Affinage

UNC119

Protein unc-119 homolog A · UniProt Q13432

Length
240 aa
Mass
27.0 kDa
Annotated
2026-06-10
48 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UNC119 is a lipid-binding chaperone that solubilizes N-terminally acylated proteins and delivers them to specific membrane compartments, a role conserved from C. elegans neurons to the mammalian photoreceptor and immune system (PMID:8582641, PMID:21642972). Its immunoglobulin-like β-sandwich fold forms a hydrophobic cavity that buries the myristoyl (or lauroyl) chain of cargo such as transducin α (Gαt1/GNAT1), the cone transducin Gnat2, NPHP3, and Src-family kinases, shielding the lipid from membranes and enabling cytoplasmic diffusion; binding depends on N-acylation and on +2/+3 residue identity that tunes affinity from subnanomolar (ciliary cargo) to micromolar (Src) (PMID:21642972, PMID:21712387, PMID:27481943). Cargo is released by an Arl3-GTP–driven allosteric switch: although both Arl2 and Arl3 bind UNC119, only Arl3·GTP retains its N-terminal amphipathic helix surface-bound and widens the myristoyl pocket to accelerate cargo release by orders of magnitude, with high-affinity cargo released exclusively by Arl3 and low-affinity cargo by either GTPase (PMID:22960633, PMID:27481943). This release occurs at the cilium, where UNC119b together with Arl3 and the Arl3-GAP RP2 forms a GTPase cycle that targets myristoylated NPHP3, and at the recycling endosome, where Arl2/3 activity liberates Src-family kinases for vesicular delivery to the plasma membrane (PMID:22085962, PMID:28740133). In photoreceptors UNC119 governs light-driven transducin solubilization and translocation of Gαt1 and Gnat2 to the outer segment, and is independently recruited to the ribbon synapse by direct interaction with the RIBEYE(B) domain and stabilized by CaBP4, where it facilitates glutamate release (PMID:21712387, PMID:18664567, PMID:18296658, PMID:37175812, PMID:41107067). In immune cells UNC119 binds and activates Lck, Fyn, Lyn, and Abl kinases and traffics LCK to the immunological synapse to sustain TCR signaling and T cell proliferation (PMID:12496276, PMID:14757743, PMID:39814552). Beyond cargo chaperoning, UNC119 directly inhibits dynamin GTPase activity to restrain endocytosis (PMID:19781630), and interacts with active KRAS and RASSF6 to stabilize p53 and promote apoptosis through a pocket-independent surface (PMID:29931788, PMID:32554467). Premature-termination mutations in UNC119 cause cone-rod dystrophy, and Unc119-deficient mice develop progressive retinal degeneration with JAK-STAT and NF-κB inflammatory activation (PMID:11006213, PMID:41107067).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 Medium

    Established that unc-119 is a nervous-system gene required for behavior, anchoring its biology to neurons before any molecular function was known.

    Evidence unc-119/lacZ reporter, genomic rescue, and null-allele phenotyping in C. elegans

    PMID:8582641

    Open questions at the time
    • No molecular activity defined
    • Cell type of action within the nervous system not resolved at this stage
  2. 1998 Medium

    Localized the mammalian ortholog (HRG4) to photoreceptor ribbon synapses, the first link to retinal neurotransmission.

    Evidence Immunofluorescence and EM localization plus Western blot in human and rat retina

    PMID:9538874

    Open questions at the time
    • No functional manipulation
    • Synaptic mechanism not defined
  3. 2000 Medium

    Defined the conserved C-terminal domain as the functional unit and tied a human truncation mutation to cone-rod dystrophy with a synaptic transmission defect, providing the first disease connection.

    Evidence Cross-species domain-truncation rescue in C. elegans; patient mutation screen with transgenic mouse ERG/histopathology

    PMID:10858820 PMID:11006213

    Open questions at the time
    • Biochemical basis of the domain function unknown
    • Dominant mechanism of the truncation not yet explained
  4. 2003 Medium

    Identified ARL2 as a direct binding partner via a PDE-delta-homologous domain, first connecting UNC119 to an Arf-like GTPase.

    Evidence Yeast two-hybrid, co-IP, direct binding, and retinal colocalization

    PMID:12527357

    Open questions at the time
    • Functional consequence of ARL2 binding undefined
    • Arl2 vs Arl3 specificity not addressed
  5. 2004 Medium

    Revealed an immune function: UNC119 activates Src-family kinases (Lck/Fyn) downstream of CD3/CD4 to drive T cell IL-2 production and proliferation, extending its role beyond the retina.

    Evidence Reciprocal co-IP, kinase assays, and genetic reconstitution in UNC119-deficient T cells (building on IL-5Rα/Lyn work in eosinophils)

    PMID:12496276 PMID:14757743

    Open questions at the time
    • Mechanism of kinase activation unclear
    • Relationship to lipid-binding pocket not yet known
  6. 2006 Medium

    Explained dominant retinal disease by showing the truncated mutant binds ARL2 with higher affinity, sequestering it and triggering mitochondrial-dependent synaptic apoptosis, while knockout revealed a separate distal photoreceptor role.

    Evidence Saturation binding affinity, TUNEL/morphometry in transgenic mice, and gene-targeted knockout with ERG/histology

    PMID:16565359 PMID:17174953

    Open questions at the time
    • Molecular cargo at distal vs synaptic compartments not identified
    • Direct vs indirect role in apoptosis unresolved
  7. 2008 High

    Defined how UNC119 is targeted to the ribbon synapse, through direct PrBP/delta-domain binding to RIBEYE(B) and stabilization by CaBP4.

    Evidence Five orthogonal binding methods with RIBEYE point mutagenesis; affinity/Y2H/co-IP plus CaBP4-KO retina analysis

    PMID:18296658 PMID:18664567

    Open questions at the time
    • How synaptic recruitment relates to the cargo-chaperone activity unclear
    • Functional output of synaptic UNC119 not yet measured
  8. 2009 Medium

    Broadened the kinase/trafficking repertoire by showing UNC119 inhibits dynamin GTPase to restrain endocytosis and inhibits Abl kinases to limit bacterial invasion.

    Evidence Co-IP, GTPase and kinase assays, multi-cargo uptake assays, and an in vivo shigellosis mouse model

    PMID:19381274 PMID:19781630

    Open questions at the time
    • Structural basis of dynamin/Abl inhibition unknown
    • Whether these activities share the lipid pocket undefined
  9. 2011 High

    Resolved the core molecular mechanism: UNC119 is a myristoyl-binding chaperone with an Ig-like β-sandwich pocket that sequesters acylated transducin α and is required for G protein localization.

    Evidence Apo and co-crystal X-ray structures, ITC, GTPase assays, and mouse/C. elegans knockouts; parallel human biochemistry showing acyl-dependent Gαt binding and transducin solubilization

    PMID:21642972 PMID:21712387

    Open questions at the time
    • Cargo-release trigger not yet defined
    • Conflicting effects on Gαt GTPase between studies
  10. 2011 High

    Placed UNC119 in a ciliary delivery cycle by showing UNC119b carries myristoylated NPHP3 and that Arl3-GTP releases cargo within an ARL3–UNC119b–RP2 GTPase module.

    Evidence Proteomics, mutagenesis with structural modeling, ciliary targeting assays, and C. elegans genetics

    PMID:22085962

    Open questions at the time
    • Why only UNC119b functions in ciliary NPHP3 targeting unexplained at structural level
    • Isoform-specific cargo repertoire incomplete
  11. 2012 High

    Defined the structural basis of Arl3 specificity: only Arl3-GTP keeps its amphipathic helix surface-bound and widens the myristoyl pocket to accelerate cargo release ~1000-fold, distinguishing it from Arl2.

    Evidence Co-crystal structures of Arl3- and Arl2-UNC119a with kinetic release and affinity assays

    PMID:22960633

    Open questions at the time
    • In vivo compartment where each GTPase acts not yet mapped
  12. 2016 High

    Established a cargo affinity code: +2/+3 residues set subnanomolar (ciliary) versus micromolar (Src) affinity, dictating whether cargo is released only by Arl3 or by both Arl2 and Arl3.

    Evidence ITC/FP binding, NPHP3-peptide co-crystal, and residue-swap mutagenesis with cellular localization

    PMID:27481943

    Open questions at the time
    • Full cargo set across tissues not enumerated
    • How affinity maps to compartment specificity in vivo only partly tested
  13. 2014 Medium

    Linked UNC119-dependent acyl-cargo transport to prenyl-cargo transport, showing Unc119 loss partially rescues the GRK1 defect of Pde6d-knockout cones.

    Evidence Pde6d;Unc119 double-knockout mice with ERG and immunolocalization

    PMID:24664735

    Open questions at the time
    • Molecular basis of the UNC119/PDE6D crosstalk unresolved
  14. 2017 Medium

    Showed how the chaperone integrates with membrane trafficking: localized Arl2/3 activity on recycling endosomes releases Src-family kinases from UNC119 for compartment-specific re-targeting, and that the cargo interaction is druggable.

    Evidence Live imaging/FRAP/knockdown of SFK distribution; competitive small-molecule inhibitor (Squarunkin A, 10 nM) with cell-based kinase readout

    PMID:28471079 PMID:28740133

    Open questions at the time
    • Endogenous spatial regulators of Arl activity not identified
    • Therapeutic relevance of inhibition untested in disease models
  15. 2018 Medium

    Uncovered a non-canonical tumor-suppressive role through RASSF6-MDM2-p53 signaling and a DNA-damage/ploidy phenotype, separate from cargo chaperoning.

    Evidence Reciprocal co-IP, knockdown, apoptosis and polyploidy assays

    PMID:29931788

    Open questions at the time
    • Direct vs indirect role in DNA repair unclear
    • Connection to the lipid pocket not addressed here
  16. 2020 Medium

    Showed UNC119A engages active KRAS through a pocket-independent surface and bridges KRAS-RASSF6-MDM2 to promote p53-dependent apoptosis, defining a tumor-suppressive axis in KRAS-mutant cancer.

    Evidence Co-IP with domain mapping, RNAi silencing, and soft-agar/migration/invasion assays

    PMID:32554467

    Open questions at the time
    • Structural basis of KRAS binding unknown
    • Whether this competes with lipid-cargo function in cells untested
  17. 2023 Medium

    Provided direct functional evidence that synaptic UNC119 sets the rate of glutamate release at rod ribbon synapses, independent of CaBP4 or calcium channels.

    Evidence Patch-clamp from retinal slices of Unc119 heterozygous and homozygous knockout mice

    PMID:37175812

    Open questions at the time
    • Molecular mechanism coupling UNC119 to release machinery undefined
    • Which synaptic partner mediates the effect unresolved
  18. 2025 Medium

    Extended the cargo and disease picture: UNC119 carries cone transducin Gnat2 to the outer segment, its loss drives inflammatory cone-rod dystrophy via JAK-STAT/NF-κB, and it traffics LCK to the immunological synapse to sustain T-ALL proliferation.

    Evidence Co-IP, Unc119-knockout mice with RNA-seq and curcumin rescue; immunofluorescence and TCR/proliferation assays in primary and T-ALL cells

    PMID:39814552 PMID:41107067

    Open questions at the time
    • Mechanism linking cargo mislocalization to inflammatory signaling unclear
    • How LCK trafficking by UNC119 integrates with prior SFK-activation data not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UNC119's distinct activities — myristoyl-cargo chaperoning, kinase activation, dynamin inhibition, synaptic glutamate release, and KRAS/RASSF6/p53 signaling — are coordinated within a single protein, and whether they share or partition structural surfaces, remains unresolved.
  • No unified model linking pocket-dependent and pocket-independent functions
  • Isoform-specific (UNC119a vs UNC119b) division of labor only partly mapped
  • Physiological cargo set across non-retinal tissues incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 2 GO:0005929 cilium 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 3 R-HSA-9709957 Sensory Perception 3 R-HSA-168256 Immune System 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
ARL2ARL3GNAT1GNAT2KRASLCKNPHP3RIBEYE
Complex memberships
ARL3-UNC119b-RP2 ciliary GTPase cycle

Evidence

Reading pass · 30 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 (unc-119/lacZ fusion reporter in neurons) and is required for locomotion, feeding, and chemosensation; loss-of-function alleles demonstrate a neural origin of the phenotype. Transgenic reporter gene (unc-119/lacZ fusion), phenotypic rescue with genomic DNA clones, characterization of multiple null alleles Genetics Medium 8582641
2001 UNC-119 acts cell-autonomously in neurons to suppress axon branching and stabilize differentiated axon architecture in adult C. elegans; post-developmental expression can rescue supernumerary branching, demonstrating a maintenance rather than developmental role. Live imaging, cell-autonomous rescue experiments with tissue-specific promoters, loss-of-function analysis Development (Cambridge, England) Medium 11641230
1998 HRG4 (UNC119) protein is localized to the cytoplasm and presynaptic membranes of photoreceptor ribbon synapses (outer plexiform layer) in human and rat retinas, consistent with a function in photoreceptor neurotransmission. Immunofluorescence microscopy (light and electron microscopic levels), Western blot analysis Investigative ophthalmology & visual science Medium 9538874
2000 The conserved C-terminal domain of human HRG4/UNC119 (and Drosophila DmUNC-119) is functionally necessary and sufficient to rescue C. elegans unc-119 mutants, while the divergent N-terminus is dispensable; function is conserved across metazoans. Transgenic rescue in C. elegans with domain-truncated human/Drosophila UNC119 constructs under the unc-119 promoter Journal of neurogenetics Medium 10858820
2000 A heterozygous premature-termination mutation in HRG4 (UNC119) causes cone-rod dystrophy; transgenic mice expressing the same truncated protein develop age-dependent retinal degeneration with defects in photoreceptor synaptic transmission (depressed b-wave, normal c-wave). Patient mutation screening, transgenic mouse model with ERG and histopathology Investigative ophthalmology & visual science Medium 11006213
2002 UNC119 associates with IL-5Rα and Src family tyrosine kinases (Lyn) and induces their catalytic activity through interaction with SH2 and SH3 domains; eosinophils transduced with UNC119 show increased Lyn activity and prolonged survival in the absence of IL-5. Yeast two-hybrid screening, co-immunoprecipitation, kinase activity assays, retroviral transduction with gain/loss-of-function The Journal of biological chemistry Medium 12496276
2003 HRG4 (UNC119) interacts with ARL2 via a conserved domain homologous to the ARL2-binding region of PDE-delta; interaction confirmed by yeast two-hybrid, co-immunoprecipitation, and direct binding assay; ARL2 colocalizes with HRG4 in the retina. Yeast two-hybrid, co-immunoprecipitation, direct binding assay, immunofluorescence colocalization FEBS letters Medium 12527357
2004 UNC119 associates with CD3 and CD4, activates Lck and Fyn in T cells, and is required for IL-2 production and T cell proliferation; UNC119-deficient T cells show dramatically reduced Lck/Fyn kinase activity, rescued by UNC119 reconstitution. Co-immunoprecipitation, kinase activity assays, genetic reconstitution, loss-of-function T cell analysis The Journal of experimental medicine Medium 14757743
2006 Truncated mutant HRG4 (UNC119) binds ARL2 with ~3-fold higher affinity than wild-type, causing sequestration of ARL2, reduction of ANT-1 in photoreceptor synaptic mitochondria, mitochondrial dysfunction, cytochrome c release, and caspase-3 activation in synapses leading to apoptosis and trans-synaptic degeneration. Saturation binding assay, Western blot, immunofluorescence, TUNEL, morphometric analysis in transgenic mouse model Investigative ophthalmology & visual science Medium 16565359
2006 Knockout of HRG4 (UNC119/MRG4) in mice causes slowly progressive retinal degeneration with dysfunction primarily in the distal photoreceptor (inner/outer segment region), distinct from the synaptic degeneration seen in truncation-mutant transgenic mice, indicating dual functionality at both synaptic and distal compartments. Gene targeting (knockout mouse), ERG, histopathology (LM and EM), TUNEL, Western blot, immunofluorescence Experimental eye research Medium 17174953
2007 UNC119 activates Fyn kinase and associates with it (co-precipitation and colocalization); UNC119 overexpression stimulates p38 (but not JNK) phosphorylation and induces α-SMA expression/myofibroblast differentiation in a Fyn- and p38 MAPK-dependent manner; UNC119 stimulates TGF-β and IL-6 production. Co-immunoprecipitation, kinase activity assay, siRNA knockdown, overexpression, SYF (Src/Yes/Fyn-null) cell rescue, p38 inhibitor experiments Journal of immunology Medium 17579091
2008 Munc119 (UNC119) is recruited to photoreceptor synaptic ribbons by direct interaction with the NADH-binding region of the RIBEYE(B) domain, requiring the PrBP/delta homology domain of Munc119; this interaction does not compete with NADH binding to RIBEYE. Five independent approaches: yeast two-hybrid, co-immunoprecipitation, affinity chromatography, direct binding assay, point mutagenesis of RIBEYE(B)E844Q The Journal of biological chemistry High 18664567
2008 CaBP4 directly interacts with UNC119 at photoreceptor synapses; CaBP4-knockout mice show reduced UNC119 levels at photoreceptor terminals, suggesting CaBP4 stabilizes UNC119 there. Affinity chromatography, yeast two-hybrid, co-immunoprecipitation, gel overlay assay, immunohistochemistry, Western blot of CaBP4-KO retinas Investigative ophthalmology & visual science Medium 18296658
2009 UNC119 directly interacts with dynamin, inhibits dynamin's GTPase activity, and decreases dynamin's association with amphiphysin; depletion of UNC119 increases, whereas overexpression inhibits, clathrin- and caveolae-based endocytosis and macropinocytosis (but not clathrin/dynamin-independent cholera toxin B uptake). Co-immunoprecipitation, GTPase activity assay, siRNA knockdown, overexpression, uptake assays with multiple cargo (transferrin, FM4-64, albumin, viruses, beads) Cellular signalling Medium 19781630
2009 UNC119 interacts with Abl family kinases and inhibits their kinase activity, thereby inhibiting Crk phosphorylation and reducing Shigella entry into cells; UNC119 knockdown in vivo enhances bacterial invasion and lethality in a pulmonary shigellosis mouse model. Co-immunoprecipitation, kinase activity assay, siRNA knockdown, cell-permeable TAT-UNC119 rescue, in vivo mouse model PloS one Medium 19381274
2011 UNC119 recognizes the acylated (myristoylated/lauroylated) N-terminus of transducin α (Gαt1) and C. elegans G proteins ODR-3 and GPA-13; crystal structure at 1.95 Å reveals an immunoglobulin-like β-sandwich fold forming a hydrophobic cavity; co-crystal with acylated Tα peptide at 2.0 Å shows the lipid chain buried in the hydrophobic pocket; UNC119 binds Tα-GTP and inhibits its GTPase activity; UNC119 deletion in mouse and C. elegans causes G protein mislocalization. X-ray crystallography (1.95 Å apo, 2.0 Å co-crystal), pulldown assays, isothermal titration calorimetry (ITC), GTPase activity assay, mouse and C. elegans knockouts with localization analysis Nature neuroscience High 21642972
2011 Human UNC119 (HRG4) binds myristoylated Gαt1 with high affinity (dependent on N-acylation, not on GTP state), can bind Gαt1-GDP and heterotrimeric transducin (Gt), displaces Gβ1γ1 from the heterotrimer, facilitates solubilization of Gt from dark-adapted rod OS membranes, and inhibits rhodopsin-dependent activation of Gt but has no effect on Gαt1 GTPase activity. Pulldown assays, ITC/binding assays, in vitro GTPase assay, membrane solubilization assay, functional G protein activation assay The Journal of biological chemistry High 21712387
2011 UNC119b (but not UNC119a) is required for ciliary targeting of the myristoylated protein NPHP3; UNC119 binding to NPHP3 requires myristoylation and maps to the N-terminal 200 residues; conserved hydrophobic β-sandwich phenylalanines are essential for myristate binding; ARL3-GTP releases myristoylated cargo from UNC119; ARL3, UNC119b, and the ARL3 GAP RP2 constitute a GTPase cycle for ciliary delivery. Proteomic approach (binding partner identification), directed mutagenesis, structural modeling, cell-based ciliary targeting assays, siRNA knockdown, C. elegans genetics Genes & development High 22085962
2012 Both Arl2 and Arl3 bind UNC119 with similar affinity, but only Arl3-GTP allosterically displaces myristoylated cargo by accelerating its release by three orders of magnitude; crystal structures of Arl3 and Arl2 in complex with UNC119a reveal that the N-terminal amphipathic helix of Arl3·GppNHp remains surface-bound (not displaced), inducing widening of the myristoyl-binding pocket—the structural basis for Arl3 specificity. X-ray crystallography (Arl3-UNC119a and Arl2-UNC119a co-crystal structures), kinetic cargo release assays, affinity measurements The EMBO journal High 22960633
2014 Poly-GA (C9orf72 DPR protein) co-aggregates with UNC119 in neurons; poly-GA expression strongly reduces soluble UNC119 levels; UNC119 knockdown alone inhibits dendritic branching and causes neurotoxicity similar to poly-GA; UNC119 overexpression partially rescues poly-GA toxicity, indicating loss-of-function as a contributing mechanism. Quantitative mass spectrometry, co-aggregation assays, siRNA knockdown, overexpression rescue in primary neurons, patient brain immunostaining Acta neuropathologica Medium 25120191
2014 Genetic epistasis: knockout of Unc119 partially rescues the GRK1 transport defect in Pde6d-knockout cone photoreceptors and restores photopic ERG b-wave amplitudes, indicating that cone transport of isoprenylated (GRK1) and acylated proteins are functionally interdependent. Double knockout mouse (Pde6d; Unc119), ERG, immunolocalization Advances in experimental medicine and biology Medium 24664735
2016 High-affinity myristoylated cargo peptides from ciliary proteins (GNAT1, NPHP3, Cystin1) bind Unc119a/b with subnanomolar to low-nanomolar affinity; non-ciliary Src peptide has low (micromolar) affinity; high-affinity cargo is released exclusively by Arl3·GppNHp, while low-affinity cargo is released by both Arl2 and Arl3; X-ray structure of myristoylated NPHP3 peptide in complex with Unc119a defines the +2/+3 residue positions as determinants of binding affinity; swapping +2/+3 residues reverses affinities and partially mislocalizes NPHP3. ITC/fluorescence polarization binding assays, X-ray crystallography, site-directed mutagenesis, cell-based localization assays The Journal of biological chemistry High 27481943
2017 UNC119 sequesters myristoylated Src family kinases (SFKs) from the cytoplasm; localized Arl2/3 activity on the recycling endosome releases SFKs from UNC119; Src is then trapped on the recycling endosome electrostatically while Fyn is trapped on the Golgi by palmitoyl acyl-transferase; vesicular trafficking restores SFK enrichment at the plasma membrane; UNC119 knockdown disrupts SFK localization and signaling activity. Live-cell imaging, FRAP, siRNA knockdown, colocalization, quantitative imaging of SFK distribution Nature communications Medium 28740133
2017 Squarunkin A, a small molecule inhibitor, selectively inhibits binding of myristoylated Src N-terminal peptide to UNC119A with IC50 of 10 nM; it binds UNC119 proteins in cell lysate and interferes with Src kinase activation, demonstrating the UNC119–cargo interaction is druggable. Competitive binding assay (IC50 determination), cell lysate engagement, Src kinase activity assay Angewandte Chemie (International ed. in English) Medium 28471079
2018 UNC119 interacts with RASSF6 and promotes the RASSF6–MDM2 interaction, stabilizing p53; UNC119 induces apoptosis via RASSF6 and p53; UNC119 depletion impairs DNA repair after DNA damage and causes polyploid cell generation. Co-immunoprecipitation, siRNA knockdown, apoptosis assays, DNA damage assays (polyploidy analysis) Cancer science Medium 29931788
2019 Lipidated, hydrocarbon-stapled peptides derived from the UNC119-binding partner Gnat1 bind UNC119a and cause accumulation of cytokinetic and binucleated cells, implicating UNC119a in the completion of cytokinesis. Hydrocarbon stapling, binding assays, cell biology assays (cytokinesis/binucleation phenotype) Chembiochem : a European journal of chemical biology Low 31680402
2020 UNC119A interacts with the active (GTP-bound) form of KRAS; the C-terminal modification of KRAS is required for this interaction; the myristoyl-binding hydrophobic pocket of UNC119A is NOT involved; UNC119A promotes KRAS binding to RASSF6, enhancing RASSF6–MDM2 interaction and p53-dependent apoptosis; UNC119A silencing promotes soft-agar colony formation, migration, and invasiveness in KRAS-mutated cancer cells. Co-immunoprecipitation, RNAi gene silencing, immunofluorescence, cell biology assays (soft-agar colony formation, migration, invasion) The Journal of biological chemistry Medium 32554467
2023 Deletion of one or both UNC119 alleles in mice reduces steady-state glutamate release rate at rod synapses (depolarizes rod bipolar cell membrane potential, decreases sensitivity, accelerates response decay, decreases Hill coefficient), without changing rod outer segment photocurrent or synaptic Ca2+ current voltage dependence; UNC119 facilitates glutamate release at rod ribbon synapses, likely via interaction with RIBEYE or other synaptic proteins rather than CaBP4 or calcium channels. Patch-clamp recordings from retinal slices in UNC119 heterozygous and homozygous knockout mice, bright-light transducin translocation experiments International journal of molecular sciences Medium 37175812
2025 UNC119 interacts with cone-specific transducin α-subunit Gnat2 and is required for translocation of Gnat2 to the outer segment in cone photoreceptors; Unc119-deficient mice show progressive cone-rod dystrophy with activation of JAK-STAT and NF-κB inflammatory pathways; a human CRD-associated UNC119 mutant competitively inhibits the UNC119–GNAT1/GNAT2 interaction; curcumin treatment suppresses inflammation and cone degeneration in Unc119-deficient retinas. Co-immunoprecipitation, Unc119 knockout mouse, RNA-seq/bioinformatics, immunofluorescence, curcumin pharmacological rescue The Journal of neuroscience Medium 41107067
2025 UNC119 directly traffics LCK to the immunological synapse in T cells; inhibiting UNC119 reduces LCK localization at the synapse without impairing LCK phosphorylation, and reduces TCR signal transduction; UNC119 sustains proliferation in T-ALL cells. Immunofluorescence localization, UNC119 inhibition (pharmacological), TCR signaling assays, proliferation assays in primary T cells and patient-derived T-ALL cells Life science alliance Medium 39814552

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 389 8582641
2014 C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta neuropathologica 261 25120191
2011 An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes & development 190 22085962
2011 UNC119 is required for G protein trafficking in sensory neurons. Nature neuroscience 147 21642972
2000 HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model. Investigative ophthalmology & visual science 103 11006213
2012 Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119. The EMBO journal 93 22960633
2004 Unc119, a novel activator of Lck/Fyn, is essential for T cell activation. The Journal of experimental medicine 76 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
2017 Small-Molecule Inhibition of the UNC119-Cargo Interaction. Angewandte Chemie (International ed. in English) 16 28471079
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
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

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