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Gene Review

TRIM23  -  tripartite motif containing 23

Homo sapiens

Synonyms: ADP-ribosylation factor domain-containing protein 1, ARD1, ARFD1, E3 ubiquitin-protein ligase TRIM23, GTP-binding protein ARD-1, ...
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Disease relevance of TRIM23

  • In H1299 and A549 lung cancer cells, hARD1-silencing RNA inhibited cell proliferation and induced G(1) arrest [1].
  • Addition of the 46-kDa amino-terminal extension (similarly synthesized in E. coli) to the GTP-binding ARF-domain of ARD1 enhanced GTPase activity and inhibited GDP dissociation [2].
  • Down-regulation of the expression of the FIH-1 and ARD-1 genes at the transcriptional level by nickel and cobalt in the human lung adenocarcinoma A549 cell line [3].

High impact information on TRIM23


Biological context of TRIM23


Anatomical context of TRIM23

  • In transfected COS-7 cells, overexpressed ARD1 and cytohesin-1 were partially colocalized, as determined by confocal fluorescence microscopy [6].
  • ARD1, expressed as a green fluorescent fusion protein, was initially associated with the Golgi network and subsequently appeared on lysosomes, suggesting that ARD1 might undergo vectorial transport between the two organelles [8].

Associations of TRIM23 with chemical compounds

  • Association of ARD1 with the Golgi apparatus required tyrosine-based motifs [8].
  • In addition, hARD1 forms protofilaments under physiological conditions of pH and temperature, as judged by electron microscopy and staining with the dyes Congo red and thioflavin T [9].
  • In NB4 cells undergoing retinoic acid mediated differentiation, the level of endogenous hARD1 and NATH protein decreases while the level of hARD2 protein is stable [10].
  • ARD-1, the acetyltransferase, acetylates HIF-1a at lysine 532, which enhances the interaction of HIF-1a with pVHL [3].
  • Independent predictors of ARFD (n = 23) were: baseline GFR (OR 0.98, CI 0.96-0.99, p = 0.012), pulmonary diagnosis other than COPD (OR 6.80, CI 1.5-30.89, p = 0.013), mechanical ventilation > 1 d (OR 6.16, CI 1.70-22.24, p = 0.006) and parenteral amphotericin B use (OR 3.04, CI 1.03-8.98, p = 0.045) [11].

Other interactions of TRIM23

  • The effector region of the ARF domain of ARD1 appeared to be critical for the specific interaction with cytohesin-1 [6].
  • In agreement, cytohesin-1, but not cytohesin-2, markedly accelerated [(35)S]guanosine 5'-3-O-(thio)triphosphate binding to ARD1 [6].
  • The rate of GDP dissociation from the C-terminal ARF domain in ARD1, is slowed by the adjacent 15 amino acids, which act as a GDP-dissociation inhibitor (GDI) domain [12].

Analytical, diagnostic and therapeutic context of TRIM23


  1. Human Arrest Defective 1 Acetylates and Activates {beta}-Catenin, Promoting Lung Cancer Cell Proliferation. Lim, J.H., Park, J.W., Chun, Y.S. Cancer Res. (2006) [Pubmed]
  2. ARD1, a 64-kDa bifunctional protein containing an 18-kDa GTP-binding ADP-ribosylation factor domain and a 46-kDa GTPase-activating domain. Vitale, N., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Down-regulation of the expression of the FIH-1 and ARD-1 genes at the transcriptional level by nickel and cobalt in the human lung adenocarcinoma A549 cell line. Ke, Q., Kluz, T., Costa, M. International journal of environmental research and public health [electronic resource]. (2005) [Pubmed]
  4. E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1). Vichi, A., Payne, D.M., Pacheco-Rodriguez, G., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Localization of ADP-ribosylation factor domain protein 1 (ARD1) in lysosomes and Golgi apparatus. Vitale, N., Horiba, K., Ferrans, V.J., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  6. Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1). Vitale, N., Pacheco-Rodriguez, G., Ferrans, V.J., Riemenschneider, W., Moss, J., Vaughan, M. J. Biol. Chem. (2000) [Pubmed]
  7. Molecular characterization of the GTPase-activating domain of ADP-ribosylation factor domain protein 1 (ARD1). Vitale, N., Moss, J., Vaughan, M. J. Biol. Chem. (1998) [Pubmed]
  8. Identification of lysosomal and Golgi localization signals in GAP and ARF domains of ARF domain protein 1. Vitale, N., Ferrans, V.J., Moss, J., Vaughan, M. Mol. Cell. Biol. (2000) [Pubmed]
  9. Characterization of the native and fibrillar conformation of the human Nalpha-acetyltransferase ARD1. Sánchez-Puig, N., Fersht, A.R. Protein Sci. (2006) [Pubmed]
  10. Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-alpha-acetyltransferase. Arnesen, T., Betts, M.J., Pendino, F., Liberles, D.A., Anderson, D., Caro, J., Kong, X., Varhaug, J.E., Lillehaug, J.R. BMC Biochem. (2006) [Pubmed]
  11. Acute renal failure after lung transplantation: incidence, predictors and impact on perioperative morbidity and mortality. Rocha, P.N., Rocha, A.T., Palmer, S.M., Davis, R.D., Smith, S.R. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2005) [Pubmed]
  12. ADP-ribosylation factor domain protein 1 (ARD1), a multifunctional protein with ubiquitin E3 ligase, GAP, and ARF domains. Vichi, A., Moss, J., Vaughan, M. Meth. Enzymol. (2005) [Pubmed]
  13. Characterization of a GDP dissociation inhibitory region of ADP-ribosylation factor domain protein ARD1. Vitale, N., Moss, J., Vaughan, M. J. Biol. Chem. (1997) [Pubmed]
  14. Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis. Chang, C.C., Lin, M.T., Lin, B.R., Jeng, Y.M., Chen, S.T., Chu, C.Y., Chen, R.J., Chang, K.J., Yang, P.C., Kuo, M.L. J. Natl. Cancer Inst. (2006) [Pubmed]
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