ID CARD9_HUMAN Reviewed; 536 AA. AC Q9H257; Q5SXM5; Q5SXM6; Q9H854; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2007, sequence version 2. DT 24-JAN-2024, entry version 187. DE RecName: Full=Caspase recruitment domain-containing protein 9 {ECO:0000303|PubMed:11053425}; DE Short=hCARD9 {ECO:0000303|PubMed:11053425}; GN Name=CARD9 {ECO:0000303|PubMed:11053425, ECO:0000312|HGNC:HGNC:16391}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASN-12, FUNCTION, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH BCL10. RX PubMed=11053425; DOI=10.1074/jbc.c000726200; RA Bertin J., Guo Y., Wang L., Srinivasula S.M., Jacobson M.D., Poyet J.-L., RA Merriam S., Du M.-Q., Dyer M.J.S., Robison K.E., DiStefano P.S., RA Alnemri E.S.; RT "CARD9 is a novel caspase recruitment domain-containing protein that RT interacts with Bcl10/CLAP and activates NF-kappa B."; RL J. Biol. Chem. 275:41082-41086(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP ASN-12. RC TISSUE=Retinoblastoma, and Synovium; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Muscle; 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-460, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [7] RP INVOLVEMENT IN IMD103, AND VARIANT IMD103 295-GLN--SER-536 DEL. RX PubMed=19864672; DOI=10.1056/nejmoa0810719; RA Glocker E.-O., Hennigs A., Nabavi M., Schaeffer A.A., Woellner C., RA Salzer U., Pfeifer D., Veelken H., Warnatz K., Tahami F., Jamal S., RA Manguiat A., Rezaei N., Amirzargar A.A., Plebani A., Hannesschlaeger N., RA Gross O., Ruland J., Grimbacher B.; RT "A homozygous CARD9 mutation in a family with susceptibility to fungal RT infections."; RL N. Engl. J. Med. 361:1727-1735(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277; SER-425; SER-483 AND RP SER-498, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [9] 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 [10] RP UBIQUITINATION AT LYS-125, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR RP LOCATION, INTERACTION WITH BCL10, AND MUTAGENESIS OF LYS-125. RX PubMed=26488816; DOI=10.1016/j.immuni.2015.10.005; RA Cao Z., Conway K.L., Heath R.J., Rush J.S., Leshchiner E.S., RA Ramirez-Ortiz Z.G., Nedelsky N.B., Huang H., Ng A., Gardet A., Cheng S.C., RA Shamji A.F., Rioux J.D., Wijmenga C., Netea M.G., Means T.K., Daly M.J., RA Xavier R.J.; RT "Ubiquitin ligase TRIM62 regulates CARD9-mediated anti-fungal immunity and RT intestinal inflammation."; RL Immunity 43:715-726(2015). RN [11] RP INVOLVEMENT IN IMD103. RX PubMed=26440558; DOI=10.1111/bjd.14082; RA Yan X.X., Yu C.P., Fu X.A., Bao F.F., Du D.H., Wang C., Wang N., Wang S.F., RA Shi Z.X., Zhou G.Z., Tian H.Q., Liu H., Zhang F.R.; RT "CARD9 mutation linked to Corynespora cassiicola infection in a Chinese RT patient."; RL Br. J. Dermatol. 174:176-179(2016). RN [12] RP INVOLVEMENT IN IMD103. RX PubMed=28984994; DOI=10.1111/myc.12701; RA Gavino C., Mellinghoff S., Cornely O.A., Landekic M., Le C., Langelier M., RA Golizeh M., Proske S., Vinh D.C.; RT "Novel bi-allelic splice mutations in CARD9 causing adult-onset Candida RT endophthalmitis."; RL Mycoses 61:61-65(2018). RN [13] RP UBIQUITINATION AT LYS-125, AND DEUBIQUITINATION AT LYS-125. RX PubMed=33093067; DOI=10.4049/immunohorizons.2000036; RA Xu W., Rush J.S., Graham D.B., Cao Z., Xavier R.J.; RT "USP15 deubiquitinates CARD9 to downregulate C-type lectin receptor- RT mediated signaling."; RL Immunohorizons 4:670-678(2020). RN [14] {ECO:0007744|PDB:6E25, ECO:0007744|PDB:6E26, ECO:0007744|PDB:6E27, ECO:0007744|PDB:6E28} RP STRUCTURE BY NMR OF 1-97 IN COMPLEX WITH ZINC, SUBUNIT, ACTIVITY RP REGULATION, AND MUTAGENESIS OF CYS-10; CYS-37 AND HIS-73. RX PubMed=30206119; DOI=10.1074/jbc.ra118.004821; RA Holliday M.J., Ferrao R., de Leon Boenig G., Estevez A., Helgason E., RA Rohou A., Dueber E.C., Fairbrother W.J.; RT "Picomolar zinc binding modulates formation of Bcl10-nucleating assemblies RT of the caspase recruitment domain (CARD) of CARD9."; RL J. Biol. Chem. 293:16803-16817(2018). RN [15] {ECO:0007744|PDB:6N2M, ECO:0007744|PDB:6N2P} RP STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS) OF 2-152 IN COMPLEX WITH RP ZINC, FUNCTION, ACTIVITY REGULATION, INTERACTION WITH BCL10, UBIQUITINATION RP AT LYS-125, SUBUNIT, DOMAIN, MUTAGENESIS OF GLU-15; ARG-35; ASP-43; LYS-58; RP ASP-66; ARG-101; PHE-103; ILE-107; GLY-111; GLY-114 AND LEU-115, AND RP CHARACTERIZATION OF VARIANT IMD103 GLN-35. RX PubMed=31296852; DOI=10.1038/s41467-019-10953-z; RA Holliday M.J., Witt A., Rodriguez Gama A., Walters B.T., Arthur C.P., RA Halfmann R., Rohou A., Dueber E.C., Fairbrother W.J.; RT "Structures of autoinhibited and polymerized forms of CARD9 reveal RT mechanisms of CARD9 and CARD11 activation."; RL Nat. Commun. 10:3070-3070(2019). RN [16] RP VARIANTS IMD103 SER-72 AND PRO-373. RX PubMed=23335372; DOI=10.1182/blood-2012-08-450551; RA Drewniak A., Gazendam R.P., Tool A.T., van Houdt M., Jansen M.H., RA van Hamme J.L., van Leeuwen E.M., Roos D., Scalais E., de Beaufort C., RA Janssen H., van den Berg T.K., Kuijpers T.W.; RT "Invasive fungal infection and impaired neutrophil killing in human CARD9 RT deficiency."; RL Blood 121:2385-2392(2013). RN [17] RP VARIANTS IMD103 CYS-101 AND 289-GLN--SER-536 DEL. RX PubMed=24131138; DOI=10.1056/nejmoa1208487; RA Lanternier F., Pathan S., Vincent Q.B., Liu L., Cypowyj S., Prando C., RA Migaud M., Taibi L., Ammar-Khodja A., Boudghene Stambouli O., Guellil B., RA Jacobs F., Goffard J.C., Schepers K., del Marmol V., Boussofara L., RA Denguezli M., Larif M., Bachelez H., Michel L., Lefranc G., Hay R., RA Jouvion G., Chretien F., Fraitag S., Bougnoux M.E., Boudia M., Abel L., RA Lortholary O., Casanova J.L., Picard C., Grimbacher B., Puel A.; RT "Deep dermatophytosis and inherited CARD9 deficiency."; RL N. Engl. J. Med. 369:1704-1714(2013). RN [18] RP VARIANT IMD103 HIS-91. RX PubMed=24704721; DOI=10.1093/cid/ciu215; RA Gavino C., Cotter A., Lichtenstein D., Lejtenyi D., Fortin C., Legault C., RA Alirezaie N., Majewski J., Sheppard D.C., Behr M.A., Foulkes W.D., RA Vinh D.C.; RT "CARD9 deficiency and spontaneous central nervous system candidiasis: RT complete clinical remission with GM-CSF therapy."; RL Clin. Infect. Dis. 59:81-84(2014). RN [19] RP VARIANT IMD103 158-GLN--SER-536 DEL, CHARACTERIZATION OF VARIANT IMD103 RP 158-GLN--SER-536 DEL, AND FUNCTION. RX PubMed=24231284; DOI=10.1016/j.jaci.2013.09.033; RA Wang X., Wang W., Lin Z., Wang X., Li T., Yu J., Liu W., Tong Z., Xu Y., RA Zhang J., Guan L., Dai L., Yang Y., Han W., Li R.; RT "CARD9 mutations linked to subcutaneous phaeohyphomycosis and TH17 cell RT deficiencies."; RL J. Allergy Clin. Immunol. 133:905-908(2014). RN [20] RP VARIANT IMD103 289-GLN--SER-536 DEL. RX PubMed=25372963; DOI=10.1001/jamadermatol.2014.2154; RA Jachiet M., Lanternier F., Rybojad M., Bagot M., Ibrahim L., Casanova J.L., RA Puel A., Bouaziz J.D.; RT "Posaconazole treatment of extensive skin and nail dermatophytosis due to RT autosomal recessive deficiency of CARD9."; RL JAMA Dermatol. 151:192-194(2015). RN [21] RP VARIANTS IMD103 GLN-35; TRP-70; 289-GLN--SER-536 DEL AND 295-GLN--SER-536 RP DEL, CHARACTERIZATION OF VARIANTS IMD103 GLN-35; TRP-70 AND RP 295-GLN--SER-536 DEL, AND FUNCTION. RX PubMed=25702837; DOI=10.1016/j.jaci.2014.12.1930; RA Lanternier F., Mahdaviani S.A., Barbati E., Chaussade H., Koumar Y., RA Levy R., Denis B., Brunel A.S., Martin S., Loop M., Peeters J., RA de Selys A., Vanclaire J., Vermylen C., Nassogne M.C., Chatzis O., Liu L., RA Migaud M., Pedergnana V., Desoubeaux G., Jouvion G., Chretien F., RA Darazam I.A., Schaeffer A.A., Netea M.G., De Bruycker J.J., Bernard L., RA Reynes J., Amazrine N., Abel L., Van der Linden D., Harrison T., Picard C., RA Lortholary O., Mansouri D., Casanova J.L., Puel A.; RT "Inherited CARD9 deficiency in otherwise healthy children and adults with RT Candida species-induced meningoencephalitis, colitis, or both."; RL J. Allergy Clin. Immunol. 135:1558-1568(2015). RN [22] RP VARIANT IMD103 LEU-101. RX PubMed=26044242; DOI=10.1007/s10875-015-0170-4; RA Grumach A.S., de Queiroz-Telles F., Migaud M., Lanternier F., Filho N.R., RA Palma S.M., Constantino-Silva R.N., Casanova J.L., Puel A.; RT "A homozygous CARD9 mutation in a Brazilian patient with deep RT dermatophytosis."; RL J. Clin. Immunol. 35:486-490(2015). RN [23] RP VARIANTS IMD103 TRP-18 AND GLU-323 DEL, CHARACTERIZATION OF VARIANT IMD103 RP TRP-18, AND FUNCTION. RX PubMed=25057046; DOI=10.1093/infdis/jiu412; RA Lanternier F., Barbati E., Meinzer U., Liu L., Pedergnana V., Migaud M., RA Heritier S., Chomton M., Fremond M.L., Gonzales E., Galeotti C., Romana S., RA Jacquemin E., Angoulvant A., Bidault V., Canioni D., Lachenaud J., RA Mansouri D., Mahdaviani S.A., Adimi P., Mansouri N., Jamshidi M., RA Bougnoux M.E., Abel L., Lortholary O., Blanche S., Casanova J.L., RA Picard C., Puel A.; RT "Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala RT infection."; RL J. Infect. Dis. 211:1241-1250(2015). RN [24] RP VARIANT IMD103 295-GLN--SER-536 DEL. RX PubMed=25933095; DOI=10.1097/inf.0000000000000736; RA Herbst M., Gazendam R., Reimnitz D., Sawalle-Belohradsky J., Groll A., RA Schlegel P.G., Belohradsky B., Renner E., Klepper J., Grimbacher B., RA Kuijpers T., Liese J.; RT "Chronic candida albicans meningitis in a 4-year-old girl with a homozygous RT mutation in the CARD9 gene (Q295X)."; RL Pediatr. Infect. Dis. J. 34:999-1002(2015). RN [25] RP VARIANT IMD103 HIS-57, CHARACTERIZATION OF VARIANT IMD103 HIS-57, AND RP FUNCTION. 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 [26] RP VARIANT IMD103 TRP-70, CHARACTERIZATION OF VARIANT IMD103 TRP-70, AND RP FUNCTION. RX PubMed=26961233; DOI=10.1007/s10875-016-0255-8; RA Alves de Medeiros A.K., Lodewick E., Bogaert D.J., Haerynck F., RA Van Daele S., Lambrecht B., Bosma S., Vanderdonckt L., Lortholary O., RA Migaud M., Casanova J.L., Puel A., Lanternier F., Lambert J., Brochez L., RA Dullaers M.; RT "Chronic and invasive fungal infections in a family with CARD9 RT deficiency."; RL J. Clin. Immunol. 36:204-209(2016). RN [27] RP VARIANT IMD103 PRO-380. RX PubMed=26941346; DOI=10.1136/bcr-2015-214117; RA Jones N., Garcez T., Newman W., Denning D.; RT "Endogenous Candida endophthalmitis and osteomyelitis associated with CARD9 RT deficiency."; RL BMJ Case Rep. 2016:0-0(2016). RN [28] RP VARIANT IMD103 HIS-91, CHARACTERIZATION OF VARIANT IMD103 HIS-91, FUNCTION, RP IDENTIFICATION IN THE CBM COMPLEX, AND INTERACTION WITH RASGRF1. RX PubMed=26521038; DOI=10.1016/j.jaci.2015.09.016; RA Gavino C., Hamel N., Zeng J.B., Legault C., Guiot M.C., Chankowsky J., RA Lejtenyi D., Lemire M., Alarie I., Dufresne S., Boursiquot J.N., RA McIntosh F., Langelier M., Behr M.A., Sheppard D.C., Foulkes W.D., RA Vinh D.C.; RT "Impaired RASGRF1/ERK-mediated GM-CSF response characterizes CARD9 RT deficiency in French-Canadians."; RL J. Allergy Clin. Immunol. 137:1178-1188(2016). RN [29] RP VARIANT IMD103 295-GLN--SER-536 DEL, CHARACTERIZATION OF VARIANT IMD103 RP 295-GLN--SER-536 DEL, AND FUNCTION. RX PubMed=27777981; DOI=10.1172/jci.insight.89890; RA Rieber N., Gazendam R.P., Freeman A.F., Hsu A.P., Collar A.L., Sugui J.A., RA Drummond R.A., Rongkavilit C., Hoffman K., Henderson C., Clark L., RA Mezger M., Swamydas M., Engeholm M., Schuele R., Neumayer B., Ebel F., RA Mikelis C.M., Pittaluga S., Prasad V.K., Singh A., Milner J.D., RA Williams K.W., Lim J.K., Kwon-Chung K.J., Holland S.M., Hartl D., RA Kuijpers T.W., Lionakis M.S.; RT "Extrapulmonary Aspergillus infection in patients with CARD9 deficiency."; RL JCI Insight 1:e89890-e89890(2016). RN [30] RP VARIANT IMD103 295-GLN--SER-536 DEL. RX PubMed=26658378; DOI=10.1097/inf.0000000000001028; RA Celmeli F., Oztoprak N., Turkkahraman D., Seyman D., Mutlu E., Frede N., RA Koeksoy S., Grimbacher B.; RT "Successful granulocyte colony-stimulating factor treatment of relapsing RT candida albicans meningoencephalitis caused by CARD9 deficiency."; RL Pediatr. Infect. Dis. J. 35:428-431(2016). RN [31] RP VARIANT IMD103 289-GLN--SER-536 DEL. RX PubMed=28391957; DOI=10.1016/j.mycmed.2017.01.001; RA Boudghene Stambouli O., Amrani N., Boudghene Stambouli K., Bouali F.; RT "Dermatophytic disease with deficit in CARD9: A new case with a brain RT impairment."; RL J. Mycol. Med. 27:250-253(2017). RN [32] RP VARIANT IMD103 295-GLN--SER-536 DEL. RX PubMed=29307770; DOI=10.1016/j.clim.2018.01.002; RA Cetinkaya P.G., Ayvaz D.C., Karaatmaca B., Gocmen R., Soeylemezoglu F., RA Bainter W., Chou J., Chatila T.A., Tezcan I.; RT "A young girl with severe cerebral fungal infection due to card 9 RT deficiency."; RL Clin. Immunol. 191:21-26(2018). RN [33] RP VARIANT IMD103 23-SER--SER-536 DEL, CHARACTERIZATION OF VARIANT IMD103 RP 23-SER--SER-536 DEL, AND FUNCTION. 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 [34] RP VARIANT IMD103 HIS-91. RX PubMed=31469433; DOI=10.1111/cup.13574; RA Nazarian R.M., Lilly E., Gavino C., Hamilos D.L., Felsenstein D., RA Vinh D.C., Googe P.B.; RT "Novel CARD9 mutation in a patient with chronic invasive dermatophyte RT infection (tinea profunda)."; RL J. Cutan. Pathol. 47:166-170(2020). RN [35] RP CHARACTERIZATION OF VARIANTS IMD103 GLN-35; TRP-70 AND 289-GLN--SER-536 RP DEL, FUNCTION, AND TISSUE SPECIFICITY. 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). RN [36] RP VARIANTS IMD103 GLU-196 AND PRO-373, CHARACTERIZATION OF VARIANTS IMD103 RP TRP-70; GLU-196 AND PRO-373, AND FUNCTION. RX PubMed=33558980; DOI=10.1007/s10875-021-00988-7; RA Imanaka Y., Taniguchi M., Doi T., Tsumura M., Nagaoka R., Shimomura M., RA Asano T., Kagawa R., Mizoguchi Y., Karakawa S., Arihiro K., Imai K., RA Morio T., Casanova J.L., Puel A., Ohara O., Kamei K., Kobayashi M., RA Okada S.; RT "Inherited CARD9 deficiency in a child with invasive disease due to RT Exophiala dermatitidis and two older but asymptomatic siblings."; RL J. Clin. Immunol. 41:975-986(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:26961233, PubMed:33558980). CARD9- CC mediated signals are essential for antifungal immunity against a subset CC of fungi from the phylum Ascomycota (PubMed:24231284, PubMed:25702837, CC PubMed:25057046, PubMed:26679537, PubMed:26961233, PubMed:26521038, CC PubMed:27777981, PubMed:29080677, PubMed:33558980). Transduces signals CC in myeloid cells downstream of C-type lectin receptors CLEC7A (dectin- CC 1), CLEC6A (dectin-2) and CLEC4E (Mincle), which detect pathogen- CC associated molecular pattern metabolites (PAMPs), such as fungal CC carbohydrates, and trigger CARD9 activation (By similarity). Upon CC activation, CARD9 homooligomerizes to form a nucleating helical CC template that recruits BCL10 via CARD-CARD interaction, thereby CC promoting polymerization of BCL10 and subsequent recruitment of MALT1: CC this leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, CC MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of CC genes encoding pro-inflammatory cytokines and chemokines CC (PubMed:11053425, PubMed:26488816, PubMed:31296852, PubMed:26961233, CC PubMed:33558980). CARD9 signaling in antigen-presenting cells links CC innate sensing of fungi to the activation of adaptive immunity and CC provides a cytokine milieu that induces the development and subsequent CC of interleukin 17-producing T helper (Th17) cells (PubMed:24231284). CC Also involved in activation of myeloid cells via classical ITAM- CC associated receptors and TLR: required for TLR-mediated activation of CC MAPK, while it is not required for TLR-induced activation of NF-kappa-B CC (By similarity). 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 (By similarity). Acts as an important regulator CC of the intestinal commensal fungi (mycobiota) component of the gut CC microbiota (PubMed:33548172). Plays an essential role in antifungal CC immunity against dissemination of gut fungi: acts by promoting CC induction of antifungal IgG antibodies response in CX3CR1(+) CC macrophages to confer protection against disseminated C.albicans or CC C.auris infection (PubMed:33548172). Also mediates immunity against CC other pathogens, such as certain bacteria, viruses and parasites; CARD9 CC signaling is however redundant with other innate immune responses (By CC similarity). In response to L.monocytogenes infection, required for the CC 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 (By similarity). {ECO:0000250|UniProtKB:A2AIV8, CC ECO:0000269|PubMed:11053425, ECO:0000269|PubMed:24231284, CC ECO:0000269|PubMed:25057046, ECO:0000269|PubMed:25702837, CC ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:26521038, CC ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:26961233, CC ECO:0000269|PubMed:27777981, ECO:0000269|PubMed:29080677, CC ECO:0000269|PubMed:31296852, ECO:0000269|PubMed:33548172, CC ECO:0000269|PubMed:33558980}. 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 CC (PubMed:31296852). 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:26488816, CC PubMed:31296852). Zinc-binding inhibits activation by stabilizing the CC CARD ground-state conformation and restricting its capacity to form CC BCL10-nucleating filaments (PubMed:30206119). CC {ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:30206119, CC ECO:0000269|PubMed:31296852}. CC -!- SUBUNIT: Monomer (PubMed:30206119). 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 (PubMed:30206119, PubMed:31296852). Homomultimer; polymerizes CC following activation, forming a nucleating helical template that seeds CC BCL10-filament formation via a CARD-CARD interaction (PubMed:31296852). CC Interacts (via CARD domain) with BCL10 (via CARD domain); interaction CC takes place following CARD9 activation and polymerization, leading to CC the formation of a filamentous CBM complex assembly (PubMed:11053425, CC PubMed:26488816, PubMed:31296852, PubMed:26521038). Component of a CBM CC complex (CARD9-BCL10, MALT1), composed of CARD9, BCL10 and MALT1 CC (PubMed:26521038). Interacts with RASGRF1 (PubMed:26521038). Interacts CC with NOD2 (via NACHT domain); interaction is direct (PubMed:24960071). CC Interacts with RIPK2 (By similarity). Interacts with VHL; without CC leading to protein degradation (By similarity). CC {ECO:0000250|UniProtKB:A2AIV8, ECO:0000250|UniProtKB:Q9EPY0, CC ECO:0000269|PubMed:11053425, ECO:0000269|PubMed:24960071, CC ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:26521038, CC ECO:0000269|PubMed:30206119, ECO:0000269|PubMed:31296852}. CC -!- INTERACTION: CC Q9H257; O14639: ABLIM1; NbExp=3; IntAct=EBI-751319, EBI-487024; CC Q9H257; Q9Y2J4-4: AMOTL2; NbExp=5; IntAct=EBI-751319, EBI-10187270; CC Q9H257; O95999: BCL10; NbExp=6; IntAct=EBI-751319, EBI-958922; CC Q9H257; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-751319, EBI-2548012; CC Q9H257; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-751319, EBI-946029; CC Q9H257; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-751319, EBI-739879; CC Q9H257; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-751319, EBI-10175300; CC Q9H257; Q96GN5: CDCA7L; NbExp=4; IntAct=EBI-751319, EBI-5278764; CC Q9H257; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-751319, EBI-10181988; CC Q9H257; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-751319, EBI-739624; CC Q9H257; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-751319, EBI-5453285; CC Q9H257; Q9UER7: DAXX; NbExp=3; IntAct=EBI-751319, EBI-77321; CC Q9H257; Q9UII6: DUSP13B; NbExp=3; IntAct=EBI-751319, EBI-749800; CC Q9H257; O60573: EIF4E2; NbExp=3; IntAct=EBI-751319, EBI-398610; CC Q9H257; Q9H5Z6: FAM124B; NbExp=3; IntAct=EBI-751319, EBI-741626; CC Q9H257; Q3B820: FAM161A; NbExp=4; IntAct=EBI-751319, EBI-719941; CC Q9H257; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-751319, EBI-742802; CC Q9H257; Q6NT76: HMBOX1; NbExp=3; IntAct=EBI-751319, EBI-2549423; CC Q9H257; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-751319, EBI-8638439; CC Q9H257; Q7L273: KCTD9; NbExp=3; IntAct=EBI-751319, EBI-4397613; CC Q9H257; P08727: KRT19; NbExp=4; IntAct=EBI-751319, EBI-742756; CC Q9H257; Q15323: KRT31; NbExp=3; IntAct=EBI-751319, EBI-948001; CC Q9H257; Q6A162: KRT40; NbExp=3; IntAct=EBI-751319, EBI-10171697; CC Q9H257; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-751319, EBI-10172150; CC Q9H257; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-751319, EBI-726510; CC Q9H257; P25800: LMO1; NbExp=3; IntAct=EBI-751319, EBI-8639312; CC Q9H257; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-751319, EBI-741037; CC Q9H257; P50222: MEOX2; NbExp=3; IntAct=EBI-751319, EBI-748397; CC Q9H257; P55081: MFAP1; NbExp=3; IntAct=EBI-751319, EBI-1048159; CC Q9H257; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-751319, EBI-10172876; CC Q9H257; Q9P286: PAK5; NbExp=5; IntAct=EBI-751319, EBI-741896; CC Q9H257; P40425: PBX2; NbExp=3; IntAct=EBI-751319, EBI-348489; CC Q9H257; Q8IXK0: PHC2; NbExp=3; IntAct=EBI-751319, EBI-713786; CC Q9H257; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-751319, EBI-10171633; CC Q9H257; Q6NYC8: PPP1R18; NbExp=4; IntAct=EBI-751319, EBI-2557469; CC Q9H257; Q14D33: RTP5; NbExp=3; IntAct=EBI-751319, EBI-10217913; CC Q9H257; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-751319, EBI-2212028; CC Q9H257; O75558: STX11; NbExp=3; IntAct=EBI-751319, EBI-714135; CC Q9H257; P63165: SUMO1; NbExp=3; IntAct=EBI-751319, EBI-80140; CC Q9H257; Q5VWN6-2: TASOR2; NbExp=3; IntAct=EBI-751319, EBI-10172380; CC Q9H257; Q8N8B7: TCEANC; NbExp=3; IntAct=EBI-751319, EBI-954696; CC Q9H257; P56279: TCL1A; NbExp=3; IntAct=EBI-751319, EBI-749995; CC Q9H257; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-751319, EBI-1105213; CC Q9H257; Q08117: TLE5; NbExp=4; IntAct=EBI-751319, EBI-717810; CC Q9H257; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-751319, EBI-2505861; CC Q9H257; P36406: TRIM23; NbExp=4; IntAct=EBI-751319, EBI-740098; CC Q9H257; Q14134: TRIM29; NbExp=3; IntAct=EBI-751319, EBI-702370; CC Q9H257; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-751319, EBI-5235829; CC Q9H257; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-751319, EBI-2130429; CC Q9H257; Q99598: TSNAX; NbExp=5; IntAct=EBI-751319, EBI-742638; CC Q9H257; Q9Y4E8: USP15; NbExp=4; IntAct=EBI-751319, EBI-1043104; CC Q9H257; Q548N1: VPS28; NbExp=3; IntAct=EBI-751319, EBI-10243107; CC Q9H257; Q8N3Z6: ZCCHC7; NbExp=3; IntAct=EBI-751319, EBI-7265024; CC Q9H257; P15622-3: ZNF250; NbExp=3; IntAct=EBI-751319, EBI-10177272; CC Q9H257; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-751319, EBI-740727; CC Q9H257; Q7Z3I7: ZNF572; NbExp=7; IntAct=EBI-751319, EBI-10172590; CC Q9H257; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-751319, EBI-6427977; CC Q9H257; Q8N720: ZNF655; NbExp=3; IntAct=EBI-751319, EBI-625509; CC Q9H257; A8K932; NbExp=3; IntAct=EBI-751319, EBI-10174671; CC Q9H257; PRO_0000449633 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-751319, EBI-25492395; CC Q9H257-2; Q9Y2J4: AMOTL2; NbExp=3; IntAct=EBI-11530605, EBI-746752; CC Q9H257-2; Q86V38: ATN1; NbExp=3; IntAct=EBI-11530605, EBI-11954292; CC Q9H257-2; O15169: AXIN1; NbExp=3; IntAct=EBI-11530605, EBI-710484; CC Q9H257-2; Q9NPB3: CABP2; NbExp=3; IntAct=EBI-11530605, EBI-12011224; CC Q9H257-2; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-11530605, EBI-3866279; CC Q9H257-2; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-11530605, EBI-11530605; CC Q9H257-2; Q9HC52: CBX8; NbExp=3; IntAct=EBI-11530605, EBI-712912; CC Q9H257-2; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-11530605, EBI-744556; CC Q9H257-2; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-11530605, EBI-10961312; CC Q9H257-2; A6NC98: CCDC88B; NbExp=3; IntAct=EBI-11530605, EBI-347573; CC Q9H257-2; Q16543: CDC37; NbExp=3; IntAct=EBI-11530605, EBI-295634; CC Q9H257-2; O14519: CDK2AP1; NbExp=3; IntAct=EBI-11530605, EBI-1052532; CC Q9H257-2; O43247-2: CIMIP4; NbExp=3; IntAct=EBI-11530605, EBI-12093053; CC Q9H257-2; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-11530605, EBI-5453285; CC Q9H257-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11530605, EBI-3867333; CC Q9H257-2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-11530605, EBI-742054; CC Q9H257-2; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-11530605, EBI-11988027; CC Q9H257-2; Q9UII6: DUSP13B; NbExp=8; IntAct=EBI-11530605, EBI-749800; CC Q9H257-2; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-11530605, EBI-2349927; CC Q9H257-2; P38919: EIF4A3; NbExp=3; IntAct=EBI-11530605, EBI-299104; CC Q9H257-2; Q3B820: FAM161A; NbExp=6; IntAct=EBI-11530605, EBI-719941; CC Q9H257-2; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-11530605, EBI-7225287; CC Q9H257-2; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-11530605, EBI-6658203; CC Q9H257-2; Q9NU39: FOXD4L1; NbExp=3; IntAct=EBI-11530605, EBI-11320806; CC Q9H257-2; O95995: GAS8; NbExp=3; IntAct=EBI-11530605, EBI-1052570; CC Q9H257-2; P55040: GEM; NbExp=3; IntAct=EBI-11530605, EBI-744104; CC Q9H257-2; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-11530605, EBI-14103818; CC Q9H257-2; P09067: HOXB5; NbExp=3; IntAct=EBI-11530605, EBI-3893317; CC Q9H257-2; O75031: HSF2BP; NbExp=3; IntAct=EBI-11530605, EBI-7116203; CC Q9H257-2; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-11530605, EBI-8638439; CC Q9H257-2; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-11530605, EBI-747204; CC Q9H257-2; Q9C086: INO80B; NbExp=3; IntAct=EBI-11530605, EBI-715611; CC Q9H257-2; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-11530605, EBI-2556193; CC Q9H257-2; Q86T90: KIAA1328; NbExp=3; IntAct=EBI-11530605, EBI-3437878; CC Q9H257-2; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-11530605, EBI-14069005; CC Q9H257-2; Q92876: KLK6; NbExp=3; IntAct=EBI-11530605, EBI-2432309; CC Q9H257-2; P19012: KRT15; NbExp=3; IntAct=EBI-11530605, EBI-739566; CC Q9H257-2; P08779: KRT16; NbExp=3; IntAct=EBI-11530605, EBI-356410; CC Q9H257-2; O95678: KRT75; NbExp=3; IntAct=EBI-11530605, EBI-2949715; CC Q9H257-2; Q6L8G8: KRTAP5-7; NbExp=3; IntAct=EBI-11530605, EBI-11987425; CC Q9H257-2; Q969R5: L3MBTL2; NbExp=3; IntAct=EBI-11530605, EBI-739909; CC Q9H257-2; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-11530605, EBI-726510; CC Q9H257-2; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-11530605, EBI-11742507; CC Q9H257-2; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-11530605, EBI-739832; CC Q9H257-2; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-11530605, EBI-1216080; CC Q9H257-2; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-11530605, EBI-348259; CC Q9H257-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11530605, EBI-16439278; CC Q9H257-2; P55081: MFAP1; NbExp=3; IntAct=EBI-11530605, EBI-1048159; CC Q9H257-2; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-11530605, EBI-10172526; CC Q9H257-2; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-11530605, EBI-741158; CC Q9H257-2; Q9P286: PAK5; NbExp=3; IntAct=EBI-11530605, EBI-741896; CC Q9H257-2; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-11530605, EBI-14066006; CC Q9H257-2; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-11530605, EBI-79165; CC Q9H257-2; Q99959-2: PKP2; NbExp=3; IntAct=EBI-11530605, EBI-10987518; CC Q9H257-2; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-11530605, EBI-2557469; CC Q9H257-2; Q99633: PRPF18; NbExp=3; IntAct=EBI-11530605, EBI-2798416; CC Q9H257-2; P25789: PSMA4; NbExp=3; IntAct=EBI-11530605, EBI-359310; CC Q9H257-2; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-11530605, EBI-1210429; CC Q9H257-2; Q8IYX7: SAXO1; NbExp=3; IntAct=EBI-11530605, EBI-3957636; CC Q9H257-2; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-11530605, EBI-748391; CC Q9H257-2; Q6ZSJ9: SHISA6; NbExp=3; IntAct=EBI-11530605, EBI-12037847; CC Q9H257-2; Q8ND83: SLAIN1; NbExp=3; IntAct=EBI-11530605, EBI-10269374; CC Q9H257-2; Q9NWH7-2: SPATA6; NbExp=3; IntAct=EBI-11530605, EBI-17860101; CC Q9H257-2; Q9NZ72: STMN3; NbExp=3; IntAct=EBI-11530605, EBI-725557; CC Q9H257-2; Q5VWN6: TASOR2; NbExp=3; IntAct=EBI-11530605, EBI-745958; CC Q9H257-2; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-11530605, EBI-11955057; CC Q9H257-2; P56279: TCL1A; NbExp=3; IntAct=EBI-11530605, EBI-749995; CC Q9H257-2; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-11530605, EBI-1105213; CC Q9H257-2; Q8IZW8: TNS4; NbExp=3; IntAct=EBI-11530605, EBI-7543499; CC Q9H257-2; Q14142: TRIM14; NbExp=3; IntAct=EBI-11530605, EBI-2820256; CC Q9H257-2; Q3SY00: TSGA10IP; NbExp=6; IntAct=EBI-11530605, EBI-10241197; CC Q9H257-2; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-11530605, EBI-10180829; CC Q9H257-2; Q9H9P5-5: UNKL; NbExp=3; IntAct=EBI-11530605, EBI-12817837; CC Q9H257-2; Q495M9: USH1G; NbExp=3; IntAct=EBI-11530605, EBI-8601749; CC Q9H257-2; O75604: USP2; NbExp=3; IntAct=EBI-11530605, EBI-743272; CC Q9H257-2; Q9H867: VCPKMT; NbExp=3; IntAct=EBI-11530605, EBI-18393784; CC Q9H257-2; Q9UK41: VPS28; NbExp=4; IntAct=EBI-11530605, EBI-727424; CC Q9H257-2; P07947: YES1; NbExp=3; IntAct=EBI-11530605, EBI-515331; CC Q9H257-2; Q05516: ZBTB16; NbExp=3; IntAct=EBI-11530605, EBI-711925; CC Q9H257-2; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-11530605, EBI-14104088; CC Q9H257-2; Q8N5A5-2: ZGPAT; NbExp=3; IntAct=EBI-11530605, EBI-10183064; CC Q9H257-2; Q9UJ78-2: ZMYM5; NbExp=3; IntAct=EBI-11530605, EBI-17634549; CC Q9H257-2; P58317: ZNF121; NbExp=3; IntAct=EBI-11530605, EBI-1228269; CC Q9H257-2; P17023: ZNF19; NbExp=3; IntAct=EBI-11530605, EBI-12884200; CC Q9H257-2; P17024: ZNF20; NbExp=3; IntAct=EBI-11530605, EBI-717634; CC Q9H257-2; Q9NZL3: ZNF224; NbExp=3; IntAct=EBI-11530605, EBI-12357267; CC Q9H257-2; P15622-3: ZNF250; NbExp=3; IntAct=EBI-11530605, EBI-10177272; CC Q9H257-2; Q9BUY5: ZNF426; NbExp=3; IntAct=EBI-11530605, EBI-743265; CC Q9H257-2; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-11530605, EBI-10172590; CC Q9H257-2; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-11530605, EBI-6427977; CC Q9H257-2; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-11530605, EBI-4395669; CC Q9H257-2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-11530605, EBI-625509; CC Q9H257-2; A0A0S2Z5X4: ZNF688; NbExp=3; IntAct=EBI-11530605, EBI-16429014; CC Q9H257-2; P0C7X2: ZNF688; NbExp=3; IntAct=EBI-11530605, EBI-4395732; CC Q9H257-2; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-11530605, EBI-10251462; CC Q9H257-2; Q3KNS6-3: ZNF829; NbExp=3; IntAct=EBI-11530605, EBI-18036029; CC Q9H257-2; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-11530605, EBI-527853; CC Q9H257-2; Q8IYH5: ZZZ3; NbExp=3; IntAct=EBI-11530605, EBI-2795524; CC Q9H257-3; A0A0S2Z4M1: AXIN1; NbExp=3; IntAct=EBI-16431743, EBI-16429430; CC Q9H257-3; Q9UK41: VPS28; NbExp=3; IntAct=EBI-16431743, EBI-727424; CC Q9H257-3; A0A0S2Z5X4: ZNF688; NbExp=3; IntAct=EBI-16431743, EBI-16429014; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11053425, CC ECO:0000269|PubMed:26488816}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9H257-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H257-2; Sequence=VSP_024392, VSP_024393; CC Name=3; CC IsoId=Q9H257-3; Sequence=VSP_024390, VSP_024391; CC -!- TISSUE SPECIFICITY: Expression is restricted to several populations of CC phagocytes, such as macrophages, monocytes, and dendritic cells CC (PubMed:33548172). Highly expressed in spleen (PubMed:11053425). Also CC detected in liver, placenta, lung, peripheral blood leukocytes and in CC brain (PubMed:11053425). {ECO:0000269|PubMed:11053425, CC ECO:0000269|PubMed:33548172}. CC -!- DOMAIN: The linker region, also named autoinhibitory interface, is CC required to prevent constitutive activation and maintain CARD9 in an CC autoinhibitory state (PubMed:31296852). Disruption of this region CC triggers polymerization and activation, leading to formation of BCL10- CC nucleating filaments (PubMed:31296852). {ECO:0000269|PubMed:31296852}. 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 (By CC similarity). Phosphorylated at Thr-531 and Thr-533 by CK2 following CC interaction with VHL, leading to inhibit the ability to activate NF- CC kappa-B (By similarity). {ECO:0000250|UniProtKB:A2AIV8, CC ECO:0000250|UniProtKB:Q9EPY0}. 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 (PubMed:26488816, PubMed:31296852). Deubiquitinated at Lys-125 CC by USP15, inhibiting CARD9 (PubMed:33093067). CC {ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:31296852, CC ECO:0000269|PubMed:33093067}. CC -!- DISEASE: Immunodeficiency 103, susceptibility to fungal infections CC (IMD103) [MIM:212050]: An autosomal recessive primary immunodeficiency CC disorder with altered immune responses and impaired clearance of fungal CC infections, selective against Candida. It is characterized by CC persistent and/or recurrent infections of the skin, nails and mucous CC membranes caused by organisms of the genus Candida, mainly Candida CC albicans. {ECO:0000269|PubMed:19864672, ECO:0000269|PubMed:23335372, CC ECO:0000269|PubMed:24131138, ECO:0000269|PubMed:24231284, CC ECO:0000269|PubMed:24704721, ECO:0000269|PubMed:25057046, CC ECO:0000269|PubMed:25372963, ECO:0000269|PubMed:25702837, CC ECO:0000269|PubMed:25933095, ECO:0000269|PubMed:26044242, CC ECO:0000269|PubMed:26440558, ECO:0000269|PubMed:26521038, CC ECO:0000269|PubMed:26658378, ECO:0000269|PubMed:26679537, CC ECO:0000269|PubMed:26941346, ECO:0000269|PubMed:26961233, CC ECO:0000269|PubMed:27777981, ECO:0000269|PubMed:28391957, CC ECO:0000269|PubMed:28984994, ECO:0000269|PubMed:29080677, CC ECO:0000269|PubMed:29307770, ECO:0000269|PubMed:31296852, CC ECO:0000269|PubMed:31469433, ECO:0000269|PubMed:33548172, CC ECO:0000269|PubMed:33558980}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Defects induce reduced CC numbers of CD4(+) Th17 lymphocytes as well as a lack of monocyte- CC derived cytokines in response to Candida strains (PubMed:23335372). CC Neutrophils show a selective Candida albicans killing defect with CC abnormal ultrastructural phagolysosomes and outgrowth of hyphae CC (PubMed:23335372). {ECO:0000269|PubMed:23335372}. CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF311287; AAG28790.1; -; mRNA. DR EMBL; AK024001; BAB14766.1; -; mRNA. DR EMBL; AK292081; BAF84770.1; -; mRNA. DR EMBL; AL592301; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW88220.1; -; Genomic_DNA. DR EMBL; BC008877; AAH08877.1; -; mRNA. DR CCDS; CCDS48057.1; -. [Q9H257-2] DR CCDS; CCDS6997.1; -. [Q9H257-1] DR RefSeq; NP_434700.2; NM_052813.4. [Q9H257-1] DR RefSeq; NP_434701.1; NM_052814.3. [Q9H257-2] DR PDB; 6E25; NMR; -; A=1-97. DR PDB; 6E26; NMR; -; A=1-97. DR PDB; 6E27; X-ray; 1.81 A; C/D=2-97. DR PDB; 6E28; X-ray; 1.36 A; C/D=2-97. DR PDB; 6N2M; NMR; -; A/B=2-142. DR PDB; 6N2P; EM; 4.00 A; A/B/C/D/E/F/G/H/I/J=2-152. DR PDBsum; 6E25; -. DR PDBsum; 6E26; -. DR PDBsum; 6E27; -. DR PDBsum; 6E28; -. DR PDBsum; 6N2M; -. DR PDBsum; 6N2P; -. DR AlphaFoldDB; Q9H257; -. DR EMDB; EMD-8976; -. DR EMDB; EMD-9332; -. DR SMR; Q9H257; -. DR BioGRID; 122094; 169. DR IntAct; Q9H257; 160. DR MINT; Q9H257; -. DR STRING; 9606.ENSP00000360797; -. DR GlyGen; Q9H257; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9H257; -. DR PhosphoSitePlus; Q9H257; -. DR BioMuta; CARD9; -. DR DMDM; 143811370; -. DR EPD; Q9H257; -. DR jPOST; Q9H257; -. DR MassIVE; Q9H257; -. DR MaxQB; Q9H257; -. DR PaxDb; 9606-ENSP00000360797; -. DR PeptideAtlas; Q9H257; -. DR ProteomicsDB; 80503; -. [Q9H257-1] DR ProteomicsDB; 80504; -. [Q9H257-2] DR ProteomicsDB; 80505; -. [Q9H257-3] DR Pumba; Q9H257; -. DR Antibodypedia; 18695; 311 antibodies from 40 providers. DR DNASU; 64170; -. DR Ensembl; ENST00000371732.10; ENSP00000360797.5; ENSG00000187796.16. [Q9H257-1] DR Ensembl; ENST00000371734.7; ENSP00000360799.3; ENSG00000187796.16. [Q9H257-2] DR Ensembl; ENST00000489932.2; ENSP00000451368.1; ENSG00000187796.16. [Q9H257-3] DR GeneID; 64170; -. DR KEGG; hsa:64170; -. DR MANE-Select; ENST00000371732.10; ENSP00000360797.5; NM_052813.5; NP_434700.2. DR UCSC; uc004chg.4; human. [Q9H257-1] DR AGR; HGNC:16391; -. DR CTD; 64170; -. DR DisGeNET; 64170; -. DR GeneCards; CARD9; -. DR HGNC; HGNC:16391; CARD9. DR HPA; ENSG00000187796; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; CARD9; -. DR MIM; 212050; phenotype. DR MIM; 607212; gene. DR neXtProt; NX_Q9H257; -. DR OpenTargets; ENSG00000187796; -. DR Orphanet; 457088; Predisposition to invasive fungal disease due to CARD9 deficiency. DR PharmGKB; PA26077; -. DR VEuPathDB; HostDB:ENSG00000187796; -. DR eggNOG; ENOG502R00K; Eukaryota. DR GeneTree; ENSGT00940000160570; -. DR HOGENOM; CLU_038057_1_0_1; -. DR InParanoid; Q9H257; -. DR OMA; MYRQRNK; -. DR OrthoDB; 4213113at2759; -. DR PhylomeDB; Q9H257; -. DR TreeFam; TF351139; -. DR PathwayCommons; Q9H257; -. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR SignaLink; Q9H257; -. DR SIGNOR; Q9H257; -. DR BioGRID-ORCS; 64170; 30 hits in 1151 CRISPR screens. DR GeneWiki; CARD9; -. DR GenomeRNAi; 64170; -. DR Pharos; Q9H257; Tbio. DR PRO; PR:Q9H257; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q9H257; Protein. DR Bgee; ENSG00000187796; Expressed in monocyte and 103 other cell types or tissues. DR ExpressionAtlas; Q9H257; baseline and differential. DR GO; GO:0032449; C:CBM complex; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0032991; C:protein-containing complex; IDA:ARUK-UCL. DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0061760; P:antifungal innate immune response; IDA:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl. DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; IMP:UniProtKB. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:UniProtKB. DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl. DR GO; GO:0002446; P:neutrophil mediated immunity; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEP:UniProtKB. DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:ARUK-UCL. DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:UniProtKB. DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IMP:UniProtKB. DR GO; GO:0045089; P:positive regulation of innate immune response; IEA:Ensembl. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IMP:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI. DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl. 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; IDA:MGI. 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; IEA:Ensembl. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR GO; GO:0032663; P:regulation of interleukin-2 production; IEA:Ensembl. DR GO; GO:1904044; P:response to aldosterone; IEA:Ensembl. DR GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl. DR GO; GO:0032495; P:response to muramyl dipeptide; IEA:Ensembl. DR GO; GO:0032494; P:response to peptidoglycan; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR CDD; cd08809; CARD_CARD9; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR042142; CARD_CARD9. DR InterPro; IPR011029; DEATH-like_dom_sf. DR PANTHER; PTHR14559; CASPASE RECRUITMENT DOMAIN FAMILY; 1. DR PANTHER; PTHR14559:SF3; CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 9; 1. DR Pfam; PF00619; CARD; 1. DR SUPFAM; SSF47986; DEATH domain; 1. DR PROSITE; PS50209; CARD; 1. DR Genevisible; Q9H257; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Coiled coil; KW Cytoplasm; Disease variant; Immunity; Innate immunity; Isopeptide bond; KW Metal-binding; Phosphoprotein; Reference proteome; Ubl conjugation; Zinc. FT CHAIN 1..536 FT /note="Caspase recruitment domain-containing protein 9" FT /id="PRO_0000144082" FT DOMAIN 6..98 FT /note="CARD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046" FT REGION 99..116 FT /note="Linker" FT /evidence="ECO:0000303|PubMed:31296852" FT REGION 427..536 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 117..277 FT /evidence="ECO:0000255" FT COILED 332..419 FT /evidence="ECO:0000255" FT COMPBIAS 484..505 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 512..528 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 3 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:31296852, FT ECO:0007744|PDB:6N2M" FT BINDING 10 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:30206119, FT ECO:0000269|PubMed:31296852, ECO:0007744|PDB:6E27, FT ECO:0007744|PDB:6N2M" FT BINDING 73 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:30206119, FT ECO:0000269|PubMed:31296852, ECO:0007744|PDB:6E27, FT ECO:0007744|PDB:6N2M" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9EPY0" FT MOD_RES 231 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:A2AIV8" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 424 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9EPY0" FT MOD_RES 425 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 431 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A2AIV8" FT MOD_RES 450 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9EPY0" FT MOD_RES 460 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087" FT MOD_RES 483 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 498 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" 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:0000269|PubMed:26488816, FT ECO:0000269|PubMed:31296852, ECO:0000269|PubMed:33093067" FT VAR_SEQ 360..366 FT /note="AIATREE -> STQMEGL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_024390" FT VAR_SEQ 367..536 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_024391" FT VAR_SEQ 482..492 FT /note="LSSGEPPEKER -> PAGLPGIGAVC (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_024392" FT VAR_SEQ 493..536 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_024393" FT VARIANT 12 FT /note="S -> N (in dbSNP:rs4077515)" FT /evidence="ECO:0000269|PubMed:11053425, FT ECO:0000269|PubMed:14702039" FT /id="VAR_048607" FT VARIANT 18 FT /note="R -> W (in IMD103; reduced cytokine production in FT response to C.albicans infection; impaired NF-kappa-B FT transcriptional activity)" FT /evidence="ECO:0000269|PubMed:25057046" FT /id="VAR_084630" FT VARIANT 23..536 FT /note="Missing (in IMD103; reduced cytokine production in FT response to C.albicans infection; impaired NF-kappa-B FT transcriptional activity)" FT /evidence="ECO:0000269|PubMed:29080677" FT /id="VAR_084631" FT VARIANT 35 FT /note="R -> Q (in IMD103; abolished homooligomerization and FT formation of BCL10-nucleating filaments; reduced cytokine FT production in response to C.albicans infection; reduced FT production IgG antibodies in response to C.albicans FT infection; dbSNP:rs1454037218)" FT /evidence="ECO:0000269|PubMed:25702837, FT ECO:0000269|PubMed:31296852, ECO:0000269|PubMed:33548172" FT /id="VAR_084632" FT VARIANT 57 FT /note="R -> H (in IMD103; reduced cytokine production in FT response to C.albicans infection; dbSNP:rs940550122)" FT /evidence="ECO:0000269|PubMed:26679537" FT /id="VAR_084633" FT VARIANT 70 FT /note="R -> W (in IMD103; reduced cytokine production in FT response to C.albicans infection; impaired NF-kappa-B FT transcriptional activity; reduced production IgG antibodies FT in response to C.albicans infection; dbSNP:rs767522068)" FT /evidence="ECO:0000269|PubMed:25702837, FT ECO:0000269|PubMed:26961233, ECO:0000269|PubMed:33548172, FT ECO:0000269|PubMed:33558980" FT /id="VAR_084634" FT VARIANT 72 FT /note="G -> S (in IMD103; dbSNP:rs398122362)" FT /evidence="ECO:0000269|PubMed:23335372" FT /id="VAR_070828" FT VARIANT 91 FT /note="Y -> H (in IMD103; does not affect formation of the FT CBM complex but impairs formation of a complex with FT RASGRF1; dbSNP:rs921151054)" FT /evidence="ECO:0000269|PubMed:24704721, FT ECO:0000269|PubMed:26521038, ECO:0000269|PubMed:31469433" FT /id="VAR_084635" FT VARIANT 101 FT /note="R -> C (in IMD103; dbSNP:rs398122364)" FT /evidence="ECO:0000269|PubMed:24131138" FT /id="VAR_070829" FT VARIANT 101 FT /note="R -> L (in IMD103)" FT /evidence="ECO:0000269|PubMed:26044242" FT /id="VAR_084636" FT VARIANT 158..536 FT /note="Missing (in IMD103; decreased production of FT cytokines in CD4(+) Th17 cells)" FT /evidence="ECO:0000269|PubMed:24231284" FT /id="VAR_084637" FT VARIANT 196 FT /note="K -> E (in IMD103; reduced cytokine production in FT response to C.albicans infection; does not affect FT NF-kappa-B transcriptional activity; dbSNP:rs768281299)" FT /evidence="ECO:0000269|PubMed:33558980" FT /id="VAR_084638" FT VARIANT 289..536 FT /note="Missing (in IMD103; reduced production IgG FT antibodies in response to C.albicans infection)" FT /evidence="ECO:0000269|PubMed:24131138, FT ECO:0000269|PubMed:25372963, ECO:0000269|PubMed:25702837, FT ECO:0000269|PubMed:28391957, ECO:0000269|PubMed:33548172" FT /id="VAR_084639" FT VARIANT 295..536 FT /note="Missing (in IMD103; reduced cytokine production in FT response to C.albicans infection)" FT /evidence="ECO:0000269|PubMed:19864672, FT ECO:0000269|PubMed:25702837, ECO:0000269|PubMed:25933095, FT ECO:0000269|PubMed:26658378, ECO:0000269|PubMed:27777981, FT ECO:0000269|PubMed:29307770" FT /id="VAR_084640" FT VARIANT 323 FT /note="Missing (in IMD103; dbSNP:rs775284320)" FT /evidence="ECO:0000269|PubMed:25057046" FT /id="VAR_084641" FT VARIANT 373 FT /note="R -> P (in IMD103; reduced cytokine production in FT response to C.albicans infection; does not affect FT NF-kappa-B transcriptional activity; dbSNP:rs149712114)" FT /evidence="ECO:0000269|PubMed:23335372, FT ECO:0000269|PubMed:33558980" FT /id="VAR_070830" FT VARIANT 380 FT /note="A -> P (in IMD103)" FT /evidence="ECO:0000269|PubMed:26941346" FT /id="VAR_084642" FT MUTAGEN 10 FT /note="C->A: Strongly reduced zinc-binding." FT /evidence="ECO:0000269|PubMed:30206119" FT MUTAGEN 15 FT /note="E->R: Abolished homooligomerization and formation of FT BCL10-nucleating filaments." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 35 FT /note="R->E: Abolished homooligomerization and formation of FT BCL10-nucleating filaments." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 37 FT /note="C->A: Does not affect zinc-binbing." FT /evidence="ECO:0000269|PubMed:30206119" FT MUTAGEN 43 FT /note="D->R: Abolished homooligomerization and formation of FT BCL10-nucleating filaments." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 58 FT /note="K->D: Abolished homooligomerization and formation of FT BCL10-nucleating filaments." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 66 FT /note="D->R: Abolished homooligomerization and formation of FT BCL10-nucleating filaments." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 73 FT /note="H->A: Strongly reduced zinc-binding." FT /evidence="ECO:0000269|PubMed:30206119" FT MUTAGEN 101 FT /note="R->Q: Disruption of the linker region, relieving FT autoinhibition and leading to activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 103 FT /note="F->L: Disruption of the linker region, relieving FT autoinhibition and leading to activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 107 FT /note="I->E: Disruption of the linker region, relieving FT autoinhibition and leading to activation of NF-kappa-B. FT Constitutively forms BCL10-nucleating filaments." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 111 FT /note="G->S: Disruption of the linker region, relieving FT autoinhibition and leading to activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 114 FT /note="G->D: Disruption of the linker region, relieving FT autoinhibition and leading to activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 115 FT /note="L->I: Disruption of the linker region, relieving FT autoinhibition and leading to activation of NF-kappa-B. FT Constitutively forms BCL10-nucleating filaments." FT /evidence="ECO:0000269|PubMed:31296852" FT MUTAGEN 125 FT /note="K->R: Reduced cytokine production in response to FT C.albicans infection. Impaired NF-kappa-B transcriptional FT activity. Does not affect interaction with BCL10." FT /evidence="ECO:0000269|PubMed:26488816" FT TURN 7..9 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 10..14 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 15..17 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 18..24 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 27..29 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 31..36 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 42..49 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 54..69 FT /evidence="ECO:0007829|PDB:6E28" FT TURN 70..72 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 73..86 FT /evidence="ECO:0007829|PDB:6E28" FT HELIX 88..95 FT /evidence="ECO:0007829|PDB:6E28" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:6N2M" FT HELIX 104..110 FT /evidence="ECO:0007829|PDB:6N2M" FT HELIX 112..138 FT /evidence="ECO:0007829|PDB:6N2M" SQ SEQUENCE 536 AA; 62241 MW; 6EB18353112F2BAC CRC64; MSDYENDDEC WSVLEGFRVT LTSVIDPSRI TPYLRQCKVL NPDDEEQVLS DPNLVIRKRK VGVLLDILQR TGHKGYVAFL ESLELYYPQL YKKVTGKEPA RVFSMIIDAS GESGLTQLLM TEVMKLQKKV QDLTALLSSK DDFIKELRVK DSLLRKHQER VQRLKEECEA GSRELKRCKE ENYDLAMRLA HQSEEKGAAL MRNRDLQLEI DQLKHSLMKA EDDCKVERKH TLKLRHAMEQ RPSQELLWEL QQEKALLQAR VQELEASVQE GKLDRSSPYI QVLEEDWRQA LRDHQEQANT IFSLRKDLRQ GEARRLRCME EKEMFELQCL ALRKDSKMYK DRIEAILLQM EEVAIERDQA IATREELHAQ HARGLQEKDA LRKQVRELGE KADELQLQVF QCEAQLLAVE GRLRRQQLET LVLSSDLEDG SPRRSQELSL PQDLEDTQLS DKGCLAGGGS PKQPFAALHQ EQVLRNPHDA GLSSGEPPEK ERRRLKESFE NYRRKRALRK MQKGWRQGEE DRENTTGSDN TDTEGS //