CARD9_MOUSE
ID CARD9_MOUSE Reviewed; 536 AA.
AC A2AIV8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Caspase recruitment domain-containing protein 9 {ECO:0000303|PubMed:16862125};
GN Name=Card9 {ECO:0000303|PubMed:16862125, ECO:0000312|MGI:MGI:2685628};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=16862125; DOI=10.1038/nature04926;
RA Gross O., Gewies A., Finger K., Schafer M., Sparwasser T., Peschel C.,
RA Forster I., Ruland J.;
RT "Card9 controls a non-TLR signalling pathway for innate anti-fungal
RT immunity.";
RL Nature 442:651-656(2006).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP NOD2 AND RIPK2.
RX PubMed=17187069; DOI=10.1038/ni1426;
RA Hsu Y.M., Zhang Y., You Y., Wang D., Li H., Duramad O., Qin X.F., Dong C.,
RA Lin X.;
RT "The adaptor protein CARD9 is required for innate immune responses to
RT intracellular pathogens.";
RL Nat. Immunol. 8:198-205(2007).
RN [5]
RP REVIEW.
RX PubMed=17514206; DOI=10.1038/ni0607-554;
RA Colonna M.;
RT "All roads lead to CARD9.";
RL Nat. Immunol. 8:554-555(2007).
RN [6]
RP FUNCTION.
RX PubMed=17486093; DOI=10.1038/ni1466;
RA Hara H., Ishihara C., Takeuchi A., Imanishi T., Xue L., Morris S.W.,
RA Inui M., Takai T., Shibuya A., Saijo S., Iwakura Y., Ohno N., Koseki H.,
RA Yoshida H., Penninger J.M., Saito T.;
RT "The adaptor protein CARD9 is essential for the activation of myeloid cells
RT through ITAM-associated and Toll-like receptors.";
RL Nat. Immunol. 8:619-629(2007).
RN [7]
RP FUNCTION.
RX PubMed=17450144; DOI=10.1038/ni1460;
RA LeibundGut-Landmann S., Gross O., Robinson M.J., Osorio F., Slack E.C.,
RA Tsoni S.V., Schweighoffer E., Tybulewicz V., Brown G.D., Ruland J.,
RA Reis e Sousa C.;
RT "Syk- and CARD9-dependent coupling of innate immunity to the induction of T
RT helper cells that produce interleukin 17.";
RL Nat. Immunol. 8:630-638(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431 AND SER-461, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION.
RX PubMed=20538615; DOI=10.1074/jbc.m110.131300;
RA Bi L., Gojestani S., Wu W., Hsu Y.M., Zhu J., Ariizumi K., Lin X.;
RT "CARD9 mediates dectin-2-induced IkappaBalpha kinase ubiquitination leading
RT to activation of NF-kappaB in response to stimulation by the hyphal form of
RT Candida albicans.";
RL J. Biol. Chem. 285:25969-25977(2010).
RN [10]
RP PHOSPHORYLATION AT THR-231, FUNCTION, ACTIVITY REGULATION, INTERACTION WITH
RP BCL10, AND MUTAGENESIS OF THR-231 AND SER-303.
RX PubMed=22265677; DOI=10.1016/j.immuni.2011.11.015;
RA Strasser D., Neumann K., Bergmann H., Marakalala M.J., Guler R.,
RA Rojowska A., Hopfner K.P., Brombacher F., Urlaub H., Baier G., Brown G.D.,
RA Leitges M., Ruland J.;
RT "Syk kinase-coupled C-type lectin receptors engage protein kinase C-delta
RT to elicit Card9 adaptor-mediated innate immunity.";
RL Immunity 36:32-42(2012).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=23732773; DOI=10.1053/j.gastro.2013.05.047;
RA Sokol H., Conway K.L., Zhang M., Choi M., Morin B., Cao Z.,
RA Villablanca E.J., Li C., Wijmenga C., Yun S.H., Shi H.N., Xavier R.J.;
RT "Card9 mediates intestinal epithelial cell restitution, T-helper 17
RT responses, and control of bacterial infection in mice.";
RL Gastroenterology 145:591-601(2013).
RN [12]
RP INTERACTION WITH NOD2.
RX PubMed=24960071; DOI=10.1016/j.febslet.2014.06.035;
RA Parkhouse R., Boyle J.P., Mayle S., Sawmynaden K., Rittinger K.,
RA Monie T.P.;
RT "Interaction between NOD2 and CARD9 involves the NOD2 NACHT and the linker
RT region between the NOD2 CARDs and NACHT domain.";
RL FEBS Lett. 588:2830-2836(2014).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24470469; DOI=10.1128/iai.01089-13;
RA Yamamoto H., Nakamura Y., Sato K., Takahashi Y., Nomura T., Miyasaka T.,
RA Ishii K., Hara H., Yamamoto N., Kanno E., Iwakura Y., Kawakami K.;
RT "Defect of CARD9 leads to impaired accumulation of gamma interferon-
RT producing memory phenotype T cells in lungs and increased susceptibility to
RT pulmonary infection with Cryptococcus neoformans.";
RL Infect. Immun. 82:1606-1615(2014).
RN [14]
RP FUNCTION.
RX PubMed=25267792; DOI=10.1084/jem.20132349;
RA Jia X.M., Tang B., Zhu L.L., Liu Y.H., Zhao X.Q., Gorjestani S., Hsu Y.M.,
RA Yang L., Guan J.H., Xu G.T., Lin X.;
RT "CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-
RT Ras for antifungal immunity.";
RL J. Exp. Med. 211:2307-2321(2014).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25621893; DOI=10.1371/journal.ppat.1004589;
RA Jhingran A., Kasahara S., Shepardson K.M., Junecko B.A., Heung L.J.,
RA Kumasaka D.K., Knoblaugh S.E., Lin X., Kazmierczak B.I., Reinhart T.A.,
RA Cramer R.A., Hohl T.M.;
RT "Compartment-specific and sequential role of MyD88 and CARD9 in chemokine
RT induction and innate defense during respiratory fungal infection.";
RL PLoS Pathog. 11:e1004589-e1004589(2015).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26679537; DOI=10.1371/journal.ppat.1005293;
RA Drummond R.A., Collar A.L., Swamydas M., Rodriguez C.A., Lim J.K.,
RA Mendez L.M., Fink D.L., Hsu A.P., Zhai B., Karauzum H., Mikelis C.M.,
RA Rose S.R., Ferre E.M., Yockey L., Lemberg K., Kuehn H.S., Rosenzweig S.D.,
RA Lin X., Chittiboina P., Datta S.K., Belhorn T.H., Weimer E.T.,
RA Hernandez M.L., Hohl T.M., Kuhns D.B., Lionakis M.S.;
RT "CARD9-dependent neutrophil recruitment protects against fungal invasion of
RT the central nervous system.";
RL PLoS Pathog. 11:e1005293-e1005293(2015).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27158904; DOI=10.1038/nm.4102;
RA Lamas B., Richard M.L., Leducq V., Pham H.P., Michel M.L., Da Costa G.,
RA Bridonneau C., Jegou S., Hoffmann T.W., Natividad J.M., Brot L., Taleb S.,
RA Couturier-Maillard A., Nion-Larmurier I., Merabtene F., Seksik P.,
RA Bourrier A., Cosnes J., Ryffel B., Beaugerie L., Launay J.M., Langella P.,
RA Xavier R.J., Sokol H.;
RT "CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan
RT into aryl hydrocarbon receptor ligands.";
RL Nat. Med. 22:598-605(2016).
RN [18]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29080677; DOI=10.1016/j.jid.2017.10.009;
RA Wang X., Zhang R., Wu W., Song Y., Wan Z., Han W., Li R.;
RT "Impaired specific antifungal immunity in CARD9-deficient patients with
RT phaeohyphomycosis.";
RL J. Invest. Dermatol. 138:607-617(2018).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32548948; DOI=10.1111/cmi.13235;
RA Kottom T.J., Nandakumar V., Hebrink D.M., Carmona E.M., Limper A.H.;
RT "A critical role for CARD9 in pneumocystis pneumonia host defence.";
RL Cell. Microbiol. 22:e13235-e13235(2020).
RN [20]
RP FUNCTION.
RX PubMed=32358020; DOI=10.4049/jimmunol.1900793;
RA Campuzano A., Zhang H., Ostroff G.R., Dos Santos Dias L., Wuethrich M.,
RA Klein B.S., Yu J.J., Lara H.H., Lopez-Ribot J.L., Hung C.Y.;
RT "CARD9-associated Dectin-1 and Dectin-2 are required for protective
RT immunity of a multivalent vaccine against coccidioides posadasii
RT infection.";
RL J. Immunol. 204:3296-3306(2020).
RN [21]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33548172; DOI=10.1016/j.cell.2021.01.016;
RA Doron I., Leonardi I., Li X.V., Fiers W.D., Semon A., Bialt-DeCelie M.,
RA Migaud M., Gao I.H., Lin W.Y., Kusakabe T., Puel A., Iliev I.D.;
RT "Human gut mycobiota tune immunity via CARD9-dependent induction of anti-
RT fungal IgG antibodies.";
RL Cell 0:0-0(2021).
CC -!- FUNCTION: Adapter protein that plays a key role in innate immune
CC response against fungi by forming signaling complexes downstream of C-
CC type lectin receptors (PubMed:16862125, PubMed:20538615,
CC PubMed:26679537, PubMed:29080677). CARD9-mediated signals are essential
CC for antifungal immunity against a subset of fungi from the phylum
CC Ascomycota (PubMed:16862125, PubMed:20538615, PubMed:24470469,
CC PubMed:25621893, PubMed:26679537, PubMed:29080677, PubMed:32548948).
CC Transduces signals in myeloid cells downstream of C-type lectin
CC receptors CLEC7A (dectin-1), CLEC6A (dectin-2) and CLEC4E (Mincle),
CC which detect pathogen-associated molecular pattern metabolites (PAMPs),
CC such as fungal carbohydrates, and trigger CARD9 activation
CC (PubMed:16862125, PubMed:20538615). Upon activation, CARD9
CC homooligomerizes to form a nucleating helical template that recruits
CC BCL10 via CARD-CARD interaction, thereby promoting polymerization of
CC BCL10 and subsequent recruitment of MALT1: this leads to activation of
CC NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14)
CC pathways which stimulate expression of genes encoding pro-inflammatory
CC cytokines and chemokines (PubMed:16862125, PubMed:20538615,
CC PubMed:22265677, PubMed:29080677). CARD9 signaling in antigen-
CC presenting cells links innate sensing of fungi to the activation of
CC adaptive immunity and provides a cytokine milieu that induces the
CC development and subsequent of interleukin 17-producing T helper (Th17)
CC cells (PubMed:17450144, PubMed:24470469, PubMed:32358020). Also
CC involved in activation of myeloid cells via classical ITAM-associated
CC receptors and TLR: required for TLR-mediated activation of MAPK, while
CC it is not required for TLR-induced activation of NF-kappa-B
CC (PubMed:17486093). CARD9 can also be engaged independently of BCL10:
CC forms a complex with RASGRF1 downstream of C-type lectin receptors,
CC which recruits and activates HRAS, leading to ERK activation and the
CC production of cytokines (PubMed:25267792). Acts as an important
CC regulator of the intestinal commensal fungi (mycobiota) component of
CC the gut microbiota (PubMed:27158904, PubMed:33548172). Plays an
CC essential role in antifungal immunity against dissemination of gut
CC fungi: acts by promoting induction of antifungal IgG antibodies
CC response in CX3CR1(+) macrophages to confer protection against
CC disseminated C.albicans or C.auris infection (PubMed:33548172). Also
CC mediates immunity against other pathogens, such as certain bacteria,
CC viruses and parasites; CARD9 signaling is however redundant with other
CC innate immune responses (PubMed:17187069, PubMed:26679537,
CC PubMed:29080677). In response to L.monocytogenes infection, required
CC for the production of inflammatory cytokines activated by intracellular
CC peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to
CC downstream activation of MAP kinases (MAPK) without activating NF-
CC kappa-B (PubMed:17187069). {ECO:0000269|PubMed:16862125,
CC ECO:0000269|PubMed:17187069, ECO:0000269|PubMed:17450144,
CC ECO:0000269|PubMed:17486093, ECO:0000269|PubMed:20538615,
CC ECO:0000269|PubMed:22265677, ECO:0000269|PubMed:24470469,
CC ECO:0000269|PubMed:25267792, ECO:0000269|PubMed:25621893,
CC ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:27158904,
CC ECO:0000269|PubMed:29080677, ECO:0000269|PubMed:32358020,
CC ECO:0000269|PubMed:32548948, ECO:0000269|PubMed:33548172}.
CC -!- ACTIVITY REGULATION: Maintained in an autoinhibited state via
CC homodimerization in which the CARD domain forms an extensive
CC interaction with the adjacent linker and coiled-coil regions (By
CC similarity). Activation downstream of C-type lectin receptors, by
CC phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers
CC disruption of the CARD domain-coiled coil interface, CARD9
CC homooligomerization and BCL10 recruitment, followed by activation of
CC NF-kappa-B and MAP kinase p38 pathways (PubMed:22265677). Zinc-binding
CC inhibits activation by stabilizing the CARD ground-state conformation
CC and restricting its capacity to form BCL10-nucleating filaments (By
CC similarity). {ECO:0000250|UniProtKB:Q9H257,
CC ECO:0000269|PubMed:22265677}.
CC -!- SUBUNIT: Monomer (By similarity). Homodimer; homodimerization is
CC mediated by the CARD domain which forms an extensive interaction with
CC the adjacent linker and coiled-coil regions; leads to an autoinhibited
CC state (By similarity). Homomultimer; polymerizes following activation,
CC forming a nucleating helical template that seeds BCL10-filament
CC formation via a CARD-CARD interaction (By similarity). Interacts (via
CC CARD domain) with BCL10 (via CARD domain); interaction takes place
CC following CARD9 activation and polymerization, leading to the formation
CC of a filamentous CBM complex assembly (PubMed:22265677). Component of a
CC CBM complex (CARD9-BCL10, MALT1), composed of CARD9, BCL10 and MALT1
CC (PubMed:22265677). Interacts with RASGRF1 (By similarity). Interacts
CC with NOD2 (via NACHT domain); interaction is direct (PubMed:17187069,
CC PubMed:24960071). Interacts with RIPK2 (PubMed:17187069). Interacts
CC with VHL; without leading to protein degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q9EPY0, ECO:0000250|UniProtKB:Q9H257,
CC ECO:0000269|PubMed:17187069, ECO:0000269|PubMed:22265677,
CC ECO:0000269|PubMed:24960071}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H257}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in myeloid cells
CC (PubMed:16862125, PubMed:17187069). Not expressed in non-lymphoid
CC organs (PubMed:16862125, PubMed:17187069).
CC {ECO:0000269|PubMed:16862125, ECO:0000269|PubMed:17187069}.
CC -!- DOMAIN: The linker region, also named autoinhibitory interface, is
CC required to prevent constitutive activation and maintain CARD9 in an
CC autoinhibitory state. Disruption of this region triggers polymerization
CC and activation, leading to formation of BCL10-nucleating filaments.
CC {ECO:0000250|UniProtKB:Q9H257}.
CC -!- PTM: Phosphorylated at Thr-231 by PRKCD downstream of C-type lectin
CC receptors activation: phosphorylation promotes interaction with BCL10,
CC followed by activation of NF-kappa-B and MAP kinase p38 pathways
CC (PubMed:22265677). Phosphorylated at Thr-531 and Thr-531 by CK2
CC following interaction with VHL, leading to inhibit the ability to
CC activate NF-kappa-B (By similarity). {ECO:0000250|UniProtKB:Q9EPY0,
CC ECO:0000269|PubMed:22265677}.
CC -!- PTM: Ubiquitinated at Lys-125 via 'Lys-27'-linked ubiquitin by TRIM62
CC downstream of C-type lectin receptors activation; leading to CARD9
CC activation, followed by activation of NF-kappa-B and MAP kinase p38
CC pathways (By similarity). Deubiquitinated at Lys-125 by USP15,
CC inhibiting CARD9 (By similarity). {ECO:0000250|UniProtKB:Q9H257}.
CC -!- DISRUPTION PHENOTYPE: Mice were born at the normal Mendelian ratio
CC without obvious anatomical defects but display impaired innate immunity
CC (PubMed:16862125, PubMed:17187069). In response to C.albicans
CC infection, mice develop fungal infections, many of which target the
CC central nervous system (CNS) (PubMed:26679537). All mice die within 5
CC days after infection by C.albicans whereas more than half of the
CC control mice survive for more than 12 days (PubMed:16862125). Impaired
CC zymosan-induced cytokine production (PubMed:16862125). No defects in
CC adaptive immunity (PubMed:16862125). Mice show impaired recruitment of
CC neutrophils in CNS after infection by C.albicans, an immune cell
CC critical for antifungal host defense (PubMed:26679537). Mice are
CC susceptible to pulmonary infection with C.neoformans and show decreased
CC Th17-related immune response (PubMed:24470469). Mice are highly
CC susceptible to phaeohyphomycosis following E.spinifera infection and
CC show impaired antifungal immunity, characterized by reduced cytokine
CC production and neutrophil recruitment (PubMed:29080677). Mice are
CC susceptible to A.fumigatus and P.pneumonia infection (PubMed:25621893,
CC PubMed:32548948). Mice are more susceptible to colitis and have an
CC increased load of gut-resident fungi (mycobiota), causing gut fungal
CC dysbiosis (PubMed:23732773, PubMed:27158904). Mice are unable to induce
CC an efficient IgG antibody response against disseminated C.albicans
CC infection (PubMed:33548172). Following infection by L.monocytogenes,
CC mice fail to clear infection and show altered cytokine production
CC (PubMed:17187069). {ECO:0000269|PubMed:16862125,
CC ECO:0000269|PubMed:17187069, ECO:0000269|PubMed:23732773,
CC ECO:0000269|PubMed:24470469, ECO:0000269|PubMed:25621893,
CC ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:27158904,
CC ECO:0000269|PubMed:29080677, ECO:0000269|PubMed:32548948,
CC ECO:0000269|PubMed:33548172}.
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DR EMBL; AL732541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC151023; AAI51024.1; -; mRNA.
DR CCDS; CCDS38084.1; -.
DR RefSeq; NP_001032836.1; NM_001037747.1.
DR AlphaFoldDB; A2AIV8; -.
DR SMR; A2AIV8; -.
DR BioGRID; 237136; 3.
DR IntAct; A2AIV8; 1.
DR MINT; A2AIV8; -.
DR STRING; 10090.ENSMUSP00000097876; -.
DR iPTMnet; A2AIV8; -.
DR PhosphoSitePlus; A2AIV8; -.
DR jPOST; A2AIV8; -.
DR MaxQB; A2AIV8; -.
DR PaxDb; A2AIV8; -.
DR PeptideAtlas; A2AIV8; -.
DR PRIDE; A2AIV8; -.
DR ProteomicsDB; 265665; -.
DR Antibodypedia; 18695; 275 antibodies from 39 providers.
DR DNASU; 332579; -.
DR Ensembl; ENSMUST00000028294; ENSMUSP00000028294; ENSMUSG00000026928.
DR Ensembl; ENSMUST00000100303; ENSMUSP00000097876; ENSMUSG00000026928.
DR GeneID; 332579; -.
DR KEGG; mmu:332579; -.
DR UCSC; uc008iut.1; mouse.
DR CTD; 64170; -.
DR MGI; MGI:2685628; Card9.
DR VEuPathDB; HostDB:ENSMUSG00000026928; -.
DR eggNOG; ENOG502R00K; Eukaryota.
DR GeneTree; ENSGT00940000160570; -.
DR HOGENOM; CLU_038057_1_0_1; -.
DR InParanoid; A2AIV8; -.
DR OMA; EDEECWI; -.
DR OrthoDB; 115953at2759; -.
DR PhylomeDB; A2AIV8; -.
DR TreeFam; TF351139; -.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR BioGRID-ORCS; 332579; 0 hits in 70 CRISPR screens.
DR PRO; PR:A2AIV8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2AIV8; protein.
DR Bgee; ENSMUSG00000026928; Expressed in granulocyte and 57 other tissues.
DR GO; GO:0032449; C:CBM complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0061760; P:antifungal innate immune response; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0051607; P:defense response to virus; IMP:MGI.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; IMP:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; IMP:MGI.
DR GO; GO:0002446; P:neutrophil mediated immunity; IMP:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:MGI.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:MGI.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IMP:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IMP:UniProtKB.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; IMP:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0032663; P:regulation of interleukin-2 production; IMP:MGI.
DR GO; GO:0032675; P:regulation of interleukin-6 production; IMP:MGI.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI.
DR GO; GO:0009620; P:response to fungus; IMP:MGI.
DR GO; GO:0032495; P:response to muramyl dipeptide; IMP:MGI.
DR GO; GO:0032494; P:response to peptidoglycan; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IMP:MGI.
DR CDD; cd08809; CARD_CARD9; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR042142; CARD_CARD9.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR Pfam; PF00619; CARD; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50209; CARD; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Coiled coil; Cytoplasm; Immunity; Innate immunity;
KW Isopeptide bond; Metal-binding; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Zinc.
FT CHAIN 1..536
FT /note="Caspase recruitment domain-containing protein 9"
FT /id="PRO_0000428725"
FT DOMAIN 6..98
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 99..116
FT /note="Linker"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT REGION 425..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 117..272
FT /evidence="ECO:0000255"
FT COILED 303..415
FT /evidence="ECO:0000255"
FT COMPBIAS 425..442
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..507
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 517..536
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT BINDING 10
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT BINDING 73
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPY0"
FT MOD_RES 231
FT /note="Phosphothreonine; by PKC/PRKCD"
FT /evidence="ECO:0000269|PubMed:22265677"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPY0"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPY0"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MOD_RES 531
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q9EPY0"
FT MOD_RES 533
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q9EPY0"
FT CROSSLNK 125
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9H257"
FT MUTAGEN 231
FT /note="T->A: Reduced phosphorylation by PKC/PRKCD, leading
FT to impaired interaction with BCL10 and decreased activation
FT of NF-kappa-B and MAP kinase p38 pathways."
FT /evidence="ECO:0000269|PubMed:22265677"
FT MUTAGEN 303
FT /note="S->A: Does not affect phosphorylation by PKC/PRKCD."
FT /evidence="ECO:0000269|PubMed:22265677"
SQ SEQUENCE 536 AA; 62462 MW; 3A5403C7A04EA2C9 CRC64;
MSDYENDDEC WSTLESFRVK LISVIDPSRI TPYLRQCKVL NPDDEEQVLS DPNLVIRKRK
VGVLLDILQR TGHKGYVAFL ESLELYYPQL YRKVTGKEPA RVFSMIIDAS GESGLTQLLM
TEVMKLQKKV QDLTALLSSK DDFIKELRVK DSLLRKHQER VQRLKEECEL SSAELKRCKD
ENYELAMCLA HLSEEKGAAL MRNRDLQLEV DRLRHSLMKA EDDCKVERKH TLKLRHAMEQ
RPSQELLWEL QQEKDLLQAR VQELQVSVQE GKLDRNSPYI QVLEEDWRQA LQEHQKQVST
IFSLRKDLRQ AETLRARCTE EKEMFELQCL ALRKDAKMYK DRIEAILLQM EEVSIERDQA
MASREELHAQ CTQSFQDKDK LRKLVRELGE KADELQLQLF QTESRLLAAE GRLKQQQLDM
LILSSDLEDS SPRNSQELSL PQDLEEDAQL SDKGVLADRE SPEQPFMALN KEHLSLTHGM
GPSSSEPPEK ERRRLKESFE NYRRKRALRK MQNSWRQGEG DRGNTTGSDN TDTEGS
