type tyrosine kinases. The Journal of biological chemistry 51 12496276
2003 Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain. FEBS letters 44 12527357
1998 Localization of HRG4, a photoreceptor protein homologous to Unc-119, in ribbon synapse. Investigative ophthalmology & visual science 44 9538874
2016 Novel Biochemical and Structural Insights into the Interaction of Myristoylated Cargo with Unc119 Protein and Their Release by Arl2/3. The Journal of biological chemistry 41 27481943
2000 The UNC-119 family of neural proteins is functionally conserved between humans, Drosophila and C. elegans. Journal of neurogenetics 40 10858820
2008 Interaction and colocalization of CaBP4 and Unc119 (MRG4) in photoreceptors. Investigative ophthalmology & visual science 38 18296658
2006 Targeted inactivation of synaptic HRG4 (UNC119) causes dysfunction in the distal photoreceptor and slow retinal degeneration, revealing a new function. Experimental eye research 37 17174953
2011 Interaction of transducin with uncoordinated 119 protein (UNC119): implications for the model of transducin trafficking in rod photoreceptors. The Journal of biological chemistry 34 21712387
1998 Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors. Investigative ophthalmology & visual science 34 9761287
2007 Unc119 regulates myofibroblast differentiation through the activation of Fyn and the p38 MAPK pathway. Journal of immunology (Baltimore, Md. : 1950) 28 17579091
2004 unc-119 homolog required for normal development of the zebrafish nervous system. Genesis (New York, N.Y. : 2000) 26 15593328
1999 Characterization of the gene for HRG4 (UNC119), a novel photoreceptor synaptic protein homologous to unc-119. Genomics 22 10329014
2017 Spatial cycles mediated by UNC119 solubilisation maintain Src family kinases plasma membrane localisation. Nature communications 21 28740133
2015 Somatic expression of unc-54 and vha-6 mRNAs declines but not pan-neuronal rgef-1 and unc-119 expression in aging Caenorhabditis elegans. Scientific reports 16 26031360
2002 Changes in retinal synaptic proteins in the transgenic model expressing a mutant HRG4 (UNC119). Investigative ophthalmology & visual science 16 11818371
2017 Small-Molecule Inhibition of the UNC119-Cargo Interaction. Angewandte Chemie (International ed. in English) 15 28471079
2009 UNC119 inhibits dynamin and dynamin-dependent endocytic processes. Cellular signalling 15 19781630
2006 Truncation mutation in HRG4 (UNC119) leads to mitochondrial ANT-1-mediated photoreceptor synaptic and retinal degeneration by apoptosis. Investigative ophthalmology & visual science 13 16565359
2009 Unc119 protects from Shigella infection by inhibiting the Abl family kinases. PloS one 12 19381274
2012 Consequences of a mutation in the UNC119 gene for T cell function in idiopathic CD4 lymphopenia. Current allergy and asthma reports 11 22729960
2019 Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 10 31679307
2006 NgUNC-119, Naegleria homologue of UNC-119, localizes to the flagellar rootlet. Gene 10 17123749
2019 Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119. Chembiochem : a European journal of chemical biology 8 31680402
2018 Photoactivatable Myristic Acid Probes for UNC119-Cargo Interactions. Chembiochem : a European journal of chemical biology 7 30129686
2024 Streamlined single shot safe harbor transgene integration in C. elegans using unc-119 rescue. microPublication biology 5 38872845
2018 UNC119 promoted cell growth and migration by Wnt/β-catenin signal and TGF-β/EMT signal pathway in hepatocellular carcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 5 30610799
2016 UNC119 mediates gambogic acid-induced cell-cycle dysregulation through the Gsk3β/β-catenin pathway in hepatocellular carcinoma cells. Anti-cancer drugs 5 27669172
2005 Novel Caenorhabditis elegans unc-119 axon outgrowth defects correlate with behavioral phenotypes that are partially rescued by nonneural unc-119. Genesis (New York, N.Y. : 2000) 5 15892079
2020 The RAS-interacting chaperone UNC119 drives the RASSF6-MDM2-p53 axis and antagonizes RAS-mediated malignant transformation. The Journal of biological chemistry 4 32554467
2018 UNC119 is a binding partner of tumor suppressor Ras-association domain family 6 and induces apoptosis and cell cycle arrest by MDM2 and p53. Cancer science 4 29931788
2014 Unc119 gene deletion partially rescues the GRK1 transport defect of Pde6d (- /-) cones. Advances in experimental medicine and biology 4 24664735
2018 UNC119 promotes the growth and migration of hepatocellular carcinoma via Wnt/β-catenin and TGF-β/EMT signaling pathways. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 3 29552781
2023 A Novel Role for UNC119 as an Enhancer of Synaptic Transmission. International journal of molecular sciences 2 37175812
2025 UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life science alliance 1 39814552
2025 Dysfunction of Unc119, a Transducin-Binding Protein, Leads to Cone-Rod Dystrophy through Activating JAK-Stat and NF-κB Inflammatory Pathways in the Mouse Retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 41107067
2019 Evolution and expression of the zebrafish unc119 paralogues indicates a conserved role in cilia. Gene expression patterns : GEP 0 31055152
2018 UNC119 promotes the growth and migration of hepatocellular carcinoma via Wnt/β/catenin and TGF/β-EMT signaling pathways. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 0 29552782