Disease relevance of UNC119

• 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 [1].
• CONCLUSIONS: Given its strong degree of evolutionary conservation and abundant and nearly exclusive expression in photoreceptors, it is likely that UNC-119 plays an important role in vision and is a strong candidate gene for retinal diseases that map to 17q11.2 [2].

High impact information on UNC119

• Identification of UNC119 as a novel activator of SRC-type tyrosine kinases [3].
• IL-5 stimulation of eosinophils increases Unc119 association with Lyn and induces its catalytic activity [3].
• 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 [3].
• Expression of HRG4 in the retina was localized to the photoreceptors by in situ hybridization [4].
• In addition to the CD4 and CD8 coreceptors, a recently described adaptor, Unc119, may link SFKs to the TCR [5].

Biological context of UNC119

• METHODS: By screening bovine, murine, and human retinal cDNA libraries, human UNC-119 clones of two varieties and a murine cDNA clone corresponding to the most abundant human transcript were isolated [2].
• Northern blot and reverse transcription-polymerase chain reaction analyses were used to determine tissue distribution of UNC-119 expression; in situ hybridization localized it in retina to photoreceptors [2].
• Cloning of human and mouse PDE delta cDNAs revealed that PDE delta is a nearly perfectly conserved polypeptide of 150 amino acids that shows partial sequence homology to photoreceptor RG4 of unknown function [6].
• The function of UNC-119 proteins has been conserved throughout evolution, as transgenic expression of the human UNC119 gene in C. elegans unc-119 mutants restores a wild-type phenotype [7].
• We determined the nucleotide sequence of a 58 kilobase region on mouse chromosome 11 that encompasses the mouse nude gene and part of the two neighboring genes, encoding a sodium/dicarboxylate co-transporter and the retinal protein 4 [8].

Anatomical context of UNC119

• Inhibition of Unc119 down-regulates eosinophil survival [3].
• We found that an arginine- and glycine-rich region of xCIRP2, termed the RG4 domain, was a target of xPRMT1 for methylation in vitro. xCIRP2 expressed in cultured cells accumulated in the nucleus as does mammalian CIRP [9].

Other interactions of UNC119

• Nine clones were fully sequenced and four of these sequences were matched to known genes for glutamine synthetase, glucosidase 1, retinal protein 4, and phosphoribosylaminoimidazole carboxylase, respectively [10].

Analytical, diagnostic and therapeutic context of UNC119

• The presence of ARL2 in the retina and co-localization with HRG4 was confirmed by Western blot and double immunofluorescence analysis, respectively [1].
• The interaction of ARL2 with HRG4 was further confirmed by co-immunoprecipitation and direct binding analysis [1].
• PURPOSE: To characterize further HRG4, a novel photoreceptor protein recently identified by subtractive cDNA cloning, by sequence analysis and immunolocalization [11].

References