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| | ==Helical assembly of the CARD9 CARD== | | ==Helical assembly of the CARD9 CARD== |
| - | <StructureSection load='6n2p' size='340' side='right'caption='[[6n2p]], [[Resolution|resolution]] 4.00Å' scene=''> | + | <SX load='6n2p' size='340' side='right' viewer='molstar' caption='[[6n2p]], [[Resolution|resolution]] 4.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n2p]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N2P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n2p]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N2P FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6n2m|6n2m]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6n2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n2p OCA], [http://pdbe.org/6n2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n2p RCSB], [http://www.ebi.ac.uk/pdbsum/6n2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n2p ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6n2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n2p OCA], [https://pdbe.org/6n2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n2p RCSB], [https://www.ebi.ac.uk/pdbsum/6n2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n2p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CARD9_HUMAN CARD9_HUMAN]] Chronic mucocutaneous candidosis;Deep dermatophytosis. The disease is caused by mutations affecting the gene represented in this entry. Defects induce reduced numbers of CD4(+) Th17 lymphocytes as well as a lack of monocyte-derived cytokines in response to Candida strains. Neutrophils show a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae (PubMed:23335372).<ref>PMID:23335372</ref> | + | [https://www.uniprot.org/uniprot/CARD9_HUMAN CARD9_HUMAN] Chronic mucocutaneous candidosis;Deep dermatophytosis. The disease is caused by mutations affecting the gene represented in this entry. Defects induce reduced numbers of CD4(+) Th17 lymphocytes as well as a lack of monocyte-derived cytokines in response to Candida strains. Neutrophils show a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae (PubMed:23335372).<ref>PMID:23335372</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CARD9_HUMAN CARD9_HUMAN]] Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells.<ref>PMID:11053425</ref> | + | [https://www.uniprot.org/uniprot/CARD9_HUMAN CARD9_HUMAN] Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells.<ref>PMID:11053425</ref> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arthur, C P]] | + | [[Category: Arthur CP]] |
| - | [[Category: Dueber, E C]] | + | [[Category: Dueber EC]] |
| - | [[Category: Fairbrother, W J]] | + | [[Category: Fairbrother WJ]] |
| - | [[Category: Holliday, M J]] | + | [[Category: Holliday MJ]] |
| - | [[Category: Rohou, A]] | + | [[Category: Rohou A]] |
| - | [[Category: Card]]
| + | |
| - | [[Category: Death domain]]
| + | |
| - | [[Category: Filament]]
| + | |
| - | [[Category: Helical assembly]]
| + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
CARD9_HUMAN Chronic mucocutaneous candidosis;Deep dermatophytosis. The disease is caused by mutations affecting the gene represented in this entry. Defects induce reduced numbers of CD4(+) Th17 lymphocytes as well as a lack of monocyte-derived cytokines in response to Candida strains. Neutrophils show a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae (PubMed:23335372).[1]
Function
CARD9_HUMAN Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells.[2]
References
- ↑ Drewniak A, Gazendam RP, Tool AT, van Houdt M, Jansen MH, van Hamme JL, van Leeuwen EM, Roos D, Scalais E, de Beaufort C, Janssen H, van den Berg TK, Kuijpers TW. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood. 2013 Mar 28;121(13):2385-92. doi: 10.1182/blood-2012-08-450551. Epub 2013 , Jan 18. PMID:23335372 doi:http://dx.doi.org/10.1182/blood-2012-08-450551
- ↑ Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL, Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES. CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B. J Biol Chem. 2000 Dec 29;275(52):41082-6. PMID:11053425 doi:http://dx.doi.org/10.1074/jbc.C000726200
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