Molecule Information

General Information of the Molecule (ID: Mol00265)

• Name: Caspase recruitment domain-containing protein 11 (CARD11) ,Homo sapiens
• Synonyms: CARD-containing MAGUK protein 1; Carma 1; CARMA1
• Molecule Type: Protein
• Gene Name: CARD11
• Gene ID: 84433
• Location: chr7:2906142-3043867[-]
• Sequence:
  MPGGGPEMDDYMETLKDEEDALWENVECNRHMLSRYINPAKLTPYLRQCKVIDEQDEDEV
  LNAPMLPSKINRAGRLLDILHTKGQRGYVVFLESLEFYYPELYKLVTGKEPTRRFSTIVV
  EEGHEGLTHFLMNEVIKLQQQMKAKDLQRCELLARLRQLEDEKKQMTLTRVELLTFQERY
  YKMKEERDSYNDELVKVKDDNYNLAMRYAQLSEEKNMAVMRSRDLQLEIDQLKHRLNKME
  EECKLERNQSLKLKNDIENRPKKEQVLELERENEMLKTKNQELQSIIQAGKRSLPDSDKA
  ILDILEHDRKEALEDRQELVNRIYNLQEEARQAEELRDKYLEEKEDLELKCSTLGKDCEM
  YKHRMNTVMLQLEEVERERDQAFHSRDEAQTQYSQCLIEKDKYRKQIRELEEKNDEMRIE
  MVRREACIVNLESKLRRLSKDSNNLDQSLPRNLPVTIISQDFGDASPRTNGQEADDSSTS
  EESPEDSKYFLPYHPPQRRMNLKGIQLQRAKSPISLKRTSDFQAKGHEEEGTDASPSSCG
  SLPITNSFTKMQPPRSRSSIMSITAEPPGNDSIVRRYKEDAPHRSTVEEDNDSGGFDALD
  LDDDSHERYSFGPSSIHSSSSSHQSEGLDAYDLEQVNLMFRKFSLERPFRPSVTSVGHVR
  GPGPSVQHTTLNGDSLTSQLTLLGGNARGSFVHSVKPGSLAEKAGLREGHQLLLLEGCIR
  GERQSVPLDTCTKEEAHWTIQRCSGPVTLHYKVNHEGYRKLVKDMEDGLITSGDSFYIRL
  NLNISSQLDACTMSLKCDDVVHVRDTMYQDRHEWLCARVDPFTDHDLDMGTIPSYSRAQQ
  LLLVKLQRLMHRGSREEVDGTHHTLRALRNTLQPEEALSTSDPRVSPRLSRASFLFGQLL
  QFVSRSENKYKRMNSNERVRIISGSPLGSLARSSLDATKLLTEKQEELDPESELGKNLSL
  IPYSLVRAFYCERRRPVLFTPTVLAKTLVQRLLNSGGAMEFTICKSDIVTRDEFLRRQKT
  ETIIYSREKNPNAFECIAPANIEAVAAKNKHCLLEAGIGCTRDLIKSNIYPIVLFIRVCE
  KNIKRFRKLLPRPETEEEFLRVCRLKEKELEALPCLYATVEPDMWGSVEELLRVVKDKIG
  EEQRKTIWVDEDQL
• Function: Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement. Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways. Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP. Stimulates the phosphorylation of BCL10. Also activates the TORC1 signaling pathway.
• Uniprot ID: CAR11_HUMAN
• Ensembl ID: ENSG00000198286
• HGNC ID: HGNC:16393

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Ibrutinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Ibrutinib
• Molecule Alteration: Missense mutation; p.Y361C
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Ibrutinib
• Molecule Alteration: Missense mutation; p.G123S
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Ibrutinib
• Molecule Alteration: Missense mutation; p.D357E
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Ibrutinib
• Molecule Alteration: Missense mutation; p.D230N
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Ibrutinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Lenalidomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Lenalidomide
• Molecule Alteration: Missense mutation; p.Y361C
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Lenalidomide
• Molecule Alteration: Missense mutation; p.G123S
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Lenalidomide
• Molecule Alteration: Missense mutation; p.D357E
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Lenalidomide
• Molecule Alteration: Missense mutation; p.D230N
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-exome sequencing assay
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Lenalidomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BCR/NF-kB signaling pathway; Activation; hsa05200
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Rec-1 cells; Lymph; Homo sapiens (Human); CVCL_1884
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Drug inhibition assay
• Mechanism Description: Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-kB-inhibitor lenalidomide.

References

• Ref 1: Genetic heterogeneity in primary and relapsed mantle cell lymphomas: Impact of recurrent CARD11 mutations. Oncotarget. 2016 Jun 21;7(25):38180-38190. doi: 10.18632/oncotarget.9500.