BCL10_HUMAN
ID BCL10_HUMAN Reviewed; 233 AA.
AC O95999; Q5VUF1;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=B-cell lymphoma/leukemia 10;
DE AltName: Full=B-cell CLL/lymphoma 10 {ECO:0000303|PubMed:9989495};
DE Short=Bcl-10 {ECO:0000303|PubMed:9989495};
DE AltName: Full=CARD-containing molecule enhancing NF-kappa-B;
DE AltName: Full=CARD-like apoptotic protein {ECO:0000303|PubMed:10364242};
DE Short=hCLAP {ECO:0000303|PubMed:10364242};
DE AltName: Full=CED-3/ICH-1 prodomain homologous E10-like regulator {ECO:0000303|PubMed:10187770};
DE Short=CIPER {ECO:0000303|PubMed:10187770};
DE AltName: Full=Cellular homolog of vCARMEN;
DE Short=cCARMEN;
DE AltName: Full=Cellular-E10 {ECO:0000303|PubMed:10400625};
DE Short=c-E10 {ECO:0000303|PubMed:10400625};
DE AltName: Full=Mammalian CARD-containing adapter molecule E10 {ECO:0000303|PubMed:10187815};
DE Short=mE10 {ECO:0000303|PubMed:10187815};
GN Name=BCL10 {ECO:0000303|PubMed:9989495, ECO:0000312|HGNC:HGNC:989};
GN Synonyms=CIPER {ECO:0000303|PubMed:10187770},
GN CLAP {ECO:0000303|PubMed:10364242};
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], TISSUE SPECIFICITY, INVOLVEMENT IN MALTOMA, AND
RP VARIANTS ILE-52; GLY-58; GLU-210 DEL AND PHE-218.
RC TISSUE=Lymphoma;
RX PubMed=9989495; DOI=10.1016/s0092-8674(00)80957-5;
RA Willis T.G., Jadayel D.M., Du M.-Q., Peng H., Perry A.R., Abdul-Rauf M.,
RA Price H., Karran L., Majekodunmi O., Wlodarska I., Pan L., Crook T.,
RA Hamoudi R., Isaacson P., Dyer M.J.S.;
RT "Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated
RT in multiple tumor types.";
RL Cell 96:35-45(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF LEU-41 AND GLY-78.
RX PubMed=10187770; DOI=10.1074/jbc.274.15.9955;
RA Koseki T., Inohara N., Chen S., Carrio R., Merino J., Hottiger M.O.,
RA Nabel G.J., Nunez G.;
RT "CIPER, a novel NF kappaB-activating protein containing a caspase
RT recruitment domain with homology to Herpesvirus-2 protein E10.";
RL J. Biol. Chem. 274:9955-9961(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10187771; DOI=10.1074/jbc.274.15.9962;
RA Thome M., Martinon F., Hofmann K., Rubio V., Steiner V., Schneider P.,
RA Mattmann C., Tschopp J.;
RT "Equine herpesvirus-2 E10 gene product, but not its cellular homologue,
RT activates NF-kappaB transcription factor and c-Jun N-terminal kinase.";
RL J. Biol. Chem. 274:9962-9968(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF LEU-28; LEU-41;
RP ILE-46; LEU-47; GLU-53 AND ILE-55.
RX PubMed=10187815; DOI=10.1074/jbc.274.15.10287;
RA Yan M., Lee J., Schilbach S., Goddard A., Dixit V.M.;
RT "mE10, a novel caspase recruitment domain-containing proapoptotic
RT molecule.";
RL J. Biol. Chem. 274:10287-10292(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=10364242; DOI=10.1074/jbc.274.25.17946;
RA Srinivasula S.M., Ahmad M., Lin J.-H., Poyet J.-L., Fernandes-Alnemri T.,
RA Tsichlis P.N., Alnemri E.S.;
RT "CLAP, a novel caspase recruitment domain-containing protein in the tumor
RT necrosis factor receptor pathway, regulates NF-kappaB activation and
RT apoptosis.";
RL J. Biol. Chem. 274:17946-17954(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Spleen;
RX PubMed=10400625; DOI=10.1074/jbc.274.29.20127;
RA Costanzo A., Guiet C., Vito P.;
RT "c-E10 is a caspase-recruiting domain-containing protein that interacts
RT with components of death receptors signaling pathway and activates nuclear
RT factor-kappaB.";
RL J. Biol. Chem. 274:20127-20132(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS SER-5; GLU-16;
RP GLU-31; ARG-57; LYS-64; GLU-101; PRO-134; ALA-168; SER-174; GLU-213 AND
RP ILE-230.
RX PubMed=10319863; DOI=10.1038/8767;
RA Zhang Q., Siebert R., Yan M., Hinzmann B., Cui X., Xue L., Rakestraw K.M.,
RA Naeve C.W., Beckmann G., Weisenburger D.D., Sanger W.G., Nowotny H.,
RA Vesely M., Callet-Bauchu E., Salles G., Dixit V.M., Rosenthal A.,
RA Schlegelberger B., Morris S.W.;
RT "Inactivating mutations and overexpression of BCL10, a caspase recruitment
RT domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32).";
RL Nat. Genet. 22:63-68(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [10]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [12]
RP PHOSPHORYLATION, AND INTERACTION WITH TRAF2.
RX PubMed=11466612; DOI=10.1038/sj.onc.1204576;
RA Yui D., Yoneda T., Oono K., Katayama T., Imaizumi K., Tohyama M.;
RT "Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis
RT signaling.";
RL Oncogene 20:4317-4323(2001).
RN [13]
RP IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, AND SUBCELLULAR LOCATION.
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 [14]
RP PHOSPHORYLATION BY IKBKB/IKKB, AND MUTAGENESIS OF 81-THR--SER-85.
RX PubMed=17213322; DOI=10.1073/pnas.0606982104;
RA Lobry C., Lopez T., Israel A., Weil R.;
RT "Negative feedback loop in T cell activation through IkappaB kinase-induced
RT phosphorylation and degradation of Bcl10.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:908-913(2007).
RN [15]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ARG-228.
RX PubMed=18264101; DOI=10.1038/ni1568;
RA Rebeaud F., Hailfinger S., Posevitz-Fejfar A., Tapernoux M., Moser R.,
RA Rueda D., Gaide O., Guzzardi M., Iancu E.M., Rufer N., Fasel N., Thome M.;
RT "The proteolytic activity of the paracaspase MALT1 is key in T cell
RT activation.";
RL Nat. Immunol. 9:272-281(2008).
RN [16]
RP FUNCTION, UBIQUITINATION AT LYS-31 AND LYS-63, AND MUTAGENESIS OF LYS-31;
RP 63-LYS--LYS-67; LYS-63 AND 105-LYS--LYS-115.
RX PubMed=18287044; DOI=10.1073/pnas.0712313105;
RA Wu C.J., Ashwell J.D.;
RT "NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-
RT mediated NF-kappaB activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3023-3028(2008).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP FUNCTION, AND INVOLVEMENT IN IMD37.
RX PubMed=25365219; DOI=10.1172/jci77493;
RA Torres J.M., Martinez-Barricarte R., Garcia-Gomez S., Mazariegos M.S.,
RA Itan Y., Boisson B., Rholvarez R., Jimenez-Reinoso A., Del Pino L.,
RA Rodriguez-Pena R., Ferreira A., Hernandez-Jimenez E., Toledano V.,
RA Cubillos-Zapata C., Diaz-Almiron M., Lopez-Collazo E., Unzueta-Roch J.L.,
RA Sanchez-Ramon S., Regueiro J.R., Lopez-Granados E., Casanova J.L.,
RA Perez de Diego R.;
RT "Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic
RT immunity.";
RL J. Clin. Invest. 124:5239-5248(2014).
RN [21]
RP FUNCTION, AND INTERACTION WITH CARD9.
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 [22]
RP SUBUNIT.
RX PubMed=27113748; DOI=10.15252/embr.201642109;
RA Afonina I.S., Van Nuffel E., Baudelet G., Driege Y., Kreike M., Staal J.,
RA Beyaert R.;
RT "The paracaspase MALT1 mediates CARD14-induced signaling in
RT keratinocytes.";
RL EMBO Rep. 17:914-927(2016).
RN [23]
RP FUNCTION, INTERACTION WITH CARD11, UBIQUITINATION AT LYS-17; LYS-31 AND
RP LYS-63, AND MUTAGENESIS OF LYS-17; LYS-31 AND LYS-63.
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 [24]
RP INTERACTION WITH CARD11 AND MALT1.
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 [25]
RP INTERACTION WITH CARD9 AND CARD11.
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 [26] {ECO:0007744|PDB:2MB9}
RP STRUCTURE BY NMR OF 1-115, FUNCTION, SUBUNIT, INTERACTION WITH CARD11,
RP IDENTIFICATION IN A CBM COMPLEX, AND MUTAGENESIS OF ARG-36; 50-GLU-ASP-51;
RP GLU-50 AND GLU-53.
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 [27]
RP VARIANTS SER-5; MET-162 AND GLU-213.
RX PubMed=10582682;
RA Lee S.H., Shin M.S., Kim H.S., Park W.S., Kim S.Y., Lee H.K., Park J.Y.,
RA Oh R.R., Jang J.J., Park K.M., Han J.Y., Kang C.S., Lee J.Y., Yoo N.J.;
RT "Point mutations and deletions of the Bcl10 gene in solid tumors and
RT malignant lymphomas.";
RL Cancer Res. 59:5674-5677(1999).
RN [28]
RP VARIANTS SER-5; GLN-45; GLN-58; SER-93; VAL-153; GLU-213 AND PHE-218.
RX PubMed=10380921; DOI=10.1016/s0092-8674(02)09765-9;
RA Apostolou S., de Rienzo A., Murthy S.S., Jhanwar S.C., Testa J.R.;
RT "Absence of BCL10 mutations in human malignant mesothelioma.";
RL Cell 97:684-686(1999).
CC -!- FUNCTION: Plays a key role in both adaptive and innate immune signaling
CC by bridging CARD domain-containing proteins to immune activation
CC (PubMed:10187770, PubMed:10364242, PubMed:10400625, PubMed:25365219,
CC PubMed:24074955). Acts by channeling adaptive and innate immune
CC signaling downstream of CARD domain-containing proteins CARD9, CARD11
CC and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12,
CC MAPK13 and/or MAPK14) pathways which stimulate expression of genes
CC encoding pro-inflammatory cytokines and chemokines (PubMed:24074955).
CC Recruited by activated CARD domain-containing proteins:
CC homooligomerized CARD domain-containing proteins form a nucleating
CC helical template that recruits BCL10 via CARD-CARD interaction, thereby
CC promoting polymerization of BCL10, subsequent recruitment of MALT1 and
CC formation of a CBM complex (PubMed:24074955). This leads to activation
CC of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14)
CC pathways which stimulate expression of genes encoding pro-inflammatory
CC cytokines and chemokines (PubMed:18287044, PubMed:27777308,
CC PubMed:24074955). Activated by CARD9 downstream of C-type lectin
CC receptors; CARD9-mediated signals are essential for antifungal immunity
CC (PubMed:26488816). Activated by CARD11 downstream of T-cell receptor
CC (TCR) and B-cell receptor (BCR) (PubMed:18264101, PubMed:18287044,
CC PubMed:27777308, PubMed:24074955). Promotes apoptosis, pro-caspase-9
CC maturation and activation of NF-kappa-B via NIK and IKK
CC (PubMed:10187815). {ECO:0000269|PubMed:10187770,
CC ECO:0000269|PubMed:10187815, ECO:0000269|PubMed:10364242,
CC ECO:0000269|PubMed:10400625, ECO:0000269|PubMed:18264101,
CC ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:24074955,
CC ECO:0000269|PubMed:25365219, ECO:0000269|PubMed:26488816,
CC ECO:0000269|PubMed:27777308}.
CC -!- SUBUNIT: Homomultimer; homooligomerized following recruitment by CARD
CC domain-containing proteins that form a nucleating helical template that
CC recruits BCL10 via CARD-CARD interaction (PubMed:24074955). Self-
CC associates by CARD-CARD interaction and interacts with other CARD-
CC proteins such as CARD9, CARD10, CARD11 and CARD14 (PubMed:26488816,
CC PubMed:27113748, PubMed:27777308, PubMed:28628108, PubMed:31296852,
CC PubMed:24074955). Forms a complex with CARD14 and MALT1; resulting in
CC the formation of a CBM (CARD14-BCL10-MALT1) complex (PubMed:27113748).
CC Forms a complex with CARD11 and MALT1; resulting in the formation of a
CC CBM (CARD11-BCL10-MALT1) complex (PubMed:28628108, PubMed:24074955).
CC Forms a complex with CARD9 and MALT1; resulting in the formation of a
CC CBM (CARD9-BCL10-MALT1) complex (By similarity). Found in a membrane
CC raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB
CC (PubMed:17287217). Binds caspase-9 with its C-terminal domain
CC (PubMed:10187815). Interacts with TRAF2 and BIRC2/c-IAP2
CC (PubMed:11466612). Interacts with PELI2 and SOCS3; these interactions
CC may be mutually exclusive (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z0H7, ECO:0000269|PubMed:10187815,
CC ECO:0000269|PubMed:11466612, ECO:0000269|PubMed:17287217,
CC ECO:0000269|PubMed:24074955, ECO:0000269|PubMed:26488816,
CC ECO:0000269|PubMed:27113748, ECO:0000269|PubMed:27777308,
CC ECO:0000269|PubMed:28628108, ECO:0000269|PubMed:31296852}.
CC -!- INTERACTION:
CC O95999; P31749: AKT1; NbExp=5; IntAct=EBI-958922, EBI-296087;
CC O95999; O95999: BCL10; NbExp=5; IntAct=EBI-958922, EBI-958922;
CC O95999; P20749: BCL3; NbExp=3; IntAct=EBI-958922, EBI-958997;
CC O95999; Q9BXL7: CARD11; NbExp=7; IntAct=EBI-958922, EBI-7006141;
CC O95999; Q9H257: CARD9; NbExp=6; IntAct=EBI-958922, EBI-751319;
CC O95999; Q9Y2V7: COG6; NbExp=5; IntAct=EBI-958922, EBI-3866319;
CC O95999; Q9Y6K9: IKBKG; NbExp=7; IntAct=EBI-958922, EBI-81279;
CC O95999; Q9UDY8: MALT1; NbExp=19; IntAct=EBI-958922, EBI-1047372;
CC O95999; Q05513: PRKCZ; NbExp=3; IntAct=EBI-958922, EBI-295351;
CC O95999; Q12933: TRAF2; NbExp=9; IntAct=EBI-958922, EBI-355744;
CC O95999; Q66677: E10; Xeno; NbExp=2; IntAct=EBI-958922, EBI-11709474;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:17287217}. Membrane raft
CC {ECO:0000269|PubMed:17287217}. Note=Appears to have a perinuclear,
CC compact and filamentous pattern of expression. Also found in the
CC nucleus of several types of tumor cells. Colocalized with DPP4 in
CC membrane rafts. {ECO:0000269|PubMed:17287217}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9989495}.
CC -!- PTM: Phosphorylated. Phosphorylation results in dissociation from TRAF2
CC and binding to BIRC2/c-IAP2 (PubMed:11466612). Phosphorylated by
CC IKBKB/IKKB (PubMed:17213322). {ECO:0000269|PubMed:11466612,
CC ECO:0000269|PubMed:17213322}.
CC -!- PTM: Ubiquitinated via both 'Lys-63'-linked and linear ('Met-1'-linked)
CC polyubiquitin chains in response to T-cell receptor (TCR) activation
CC (PubMed:18287044, PubMed:27777308). Ubiquitination is recognized by
CC IKBKG/NEMO, the regulatory subunit of I-kappa-B kinase (IKK), and is
CC required for TCR-induced NF-kappa-B activation (PubMed:18287044,
CC PubMed:27777308). Linear ubiquitination at Lys-17, Lys-31 and Lys-63 is
CC mediated by RNF31/HOIP; linear ubiquitination is recognized with much
CC higher affinity than 'Lys-63'-linked ubiquitin by IKBKG/NEMO
CC (PubMed:27777308). CARD11 is required for linear ubiquitination by HOIP
CC by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308).
CC {ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:27777308}.
CC -!- PTM: Proteolytically cleaved by MALT1; required for T-cell activation.
CC {ECO:0000269|PubMed:18264101}.
CC -!- DISEASE: Note=A chromosomal aberration involving BCL10 is recurrent in
CC low-grade mucosa-associated lymphoid tissue (MALT lymphoma).
CC Translocation t(1;14)(p22;q32). Although the BCL10/IgH translocation
CC leaves the coding region of BCL10 intact, frequent BCL10 mutations
CC could be attributed to the Ig somatic hypermutation mechanism resulting
CC in nucleotide transitions. {ECO:0000269|PubMed:9989495}.
CC -!- DISEASE: Immunodeficiency 37 (IMD37) [MIM:616098]: A form of primary
CC combined immunodeficiency, a group of disorders characterized by severe
CC recurrent infections, with normal numbers or an absence of T and B
CC lymphocytes, and impaired cellular and humoral immunity. IMD37 is
CC characterized by hypogammaglobulinemia without lymphopenia, but with
CC profoundly reduced memory B cells and memory T cells, and increased
CC numbers of circulating naive lymphocytes. Inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:25365219}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Lymphoma, mucosa-associated lymphoid type (MALTOMA)
CC [MIM:137245]: A subtype of non-Hodgkin lymphoma, originating in mucosa-
CC associated lymphoid tissue. MALT lymphomas occur most commonly in the
CC gastro-intestinal tract but have been described in a variety of
CC extranodal sites including the ocular adnexa, salivary gland, thyroid,
CC lung, thymus, and breast. Histologically, they are characterized by an
CC infiltrate of small to medium-sized lymphocytes with abundant cytoplasm
CC and irregularly shaped nuclei. Scattered transformed blasts (large
CC cells) also are present. Non-malignant reactive follicles are observed
CC frequently. A pivotal feature is the presence of lymphoepithelial
CC lesions, with invasion and partial destruction of mucosal glands and
CC crypts by aggregates of tumor cells. {ECO:0000269|PubMed:9989495}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BCL10ID222ch1p22.html";
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; AJ006288; CAA06955.1; -; mRNA.
DR EMBL; AF057700; AAD15800.1; -; mRNA.
DR EMBL; AF100338; AAD16428.1; -; mRNA.
DR EMBL; AF127386; AAD32597.1; -; mRNA.
DR EMBL; AF134395; AAD39147.1; -; mRNA.
DR EMBL; AF105066; AAF06894.1; -; mRNA.
DR EMBL; AF082283; AAC99767.1; -; mRNA.
DR EMBL; AF097732; AAD24918.1; -; Genomic_DNA.
DR EMBL; AK291346; BAF84035.1; -; mRNA.
DR EMBL; AL590113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73208.1; -; Genomic_DNA.
DR EMBL; BC053617; AAH53617.1; -; mRNA.
DR CCDS; CCDS704.1; -.
DR RefSeq; NP_003912.1; NM_003921.4.
DR PDB; 2MB9; NMR; -; A=1-115.
DR PDB; 6BZE; EM; 4.00 A; A/B/C/D/E/F/G/H=10-115.
DR PDB; 6GK2; EM; 4.90 A; H=10-115.
DR PDBsum; 2MB9; -.
DR PDBsum; 6BZE; -.
DR PDBsum; 6GK2; -.
DR AlphaFoldDB; O95999; -.
DR BMRB; O95999; -.
DR SMR; O95999; -.
DR BioGRID; 114429; 83.
DR CORUM; O95999; -.
DR DIP; DIP-29740N; -.
DR IntAct; O95999; 41.
DR MINT; O95999; -.
DR STRING; 9606.ENSP00000359612; -.
DR GlyGen; O95999; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95999; -.
DR PhosphoSitePlus; O95999; -.
DR SwissPalm; O95999; -.
DR BioMuta; BCL10; -.
DR EPD; O95999; -.
DR jPOST; O95999; -.
DR MassIVE; O95999; -.
DR PaxDb; O95999; -.
DR PeptideAtlas; O95999; -.
DR PRIDE; O95999; -.
DR ProteomicsDB; 51178; -.
DR Antibodypedia; 4526; 1327 antibodies from 48 providers.
DR CPTC; O95999; 1 antibody.
DR DNASU; 8915; -.
DR Ensembl; ENST00000648566.1; ENSP00000498104.1; ENSG00000142867.14.
DR GeneID; 8915; -.
DR KEGG; hsa:8915; -.
DR MANE-Select; ENST00000648566.1; ENSP00000498104.1; NM_003921.5; NP_003912.1.
DR UCSC; uc021opd.3; human.
DR CTD; 8915; -.
DR DisGeNET; 8915; -.
DR GeneCards; BCL10; -.
DR HGNC; HGNC:989; BCL10.
DR HPA; ENSG00000142867; Low tissue specificity.
DR MalaCards; BCL10; -.
DR MIM; 137245; phenotype.
DR MIM; 603517; gene.
DR MIM; 616098; phenotype.
DR neXtProt; NX_O95999; -.
DR OpenTargets; ENSG00000142867; -.
DR Orphanet; 52417; MALT lymphoma.
DR PharmGKB; PA25299; -.
DR VEuPathDB; HostDB:ENSG00000142867; -.
DR eggNOG; ENOG502RXGH; Eukaryota.
DR GeneTree; ENSGT00490000043442; -.
DR HOGENOM; CLU_103803_0_0_1; -.
DR InParanoid; O95999; -.
DR OMA; HPDGEQS; -.
DR OrthoDB; 1472514at2759; -.
DR PhylomeDB; O95999; -.
DR TreeFam; TF328636; -.
DR PathwayCommons; O95999; -.
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 Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; O95999; -.
DR SIGNOR; O95999; -.
DR BioGRID-ORCS; 8915; 22 hits in 1089 CRISPR screens.
DR ChiTaRS; BCL10; human.
DR GeneWiki; BCL10; -.
DR GenomeRNAi; 8915; -.
DR Pharos; O95999; Tbio.
DR PRO; PR:O95999; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O95999; protein.
DR Bgee; ENSG00000142867; Expressed in esophagus squamous epithelium and 190 other tissues.
DR ExpressionAtlas; O95999; baseline and differential.
DR Genevisible; O95999; HS.
DR GO; GO:0032449; C:CBM complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0002096; C:polkadots; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0140296; F:general transcription initiation factor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IMP:UniProtKB.
DR GO; GO:0061760; P:antifungal innate immune response; ISS:UniProtKB.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0008219; P:cell death; IDA:UniProtKB.
DR GO; GO:0006968; P:cellular defense response; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEP:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:ARUK-UCL.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; NAS:GO_Central.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IEA:GOC.
DR GO; GO:0032761; P:positive regulation of lymphotoxin A production; NAS:GO_Central.
DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; NAS:GO_Central.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0050870; P:positive regulation of T cell activation; IEA:Ensembl.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0032094; P:response to food; IDA:UniProtKB.
DR GO; GO:0070231; P:T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IDA:UniProtKB.
DR CDD; cd08810; CARD_BCL10; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR033238; BCL10/E10.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR042143; CARD_BCL10.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR PANTHER; PTHR34920; PTHR34920; 1.
DR Pfam; PF00619; CARD; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50209; CARD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Adaptive immunity; Apoptosis;
KW Chromosomal rearrangement; Cytoplasm; Disease variant; Immunity;
KW Innate immunity; Isopeptide bond; Membrane; Phosphoprotein;
KW Reference proteome; Tumor suppressor; Ubl conjugation.
FT CHAIN 1..233
FT /note="B-cell lymphoma/leukemia 10"
FT /id="PRO_0000144074"
FT DOMAIN 13..101
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 187..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 228..229
FT /note="Cleavage; by MALT1"
FT /evidence="ECO:0000269|PubMed:18264101"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT CROSSLNK 17
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27777308"
FT CROSSLNK 31
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:18287044,
FT ECO:0000269|PubMed:27777308"
FT CROSSLNK 63
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:18287044,
FT ECO:0000269|PubMed:27777308"
FT VARIANT 5
FT /note="A -> S (found in a MALT lymphoma sample; unknown
FT pathological significance; dbSNP:rs12037217)"
FT /evidence="ECO:0000269|PubMed:10319863,
FT ECO:0000269|PubMed:10380921, ECO:0000269|PubMed:10582682"
FT /id="VAR_013208"
FT VARIANT 16
FT /note="V -> E (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013209"
FT VARIANT 31
FT /note="K -> E (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013210"
FT VARIANT 45
FT /note="K -> Q"
FT /evidence="ECO:0000269|PubMed:10380921"
FT /id="VAR_013211"
FT VARIANT 52
FT /note="T -> I (found in a mesothelioma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:9989495"
FT /id="VAR_013212"
FT VARIANT 57
FT /note="C -> R (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013213"
FT VARIANT 58
FT /note="R -> G (found in a germ cell tumor sample; unknown
FT pathological significance; dbSNP:rs121918314)"
FT /evidence="ECO:0000269|PubMed:9989495"
FT /id="VAR_013214"
FT VARIANT 58
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:10380921"
FT /id="VAR_013215"
FT VARIANT 64
FT /note="R -> K (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013216"
FT VARIANT 93
FT /note="N -> S"
FT /evidence="ECO:0000269|PubMed:10380921"
FT /id="VAR_013217"
FT VARIANT 101
FT /note="D -> E (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013218"
FT VARIANT 134
FT /note="S -> P (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013219"
FT VARIANT 153
FT /note="M -> V"
FT /evidence="ECO:0000269|PubMed:10380921"
FT /id="VAR_013220"
FT VARIANT 162
FT /note="T -> M (found in a testicular teratoma sample;
FT somatic mutation; dbSNP:rs200837308)"
FT /evidence="ECO:0000269|PubMed:10582682"
FT /id="VAR_077898"
FT VARIANT 168
FT /note="T -> A (found in a MALT lymphoma sample; unknown
FT pathological significance; dbSNP:rs1384278393)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013221"
FT VARIANT 174
FT /note="L -> S (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013222"
FT VARIANT 210
FT /note="Missing (found in a follicular lymphoma sample;
FT unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:9989495"
FT /id="VAR_013223"
FT VARIANT 213
FT /note="G -> E (found in a MALT lymphoma sample; unknown
FT pathological significance; dbSNP:rs3768235)"
FT /evidence="ECO:0000269|PubMed:10319863,
FT ECO:0000269|PubMed:10380921, ECO:0000269|PubMed:10582682"
FT /id="VAR_013224"
FT VARIANT 218
FT /note="S -> F (found in a germ cell tumor and other cancer
FT cell lines; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:10380921,
FT ECO:0000269|PubMed:9989495"
FT /id="VAR_013225"
FT VARIANT 230
FT /note="V -> I (found in a MALT lymphoma sample; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:10319863"
FT /id="VAR_013226"
FT MUTAGEN 17
FT /note="K->R: Decreased linear ubiquitination and impaired
FT ability to activate NF-kappa-B; when associated with R-31
FT and R-63."
FT /evidence="ECO:0000269|PubMed:27777308"
FT MUTAGEN 28
FT /note="L->A: Abolishes cell death-inducing capability."
FT /evidence="ECO:0000269|PubMed:10187815"
FT MUTAGEN 31
FT /note="K->R: Decreased ubiquitination and ability to bind
FT NEMO; when associated with 63-R--R-67. Decreased
FT ubiquitination and ability to bind NEMO, impaired ability
FT to activate NF-kappa-B; when associated with R-63.
FT Decreased linear ubiquitination and impaired ability to
FT activate NF-kappa-B; when associated with R-17 and R-63."
FT /evidence="ECO:0000269|PubMed:18287044,
FT ECO:0000269|PubMed:27777308"
FT MUTAGEN 36
FT /note="R->E: Abolished homomultimerization and formation of
FT a CBM complex, abolished ability to activate NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:24074955"
FT MUTAGEN 41
FT /note="L->A: Abolishes cell death-inducing capability."
FT /evidence="ECO:0000269|PubMed:10187770,
FT ECO:0000269|PubMed:10187815"
FT MUTAGEN 41
FT /note="L->Q: Abolishes NF-kappa-B activation and
FT homo/heterodimerization."
FT /evidence="ECO:0000269|PubMed:10187770,
FT ECO:0000269|PubMed:10187815"
FT MUTAGEN 46
FT /note="I->A: Abolishes cell death-inducing capability."
FT /evidence="ECO:0000269|PubMed:10187815"
FT MUTAGEN 47
FT /note="L->A: Abolishes cell death-inducing capability."
FT /evidence="ECO:0000269|PubMed:10187815"
FT MUTAGEN 50..51
FT /note="ED->RR: Abolished homomultimerization and formation
FT of a CBM complex."
FT /evidence="ECO:0000269|PubMed:24074955"
FT MUTAGEN 50
FT /note="E->R: Abolished homomultimerization and formation of
FT a CBM complex, abolished ability to activate NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:24074955"
FT MUTAGEN 53
FT /note="E->A: Abolishes cell death-inducing capability."
FT /evidence="ECO:0000269|PubMed:10187815"
FT MUTAGEN 53
FT /note="E->R: Abolished homomultimerization and formation of
FT a CBM complex, abolished ability to activate NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:24074955"
FT MUTAGEN 55
FT /note="I->A: Abolishes cell death-inducing capability."
FT /evidence="ECO:0000269|PubMed:10187815"
FT MUTAGEN 63..67
FT /note="KRAGK->RRAGR: Decreased ubiquitination and ability
FT to bind NEMO; when associated with R-31."
FT /evidence="ECO:0000269|PubMed:18287044"
FT MUTAGEN 63
FT /note="K->R: Decreased ubiquitination and ability to bind
FT NEMO, impaired ability to activate NF-kappa-B; when
FT associated with R-31. Decreased linear ubiquitination and
FT impaired ability to activate NF-kappa-B; when associated
FT with R-17 and R-31."
FT /evidence="ECO:0000269|PubMed:18287044,
FT ECO:0000269|PubMed:27777308"
FT MUTAGEN 78
FT /note="G->R: Abolishes NF-kappa-B activation."
FT /evidence="ECO:0000269|PubMed:10187770"
FT MUTAGEN 81..85
FT /note="TLVES->ALVEA: Complete loss of IKBKB/IKKB-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:17213322"
FT MUTAGEN 105..115
FT /note="KLRNIKLEHLK->RLRNIRLEHLR: Does not affect
FT ubiquitination and ability to bind NEMO."
FT /evidence="ECO:0000269|PubMed:18287044"
FT MUTAGEN 228
FT /note="R->G: Abolishes MALT1-mediated cleavage."
FT /evidence="ECO:0000269|PubMed:18264101"
FT MUTAGEN 231
FT /note="S->A: Promotes NF-kappa-B activation."
FT HELIX 11..14
FT /evidence="ECO:0007829|PDB:2MB9"
FT HELIX 17..28
FT /evidence="ECO:0007829|PDB:2MB9"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:2MB9"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:2MB9"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:2MB9"
FT HELIX 49..53
FT /evidence="ECO:0007829|PDB:2MB9"
FT TURN 54..57
FT /evidence="ECO:0007829|PDB:2MB9"
FT HELIX 61..72
FT /evidence="ECO:0007829|PDB:2MB9"
FT TURN 76..79
FT /evidence="ECO:0007829|PDB:2MB9"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:2MB9"
FT STRAND 89..92
FT /evidence="ECO:0007829|PDB:2MB9"
FT HELIX 94..105
FT /evidence="ECO:0007829|PDB:2MB9"
FT HELIX 107..113
FT /evidence="ECO:0007829|PDB:2MB9"
SQ SEQUENCE 233 AA; 26252 MW; F87C97F2B784BA4B CRC64;
MEPTAPSLTE EDLTEVKKDA LENLRVYLCE KIIAERHFDH LRAKKILSRE DTEEISCRTS
SRKRAGKLLD YLQENPKGLD TLVESIRREK TQNFLIQKIT DEVLKLRNIK LEHLKGLKCS
SCEPFPDGAT NNLSRSNSDE SNFSEKLRAS TVMYHPEGES STTPFFSTNS SLNLPVLEVG
RTENTIFSST TLPRPGDPGA PPLPPDLQLE EEGTCANSSE MFLPLRSRTV SRQ
