Biology:Uncoordinated-119 (Unc-119)

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Uncoordinated-119 (Unc-119) is a protein that has been identified in C. elegans, humans, mice, zebrafish, rabbits, pig, calf, monkey, and protozoa.[1] They have been classified in the GMP phophodiesterase, delta superfamily.[2] Unc-119 proteins are categorized into their own family but are shown to be ancestrally related to PrBP (prenyl binding protein) and rhoGDI. It has been given many different names: Retinal Protein 4, HRG4, POC7 Centriolar Protein Homolog A, IMD13, POC7A, and RG4.  

Structure and function

Unc-119 in C. elegans is approximately 240 amino acids[3] and has a mass of ~26 kDa.[4] Using x-ray crystallography the protein's crystal structure was observed and found to have a resolution of 1.95 Å.[5] It has an immunoglobulin-like β-sandwich folding structure, resulting in a narrow, hydrophobic pocket.[6] This pocket has ability to bind to lauroyl (C12) and myristoyl (C14) acyltransferase side chains as a transporter or lipid-binding chaperone.[5] Unc-119 helps with motility of cilium. It is needed for cilia to maintain formation and function. This is a conserved responsibility from animals to protozoa.

Role in cells

UNC-119 has been found to be involved in synaptic functions, signal transduction, endosome recycling, uptake of bacteria and endocytosis, protein trafficking, lipid-binding chaperone, and a mediator on Src family kinase signals.[7][8]

The UNC-119 protein plays key roles in the movement and feeding in the C. elegans, because it is essential in the development and function of their nervous system. One mutation observed was in the expression patterns when the mutant fuses with lacZ.[6] When this protein is mutated or deleted, C. elegans were found to have problems moving, even to the point of complete paralysis. It was also proposed that a mutation could cause the C. elegans to lose the ability to recognize their food. When the organism possesses a mutated UNC-119, they have been shown to experience uncoordinated movement, a defect causing weak egg laying, and the inability to form dauer larvae.[8]

In H. sapiens, Unc-119 has been identified on chromosome 17 and is found predominantly in the retina (HRG4). It has been localized to the photo-receptor synapses in the outer plexiform layer of the retina, and suggested to play a role in the mechanism of photoreceptor neurotransmitter release through the synaptic vesicle cycle. Two transcript variants encoding different isoforms have been described for this gene. The encoded product shares strong homology with the C. elegans unc119 protein and it can functionally complement the C. elegans unc119 mutation.

Unc-119 has also been identified in other areas in humans, such as the liver, kidneys, brain, and fibroblasts.[6] It has also been found to play an important role within the T-cell receptor function[4] and interleukin-5 receptor (IL-5R) Unc-119 is an essential activator of both Lck and Fyn by interacting with their SH2- and SH3-binding domains. Mutation of the Unc-119 gene has been found to severely disrupt the T-cell receptor pathway. It has been suggested to be a cause of an immunodeficiency disordered known as idiopathic CD4 lymphopenia (ICL) due to the reduced t-cell stimulation.[5]

Interactions

Protein unc-119 homolog has been shown to interact with:


References

  1. ↑ "Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors". Investigative Ophthalmology & Visual Science 39 (11): 2085–94. October 1998. PMID 9761287. 
  2. ↑ "Sorting of lipidated cargo by the Arl2/Arl3 system". Small GTPases 7 (4): 222–230. October 2016. doi:10.1080/21541248.2016.1224454. PMID 27806215. 
  3. ↑ "Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system". Genetics 141 (3): 977–88. November 1995. doi:10.1093/genetics/141.3.977. PMID 8582641. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "Unc119, a novel activator of Lck/Fyn, is essential for T cell activation". The Journal of Experimental Medicine 199 (3): 369–79. February 2004. doi:10.1084/jem.20030589. PMID 14757743. 
  5. ↑ 5.0 5.1 5.2 "Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins". Vision Research 75: 26–32. December 2012. doi:10.1016/j.visres.2012.08.012. PMID 23000199. 
  6. ↑ 6.0 6.1 6.2 "Coordinating the uncoordinated: UNC119 trafficking in cilia". European Journal of Cell Biology 96 (7): 643–652. October 2017. doi:10.1016/j.ejcb.2017.09.001. PMID 28935136. 
  7. ↑ "UNC119a bridges the transmission of Fyn signals to Rab11, leading to the completion of cytokinesis". Cell Cycle 12 (8): 1303–1315. April 2013. doi:10.4161/cc.24404. PMID 23535298. 
  8. ↑ 8.0 8.1 "The UNC-119 family of neural proteins is functionally conserved between humans, Drosophila and C. elegans". Journal of Neurogenetics 13 (4): 191–212. January 2000. doi:10.3109/01677060009084494. PMID 10858820. 
  9. ↑ "Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain". FEBS Letters 534 (1–3): 26–32. January 2003. doi:10.1016/S0014-5793(02)03766-3. PMID 12527357. 
  10. ↑ "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. September 2005. doi:10.1016/j.cell.2005.08.029. PMID 16169070. 
  11. ↑ "ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and shared effectors: characterizing ARL1-binding proteins". The Journal of Biological Chemistry 276 (25): 22826–37. June 2001. doi:10.1074/jbc.M102359200. PMID 11303027. 
  12. ↑ 12.0 12.1 "Identification of UNC119 as a novel activator of SRC-type tyrosine kinases". The Journal of Biological Chemistry 278 (10): 8837–45. March 2003. doi:10.1074/jbc.M208261200. PMID 12496276. 
  13. ↑ "RIBEYE recruits Munc119, a mammalian ortholog of the Caenorhabditis elegans protein unc119, to synaptic ribbons of photoreceptor synapses". The Journal of Biological Chemistry 283 (39): 26461–7. September 2008. doi:10.1074/jbc.M801625200. PMID 18664567. 

Further reading

  • "Identification of UNC119 as a novel activator of SRC-type tyrosine kinases". The Journal of Biological Chemistry 278 (10): 8837–45. March 2003. doi:10.1074/jbc.M208261200. PMID 12496276. 
  • "Characterization of the gene for HRG4 (UNC119), a novel photoreceptor synaptic protein homologous to unc-119". Genomics 57 (3): 446–50. May 1999. doi:10.1006/geno.1999.5791. PMID 10329014. 
  • "Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain". FEBS Letters 534 (1–3): 26–32. January 2003. doi:10.1016/S0014-5793(02)03766-3. PMID 12527357. 
  • "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R. 
  • "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. September 2005. doi:10.1016/j.cell.2005.08.029. PMID 16169070. 
  • "Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors". Investigative Ophthalmology & Visual Science 39 (11): 2085–94. October 1998. PMID 9761287. 
  • "ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and shared effectors: characterizing ARL1-binding proteins". The Journal of Biological Chemistry 276 (25): 22826–37. June 2001. doi:10.1074/jbc.M102359200. PMID 11303027. 
  • "Unc119 regulates myofibroblast differentiation through the activation of Fyn and the p38 MAPK pathway". Journal of Immunology 179 (1): 682–90. July 2007. doi:10.4049/jimmunol.179.1.682. PMID 17579091. 

External links

  • Overview of all the structural information available in the PDB for UniProt: Q13432 (Protein unc-119 homolog A) at the PDBe-KB.




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