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Gene Review

NSFL1C  -  NSFL1 (p97) cofactor (p47)

Homo sapiens

Synonyms: NSFL1 cofactor p47, P47, UBX domain-containing protein 2C, UBX1, UBXD10, ...
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Disease relevance of NSFL1C

  • Elimination of different p47 GTPases in mice by gene targeting severely cripples IFN-gamma-regulated defence against Toxoplasma gondii, Listeria monocytogenes, Mycobacterium spp. and other pathogens [1].

High impact information on NSFL1C

  • p47 is a cofactor for p97-mediated membrane fusion [2].
  • Here, we report the three-dimensional cryo-electron microscopy structures at approximately 20 A resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion [3].
  • The p47 SEP domain adopts a novel fold with a betabetabetaalphaalphabeta secondary structure arrangement, where beta4 pairs in a parallel fashion to beta1 [4].
  • The phosphorylated p47 does not bind to Golgi membranes [5].
  • The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle [5].

Biological context of NSFL1C

  • For the cell-cycle regulation of the p97/p47 pathway, it has been reported that the localization and phosphorylation-dephosphorylation of p47 are crucial [6].
  • One of these p47 GTPases (Iigp1) was shown by small interfering RNA silencing experiments to specifically inhibit human strains, but not the mouse strain [7].
  • With most stimuli activation of the oxidase is accompanied by multisite phosphorylation of the 47-kDa cytosolic oxidase factor (p47) which translocates from cytosol to membranes [8].
  • PPARgamma-mediated down-regulation of p47 phagocyte oxidase, a component of the NAD(P)H oxidase system, was identified as one molecular mechanism causing inhibition of superoxide radical formation [9].
  • Transcriptional mapping demonstrated that an early 4.2-kb RNA encoded the p47 open reading frame and probably overlapped the 39K delayed-early gene [10].

Anatomical context of NSFL1C


Associations of NSFL1C with chemical compounds

  • In the cytosol of phorbol myristate acetate-activated neutrophils eight distinct p47 phosphoproteins were present [8].
  • Platelets adhered to the immobilized octapeptide, and anti-bodies directed against other platelet collagen receptors (glycoprotein (GP) Ia/IIa, GP IV, p65, p47) did not impair this adhesion [14].
  • In the presence of 16.7 mmol/l glucose protein production of p47( phox ) was increased by 1.7-fold in isolated rat islets after 1 h, while in the presence of 0.1 mmol/l palmitic acid or 5 ng/ml IL-1beta it was increased by 1.4-fold or 1.8-fold, respectively [15].
  • RESULTS: Incubation for 24 h in 0.1 mmol/l palmitic acid or a pro-inflammatory cytokine cocktail increased p47( phox ) protein production by 1.5-fold or by 1.75-fold, respectively, in the BRIN BD11 beta cell line [15].
  • Both BAPTA and Ro 31-8220 prevented 5HT secretion from intact platelets; however, in Ca2+-depleted, -permeable platelets, cathepsin G was able to evoke 5HT secretion and p47 phosphorylation independently of [Ca2+]i increase, both effects being hampered by Ro 31-8220 [16].

Physical interactions of NSFL1C

  • Additional recent findings suggest that ER maintenance also requires ongoing homotypic membrane fusion, possibly controlled by the p97/p47/VICP135 protein complex [17].

Other interactions of NSFL1C

  • The principal role of the p97-p47 complex is in regulation of membrane fusion events [4].
  • A second essential cofactor, VCIP135, was identified as a p97/p47/syntaxin5-interacting protein [6].
  • The N-terminal domain of valosine-containing protein serves as an interface to its adaptor proteins p47 and Ufd1, whereas the physiologic interaction partner of the N-terminal domain of PEX1 remains unknown [18].

Analytical, diagnostic and therapeutic context of NSFL1C


  1. p47 GTPases: regulators of immunity to intracellular pathogens. Taylor, G.A., Feng, C.G., Sher, A. Nat. Rev. Immunol. (2004) [Pubmed]
  2. p47 is a cofactor for p97-mediated membrane fusion. Kondo, H., Rabouille, C., Newman, R., Levine, T.P., Pappin, D., Freemont, P., Warren, G. Nature (1997) [Pubmed]
  3. Conformational changes in the AAA ATPase p97-p47 adaptor complex. Beuron, F., Dreveny, I., Yuan, X., Pye, V.E., McKeown, C., Briggs, L.C., Cliff, M.J., Kaneko, Y., Wallis, R., Isaacson, R.L., Ladbury, J.E., Matthews, S.J., Kondo, H., Zhang, X., Freemont, P.S. EMBO J. (2006) [Pubmed]
  4. Structure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97. Yuan, X., Simpson, P., McKeown, C., Kondo, H., Uchiyama, K., Wallis, R., Dreveny, I., Keetch, C., Zhang, X., Robinson, C., Freemont, P., Matthews, S. EMBO J. (2004) [Pubmed]
  5. The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle. Uchiyama, K., Jokitalo, E., Lindman, M., Jackman, M., Kano, F., Murata, M., Zhang, X., Kondo, H. J. Cell Biol. (2003) [Pubmed]
  6. p97/p47-Mediated biogenesis of Golgi and ER. Uchiyama, K., Kondo, H. J. Biochem. (2005) [Pubmed]
  7. Chlamydial IFN-gamma immune evasion is linked to host infection tropism. Nelson, D.E., Virok, D.P., Wood, H., Roshick, C., Johnson, R.M., Whitmire, W.M., Crane, D.D., Steele-Mortimer, O., Kari, L., McClarty, G., Caldwell, H.D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Phosphorylation of neutrophil 47-kDa cytosolic oxidase factor. Translocation to membrane is associated with distinct phosphorylation events. Rotrosen, D., Leto, T.L. J. Biol. Chem. (1990) [Pubmed]
  9. Activation of peroxisome proliferator-activated receptor gamma by nitric oxide in monocytes/macrophages down-regulates p47phox and attenuates the respiratory burst. Von Knethen, A., Brüne, B. J. Immunol. (2002) [Pubmed]
  10. Sequence, transcriptional mapping, and overexpression of p47, a baculovirus gene regulating late gene expression. Carstens, E.B., Lu, A.L., Chan, H.L. J. Virol. (1993) [Pubmed]
  11. Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1-Npl4. Meyer, H.H., Wang, Y., Warren, G. EMBO J. (2002) [Pubmed]
  12. p37 Is a p97 Adaptor Required for Golgi and ER Biogenesis in Interphase and at the End of Mitosis. Uchiyama, K., Totsukawa, G., Puhka, M., Kaneko, Y., Jokitalo, E., Dreveny, I., Beuron, F., Zhang, X., Freemont, P., Kondo, H. Dev. Cell (2006) [Pubmed]
  13. Functional reconstitution of the phagocyte NADPH oxidase by transfection of its multiple components in a heterologous system. de Mendez, I., Leto, T.L. Blood (1995) [Pubmed]
  14. A new platelet receptor specific to type III collagen. Type III collagen-binding protein. Monnet, E., Fauvel-Lafève, F. J. Biol. Chem. (2000) [Pubmed]
  15. Glucose, palmitate and pro-inflammatory cytokines modulate production and activity of a phagocyte-like NADPH oxidase in rat pancreatic islets and a clonal beta cell line. Morgan, D., Oliveira-Emilio, H.R., Keane, D., Hirata, A.E., Santos da Rocha, M., Bordin, S., Curi, R., Newsholme, P., Carpinelli, A.R. Diabetologia (2007) [Pubmed]
  16. Different requirement of intracellular calcium and protein kinase C for arachidonic acid release and serotonin secretion in cathepsin G-activated platelets. Rotondo, S., Evangelista, V., Manarini, S., de Gaetano, G., Cerletti, C. Thromb. Haemost. (1997) [Pubmed]
  17. Morphogenesis of the endoplasmic reticulum: beyond active membrane expansion. Vedrenne, C., Hauri, H.P. Traffic (2006) [Pubmed]
  18. The common phospholipid-binding activity of the N-terminal domains of PEX1 and VCP/p97. Shiozawa, K., Goda, N., Shimizu, T., Mizuguchi, K., Kondo, N., Shimozawa, N., Shirakawa, M., Hiroaki, H. FEBS J. (2006) [Pubmed]
  19. Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape. McCaffrey, R.L., Allen, L.A. J. Leukoc. Biol. (2006) [Pubmed]
  20. Autophagic Elimination of Intracellular Parasites: Convergent Induction by IFN-gamma and CD40 Ligation? Yap, G.S., Ling, Y., Zhao, Y. Autophagy (2007) [Pubmed]
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