CARD9_HUMAN
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 03-AUG-2022, entry version 179.
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 CANDF2, AND VARIANT CANDF2 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 CANDF2.
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 CANDF2.
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 CANDF2 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 CANDF2 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 CANDF2 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 CANDF2 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 CANDF2 158-GLN--SER-536 DEL, CHARACTERIZATION OF VARIANT CANDF2
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 CANDF2 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 CANDF2 GLN-35; TRP-70; 289-GLN--SER-536 DEL AND 295-GLN--SER-536
RP DEL, CHARACTERIZATION OF VARIANTS CANDF2 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 CANDF2 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 CANDF2 TRP-18 AND GLU-323 DEL, CHARACTERIZATION OF VARIANT CANDF2
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 CANDF2 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 CANDF2 HIS-57, CHARACTERIZATION OF VARIANT CANDF2 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 CANDF2 TRP-70, CHARACTERIZATION OF VARIANT CANDF2 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 CANDF2 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 CANDF2 HIS-91, CHARACTERIZATION OF VARIANT CANDF2 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 CANDF2 295-GLN--SER-536 DEL, CHARACTERIZATION OF VARIANT CANDF2
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 CANDF2 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 CANDF2 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 CANDF2 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 CANDF2 23-SER--SER-536 DEL, CHARACTERIZATION OF VARIANT CANDF2
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 CANDF2 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 CANDF2 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 CANDF2 GLU-196 AND PRO-373, CHARACTERIZATION OF VARIANTS CANDF2
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: DUSP13; 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; 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: DUSP13; 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; O43247-2: TEX33; NbExp=3; IntAct=EBI-11530605, EBI-12093053;
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: Candidiasis, familial, 2 (CANDF2) [MIM:212050]: A primary
CC immunodeficiency disorder with altered immune responses and impaired
CC clearance of fungal infections, selective against Candida. It is
CC characterized by persistent and/or recurrent infections of the skin,
CC nails and mucous membranes caused by organisms of the genus Candida,
CC mainly Candida albicans. {ECO:0000269|PubMed:19864672,
CC ECO:0000269|PubMed:23335372, ECO:0000269|PubMed:24131138,
CC ECO:0000269|PubMed:24231284, ECO:0000269|PubMed:24704721,
CC ECO:0000269|PubMed:25057046, ECO:0000269|PubMed:25372963,
CC ECO:0000269|PubMed:25702837, ECO:0000269|PubMed:25933095,
CC ECO:0000269|PubMed:26044242, ECO:0000269|PubMed:26440558,
CC ECO:0000269|PubMed:26521038, ECO:0000269|PubMed:26658378,
CC ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:26941346,
CC ECO:0000269|PubMed:26961233, ECO:0000269|PubMed:27777981,
CC ECO:0000269|PubMed:28391957, ECO:0000269|PubMed:28984994,
CC ECO:0000269|PubMed:29080677, ECO:0000269|PubMed:29307770,
CC ECO:0000269|PubMed:31296852, ECO:0000269|PubMed:31469433,
CC ECO:0000269|PubMed:33548172, ECO:0000269|PubMed:33558980}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. Defects induce reduced numbers of CD4(+) Th17 lymphocytes as
CC well as a lack of monocyte-derived cytokines in response to Candida
CC strains (PubMed:23335372). Neutrophils show a selective Candida
CC albicans killing defect with abnormal ultrastructural phagolysosomes
CC and outgrowth of hyphae (PubMed:23335372).
CC {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 SMR; Q9H257; -.
DR BioGRID; 122094; 169.
DR IntAct; Q9H257; 160.
DR MINT; Q9H257; -.
DR STRING; 9606.ENSP00000360797; -.
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; Q9H257; -.
DR PeptideAtlas; Q9H257; -.
DR PRIDE; Q9H257; -.
DR ProteomicsDB; 80503; -. [Q9H257-1]
DR ProteomicsDB; 80504; -. [Q9H257-2]
DR ProteomicsDB; 80505; -. [Q9H257-3]
DR Antibodypedia; 18695; 275 antibodies from 39 providers.
DR DNASU; 64170; -.
DR Ensembl; ENST00000371732.10; ENSP00000360797.5; ENSG00000187796.15. [Q9H257-1]
DR Ensembl; ENST00000371734.7; ENSP00000360799.3; ENSG00000187796.15. [Q9H257-2]
DR Ensembl; ENST00000489932.2; ENSP00000451368.1; ENSG00000187796.15. [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 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; DAKMYRQ; -.
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; 13 hits in 1075 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 102 other tissues.
DR ExpressionAtlas; Q9H257; baseline and differential.
DR Genevisible; Q9H257; HS.
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:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
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: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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP: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: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; -; 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 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 CANDF2; 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 CANDF2; 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 CANDF2; 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 CANDF2; 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 CANDF2; 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 CANDF2; dbSNP:rs398122362)"
FT /evidence="ECO:0000269|PubMed:23335372"
FT /id="VAR_070828"
FT VARIANT 91
FT /note="Y -> H (in CANDF2; 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 CANDF2; dbSNP:rs398122364)"
FT /evidence="ECO:0000269|PubMed:24131138"
FT /id="VAR_070829"
FT VARIANT 101
FT /note="R -> L (in CANDF2)"
FT /evidence="ECO:0000269|PubMed:26044242"
FT /id="VAR_084636"
FT VARIANT 158..536
FT /note="Missing (in CANDF2; 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 CANDF2; reduced cytokine production in
FT response to C.albicans infection; does not affect NF-kappa-
FT B transcriptional activity; dbSNP:rs768281299)"
FT /evidence="ECO:0000269|PubMed:33558980"
FT /id="VAR_084638"
FT VARIANT 289..536
FT /note="Missing (in CANDF2; 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 CANDF2; 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 CANDF2; dbSNP:rs775284320)"
FT /evidence="ECO:0000269|PubMed:25057046"
FT /id="VAR_084641"
FT VARIANT 373
FT /note="R -> P (in CANDF2; reduced cytokine production in
FT response to C.albicans infection; does not affect NF-kappa-
FT 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 CANDF2)"
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
