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. 1996 Nov;5(11):2353–2357. doi: 10.1002/pro.5560051122

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains?

C P Ponting 1
PMCID: PMC2143296  PMID: 8931154

Abstract

Two SH3 domain-containing cytosolic components of the NADPH oxidase, p47phox and p40phox, are shown by analyses of their sequences to contain single copies of a novel class of domain, the PX (phox) domain. Homologous domains are demonstrated to be present in the Cpk class of phosphatidylinositol 3-kinase, S. cerevisiae Bem1p, and S. pombe Scd2, and a large family of human sorting nexin 1 (SNX1) homologues. The majority of these domains contains a polyproline motif, typical of SH3 domain-binding proteins. Two further findings are reported. A third NADPH oxidase subunit, p67phox, is shown to contain four tetratricopeptide repeats (TPRs) within its N-terminal RaclGTP-binding region, and a 28 residue motif in p40phox is demonstrated to be present in protein kinase C isoforms iota/lambda and zeta, and in three ZZ domain-containing proteins.

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Selected References

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  1. Birney E., Thompson J. D., Gibson T. J. PairWise and SearchWise: finding the optimal alignment in a simultaneous comparison of a protein profile against all DNA translation frames. Nucleic Acids Res. 1996 Jul 15;24(14):2730–2739. doi: 10.1093/nar/24.14.2730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Campbell I. G., Nicolai H. M., Foulkes W. D., Senger G., Stamp G. W., Allan G., Boyer C., Jones K., Bast R. C., Jr, Solomon E. A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1. Hum Mol Genet. 1994 Apr;3(4):589–594. doi: 10.1093/hmg/3.4.589. [DOI] [PubMed] [Google Scholar]
  3. Castresana J., Saraste M. Does Vav bind to F-actin through a CH domain? FEBS Lett. 1995 Oct 30;374(2):149–151. doi: 10.1016/0014-5793(95)01098-y. [DOI] [PubMed] [Google Scholar]
  4. Chan D. C., Bedford M. T., Leder P. Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains. EMBO J. 1996 Mar 1;15(5):1045–1054. [PMC free article] [PubMed] [Google Scholar]
  5. Chang E. C., Barr M., Wang Y., Jung V., Xu H. P., Wigler M. H. Cooperative interaction of S. pombe proteins required for mating and morphogenesis. Cell. 1994 Oct 7;79(1):131–141. doi: 10.1016/0092-8674(94)90406-5. [DOI] [PubMed] [Google Scholar]
  6. Chenevert J. Cell polarization directed by extracellular cues in yeast. Mol Biol Cell. 1994 Nov;5(11):1169–1175. doi: 10.1091/mbc.5.11.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dezelee S., Bras F., Contamine D., Lopez-Ferber M., Segretain D., Teninges D. Molecular analysis of ref(2)P, a Drosophila gene implicated in sigma rhabdovirus multiplication and necessary for male fertility. EMBO J. 1989 Nov;8(11):3437–3446. doi: 10.1002/j.1460-2075.1989.tb08508.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Diekmann D., Abo A., Johnston C., Segal A. W., Hall A. Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity. Science. 1994 Jul 22;265(5171):531–533. doi: 10.1126/science.8036496. [DOI] [PubMed] [Google Scholar]
  9. Ding J., Vlahos C. J., Liu R., Brown R. F., Badwey J. A. Antagonists of phosphatidylinositol 3-kinase block activation of several novel protein kinases in neutrophils. J Biol Chem. 1995 May 12;270(19):11684–11691. doi: 10.1074/jbc.270.19.11684. [DOI] [PubMed] [Google Scholar]
  10. Ekena K., Stevens T. H. The Saccharomyces cerevisiae MVP1 gene interacts with VPS1 and is required for vacuolar protein sorting. Mol Cell Biol. 1995 Mar;15(3):1671–1678. doi: 10.1128/mcb.15.3.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. English J. M., Vanderbilt C. A., Xu S., Marcus S., Cobb M. H. Isolation of MEK5 and differential expression of alternatively spliced forms. J Biol Chem. 1995 Dec 1;270(48):28897–28902. doi: 10.1074/jbc.270.48.28897. [DOI] [PubMed] [Google Scholar]
  12. Fuchs A., Dagher M. C., Vignais P. V. Mapping the domains of interaction of p40phox with both p47phox and p67phox of the neutrophil oxidase complex using the two-hybrid system. J Biol Chem. 1995 Mar 17;270(11):5695–5697. doi: 10.1074/jbc.270.11.5695. [DOI] [PubMed] [Google Scholar]
  13. Greco A., Mariani C., Miranda C., Lupas A., Pagliardini S., Pomati M., Pierotti M. A. The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. Mol Cell Biol. 1995 Nov;15(11):6118–6127. doi: 10.1128/mcb.15.11.6118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hirano T., Kinoshita N., Morikawa K., Yanagida M. Snap helix with knob and hole: essential repeats in S. pombe nuclear protein nuc2+. Cell. 1990 Jan 26;60(2):319–328. doi: 10.1016/0092-8674(90)90746-2. [DOI] [PubMed] [Google Scholar]
  15. Kurten R. C., Cadena D. L., Gill G. N. Enhanced degradation of EGF receptors by a sorting nexin, SNX1. Science. 1996 May 17;272(5264):1008–1010. doi: 10.1126/science.272.5264.1008. [DOI] [PubMed] [Google Scholar]
  16. Leeuw T., Fourest-Lieuvin A., Wu C., Chenevert J., Clark K., Whiteway M., Thomas D. Y., Leberer E. Pheromone response in yeast: association of Bem1p with proteins of the MAP kinase cascade and actin. Science. 1995 Nov 17;270(5239):1210–1213. doi: 10.1126/science.270.5239.1210. [DOI] [PubMed] [Google Scholar]
  17. Leto T. L., Lomax K. J., Volpp B. D., Nunoi H., Sechler J. M., Nauseef W. M., Clark R. A., Gallin J. I., Malech H. L. Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src. Science. 1990 May 11;248(4956):727–730. doi: 10.1126/science.1692159. [DOI] [PubMed] [Google Scholar]
  18. Lyons D. M., Mahanty S. K., Choi K. Y., Manandhar M., Elion E. A. The SH3-domain protein Bem1 coordinates mitogen-activated protein kinase cascade activation with cell cycle control in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Aug;16(8):4095–4106. doi: 10.1128/mcb.16.8.4095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MacDougall L. K., Domin J., Waterfield M. D. A family of phosphoinositide 3-kinases in Drosophila identifies a new mediator of signal transduction. Curr Biol. 1995 Dec 1;5(12):1404–1415. doi: 10.1016/s0960-9822(95)00278-8. [DOI] [PubMed] [Google Scholar]
  20. Matsui Y., Matsui R., Akada R., Toh-e A. Yeast src homology region 3 domain-binding proteins involved in bud formation. J Cell Biol. 1996 May;133(4):865–878. doi: 10.1083/jcb.133.4.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McPhail L. C., Qualliotine-Mann D., Waite K. A. Cell-free activation of neutrophil NADPH oxidase by a phosphatidic acid-regulated protein kinase. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7931–7935. doi: 10.1073/pnas.92.17.7931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. Proc Natl Acad Sci U S A. 1989 May;86(9):3099–3103. doi: 10.1073/pnas.86.9.3099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Park I., Chung J., Walsh C. T., Yun Y., Strominger J. L., Shin J. Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12338–12342. doi: 10.1073/pnas.92.26.12338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Peterson J., Zheng Y., Bender L., Myers A., Cerione R., Bender A. Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast. J Cell Biol. 1994 Dec;127(5):1395–1406. doi: 10.1083/jcb.127.5.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ponting C. P., Blake D. J., Davies K. E., Kendrick-Jones J., Winder S. J. ZZ and TAZ: new putative zinc fingers in dystrophin and other proteins. Trends Biochem Sci. 1996 Jan;21(1):11–13. [PubMed] [Google Scholar]
  26. Ponting C. P., Kerr I. D. A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues. Protein Sci. 1996 May;5(5):914–922. doi: 10.1002/pro.5560050513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ponting C. P., Parker P. J. Extending the C2 domain family: C2s in PKCs delta, epsilon, eta, theta, phospholipases, GAPs, and perforin. Protein Sci. 1996 Jan;5(1):162–166. doi: 10.1002/pro.5560050120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Prigmore E., Ahmed S., Best A., Kozma R., Manser E., Segal A. W., Lim L. A 68-kDa kinase and NADPH oxidase component p67phox are targets for Cdc42Hs and Rac1 in neutrophils. J Biol Chem. 1995 May 5;270(18):10717–10722. doi: 10.1074/jbc.270.18.10717. [DOI] [PubMed] [Google Scholar]
  29. Schuler G. D., Altschul S. F., Lipman D. J. A workbench for multiple alignment construction and analysis. Proteins. 1991;9(3):180–190. doi: 10.1002/prot.340090304. [DOI] [PubMed] [Google Scholar]
  30. Segal A. W. The electron transport chain of the microbicidal oxidase of phagocytic cells and its involvement in the molecular pathology of chronic granulomatous disease. J Clin Invest. 1989 Jun;83(6):1785–1793. doi: 10.1172/JCI114083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sikorski R. S., Boguski M. S., Goebl M., Hieter P. A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell. 1990 Jan 26;60(2):307–317. doi: 10.1016/0092-8674(90)90745-z. [DOI] [PubMed] [Google Scholar]
  32. Sikorski R. S., Michaud W. A., Hieter P. p62cdc23 of Saccharomyces cerevisiae: a nuclear tetratricopeptide repeat protein with two mutable domains. Mol Cell Biol. 1993 Feb;13(2):1212–1221. doi: 10.1128/mcb.13.2.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tatusov R. L., Altschul S. F., Koonin E. V. Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12091–12095. doi: 10.1073/pnas.91.25.12091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Virbasius J. V., Guilherme A., Czech M. P. Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain. J Biol Chem. 1996 Jun 7;271(23):13304–13307. doi: 10.1074/jbc.271.23.13304. [DOI] [PubMed] [Google Scholar]
  36. Wada Y., Anraku Y. Genes for directing vacuolar morphogenesis in Saccharomyces cerevisiae. II. VAM7, a gene for regulating morphogenic assembly of the vacuoles. J Biol Chem. 1992 Sep 15;267(26):18671–18675. [PubMed] [Google Scholar]
  37. Wientjes F. B., Hsuan J. J., Totty N. F., Segal A. W. p40phox, a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains. Biochem J. 1993 Dec 15;296(Pt 3):557–561. doi: 10.1042/bj2960557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zheng Y., Bender A., Cerione R. A. Interactions among proteins involved in bud-site selection and bud-site assembly in Saccharomyces cerevisiae. J Biol Chem. 1995 Jan 13;270(2):626–630. doi: 10.1074/jbc.270.2.626. [DOI] [PubMed] [Google Scholar]
  39. de Boer M., Hilarius-Stokman P. M., Hossle J. P., Verhoeven A. J., Graf N., Kenney R. T., Seger R., Roos D. Autosomal recessive chronic granulomatous disease with absence of the 67-kD cytosolic NADPH oxidase component: identification of mutation and detection of carriers. Blood. 1994 Jan 15;83(2):531–536. [PubMed] [Google Scholar]
  40. de Mendez I., Adams A. G., Sokolic R. A., Malech H. L., Leto T. L. Multiple SH3 domain interactions regulate NADPH oxidase assembly in whole cells. EMBO J. 1996 Mar 15;15(6):1211–1220. [PMC free article] [PubMed] [Google Scholar]

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