CAR11_HUMAN
ID CAR11_HUMAN Reviewed; 1154 AA.
AC Q9BXL7; A4D1Z7; Q2NKN7; Q548H3;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Caspase recruitment domain-containing protein 11 {ECO:0000303|PubMed:11278692};
DE AltName: Full=CARD-containing MAGUK protein 1 {ECO:0000303|PubMed:11356195};
DE Short=Carma 1 {ECO:0000303|PubMed:11356195};
GN Name=CARD11 {ECO:0000303|PubMed:11278692, ECO:0000312|HGNC:HGNC:16393};
GN Synonyms=CARMA1 {ECO:0000303|PubMed:11356195};
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], FUNCTION, INTERACTION WITH BCL10, AND TISSUE
RP SPECIFICITY.
RX PubMed=11278692; DOI=10.1074/jbc.m010512200;
RA Bertin J., Wang L., Guo Y., Jacobson M.D., Poyet J.-L., Srinivasula S.M.,
RA Merriam S., DiStefano P.S., Alnemri E.S.;
RT "CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-
RT associated guanylate kinase (MAGUK) family members that interact with Bcl10
RT and activate NF-kappaB.";
RL J. Biol. Chem. 276:11877-11882(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-1154, FUNCTION, AND INTERACTION WITH BCL10.
RX PubMed=11356195; DOI=10.1016/s0014-5793(01)02414-0;
RA Gaide O., Martinon F., Micheau O., Bonnet D., Thome M., Tschopp J.;
RT "Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10
RT phosphorylation and NF-kappaB activation.";
RL FEBS Lett. 496:121-127(2001).
RN [6]
RP ERRATUM OF PUBMED:11356195.
RA Gaide O., Martinon F., Micheau O., Bonnet D., Thome M., Tschopp J.;
RL FEBS Lett. 505:198-198(2001).
RN [7]
RP FUNCTION.
RX PubMed=12356734; DOI=10.1093/emboj/cdf505;
RA Pomerantz J.L., Denny E.M., Baltimore D.;
RT "CARD11 mediates factor-specific activation of NF-kappaB by the T cell
RT receptor complex.";
RL EMBO J. 21:5184-5194(2002).
RN [8]
RP IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, FUNCTION, INTERACTION WITH DPP4,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17287217; DOI=10.1074/jbc.m609157200;
RA Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., Takahashi N.,
RA Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C.;
RT "Caveolin-1 triggers T-cell activation via CD26 in association with
RT CARMA1.";
RL J. Biol. Chem. 282:10117-10131(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-593 AND SER-925, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INVOLVEMENT IN IMD11A.
RX PubMed=23374270; DOI=10.1016/j.jaci.2012.11.050;
RA Stepensky P., Keller B., Buchta M., Kienzler A.K., Elpeleg O., Somech R.,
RA Cohen S., Shachar I., Miosge L.A., Schlesier M., Fuchs I., Enders A.,
RA Eibel H., Grimbacher B., Warnatz K.;
RT "Deficiency of caspase recruitment domain family, member 11 (CARD11),
RT causes profound combined immunodeficiency in human subjects.";
RL J. Allergy Clin. Immunol. 131:477-485(2013).
RN [12]
RP INVOLVEMENT IN BENTA, VARIANTS BENTA SER-123 AND GLY-134, AND
RP CHARACTERIZATION OF VARIANTS BENTA SER-123 AND GLY-134.
RX PubMed=23129749; DOI=10.1084/jem.20120831;
RA Snow A.L., Xiao W., Stinson J.R., Lu W., Chaigne-Delalande B., Zheng L.,
RA Pittaluga S., Matthews H.F., Schmitz R., Jhavar S., Kuchen S., Kardava L.,
RA Wang W., Lamborn I.T., Jing H., Raffeld M., Moir S., Fleisher T.A.,
RA Staudt L.M., Su H.C., Lenardo M.J.;
RT "Congenital B cell lymphocytosis explained by novel germline CARD11
RT mutations.";
RL J. Exp. Med. 209:2247-2261(2012).
RN [13]
RP INVOLVEMENT IN IMD11A, VARIANT IMD11A 945-GLN--LEU-1154 DEL, AND
RP CHARACTERIZATION OF VARIANT IMD11A 945-GLN--LEU-1154 DEL.
RX PubMed=23561803; DOI=10.1016/j.jaci.2013.02.012;
RA Greil J., Rausch T., Giese T., Bandapalli O.R., Daniel V.,
RA Bekeredjian-Ding I., Stuetz A.M., Drees C., Roth S., Ruland J.,
RA Korbel J.O., Kulozik A.E.;
RT "Whole-exome sequencing links caspase recruitment domain 11 (CARD11)
RT inactivation to severe combined immunodeficiency.";
RL J. Allergy Clin. Immunol. 131:1376-1383(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448; SER-512; SER-535;
RP SER-593; SER-886 AND SER-925, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [15]
RP FUNCTION, AND INTERACTION WITH BCL10.
RX PubMed=27777308; DOI=10.1074/jbc.m116.754028;
RA Yang Y.K., Yang C., Chan W., Wang Z., Deibel K.E., Pomerantz J.L.;
RT "Molecular determinants of scaffold-induced linear ubiquitinylation of B
RT Cell Lymphoma/Leukemia 10 (Bcl10) during T cell receptor and oncogenic
RT caspase recruitment domain-containing protein 11 (CARD11) signaling.";
RL J. Biol. Chem. 291:25921-25936(2016).
RN [16]
RP INVOLVEMENT IN IMD11B, VARIANTS IMD11B ASP-57; PRO-194 AND TRP-975,
RP CHARACTERIZATION OF VARIANTS IMD11B ASP-57; PRO-194 AND TRP-975,
RP CHARACTERIZATION OF VARIANT BENTA GLY-134, FUNCTION, AND INTERACTION WITH
RP BCL10.
RX PubMed=28628108; DOI=10.1038/ng.3898;
RA Ma C.A., Stinson J.R., Zhang Y., Abbott J.K., Weinreich M.A., Hauk P.J.,
RA Reynolds P.R., Lyons J.J., Nelson C.G., Ruffo E., Dorjbal B., Glauzy S.,
RA Yamakawa N., Arjunaraja S., Voss K., Stoddard J., Niemela J., Zhang Y.,
RA Rosenzweig S.D., McElwee J.J., DiMaggio T., Matthews H.F., Jones N.,
RA Stone K.D., Palma A., Oleastro M., Prieto E., Bernasconi A.R., Dubra G.,
RA Danielian S., Zaiat J., Marti M.A., Kim B., Cooper M.A., Romberg N.,
RA Meffre E., Gelfand E.W., Snow A.L., Milner J.D.;
RT "Germline hypomorphic CARD11 mutations in severe atopic disease.";
RL Nat. Genet. 49:1192-1201(2017).
RN [17]
RP DOMAIN, AND INTERACTION WITH BCL10.
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 [18] {ECO:0007744|PDB:4LWD}
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 18-110, FUNCTION, SUBUNIT,
RP INTERACTION WITH BCL10, AND IDENTIFICATION IN A CBM COMPLEX.
RX PubMed=24074955; DOI=10.1016/j.molcel.2013.08.032;
RA Qiao Q., Yang C., Zheng C., Fontan L., David L., Yu X., Bracken C.,
RA Rosen M., Melnick A., Egelman E.H., Wu H.;
RT "Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-
RT induced filamentous assembly.";
RL Mol. Cell 51:766-779(2013).
RN [19] {ECO:0007744|PDB:4JUP}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 21-116, DISULFIDE BOND, SUBUNIT,
RP AND MUTAGENESIS OF CYS-28.
RX PubMed=24224005; DOI=10.1371/journal.pone.0079778;
RA Jang T.H., Park J.H., Park H.H.;
RT "Novel disulfide bond-mediated dimerization of the CARD domain was revealed
RT by the crystal structure of CARMA1 CARD.";
RL PLoS ONE 8:e79778-e79778(2013).
CC -!- FUNCTION: Adapter protein that plays a key role in adaptive immune
CC response by transducing the activation of NF-kappa-B downstream of T-
CC cell receptor (TCR) and B-cell receptor (BCR) engagement
CC (PubMed:11278692, PubMed:11356195, PubMed:12356734). Transduces signals
CC downstream TCR or BCR activation via the formation of a multiprotein
CC complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP
CC kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways
CC (PubMed:11356195). Upon activation in response to TCR or BCR
CC triggering, CARD11 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 I-kappa-B kinase (IKK) phosphorylation and degradation,
CC and release of NF-kappa-B proteins for nuclear translocation
CC (PubMed:24074955). Its binding to DPP4 induces T-cell proliferation and
CC NF-kappa-B activation in a T-cell receptor/CD3-dependent manner
CC (PubMed:17287217). Promotes linear ubiquitination of BCL10 by promoting
CC the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). Stimulates the
CC phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1
CC signaling pathway (PubMed:28628108). {ECO:0000269|PubMed:11278692,
CC ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:12356734,
CC ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:24074955,
CC ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28628108}.
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 T-cell receptor (TCR) by
CC phosphorylation by PRKCB and PRKCQ triggers CARD11 homooligomerization
CC and BCL10 recruitment, followed by activation of NF-kappa-B (By
CC similarity). {ECO:0000250|UniProtKB:Q8CIS0,
CC ECO:0000269|PubMed:31296852}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:24224005). Homomultimer;
CC polymerizes following activation, forming a nucleating helical template
CC that seeds BCL10-filament formation via a CARD-CARD interaction
CC (PubMed:24074955). Interacts (via CARD domain) with BCL10 (via CARD
CC domain); interaction takes place following CARD11 activation and
CC polymerization, leading to the formation of a filamentous CBM complex
CC assembly (PubMed:11278692, PubMed:11356195, PubMed:27777308,
CC PubMed:24074955, PubMed:31296852). Component of a CBM complex (CARD11-
CC BCL10-MALT1) complex involved in NF-kappa-B activation
CC (PubMed:28628108, PubMed:24074955). Found in a membrane raft complex,
CC at least composed of BCL10, CARD11, DPP4 and IKBKB (PubMed:17287217).
CC Interacts (via PDZ domain) with DPP4 (via cytoplasmic tail)
CC (PubMed:17287217). {ECO:0000269|PubMed:11278692,
CC ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:17287217,
CC ECO:0000269|PubMed:24074955, ECO:0000269|PubMed:24224005,
CC ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28628108,
CC ECO:0000269|PubMed:31296852}.
CC -!- INTERACTION:
CC Q9BXL7; O95999: BCL10; NbExp=7; IntAct=EBI-7006141, EBI-958922;
CC Q9BXL7; Q13191-1: CBLB; NbExp=4; IntAct=EBI-7006141, EBI-15555129;
CC Q9BXL7; P48729: CSNK1A1; NbExp=5; IntAct=EBI-7006141, EBI-1383726;
CC Q9BXL7; P48729-1: CSNK1A1; NbExp=5; IntAct=EBI-7006141, EBI-10106282;
CC Q9BXL7; Q9UDY8: MALT1; NbExp=2; IntAct=EBI-7006141, EBI-1047372;
CC Q9BXL7; Q05655: PRKCD; NbExp=7; IntAct=EBI-7006141, EBI-704279;
CC Q9BXL7; P70218: Map4k1; Xeno; NbExp=2; IntAct=EBI-7006141, EBI-2906801;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17287217}. Membrane
CC raft {ECO:0000269|PubMed:17287217}. Note=Colocalized with DPP4 in
CC membrane rafts. {ECO:0000269|PubMed:17287217}.
CC -!- TISSUE SPECIFICITY: Detected in adult peripheral blood leukocytes,
CC thymus, spleen and liver. Also found in promyelocytic leukemia HL-60
CC cells, chronic myelogenous leukemia K-562 cells, Burkitt's lymphoma
CC Raji cells and colorectal adenocarcinoma SW480 cells. Not detected in
CC HeLaS3, MOLT-4, A-549 and G431 cells. {ECO:0000269|PubMed:11278692}.
CC -!- DOMAIN: The linker region, also named autoinhibitory interface, is less
CC inhibitory on its own than that of CARD9 (PubMed:31296852). The linker
CC region together with the inhibitory domain (ID) are required to prevent
CC constitutive activation and maintain CARD11 in an autoinhibitory state
CC (PubMed:31296852). Disruption of the inhibitory domain (ID) region
CC triggers polymerization and activation, leading to formation of BCL10-
CC nucleating filaments (PubMed:31296852). {ECO:0000269|PubMed:31296852}.
CC -!- PTM: Phosphorylation at Ser-559, Ser-644 and Ser-652 by PRKCB and PRKCQ
CC leads to a shift from an inactive to an active form that activates the
CC NF-kappa-B signaling. {ECO:0000250|UniProtKB:Q8CIS0}.
CC -!- DISEASE: B-cell expansion with NFKB and T-cell anergy (BENTA)
CC [MIM:616452]: An autosomal dominant condition characterized by onset in
CC infancy of splenomegaly and polyclonal expansion of B cells, resulting
CC in peripheral lymphocytosis. Affected individuals also show mild immune
CC dysfunction, including some defective antibody responses and T-cell
CC anergy. There may be a predisposition to the development of B-cell
CC malignancy. {ECO:0000269|PubMed:23129749, ECO:0000269|PubMed:28628108}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Immunodeficiency 11 A (IMD11A) [MIM:615206]: An autosomal
CC recessive primary immunodeficiency characterized by normal numbers of T
CC and B-lymphocytes, but defective intracellular signaling. There is a
CC block in B-cell differentiation with increased numbers of transitional
CC B-cells and hypogammaglobulinemia, as well as decreased numbers of
CC regulatory T-cells and defects in T-cell function.
CC {ECO:0000269|PubMed:23374270, ECO:0000269|PubMed:23561803}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Immunodeficiency 11B with atopic dermatitis (IMD11B)
CC [MIM:617638]: An autosomal dominant disorder of immune dysfunction
CC characterized by onset of moderate to severe atopic dermatitis in early
CC childhood. Some patients may have recurrent infections and other
CC variable immune abnormalities. Laboratory studies show defects in T-
CC cell activation, increased IgE, and eosinophilia.
CC {ECO:0000269|PubMed:28628108}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG53402.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI11720.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAQ96893.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAL23962.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF322641; AAG53402.1; ALT_INIT; mRNA.
DR EMBL; AC004906; AAQ96893.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH236953; EAL23962.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC111719; AAI11720.2; ALT_INIT; mRNA.
DR EMBL; AF352576; AAL34460.1; -; mRNA.
DR CCDS; CCDS5336.2; -.
DR RefSeq; NP_001311210.1; NM_001324281.1.
DR RefSeq; NP_115791.3; NM_032415.5.
DR RefSeq; XP_011513888.1; XM_011515586.2.
DR PDB; 4JUP; X-ray; 3.20 A; A/B=21-116.
DR PDB; 4LWD; X-ray; 1.79 A; A=18-110.
DR PDBsum; 4JUP; -.
DR PDBsum; 4LWD; -.
DR AlphaFoldDB; Q9BXL7; -.
DR SMR; Q9BXL7; -.
DR BioGRID; 124073; 32.
DR CORUM; Q9BXL7; -.
DR DIP; DIP-41797N; -.
DR IntAct; Q9BXL7; 18.
DR MINT; Q9BXL7; -.
DR STRING; 9606.ENSP00000380150; -.
DR iPTMnet; Q9BXL7; -.
DR PhosphoSitePlus; Q9BXL7; -.
DR BioMuta; CARD11; -.
DR DMDM; 172046231; -.
DR EPD; Q9BXL7; -.
DR jPOST; Q9BXL7; -.
DR MassIVE; Q9BXL7; -.
DR MaxQB; Q9BXL7; -.
DR PaxDb; Q9BXL7; -.
DR PeptideAtlas; Q9BXL7; -.
DR PRIDE; Q9BXL7; -.
DR ProteomicsDB; 79450; -.
DR Antibodypedia; 11155; 331 antibodies from 45 providers.
DR DNASU; 84433; -.
DR Ensembl; ENST00000396946.9; ENSP00000380150.4; ENSG00000198286.10.
DR GeneID; 84433; -.
DR KEGG; hsa:84433; -.
DR MANE-Select; ENST00000396946.9; ENSP00000380150.4; NM_032415.7; NP_115791.3.
DR UCSC; uc003smv.5; human.
DR CTD; 84433; -.
DR DisGeNET; 84433; -.
DR GeneCards; CARD11; -.
DR HGNC; HGNC:16393; CARD11.
DR HPA; ENSG00000198286; Tissue enhanced (lymphoid).
DR MalaCards; CARD11; -.
DR MIM; 607210; gene.
DR MIM; 615206; phenotype.
DR MIM; 616452; phenotype.
DR MIM; 617638; phenotype.
DR neXtProt; NX_Q9BXL7; -.
DR OpenTargets; ENSG00000198286; -.
DR Orphanet; 464336; BENTA disease.
DR Orphanet; 300324; Persistent polyclonal B-cell lymphocytosis.
DR Orphanet; 357237; Severe combined immunodeficiency due to CARD11 deficiency.
DR PharmGKB; PA26073; -.
DR VEuPathDB; HostDB:ENSG00000198286; -.
DR eggNOG; KOG0708; Eukaryota.
DR GeneTree; ENSGT00940000158573; -.
DR HOGENOM; CLU_009760_1_0_1; -.
DR InParanoid; Q9BXL7; -.
DR OMA; MWSSVEE; -.
DR OrthoDB; 115953at2759; -.
DR PhylomeDB; Q9BXL7; -.
DR TreeFam; TF351139; -.
DR PathwayCommons; Q9BXL7; -.
DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR SignaLink; Q9BXL7; -.
DR SIGNOR; Q9BXL7; -.
DR BioGRID-ORCS; 84433; 25 hits in 1083 CRISPR screens.
DR ChiTaRS; CARD11; human.
DR GeneWiki; CARD11; -.
DR GenomeRNAi; 84433; -.
DR Pharos; Q9BXL7; Tbio.
DR PRO; PR:Q9BXL7; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9BXL7; protein.
DR Bgee; ENSG00000198286; Expressed in granulocyte and 154 other tissues.
DR ExpressionAtlas; Q9BXL7; baseline and differential.
DR Genevisible; Q9BXL7; HS.
DR GO; GO:0032449; C:CBM complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB.
DR GO; GO:0004385; F:guanylate kinase activity; NAS:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0045577; P:regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0045580; P:regulation of T cell differentiation; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; IDA:UniProtKB.
DR GO; GO:0045061; P:thymic T cell selection; IEA:Ensembl.
DR GO; GO:0038202; P:TORC1 signaling; IMP:UniProtKB.
DR CDD; cd08808; CARD_CARD11_CARMA1; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR033538; CARD11.
DR InterPro; IPR042141; CARD_CARD11.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR14559:SF4; PTHR14559:SF4; 1.
DR Pfam; PF00619; CARD; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50209; CARD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Disease variant; Disulfide bond;
KW Immunity; Isopeptide bond; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..1154
FT /note="Caspase recruitment domain-containing protein 11"
FT /id="PRO_0000144086"
FT DOMAIN 18..110
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 667..755
FT /note="PDZ"
FT DOMAIN 973..1140
FT /note="Guanylate kinase-like"
FT REGION 111..128
FT /note="Linker"
FT /evidence="ECO:0000305|PubMed:31296852"
FT REGION 450..666
FT /note="Inhibitory domain (ID)"
FT /evidence="ECO:0000303|PubMed:31296852"
FT REGION 460..626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 130..449
FT /evidence="ECO:0000255"
FT COMPBIAS 462..477
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..566
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 572..591
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..626
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 559
FT /note="Phosphoserine; by PKC/PRKCB and PKC/PRKCQ"
FT /evidence="ECO:0000250|UniProtKB:Q8CIS0"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 644
FT /note="Phosphoserine; by PKC/PRKCB and PKC/PRKCQ"
FT /evidence="ECO:0000250|UniProtKB:Q8CIS0"
FT MOD_RES 652
FT /note="Phosphoserine; by PKC/PRKCB and PKC/PRKCQ"
FT /evidence="ECO:0000250|UniProtKB:Q8CIS0"
FT MOD_RES 886
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 925
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT DISULFID 28
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:24224005,
FT ECO:0007744|PDB:4JUP"
FT VARIANT 57
FT /note="E -> D (in IMD11B; no effect on protein abundance;
FT decreased interaction with BCL10; dominant negative effect
FT on NF-kappa-B signaling; dominant negative effect on TORC1
FT signaling)"
FT /evidence="ECO:0000269|PubMed:28628108"
FT /id="VAR_079284"
FT VARIANT 123
FT /note="G -> S (in BENTA; results in protein aggregation;
FT constitutive activation of NF-kappa-B signaling;
FT dbSNP:rs387907352)"
FT /evidence="ECO:0000269|PubMed:23129749"
FT /id="VAR_069710"
FT VARIANT 134
FT /note="E -> G (in BENTA; results in protein aggregation;
FT constitutive activation of NF-kappa-B signaling;
FT dbSNP:rs387907351)"
FT /evidence="ECO:0000269|PubMed:23129749,
FT ECO:0000269|PubMed:28628108"
FT /id="VAR_069711"
FT VARIANT 194
FT /note="L -> P (in IMD11B; no effect on protein abundance;
FT decreased interaction with BCL10; dominant negative effect
FT on NF-kappa-B signaling; dominant negative effect on TORC1
FT signaling)"
FT /evidence="ECO:0000269|PubMed:28628108"
FT /id="VAR_079285"
FT VARIANT 670
FT /note="T -> M (in dbSNP:rs3735134)"
FT /id="VAR_028117"
FT VARIANT 694
FT /note="S -> L (in dbSNP:rs3735133)"
FT /id="VAR_028118"
FT VARIANT 945..1154
FT /note="Missing (in IMD11A; results in defective NF-kappa-B
FT activation)"
FT /evidence="ECO:0000269|PubMed:23561803"
FT /id="VAR_079158"
FT VARIANT 975
FT /note="R -> W (in IMD11B; no effect on protein abundance;
FT dominant negative effect on NF-kappaB signaling; dominant
FT negative effect on TORC1 signaling; dbSNP:rs1064795307)"
FT /evidence="ECO:0000269|PubMed:28628108"
FT /id="VAR_079286"
FT MUTAGEN 28
FT /note="C->A: Abolished homodimerization."
FT /evidence="ECO:0000269|PubMed:24224005"
FT CONFLICT 815
FT /note="L -> P (in Ref. 1; AAG53402)"
FT /evidence="ECO:0000305"
FT HELIX 24..27
FT /evidence="ECO:0007829|PDB:4LWD"
FT HELIX 30..36
FT /evidence="ECO:0007829|PDB:4LWD"
FT HELIX 39..48
FT /evidence="ECO:0007829|PDB:4LWD"
FT HELIX 54..61
FT /evidence="ECO:0007829|PDB:4LWD"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:4LWD"
FT HELIX 74..80
FT /evidence="ECO:0007829|PDB:4LWD"
FT HELIX 84..98
FT /evidence="ECO:0007829|PDB:4LWD"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:4LWD"
SQ SEQUENCE 1154 AA; 133284 MW; 2F3512D903795D18 CRC64;
MPGGGPEMDD YMETLKDEED ALWENVECNR HMLSRYINPA KLTPYLRQCK VIDEQDEDEV
LNAPMLPSKI NRAGRLLDIL HTKGQRGYVV FLESLEFYYP ELYKLVTGKE PTRRFSTIVV
EEGHEGLTHF LMNEVIKLQQ QMKAKDLQRC ELLARLRQLE DEKKQMTLTR VELLTFQERY
YKMKEERDSY NDELVKVKDD NYNLAMRYAQ LSEEKNMAVM RSRDLQLEID QLKHRLNKME
EECKLERNQS LKLKNDIENR PKKEQVLELE RENEMLKTKN QELQSIIQAG KRSLPDSDKA
ILDILEHDRK EALEDRQELV NRIYNLQEEA RQAEELRDKY LEEKEDLELK CSTLGKDCEM
YKHRMNTVML QLEEVERERD QAFHSRDEAQ TQYSQCLIEK DKYRKQIREL EEKNDEMRIE
MVRREACIVN LESKLRRLSK DSNNLDQSLP RNLPVTIISQ DFGDASPRTN GQEADDSSTS
EESPEDSKYF LPYHPPQRRM NLKGIQLQRA KSPISLKRTS DFQAKGHEEE GTDASPSSCG
SLPITNSFTK MQPPRSRSSI MSITAEPPGN DSIVRRYKED APHRSTVEED NDSGGFDALD
LDDDSHERYS FGPSSIHSSS SSHQSEGLDA YDLEQVNLMF RKFSLERPFR PSVTSVGHVR
GPGPSVQHTT LNGDSLTSQL TLLGGNARGS FVHSVKPGSL AEKAGLREGH QLLLLEGCIR
GERQSVPLDT CTKEEAHWTI QRCSGPVTLH YKVNHEGYRK LVKDMEDGLI TSGDSFYIRL
NLNISSQLDA CTMSLKCDDV VHVRDTMYQD RHEWLCARVD PFTDHDLDMG TIPSYSRAQQ
LLLVKLQRLM HRGSREEVDG THHTLRALRN TLQPEEALST SDPRVSPRLS RASFLFGQLL
QFVSRSENKY KRMNSNERVR IISGSPLGSL ARSSLDATKL LTEKQEELDP ESELGKNLSL
IPYSLVRAFY CERRRPVLFT PTVLAKTLVQ RLLNSGGAME FTICKSDIVT RDEFLRRQKT
ETIIYSREKN PNAFECIAPA NIEAVAAKNK HCLLEAGIGC TRDLIKSNIY PIVLFIRVCE
KNIKRFRKLL PRPETEEEFL RVCRLKEKEL EALPCLYATV EPDMWGSVEE LLRVVKDKIG
EEQRKTIWVD EDQL
