unc-119 lipid binding chaperone | Lipid binding chaperones | IUPHAR Guide to IMMUNOPHARMACOLOGY

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unc-119 lipid binding chaperone

  Target has curated data in GtoImmuPdb

Target id: 3011

Nomenclature: unc-119 lipid binding chaperone

Family: Lipid binding chaperones

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 240 17q11.2 UNC119 unc-119 lipid binding chaperone
Mouse - 262 Chromosome 11, 46.74 cM, cytoband B5 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
RG4 (retinal gene 4) | unc-119 | uncoordinated (UNC)119
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
squarunkin A 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].
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 3 GO processes
GO:1900186 negative regulation of clathrin-dependent endocytosis ISS
GO:2001287 negative regulation of caveolin-mediated endocytosis ISS
click arrow to show/hide IEA associations
GO:0006897 endocytosis IEA
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, [Epub ahead of print]. [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 30/05/2018. Accessed on 09/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3011.