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WDR48  -  WD repeat domain 48

Homo sapiens

Synonyms: KIAA1449, P80, SPG60, UAF1, USP1-associated factor 1, ...
 
 
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Disease relevance of WDR48

  • Distinct roles of cellular Lck and p80 proteins in herpesvirus saimiri Tip function on lipid rafts [1].
  • TP3-pokeweed antiviral protein (PAP) immunotoxin is directed against the p80 antigen on osteosarcoma cells [2].
  • A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80) [3].
  • Peak tetanus tension at 20 and 80 Hz (P20 and P80, respectively) declined (P<0.001), concurrently with a decrement of the P20 x P80(-1) ratio (-37.3+/-16.6%; P<0.001) [4].
  • In Mycoplasma hominis, HinT is concomitantly expressed with the proteins P60 and P80, two domains of a surface exposed membrane complex, and in addition interacts with the P80 moiety [5].
 

Psychiatry related information on WDR48

  • METHODS: Behavioral measures, including prepulse inhibition (PPI) and total locomotor activity, after amphetamine exposure were assessed at postnatal day 20 (P20) (prepuberty), P40 (puberty), P60 (postpuberty), and P80 (adulthood) in animals previously exposed to allopregnanolone (10 mg/kg) on P2 and P5 [6].
 

High impact information on WDR48

  • Herpesviral protein targets a cellular WD repeat endosomal protein to downregulate T lymphocyte receptor expression [7].
  • Remarkably, these actions of Tip are functionally and genetically separable: the N-terminal p80 interaction is responsible for TCR downregulation and the C-terminal Lck interaction is responsible for CD4 downregulation [7].
  • Consequently, Tip interactions with Lck and p80 result in downregulation of T cell receptor (TCR) and CD4 surface expression [7].
  • Here we demonstrate that Tip targets a lysosomal protein p80, which consists of an N-terminal WD repeat domain and a C-terminal coiled-coil domain [7].
  • Interaction of Tip with p80 facilitated lysosomal vesicle formation and subsequent recruitment of Lck into the lysosomes for degradation [7].
 

Chemical compound and disease context of WDR48

 

Biological context of WDR48

 

Anatomical context of WDR48

  • We purified the 80-kilodalton protein (p80) to homogeneity by detergent solubilization of promastigote membranes, immunoaffinity chromatography, and ion-exchange chromatography [12].
  • We studied axon order in the primary visual pathway and in nine retinorecipient nuclei of a small marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata) using animals at postnatal day (P) 40 and P80 [13].
  • We have identified an 80 kDa protein in ejaculated bull spermatozoa (p80) which is found in acrosomal and post-acrosomal areas of the head [10].
  • The localization of p80 on spermatozoa, determined by indirect immunofluorescence using a monoclonal antibody, shows the protein in acrosomal and post acrosomal areas of the head with an increase in the signal intensity as sperm progress through the epididymis [10].
 

Associations of WDR48 with chemical compounds

  • Thus, the signaling and targeting functions of HVS Tip rely on two functionally and genetically separable mechanisms that independently target cellular Lck tyrosine kinase and p80 endosomal protein [1].
  • Ketamine increased P20/N40 amplitude and decreased P80 amplitude [14].
  • An exploratory in-vivo study was performed in the pig with phosphatidylserine in two formulations; either in the form of PS/PC liposomes or together with Polysorbate 80 in the form of mixed micelles (phosphatidylserine/P80) [15].
  • It has now been investigated whether histamine inhibits lymphokine production by various subsets of CD4+ human T cells separated with the Leu-8 (p80) and Leu-18 (anti-CD45R;p220) monoclonal antibodies (MoAb) [16].
  • Both complexes contain the UAF1 protein as a bona fide subunit [17].

References

  1. Distinct roles of cellular Lck and p80 proteins in herpesvirus saimiri Tip function on lipid rafts. Park, J., Cho, N.H., Choi, J.K., Feng, P., Choe, J., Jung, J.U. J. Virol. (2003) [Pubmed]
  2. Antitumor activity of TP3(anti-p80)-pokeweed antiviral protein immunotoxin in hamster cheek pouch and severe combined immunodeficient mouse xenograft models of human osteosarcoma. Ek, O., Waurzyniak, B., Myers, D.E., Uckun, F.M. Clin. Cancer Res. (1998) [Pubmed]
  3. Expression of the ALK protein by anaplastic large-cell lymphomas correlates with high proliferative activity. Leoncini, L., Lazzi, S., Scano, D., Mura, A., Onida, A., Massarelli, G., Tosi, P., Barbini, P., Cevenini, G., Massai, M.R., Pileri, S., Falini, B., Giordano, A., Kraft, R., Laissue, J.A., Cottier, H. Int. J. Cancer (2000) [Pubmed]
  4. Why does knee extensor muscles torque decrease after eccentric-type exercise? Martin, V., Millet, G.Y., Lattier, G., Perrod, L. The Journal of sports medicine and physical fitness. (2005) [Pubmed]
  5. HinT proteins and their putative interaction partners in Mollicutes and Chlamydiaceae. Hopfe, M., Hegemann, J.H., Henrich, B. BMC Microbiol. (2005) [Pubmed]
  6. Neonatal neurosteroid administration results in development-specific alterations in prepulse inhibition and locomotor activity: neurosteroids alter prepulse inhibition and locomotor activity. Gizerian, S.S., Moy, S.S., Lieberman, J.A., Grobin, A.C. Psychopharmacology (Berl.) (2006) [Pubmed]
  7. Herpesviral protein targets a cellular WD repeat endosomal protein to downregulate T lymphocyte receptor expression. Park, J., Lee, B.S., Choi, J.K., Means, R.E., Choe, J., Jung, J.U. Immunity (2002) [Pubmed]
  8. Role of antigen selectivity in autoimmune responses to the Ku (p70/p80) antigen. Reeves, W.H., Sthoeger, Z.M., Lahita, R.G. J. Clin. Invest. (1989) [Pubmed]
  9. Effects of chronic olanzapine and haloperidol differ on the mouse N1 auditory evoked potential. Maxwell, C.R., Liang, Y., Weightman, B.D., Kanes, S.J., Abel, T., Gur, R.E., Turetsky, B.I., Bilker, W.B., Lenox, R.H., Siegel, S.J. Neuropsychopharmacology (2004) [Pubmed]
  10. Identification of the bull sperm p80 protein as a PH-20 ortholog and its modification during the epididymal transit. Morin, G., Lalancette, C., Sullivan, R., Leclerc, P. Mol. Reprod. Dev. (2005) [Pubmed]
  11. p130-Angiomotin associates to actin and controls endothelial cell shape. Ernkvist, M., Aase, K., Ukomadu, C., Wohlschlegel, J., Blackman, R., Veitonmäki, N., Bratt, A., Dutta, A., Holmgren, L. FEBS J. (2006) [Pubmed]
  12. Purification and characterization of an 80-kilodalton membrane protein from Leishmania donovani. White, A.C., McMahon-Pratt, D. Infect. Immun. (1988) [Pubmed]
  13. Topographic order of retinofugal axons in a marsupial: implications for map formation in visual nuclei. Dunlop, S.A., Tee, L.B., Beazley, L.D. J. Comp. Neurol. (2000) [Pubmed]
  14. The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components. Connolly, P.M., Maxwell, C., Liang, Y., Kahn, J.B., Kanes, S.J., Abel, T., Gur, R.E., Turetsky, B.I., Siegel, S.J. Neurochem. Res. (2004) [Pubmed]
  15. Recombinant factor VIII SQ--stability of VIII: C in homogenates from porcine, monkey and human subcutaneous tissue. Fatouros, A., Lidén, Y., Sjöström, B. J. Pharm. Pharmacol. (2000) [Pubmed]
  16. Inhibitory effects of histamine on interleukin 2 and gamma interferon production of different human T helper cell subsets. Dohlsten, M., Hedlund, G., Sjögren, H.O., Carlsson, R. Scand. J. Immunol. (1988) [Pubmed]
  17. UAF1 is a subunit of multiple deubiquitinating enzyme complexes. Cohn, M.A., Kee, Y., Haas, W., Gygi, S.P., D'Andrea, A.D. J. Biol. Chem. (2009) [Pubmed]
 
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