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Gene Review

CNTN3  -  contactin 3 (plasmacytoma associated)

Homo sapiens

Synonyms: BIG-1, Brain-derived immunoglobulin superfamily protein 1, Contactin-3, KIAA1496, PANG, ...
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Disease relevance of CNTN3

  • A new member of the immunoglobulin/fibronectin superfamily of adhesion molecules, Pang (plasmacytoma-associated neuronal glycoprotein), was recently isolated from a plasmacytoma [1].
  • Physical (PCS), mental (MCS), and kidney disease component summary (KDCS) scores were computed [2].
  • We consider PCS to be a valid alternative treatment for TTP relapses, and we have found that the best results are obtained when it is associated with anti-platelet agents [3].
  • RESULTS: Body weight was inversely correlated (level p<or=0.005) to the SF-36 items: physical functioning (PF, -0.452), role limitations due to physical functioning (-0.279), role limitations due to emotional functioning (-0.256), vitality (-0.200), general health (GH, -0.367) and physical component score (PCS, -0.400) [4].
  • Examination of the subscales within the FACT-P instrument demonstrated statistically significant changes over time for the following: physical well-being (PWB), functional well-being (FWB), and prostate cancer (PCS) [5].

Psychiatry related information on CNTN3

  • SF-36 Physical Health (PCS) and Mental Health (MCS) component scores were computed at baseline and after a 2-year follow-up [6].
  • The association of PCS and MCS with the presence of psychopathology (Marked or DSM IV discomfort) was assessed by means of logistic regression [7].
  • The favourable influence of PCS on the depressive syndrome is considered to be largely linked to the anticholinergic effect of the drugs [8].
  • OBJECTIVE: To examine aggression, antisocial behavior, and substance abuse in young adult survivors of pediatric cancer (PCS) relative to case control peers (CC) [9].
  • In contrast, recognized mood disorders demonstrated slightly higher PCS scores [10].

High impact information on CNTN3

  • By electron microscopy, Golgi membranes in BIG1-depleted cells were less sharply defined than those in mock or BIG2 siRNA-treated cells, with more vesicle-like structures at the transface [11].
  • These results indicate a previously unrecognized role for BIG1 in the glycosylation of beta1 by Golgi enzymes, which is critical for its function in developmental and other vital cell processes [11].
  • Mutation (712KPK714) of the nuclear localization signal inhibited BIG1 accumulation in nuclei, and PKA-catalyzed phosphorylation of S883, although necessary, was not sufficient for nuclear accumulation, as shown by the double mutation S883D/nuclear localization signal [12].
  • Biochemical analyses and immunofluorescence microscopy demonstrated BIG1 in nuclei as well as membranes and cytosol of serum-starved HepG2 cells [12].
  • A role for microtubules in cAMP-induced translocation of BIG1 is inferred from its inhibition by nocodazole [12].

Biological context of CNTN3


Anatomical context of CNTN3

  • Western blot analysis of subcellular fractions demonstrated translocation of BIG2 (and BIG1) from cytosol to the Golgi and other membrane structures after incubation of cells with 8-Br-cAMP or forskolin [16].
  • Binding of BIG1, BIG2, and ARF to membranes was also increased by L-732,531, an agonist structurally related to FK506, but was not increased by a related antagonist, L-685,818, nor by cyclosporin A or rapamycin [14].
  • Binding of BIG1, BIG2, and ARF to cell membranes in vitro was increased by guanosine 5'-[gamma-thio]triphosphate, and further increases were induced by FK506 [14].
  • The association was confirmed by immunoprecipitation of both endogenous BIG1 and FKBP13 from Jurkat T cells with antibodies against either one [14].
  • BIG1 was also identified by Western blot analyses in purified subnuclear fractions (e.g., nucleoli and nuclear matrix) [15].

Associations of CNTN3 with chemical compounds

  • Interestingly, we have found that AMY-1 interacts with BIG2 and BIG1, both of which are high molecular weight guanine-nucleotide exchange factors for ADP-ribosylation factors (ARFs) and mainly localize to the TGN [17].
  • Unlike the GEP activity of BIG1 and BIG2, the acceleration by cytohesins of guanine nucleotide exchange to generate active ARF-GTP is not inhibited by the fungal metabolite brefeldin, A (BFA) [18].
  • Mutant BIG1 (S883A) in which Ala replaced Ser-883, a putative PKA phosphorylation site, did not move to the nucleus with cAMP addition, whereas replacement with Asp (S883D) resulted in nuclear accumulation of BIG1 without or with cAMP exposure, consistent with the mechanistic importance of a negative charge at that site [12].
  • BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein, is required for correct glycosylation and function of integrin beta1 [11].
  • To examine these materials, differential scanning calorimetry (DSC), (1)H NMR, and temperature-programmed photon correlation spectroscopy (TP-PCS) have been employed [19].

Analytical, diagnostic and therapeutic context of CNTN3

  • Health status was assessed with the physical and mental component summary score of the SF-36 (PCS and MCS), the symptoms dimension of the KDQOL-SF, and the Karnofsky Scale [20].
  • Although protamine and mu appear to destabilize pDNA double helix character to similar extents, according to CD thermal titration analyses, PCS studies show that interactions between mu and pDNA result in the formation of significantly more size-stable condensed particles than protamine [21].
  • We submitted three patients in TTP relapse to plasma exchange with reinfusion of PCS [3].
  • Thirty-eight men who had cystectomy and ileal conduit had a mean PCS of 41.4 (8.5) and a mean MCS of 48.2 (10.7) [22].
  • BACKGROUND: Commonly used measures such as the Physical Component Scale of the Short Form 36-item health survey (PCS) are undefined at death, limiting longitudinal analyses to survivors, a healthier cohort that cannot be identified prospectively, and that might have had little change in health [23].


  1. Plasmacytoma-associated neuronal glycoprotein, Pang, maps to mouse chromosome 6 and human chromosome 3. Mock, B.A., Connelly, M.A., McBride, O.W., Kozak, C.A., Marcu, K.B. Genomics (1996) [Pubmed]
  2. Health-related quality of life predicts outcomes but is not affected by peritoneal clearance: The ADEMEX trial. Paniagua, R., Amato, D., Vonesh, E., Guo, A., Mujais, S. Kidney Int. (2005) [Pubmed]
  3. Refractory thrombotic thrombocytopenic purpura: successful treatment by plasmapheresis with plasma cryosupernatant. Molinari, E., Costamagna, L., Perotti, C., Isernia, P., Pagani, A., Salvaneschi, L. Haematologica (1993) [Pubmed]
  4. Body mass index and quality of life in community-dwelling patients with schizophrenia. Strassnig, M., Brar, J.S., Ganguli, R. Schizophr. Res. (2003) [Pubmed]
  5. A preliminary analysis of health-related quality of life in the first year after permanent source interstitial brachytherapy (PIB) for clinically localized prostate cancer. Lee, W.R., McQuellon, R.P., Harris-Henderson, K., Case, L.D., McCullough, D.L. Int. J. Radiat. Oncol. Biol. Phys. (2000) [Pubmed]
  6. Evaluating the performance of medicare fee-for-service providers using the health outcomes survey: a comparison of two methods. Trisolini, M.G., Smith, K.W., McCall, N.T., Pope, G.C., Klosterman, M. Medical care. (2005) [Pubmed]
  7. Efficacy of the SF-36 questionnaire in identifying obese patients with psychological discomfort. Callegari, A., Michelini, I., Sguazzin, C., Catona, A., Klersy, C. Obesity surgery : the official journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. (2005) [Pubmed]
  8. Clinical notes on the possible anticholinergic reversal of depressive syndromes. Ungvári, G., Karczag, I., Gerevich, J., Pethö, B. Pharmacopsychiatria. (1981) [Pubmed]
  9. Aggression, antisocial behavior, and substance abuse in survivors of pediatric cancer: possible protective effects of cancer and its treatment. Verrill, J.R., Schafer, J., Vannatta, K., Noll, R.B. Journal of pediatric psychology. (2000) [Pubmed]
  10. Health-related quality of life in primary care patients with recognized and unrecognized mood and anxiety disorders. Cass, A.R., Volk, R.J., Nease, D.E. International journal of psychiatry in medicine. (1999) [Pubmed]
  11. BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein, is required for correct glycosylation and function of integrin beta1. Shen, X., Hong, M.S., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  12. Effect of protein kinase A on accumulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei. Citterio, C., Jones, H.D., Pacheco-Rodriguez, G., Islam, A., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  13. Purification and cloning of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors. Togawa, A., Morinaga, N., Ogasawara, M., Moss, J., Vaughan, M. J. Biol. Chem. (1999) [Pubmed]
  14. Interaction of FK506-binding protein 13 with brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1): effects of FK506. Padilla, P.I., Chang, M.J., Pacheco-Rodriguez, G., Adamik, R., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  15. Nuclear localization and molecular partners of BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors. Padilla, P.I., Pacheco-Rodriguez, G., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  16. Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2). Li, H., Adamik, R., Pacheco-Rodriguez, G., Moss, J., Vaughan, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  17. AMY-1 (associate of Myc-1) localization to the trans-Golgi network through interacting with BIG2, a guanine-nucleotide exchange factor for ADP-ribosylation factors. Ishizaki, R., Shin, H.W., Iguchi-Ariga, S.M., Ariga, H., Nakayama, K. Genes Cells (2006) [Pubmed]
  18. Cytohesin-1: structure, function, and ARF activation. Pacheco-Rodriguez, G., Moss, J., Vaughan, M. Meth. Enzymol. (2005) [Pubmed]
  19. Tunable swelling kinetics in core--shell hydrogel nanoparticles. Gan, D., Lyon, L.A. J. Am. Chem. Soc. (2001) [Pubmed]
  20. Adjustment for comorbidity in studies on health status in ESRD patients: which comorbidity index to use? Van Manen, J.G., Korevaar, J.C., Dekker, F.W., Boeschoten, E.W., Bossuyt, P.M., Krediet, R.T. J. Am. Soc. Nephrol. (2003) [Pubmed]
  21. Biophysical characterization of the DNA binding and condensing properties of adenoviral core peptide mu. Keller, M., Tagawa, T., Preuss, M., Miller, A.D. Biochemistry (2002) [Pubmed]
  22. The type of urinary diversion after radical cystectomy significantly impacts on the patient's quality of life. McGuire, M.S., Grimaldi, G., Grotas, J., Russo, P. Ann. Surg. Oncol. (2000) [Pubmed]
  23. Accounting for deaths in longitudinal studies using the SF-36: the performance of the Physical Component Scale of the Short Form 36-item health survey and the PCTD. Diehr, P., Patrick, D.L., McDonell, M.B., Fihn, S.D. Medical care. (2003) [Pubmed]
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