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unc-119 lipid binding chaperone

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 3011

Nomenclature: unc-119 lipid binding chaperone

Family: Lipid binding chaperones

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 240 17q11.2 UNC119 unc-119 lipid binding chaperone
Mouse - 240 11 46.74 cM Unc119 unc-119 lipid binding chaperone
Rat - 240 10q25 Unc119 unc-119 lipid binding chaperone
Gene and Protein Information Comments
The most abundant transcript from the human gene encodes a protein of 240 amino acids (isoform a). A second transcript variant that produces a shorter isoform (b; 220 aa) has also been identified. The mouse gene produces several transcript variants encoding different protein isoforms. Mouse isoform 1 is the longest, isoform 2 is 240 aa and may be the equivalent of human isoform 1.
Previous and Unofficial Names Click here for help
RG4 (retinal gene 4) | unc-119 | uncoordinated (UNC)119
Database Links Click here for help
Alphafold Q13432 (Hs), Q9Z2R6 (Mm), Q62885 (Rn)
Ensembl Gene ENSG00000109103 (Hs), ENSMUSG00000002058 (Mm), ENSRNOG00000011060 (Rn)
Entrez Gene 9094 (Hs), 22248 (Mm), 29402 (Rn)
Human Protein Atlas ENSG00000109103 (Hs)
KEGG Gene hsa:9094 (Hs), mmu:22248 (Mm), rno:29402 (Rn)
OMIM 604011 (Hs)
Pharos Q13432 (Hs)
RefSeq Nucleotide NM_005148 (Hs), NM_001313985 (Mm), NM_011676 (Mm), NM_017188 (Rn)
RefSeq Protein NP_005139 (Hs), NP_035806 (Mm), NP_001300914 (Mm), NP_058884 (Rn)
UniProtKB Q13432 (Hs), Q9Z2R6 (Mm), Q62885 (Rn)
Wikipedia UNC119 (Hs)
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
squarunkin A Small molecule or natural product Hs Binding 8.0 pIC50 6
⤷ pIC50 8.0 (IC50 1x10-8 M) [6]
Description: Measuring inhibition of the binding of a myristoylated peptide representing the N-terminus of Src kinase to UNC119.
Immunopharmacology Comments
UNC119's role in regulating lymphocyte-specific protein tyrosine kinase (Lck) activity has been reported to be essential for the formation of immunological synapses and activation of T cells [4]. Regulation of Fyn kinase and the p38MAP kinase pathwya via UNC119 is involved in fibrotic processes [7].
General Comments
Uncoordinated 119 protein (UNC119) is a lipid binding chaperone that regulates the cellular localisation and activity of proteins that are N-Terminal myristoylated [1]. Cargo proteins that utilise UNC119 include ciliary proteins (e.g. nephrocystin-3) [5,8], N-acylated G protein α-subunits [3,5,9] and N-myristoylated Src family tyrosine kinases (Src, Lck, Lyn and Fyn) [4,7]. UNC119's chaperone function is important for the spatial regulation of the Src family kinases [2]. As Src is a major oncogene, being able to disrupt the UNC119-Src interaction to bring about reduced Src activity has potential implications for cancer drug discovery. Small molecules designed to selectively inhibit UNC119-Src binding will help determine if this is a viable alternative to the use of Src kinase inhibitors in oncology [6].

References

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1. Constantine R, Zhang H, Gerstner CD, Frederick JM, Baehr W. (2012) Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins. Vision Res, 75: 26-32. [PMID:23000199]

2. Erwin N, Dwivedi M, Mejuch T, Waldmann H, Winter R. (2018) UNC119A Decreases the Membrane Binding of Myristoylated c-Src. Chembiochem, 19 (14): 1482-1487. [PMID:29700916]

3. Gopalakrishna KN, Doddapuneni K, Boyd KK, Masuho I, Martemyanov KA, Artemyev NO. (2011) Interaction of transducin with uncoordinated 119 protein (UNC119): implications for the model of transducin trafficking in rod photoreceptors. J Biol Chem, 286 (33): 28954-62. [PMID:21712387]

4. Gorska MM, Liang Q, Karim Z, Alam R. (2009) Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation. J Immunol, 183 (3): 1675-84. [PMID:19592652]

5. Jaiswal M, Fansa EK, Kösling SK, Mejuch T, Waldmann H, Wittinghofer A. (2016) Novel Biochemical and Structural Insights into the Interaction of Myristoylated Cargo with Unc119 Protein and Their Release by Arl2/3. J Biol Chem, 291 (39): 20766-78. [PMID:27481943]

6. Mejuch T, Garivet G, Hofer W, Kaiser N, Fansa EK, Ehrt C, Koch O, Baumann M, Ziegler S, Wittinghofer A et al.. (2017) Small-Molecule Inhibition of the UNC119-Cargo Interaction. Angew Chem Int Ed Engl, 56 (22): 6181-6186. [PMID:28471079]

7. Vepachedu R, Gorska MM, Singhania N, Cosgrove GP, Brown KK, Alam R. (2007) Unc119 regulates myofibroblast differentiation through the activation of Fyn and the p38 MAPK pathway. J Immunol, 179 (1): 682-90. [PMID:17579091]

8. Wright KJ, Baye LM, Olivier-Mason A, Mukhopadhyay S, Sang L, Kwong M, Wang W, Pretorius PR, Sheffield VC, Sengupta P et al.. (2011) An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev, 25 (22): 2347-60. [PMID:22085962]

9. Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW et al.. (2011) UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci, 14 (7): 874-80. [PMID:21642972]

How to cite this page

Lipid binding chaperones: unc-119 lipid binding chaperone. Last modified on 03/08/2023. Accessed on 03/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3011.