UNC119

Summary

Gene Symbol: UNC119
Description: unc-119 lipid binding chaperone
Alias: HRG4, IMD13, POC7, POC7A, protein unc-119 homolog A, POC7 centriolar protein homolog A, retinal protein 4, unc-119 homolog
Species: human
Products:     UNC119

Top Publications

  1. Higashide T, Murakami A, McLaren M, Inana G. Cloning of the cDNA for a novel photoreceptor protein. J Biol Chem. 1996;271:1797-804 pubmed
    ..cDNA cloning strategy was used to isolate a 1381-base pair human retina-specific cDNA, human retinal gene 4 (HRG4), which hybridized to a 1...
  2. Pan X, Rudolph J, Abraham L, Habermann A, Haller C, Krijnse Locker J, et al. HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling. Blood. 2012;119:786-97 pubmed publisher
    ..Overexpression of the Lck PM transporter Unc119 restores Nef-induced subversions of Lck trafficking and TCR signaling...
  3. Karim Z, Vepachedu R, Gorska M, Alam R. UNC119 inhibits dynamin and dynamin-dependent endocytic processes. Cell Signal. 2010;22:128-37 pubmed publisher
    b>Unc119 is an adapter signaling molecule, which regulates activation of tyrosine kinases in T cells, eosinophils and fibroblasts. It plays an important role in the photoreceptor synapses of the retina...
  4. Higashide T, McLaren M, Inana G. Localization of HRG4, a photoreceptor protein homologous to Unc-119, in ribbon synapse. Invest Ophthalmol Vis Sci. 1998;39:690-8 pubmed
    To characterize further HRG4, a novel photoreceptor protein recently identified by subtractive cDNA cloning, by sequence analysis and immunolocalization. The rat homolog of HRG4, RRG4 was expressed and used to prepare an antibody...
  5. Higashide T, Inana G. Characterization of the gene for HRG4 (UNC119), a novel photoreceptor synaptic protein homologous to unc-119. Genomics. 1999;57:446-50 pubmed
    HRG4 (HGMW-approved symbol UNC119) is a novel human photoreceptor-enriched gene coding for a 240-amino-acid protein...
  6. Cen O, Gorska M, Stafford S, Sur S, Alam R. Identification of UNC119 as a novel activator of SRC-type tyrosine kinases. J Biol Chem. 2003;278:8837-45 pubmed
    ..Through yeast two-hybrid screening we have cloned and characterized a new signaling molecule, Unc119, that associates with IL-5Ralpha and Src family tyrosine kinases...
  7. Kobayashi A, Kubota S, Mori N, McLaren M, Inana G. Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain. FEBS Lett. 2003;534:26-32 pubmed
    Human retinal gene 4 (HRG4) (UNC119) is a photoreceptor synaptic protein of unknown function, shown when mutated to cause retinal degeneration in a patient and in a confirmatory transgenic model...
  8. Gorska M, Stafford S, Cen O, Sur S, Alam R. Unc119, a novel activator of Lck/Fyn, is essential for T cell activation. J Exp Med. 2004;199:369-79 pubmed
    ..Here, we report that the novel Src homology (SH) 3/SH2 ligand-Uncoordinated 119 (Unc119) associates with CD3 and CD4, and activates Lck and Fyn...
  9. Vepachedu R, Gorska M, Singhania N, Cosgrove G, Brown K, Alam R. Unc119 regulates myofibroblast differentiation through the activation of Fyn and the p38 MAPK pathway. J Immunol. 2007;179:682-90 pubmed
    b>Unc119 is an adaptor protein that is involved in the development of the vertebrate nervous system...

More Information

Publications40

  1. Wright K, Baye L, Olivier Mason A, Mukhopadhyay S, Sang L, Kwong M, et al. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev. 2011;25:2347-60 pubmed publisher
    ..Using a proteomic approach, we identified the ARL3 effector UNC119 as a binding partner of the myristoylated ciliopathy protein nephrocystin-3 (NPHP3)...
  2. Gopalakrishna K, Doddapuneni K, Boyd K, Masuho I, Martemyanov K, Artemyev N. Interaction of transducin with uncoordinated 119 protein (UNC119): implications for the model of transducin trafficking in rod photoreceptors. J Biol Chem. 2011;286:28954-62 pubmed publisher
    ..A mammalian uncoordinated 119 protein (UNC119), also known as Retina Gene 4 protein (RG4), has been recently implicated in transducin transport to the OS in the ..
  3. Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang Y, et al. UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci. 2011;14:874-80 pubmed publisher
    b>UNC119 is widely expressed among vertebrates and other phyla. We found that UNC119 recognized the acylated N terminus of the rod photoreceptor transducin α (Tα) subunit and Caenorhabditis elegans G proteins ODR-3 and GPA-13...
  4. Gorska M, Liang Q, Karim Z, Alam R. Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation. J Immunol. 2009;183:1675-84 pubmed publisher
    ..The transport depends on the adaptor protein Uncoordinated 119 (Unc119), on the GTPase rat brain 11 (Rab11), and on the actin cytoskeleton. Unc119 regulates the activation of Rab11...
  5. Garivet G, Hofer W, Konitsiotis A, Klein C, Kaiser N, Mejuch T, et al. Small-Molecule Inhibition of the UNC-Src Interaction Impairs Dynamic Src Localization in Cells. Cell Chem Biol. 2019;: pubmed publisher
    ..We describe the discovery of a potent and specific inhibitor of the UNC119-Src interaction with unprecedented chemotype...
  6. Toyama R, Chen X, Jhawar N, Aamar E, Epstein J, Reany N, et al. Transcriptome analysis of the zebrafish pineal gland. Dev Dyn. 2009;238:1813-26 pubmed publisher
    ..Among the multiple candidate genes suggested by these data, we note the identification of a tissue-specific form of the unc119 gene with a possible role in pineal development.
  7. Hanke Gogokhia C, Frederick J, Zhang H, Baehr W. Binary Function of ARL3-GTP Revealed by Gene Knockouts. Adv Exp Med Biol. 2018;1074:317-325 pubmed publisher
    b>UNC119 and PDE? are lipid-binding proteins and are thought to form diffusible complexes with transducin-? and prenylated OS proteins, respectively, to mediate their trafficking to photoreceptor outer segments...
  8. Baehr W. Membrane protein transport in photoreceptors: the function of PDEδ: the Proctor lecture. Invest Ophthalmol Vis Sci. 2014;55:8653-66 pubmed publisher
    ..fold that is closely related in structure to other lipid-binding proteins, for example, Uncoordinated 119 (UNC119) and RhoGDI...
  9. May S, Hornburg D, Schludi M, Arzberger T, Rentzsch K, Schwenk B, et al. C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta Neuropathol. 2014;128:485-503 pubmed publisher
    ..Among the other interacting proteins, we identified the transport factor Unc119, which has been previously linked to neuromuscular and axonal function, as a poly-GA co-aggregating protein...
  10. Toyama R, Kim M, Rebbert M, Gonzales J, BURGESS H, Dawid I. Habenular commissure formation in zebrafish is regulated by the pineal gland-specific gene unc119c. Dev Dyn. 2013;242:1033-42 pubmed publisher
    ..Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all ..
  11. Keller L, Geimer S, Romijn E, Yates J, Zamora I, Marshall W. Molecular architecture of the centriole proteome: the conserved WD40 domain protein POC1 is required for centriole duplication and length control. Mol Biol Cell. 2009;20:1150-66 pubmed publisher
    ..in CEP290, MKS1, OFD1, and AHI1/Jouberin proteins and cone-rod dystrophy syndrome genes, including UNC-119/HRG4, NPHP4, and RPGR1...
  12. Schludi M, May S, Grässer F, Rentzsch K, Kremmer E, Küpper C, et al. Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing. Acta Neuropathol. 2015;130:537-55 pubmed publisher
    ..In patients, neuronal inclusions of poly-GR, poly-GP and the poly-GA interacting protein Unc119 were less abundant than poly-GA inclusions, but showed similar regional and subcellular distribution...
  13. Nakajima Y, Kiyonari H, Mukumoto Y, Yokoyama T. The Inv compartment of renal cilia is an intraciliary signal-activating center to phosphorylate ANKS6. Kidney Int. 2018;93:1108-1117 pubmed publisher
    ..Mutant NPHP3 was absent the binding capacity of UNC119, a carrier protein responsible for the delivery of myristoylated cargo to the cilium, so ciliary localization was ..
  14. Rainy N, Etzion T, Alon S, Pomeranz A, Nisgav Y, Livnat T, et al. Knockdown of unc119c results in visual impairment and early-onset retinal dystrophy in zebrafish. Biochem Biophys Res Commun. 2016;473:1211-1217 pubmed publisher
    b>UNC119 proteins are involved in G protein trafficking in mouse retinal photoreceptors and Caenorhabditis elegans olfactory neurons...
  15. Lei B, Chai W, Wang Z, Liu R. Highly expressed UNC119 promotes hepatocellular carcinoma cell proliferation through Wnt/β-catenin signaling and predicts a poor prognosis. Am J Cancer Res. 2015;5:3123-34 pubmed
    UNC119, also known as Retinal Protein 4 (HRG4) is significantly up-regulated in hepatocellular carcinoma (HCC) tissues...
  16. Mejuch T, van Hattum H, Triola G, Jaiswal M, Waldmann H. Specificity of Lipoprotein Chaperones for the Characteristic Lipidated Structural Motifs of their Cognate Lipoproteins. Chembiochem. 2015;16:2460-5 pubmed publisher
    ..In contrast, UNC119 proteins bind only mono-N-myristoylated, but do not recognise doubly lipidated and S-isoprenylated peptides at the ..
  17. Lee Y, Chung S, Baek I, Lee T, Paik S, Lee J. UNC119a bridges the transmission of Fyn signals to Rab11, leading to the completion of cytokinesis. Cell Cycle. 2013;12:1303-15 pubmed publisher
    ..These results suggest that UNC119a plays a key role in the Fyn signal transduction pathway, which regulates the completion of cytokinesis via Rab11. ..
  18. Swanson D, Chang J, Campochiaro P, Zack D, Valle D. Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors. Invest Ophthalmol Vis Sci. 1998;39:2085-94 pubmed
    ..Rat and human cDNAs of UNC-119 have been previously reported as human retinal gene 4 and rat retinal gene 4 (HRG4 and RRG4)...
  19. Veltel S, Kravchenko A, Ismail S, Wittinghofer A. Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP complex. FEBS Lett. 2008;582:2501-7 pubmed publisher
    ..Here, we have characterized Arl2/3 interactions. We show the formation of a ternary complex between Arl3, its cognate GAP RP2 and its retinal effector HRG4. This complex seems to be important for photoreceptor function.
  20. Jean F, Pilgrim D. Coordinating the uncoordinated: UNC119 trafficking in cilia. Eur J Cell Biol. 2017;96:643-652 pubmed publisher
    ..One essential factor is UNC119, which interacts with known IFT molecular switches to transport ciliary cargos...
  21. Jaiswal M, Fansa E, Kösling S, Mejuch T, Waldmann H, Wittinghofer A. Novel Biochemical and Structural Insights into the Interaction of Myristoylated Cargo with Unc119 Protein and Their Release by Arl2/3. J Biol Chem. 2016;291:20766-78 pubmed publisher
    ..The affinity between myristoylated cargo and carrier protein, Unc119, varies between subnanomolar and micromolar...
  22. Lokaj M, Kösling S, Koerner C, Lange S, van Beersum S, van Reeuwijk J, et al. The Interaction of CCDC104/BARTL1 with Arl3 and Implications for Ciliary Function. Structure. 2015;23:2122-32 pubmed publisher
    ..a specific release factor for myristoylated and farnesylated ciliary cargo molecules by binding to the effectors Unc119 and PDE6δ. Here we describe a newly identified Arl3 binding partner, CCDC104/CFAP36...
  23. Konitsiotis A, Roßmannek L, Stanoev A, Schmick M, Bastiaens P. Spatial cycles mediated by UNC119 solubilisation maintain Src family kinases plasma membrane localisation. Nat Commun. 2017;8:114 pubmed publisher
    ..The solubilising factor UNC119 sequesters myristoylated Src family protein tyrosine kinases from the cytoplasm, enhancing their diffusion to ..
  24. Ismail S, Chen Y, Miertzschke M, Vetter I, Koerner C, Wittinghofer A. Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119. EMBO J. 2012;31:4085-94 pubmed publisher
    ..b>UNC119/HRG4 is responsible for ciliary delivery of myristoylated cargo...
  25. Sinha S, Majumder A, Belcastro M, Sokolov M, Artemyev N. Expression and subcellular distribution of UNC119a, a protein partner of transducin ? subunit in rod photoreceptors. Cell Signal. 2013;25:341-8 pubmed publisher
    ..As a dominant partner, G?(t1) may potentially modulate the function of other known UNC119a-interacting proteins involved in photoreceptor ciliary trafficking and synaptic regulation, in a light-dependent manner. ..
  26. Huang L, Xiao X, Li S, Jia X, Wang P, Sun W, et al. Molecular genetics of cone-rod dystrophy in Chinese patients: New data from 61 probands and mutation overview of 163 probands. Exp Eye Res. 2016;146:252-8 pubmed publisher
    ..8%), ALMS1 (3.1%), GUCY2D (3.1%), CACNA1F (2.5%), CRX (1.8%), PDE6C (1.8%), CNGB3 (1.8%), GUCA1A (1.2%), UNC119 (0.6%), RPGRIP1 (1.2%), RDH12 (0.6%), KCNV2 (0.6%), C21orf2 (0.6%), CEP290 (0.6%), USH2A (0.6%) and SNRNP200 (0...
  27. Gorska M, Goplen N, Liang Q, Alam R. Uncoordinated 119 preferentially induces Th2 differentiation and promotes the development of asthma. J Immunol. 2010;184:4488-96 pubmed publisher
    ..balance and the development of allergic asthma are strongly affected by the signaling protein uncoordinated 119 (Unc119). The expression of this adaptor protein is significantly increased in Th2 cells...
  28. Gorska M, Alam R. Consequences of a mutation in the UNC119 gene for T cell function in idiopathic CD4 lymphopenia. Curr Allergy Asthma Rep. 2012;12:396-401 pubmed publisher
    ..TCR activates LCK through the adaptor protein uncoordinated 119 (UNC119)...
  29. Stephen L, Ismail S. Shuttling and sorting lipid-modified cargo into the cilia. Biochem Soc Trans. 2016;44:1273-1280 pubmed
  30. Van Valkenburgh H, Shern J, Sharer J, Zhu X, Kahn R. ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and shared effectors: characterizing ARL1-binding proteins. J Biol Chem. 2001;276:22826-37 pubmed
    ..These data reveal a complex network of interactions between GTPases in the ARF family and their effectors and reveal a potential for cross-talk not demonstrated previously. ..
  31. Abraham L, Fackler O. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun Signal. 2012;10:39 pubmed publisher
    ..We also discuss the implications of these alterations in the context of HIV-1 infection and in light of current concepts of TCR signal transduction. ..