Uncoordinated-119 (Unc-119)

Uncoordinated-119 (Unc-119) is a protein identified in a varieties of species including, C. elegans, humans, mice, zebrafish, rabbits, pig, calf, monkey, and protozoa. This proteins have been classified in the GMP phosphodiesterase, delta superfamily. Although Unc-119 proteins are categorized into their own family, they are shown to be ancestrally related to PrBP (prenyl binding protein) and rhoGDI. They are also known by several other names: Retinal Protein 4, HRG4, POC7 Centriolar Protein Homolog A, IMD13, POC7A, and RG4.

Structure and function
In C. elegans, Unc-119 consistent of approximately 240 amino acids with a mass of around ~26 kDa. Using x-ray crystallography the protein's crystal structure was observed and found to have a resolution of 1.95 Å. It has an immunoglobulin-like β-sandwich folding structure, resulting in a narrow, hydrophobic pocket. This pocket can bind to lauroyl (C12) and myristoyl (C14) acyltransferase side chains, functioning as a transporter or lipid-binding chaperone. Unc-119 is crucial for the motility of cilium, maintaining their formation and function. This role 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.

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. 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.

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. It has also been found to play an important role within the T-cell receptor function 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 disorder known as idiopathic CD4 lymphopenia (ICL) due to the reduced t-cell stimulation.

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


 * ARL2
 * ARL3
 * CD247
 * CD4
 * FYN
 * IL5RA
 * LYN
 * Lck
 * RIBEYE