CARD9

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Caspase recruitment domain family, member 9
Identifiers
Symbols CARD9 ; CANDF2; hCARD9
External IDs OMIM607212 MGI2685628 HomoloGene14150 GeneCards: CARD9 Gene
Orthologs
Species Human Mouse
Entrez 64170 332579
Ensembl ENSG00000187796 ENSMUSG00000026928
UniProt Q9H257 A2AIV8
RefSeq (mRNA) NM_052813 NM_001037747
RefSeq (protein) NP_434700 NP_001032836
Location (UCSC) Chr 9:
139.26 – 139.27 Mb
Chr 2:
26.35 – 26.36 Mb
PubMed search [1] [2]

Caspase recruitment domain-containing protein 9 is an adaptor protein that in humans is encoded by the CARD9 gene.[1][2]

Function[edit]

CARD9 is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a positive regulator of apoptosis and NF-κB activation, and is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-κB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined.[2]

Clinical significance[edit]

It recently became clear that Card9 plays important roles as part of the innate immune response for the defense against pathogens such as yeasts. Card9 mediates signals from so called pattern recognition receptors (Dectin-1) to downstream signalling pathways such as NF-κB and by this activates pro-inflammatory cytokines (TNF, IL-23, IL-6, IL-2) and an anti-inflammatory cytokine (IL-10) and subsequently an appropriate innate and adaptive immune response for the efficient clearance of the infection.[3] Importantly, it was reported that an autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9.[4] Mutations in this gene have been associated to inflammatory diseases such as Ankylosing spondylitis and inflammatory bowel disease/Crohn's Disease and Ulcerative Colitis.[5][6]

Interactions[edit]

CARD9 has been shown to interact with BCL10.[7]

References[edit]

  1. ^ Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL, Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES (Jan 2001). "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J Biol Chem 275 (52): 41082–6. doi:10.1074/jbc.C000726200. PMID 11053425. 
  2. ^ a b "Entrez Gene: CARD9 caspase recruitment domain family, member 9". 
  3. ^ Gross O, Gewies A, Finger K, Schaefer M, Sparwasser T, Peschel C, Foerster I, and Ruland J (Aug 2006). "Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity". Nature 442 (7103): 651–6. doi:10.1038/nature04926. PMID 16862125. 
  4. ^ Glockner EO, Hennigs A, Navabi M, Schaffner AA, Woellner C, Salzer U, Pfeifer D, Veelken H, Warnatz K, Tahami F, Manguiat A, Rezaei N, Amirzargar AA, Plebani A, Hennesschlager N, Gross O, Ruland J, Grimbacher B (Oct 2009). "A homozygous CARD9 mutation in a family with susceptibility to fungal infections". N Engl J Med. 361 (18): 1798–801. doi:10.1056/NEJMoa0810719. PMC 2793117. PMID 19864672. 
  5. ^ Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, Oppermann U, Dilthey A, Pirinen M, Stone MA, Appleton L, Moutsianas L, Leslie S, Wordsworth T, Kenna TJ, Karaderi T, Thomas GP, Ward MM, Weisman MH, Farrar C, Bradbury LA, Danoy P, Inman RD, Maksymowych W, Gladman D, Rahman P; Spondyloarthritis Research Consortium of Canada (SPARCC), Morgan A, Marzo-Ortega H, Bowness P, Gaffney K, Gaston JS, Smith M, Bruges-Armas J, Couto AR, Sorrentino R, Paladini F, Ferreira MA, Xu H, Liu Y, Jiang L, Lopez-Larrea C, Díaz-Peña R, López-Vázquez A, Zayats T, Band G, Bellenguez C, Blackburn H, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Corvin A, Craddock N, Deloukas P, Dronov S, Duncanson A, Edkins S, Freeman C, Gillman M, Gray E, Gwilliam R, Hammond N, Hunt SE, Jankowski J, Jayakumar A, Langford C, Liddle J, Markus HS, Mathew CG, McCann OT, McCarthy MI, Palmer CN, Peltonen L, Plomin R, Potter SC, Rautanen A, Ravindrarajah R, Ricketts M, Samani N, Sawcer SJ, Strange A, Trembath RC, Viswanathan AC, Waller M, Weston P, Whittaker P, Widaa S, Wood NW, McVean G, Reveille JD, Wordsworth BP, Brown MA, Donnelly P; Australo-Anglo-American Spondyloarthritis Consortium (TASC); Wellcome Trust Case Control Consortium 2 (WTCCC2). (August 2011). "Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.". Nat. Genet. 43 (8): 761–767. doi:10.1038/ng.873. PMID 21743469. 
  6. ^ Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, Boucher G, Ripke S, Ellinghaus D, Burtt N, Fennell T, Kirby A, Latiano A, Goyette P, Green T, Halfvarson J, Haritunians T, Korn JM, Kuruvilla F, Lagacé C, Neale B, Lo KS, Schumm P, Törkvist L; National Institute of Diabetes and Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium (NIDDK IBDGC); United Kingdom Inflammatory Bowel Disease Genetics Consortium; International Inflammatory Bowel Disease Genetics Consortium, Dubinsky MC, Brant SR, Silverberg MS, Duerr RH, Altshuler D, Gabriel S, Lettre G, Franke A, D'Amato M, McGovern DP, Cho JH, Rioux JD, Xavier RJ, Daly MJ. (November 2011). "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.". Nat. Genet. 43 (11): 1066–73. doi:10.1038/ng.952. PMID 21983784. 
  7. ^ Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL, Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES (December 2000). "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J. Biol. Chem. 275 (52): 41082–6. doi:10.1074/jbc.C000726200. PMID 11053425. 

Further reading[edit]