Uncoordinated-119 (Unc-119)

Last updated
UNC119
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases UNC119 , HRG4, IMD13, POC7, POC7A, Protein unc-119 homolog, unc-119 lipid binding chaperone
External IDs MGI: 1328357; HomoloGene: 3778; GeneCards: UNC119; OMA:UNC119 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9094

22248

Ensembl

ENSG00000109103

ENSMUSG00000002058

UniProt

Q13432

Q9Z2R6

RefSeq (mRNA)

NM_005148
NM_054035
NM_001330166

NM_011676
NM_001313985
NM_001313986
NM_001313987
NM_001313988

Contents

RefSeq (protein)

NP_001317095
NP_005139
NP_473376

NP_001300914
NP_001300915
NP_001300916
NP_001300917
NP_035806

Location (UCSC) Chr 17: 28.55 – 28.55 Mb Chr 11: 78.23 – 78.24 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] This proteins have been classified in the GMP phosphodiesterase, delta superfamily. [6] 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 [7] with a mass of around ~26 kDa. [8] Using x-ray crystallography the protein's crystal structure was observed and found to have a resolution of 1.95 Å. [9] It has an immunoglobulin-like β-sandwich folding structure, resulting in a narrow, hydrophobic pocket. [10] This pocket can bind to lauroyl (C12) and myristoyl (C14) acyltransferase side chains, functioning as a transporter or lipid-binding chaperone. [9] 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. [11] [12]

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. [10] 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. [12]

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. [10] It has also been found to play an important role within the T-cell receptor function [8] 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. [9]

Interactions

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

Related Research Articles

<span class="mw-page-title-main">CD4</span> Marker on immune cells

In molecular biology, CD4 is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984. In humans, the CD4 protein is encoded by the CD4 gene.

<span class="mw-page-title-main">Tyrosin-protein kinase Lck</span> Lymphocyte protein

Tyrosin-protein kinase Lck is a 56 kDa protein that is found inside lymphocytes and encoded in the human by the LCK gene. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

<span class="mw-page-title-main">ADP ribosylation factor</span> Group of proteins

ADP ribosylation factors (ARFs) are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally associate with membranes because of N-terminus myristoylation. They function as regulators of vesicular traffic and actin remodelling.

<span class="mw-page-title-main">Recoverin</span> Protein-coding gene in the species Homo sapiens

Recoverin is a 23 kilodalton (kDa) neuronal calcium-binding protein that is primarily detected in the photoreceptor cells of the eye. It plays a key role in the inhibition of rhodopsin kinase, a molecule which regulates the phosphorylation of rhodopsin. A reduction in this inhibition helps regulate sensory adaptation in the retina, since the light-dependent channel closure in photoreceptors causes calcium levels to decrease, which relieves the inhibition of rhodopsin kinase by calcium-bound recoverin, leading to a more rapid inactivation of metarhodopsin II.

<span class="mw-page-title-main">Linker for activation of T cells</span> Protein-coding gene in the species Homo sapiens

The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein involved in the T-cell antigen receptor signal transduction pathway which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.

<span class="mw-page-title-main">FYN</span> Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.

<span class="mw-page-title-main">LYN</span> Mammalian protein found in Homo sapiens

Tyrosine-protein kinase Lyn is a protein that in humans is encoded by the LYN gene.

<span class="mw-page-title-main">PTPN6</span> Protein-coding gene in humans

Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.

<span class="mw-page-title-main">T-cell surface glycoprotein CD3 zeta chain</span> Protein-coding gene in the species Homo sapiens

T-cell surface glycoprotein CD3 zeta chain also known as T-cell receptor T3 zeta chain or CD247 is a protein that in humans is encoded by the CD247 gene.

<span class="mw-page-title-main">DLG4</span> Mammalian protein found in Homo sapiens

PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene.

<span class="mw-page-title-main">PTK2B</span> Protein-coding gene in humans

Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.

<span class="mw-page-title-main">ARHGEF7</span> Protein-coding gene in humans

Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.

<span class="mw-page-title-main">GIT1</span> Protein-coding gene in humans

ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene.

<span class="mw-page-title-main">FYB</span> Protein-coding gene in the species Homo sapiens

FYN binding protein (FYB-120/130), also known as FYB, ADAP, and SLAP-130 is a protein that is encoded by the FYB gene in humans. The protein is expressed in T cells, monocytes, mast cells, macrophages, NK cells, but not B cells. FYB is a multifunctional protein involved in post-activation T cell signaling, lymphocyte cytokine production, cell adhesion, and actin remodeling.

<span class="mw-page-title-main">ARR3</span> Protein-coding gene in humans

Arrestin-C, also known as retinal cone arrestin-3, is a protein that in humans is encoded by the ARR3 gene.

<span class="mw-page-title-main">ARL3</span> Protein-coding gene in the species Homo sapiens

ADP-ribosylation factor-like protein 3 is a protein that in humans is encoded by the ARL3 gene.

<span class="mw-page-title-main">UNC13B</span> Protein-coding gene in the species Homo sapiens

Protein unc-13 homolog B is a protein that in humans is encoded by the UNC13B gene.

<span class="mw-page-title-main">ARL1</span> Protein-coding gene in humans

ADP-ribosylation factor-like protein 1 is a protein that in humans is encoded by the ARL1 gene.

<span class="mw-page-title-main">ARL2</span> Protein-coding gene in the species Homo sapiens

ADP-ribosylation factor-like protein 2 is a protein that in humans is encoded by the ARL2 gene.

<span class="mw-page-title-main">RICS (gene)</span> Protein-coding gene in the species Homo sapiens

Rho GTPase-activating protein 32 is a protein that in humans is encoded by the RICS gene. RICS has two known isoforms, RICS that are expressed primarily at neurite growth cones, and at the post synaptic membranes, and PX-RICS which is more widely expressed in the endoplasmic reticulum, Golgi apparatus and endosomes. The only known domain of the RICS is the RhoGAP domain, whilst PX-RICS has an additional Phox homology and SH3 domain.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000109103 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000002058 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Swanson DA, Chang JT, Campochiaro PA, Zack DJ, Valle D (October 1998). "Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors". Investigative Ophthalmology & Visual Science. 39 (11): 2085–94. PMID   9761287.
  6. ↑ Fansa EK, Wittinghofer A (October 2016). "Sorting of lipidated cargo by the Arl2/Arl3 system". Small GTPases. 7 (4): 222–230. doi:10.1080/21541248.2016.1224454. PMC   5129900 . PMID   27806215.
  7. ↑ Maduro M, Pilgrim D (November 1995). "Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system". Genetics. 141 (3): 977–88. doi:10.1093/genetics/141.3.977. PMC   1206859 . PMID   8582641.
  8. 1 2 3 4 5 6 Gorska MM, Stafford SJ, Cen O, Sur S, Alam R (February 2004). "Unc119, a novel activator of Lck/Fyn, is essential for T cell activation". The Journal of Experimental Medicine. 199 (3): 369–79. doi:10.1084/jem.20030589. PMC   2211793 . PMID   14757743.
  9. 1 2 3 Constantine R, Zhang H, Gerstner CD, Frederick JM, Baehr W (December 2012). "Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins". Vision Research. 75: 26–32. doi:10.1016/j.visres.2012.08.012. PMC   3514684 . PMID   23000199.
  10. 1 2 3 Jean F, Pilgrim D (October 2017). "Coordinating the uncoordinated: UNC119 trafficking in cilia". European Journal of Cell Biology. 96 (7): 643–652. doi:10.1016/j.ejcb.2017.09.001. PMID   28935136.
  11. ↑ Lee Y, Chung S, Baek IK, Lee TH, Paik SY, Lee J (April 2013). "UNC119a bridges the transmission of Fyn signals to Rab11, leading to the completion of cytokinesis". Cell Cycle. 12 (8): 1303–1315. doi:10.4161/cc.24404. PMC   3674094 . PMID   23535298.
  12. 1 2 Maduro MF, Gordon M, Jacobs R, Pilgrim DB (January 2000). "The UNC-119 family of neural proteins is functionally conserved between humans, Drosophila and C. elegans". Journal of Neurogenetics. 13 (4): 191–212. doi:10.3109/01677060009084494. PMID   10858820. S2CID   36103225.
  13. ↑ Kobayashi A, Kubota S, Mori N, McLaren MJ, Inana G (January 2003). "Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain". FEBS Letters. 534 (1–3): 26–32. doi: 10.1016/S0014-5793(02)03766-3 . PMID   12527357. S2CID   22603052.
  14. ↑ Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl: 11858/00-001M-0000-0010-8592-0 . PMID   16169070. S2CID   8235923.
  15. ↑ Van Valkenburgh H, Shern JF, Sharer JD, Zhu X, Kahn RA (June 2001). "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. doi: 10.1074/jbc.M102359200 . PMID   11303027.
  16. 1 2 Cen O, Gorska MM, Stafford SJ, Sur S, Alam R (March 2003). "Identification of UNC119 as a novel activator of SRC-type tyrosine kinases". The Journal of Biological Chemistry. 278 (10): 8837–45. doi: 10.1074/jbc.M208261200 . PMID   12496276.
  17. ↑ Alpadi K, Magupalli VG, Käppel S, Köblitz L, Schwarz K, Seigel GM, Sung CH, Schmitz F (September 2008). "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. doi: 10.1074/jbc.M801625200 . PMC   3258921 . PMID   18664567.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.