| Structural highlights
1k4u is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | NCF2 (Homo sapiens), NCF1 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[NCF2_HUMAN] Defects in NCF2 are a cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 2 (CGD2) [MIM:233710]. Chronic granulomatous disease is a genetically heterogeneous disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.[1] [2] [3] [4] [5] [6] [7] [8] [9] [NCF1_HUMAN] Defects in NCF1 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 1 (CGD1) [MIM:233700]. Chronic granulomatous disease is a genetically heterogeneous disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.[10] [11]
Function
[NCF2_HUMAN] NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). [NCF1_HUMAN] NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).[12]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The basic function of the Src homology 3 (SH3) domain is considered to be binding to proline-rich sequences containing a PxxP motif. Recently, many SH3 domains, including those from Grb2 and Pex13p, were reported to bind sequences lacking a PxxP motif. We report here that the 22 residue peptide lacking a PxxP motif, derived from p47(phox), binds to the C-terminal SH3 domain from p67(phox). We applied the NMR cross-saturation method to locate the interaction sites for the non-PxxP peptides on their cognate SH3 domains from p67(phox), Grb2 and Pex13p. The binding site of the Grb2 SH3 partially overlapped the conventional PxxP-binding site, whereas those of p67(phox) and Pex13p SH3s are located in different surface regions. The non-PxxP peptide from p47(phox) binds to the p67(phox) SH3 more tightly when it extends to the N-terminus to include a typical PxxP motif, which enabled the structure determination of the complex, to reveal that the non-PxxP peptide segment interacted with the p67(phox) SH3 in a compact helix-turn-helix structure (PDB entry 1K4U).
Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p.,Kami K, Takeya R, Sumimoto H, Kohda D EMBO J. 2002 Aug 15;21(16):4268-76. PMID:12169629[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ de Boer M, Hilarius-Stokman PM, Hossle JP, Verhoeven AJ, Graf N, Kenney RT, 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):531-6. PMID:8286749
- ↑ Bonizzato A, Russo MP, Donini M, Dusi S. Identification of a double mutation (D160V-K161E) in the p67phox gene of a chronic granulomatous disease patient. Biochem Biophys Res Commun. 1997 Feb 24;231(3):861-3. PMID:9070911 doi:S0006-291X(97)96204-5
- ↑ Patino PJ, Rae J, Noack D, Erickson R, Ding J, de Olarte DG, Curnutte JT. Molecular characterization of autosomal recessive chronic granulomatous disease caused by a defect of the nicotinamide adenine dinucleotide phosphate (reduced form) oxidase component p67-phox. Blood. 1999 Oct 1;94(7):2505-14. PMID:10498624
- ↑ Noack D, Rae J, Cross AR, Munoz J, Salmen S, Mendoza JA, Rossi N, Curnutte JT, Heyworth PG. Autosomal recessive chronic granulomatous disease caused by novel mutations in NCF-2, the gene encoding the p67-phox component of phagocyte NADPH oxidase. Hum Genet. 1999 Nov;105(5):460-7. PMID:10598813
- ↑ Cross AR, Noack D, Rae J, Curnutte JT, Heyworth PG. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (first update). Blood Cells Mol Dis. 2000 Oct;26(5):561-5. PMID:11112388 doi:10.1006/bcmd.2000.0333
- ↑ El Kares R, Barbouche MR, Elloumi-Zghal H, Bejaoui M, Chemli J, Mellouli F, Tebib N, Abdelmoula MS, Boukthir S, Fitouri Z, M'Rad S, Bouslama K, Touiri H, Abdelhak S, Dellagi MK. Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia. J Hum Genet. 2006;51(10):887-95. Epub 2006 Aug 26. PMID:16937026 doi:10.1007/s10038-006-0039-8
- ↑ Yu G, Hong DK, Dionis KY, Rae J, Heyworth PG, Curnutte JT, Lewis DB. Focus on FOCIS: the continuing diagnostic challenge of autosomal recessive chronic granulomatous disease. Clin Immunol. 2008 Aug;128(2):117-26. doi: 10.1016/j.clim.2008.05.008. PMID:18625437 doi:10.1016/j.clim.2008.05.008
- ↑ Koker MY, Sanal O, van Leeuwen K, de Boer M, Metin A, Patiroglu T, Ozgur TT, Tezcan I, Roos D. Four different NCF2 mutations in six families from Turkey and an overview of NCF2 gene mutations. Eur J Clin Invest. 2009 Oct;39(10):942-51. doi: 10.1111/j.1365-2362.2009.02195.x., Epub 2009 Jul 17. PMID:19624736 doi:10.1111/j.1365-2362.2009.02195.x
- ↑ Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, van Leeuwen K, Koker MY, Wolach B, Roesler J, Malech HL, Holland SM, Gallin JI, Stasia MJ. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis. 2010 Apr 15;44(4):291-9. doi: 10.1016/j.bcmd.2010.01.009., Epub 2010 Feb 18. PMID:20167518 doi:10.1016/j.bcmd.2010.01.009
- ↑ Casimir CM, Bu-Ghanim HN, Rodaway AR, Bentley DL, Rowe P, Segal AW. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2753-7. PMID:2011585
- ↑ Noack D, Rae J, Cross AR, Ellis BA, Newburger PE, Curnutte JT, Heyworth PG. Autosomal recessive chronic granulomatous disease caused by defects in NCF-1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF-1 pseudogenes. Blood. 2001 Jan 1;97(1):305-11. PMID:11133775
- ↑ Kilpatrick LE, Sun S, Li H, Vary TC, Korchak HM. Regulation of TNF-induced oxygen radical production in human neutrophils: role of delta-PKC. J Leukoc Biol. 2010 Jan;87(1):153-64. doi: 10.1189/jlb.0408230. Epub 2009 Oct 2. PMID:19801500 doi:10.1189/jlb.0408230
- ↑ Kami K, Takeya R, Sumimoto H, Kohda D. Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p. EMBO J. 2002 Aug 15;21(16):4268-76. PMID:12169629
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