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FLASH GENE
Symbol CARD11 contributors: mct/npt/pgu - updated : 09-12-2020
HGNC name caspase recruitment domain family, member 11
HGNC id 16393
DNA
TYPE functioning gene
STRUCTURE 137.73 kb     25 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
25 - 4372 132 1147 - 2002 12154360
26 - 4348 - 1154 - 2002 12154360
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node   highly Homo sapiens
 thymus   highly Homo sapiens
 tonsils   highly Homo sapiens
Skin/Tegumentskin     Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunelymphocyte Homo sapiens
Lymphoid/ImmuneT cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal CARD domain
  • a central coiled-coil domain
  • seven functional domains
  • a LATCH domain playing a crucial role mediating autoinhibition of the CARD and coiled-coil domains
  • a C terminal tripartite domain comprised of a PDZ, a SH3 homology and a MAGUK domains
  • mono polymer oligo
    HOMOLOGY
    intraspecies homolog to CARD14
    Homologene
    FAMILY
  • MAGUK membrane associated guanylate kinase family
  • CARD family
  • CATEGORY adaptor , chaperone/stress , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • can be expressed in several compartments, including cytosol, and lipid raft and nonraft membrane fractions in unstimulated T cells
  • basic FUNCTION
  • critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent JNK activation
  • involved in factor- specific activation of NF-kappaB by the TCR complex and establishing a role for a MAGUK family member in antigen receptor signaling
  • involved in both the innate and adaptive immune systems
  • playing a critical role in mediating activation of the NFkappaB transcription factor following antigen receptor stimulation of both B and T lymphocytes
  • is a key upstream signaling component responsible for the constitutive IkappaB kinase activity in activated B-cell-like DLBCL
  • playing a critical role for coupling the common elements of the NF-kappaB pathway to the T-cell receptor (TCR) and CD28
  • serves as a physiological substrate for MAP4K1 upon TCR stimulation
  • role in regulatory T Cell regulation involves both NF-KB activation and IL2 receptor signaling
  • TRAF2 and CARD11 serve as keystones for formation of the full TNFRSF4 signalosome and for allowing NFkB activation by TNFRSF4 in T cells
  • is an adapter that links the TCR to NFKB1 activity, cell survival, and proliferation
  • is an essential adaptor protein that links Ag receptors to NFKB1 activation
  • CARD11/BCL10/MALT1 (CBM) signalosome mediates antigen receptor-induced NFKB1 signaling to regulate multiple lymphocyte functions
  • CARD11, BCL10, and MALT1, that have complex 5'UTRs and encode proteins with short half-lives, are involved in BCR signaling
  • CARD11-mediated alterations in NFKB1 signaling may be an early event in the development of cutaneous squamous cell carcinoma (cSCC)
  • functions as a key signaling scaffold that controls antigen-induced lymphocyte activation during the adaptive immune response
  • CARD11 has evolved to actively coordinate scaffold opening and the induction of enzymatic activity among recruited cofactors during antigen receptor signaling
  • is required for B cell receptor-mediated activation of NFKB1
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • CARD11-BCL10-MALT1 (CBM) complex connects T-cell receptor (TCR) signalling to the canonical IkappaB kinase (IKK)/NF (nuclear factor)-kappaB pathway
  • TCR/CARD11/NFKB1 axis is an essential T-cell–intrinsic pathway for functional activity of the Th17 transcriptional machinery
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with BCL10 via its caspase-recruitment domain (CARD)
  • CARD11 and CARD10 physically associate with IKBKG /NFkappaB essential modulator (IkappaKgamma-NEMO) in lymphoid and non-lymphoid cells
  • physical and functional interaction between AKT1 and CARD11 and for Akt-dependent phosphorylation of BCL10
  • interaction partner of PPP2R1A (is associated with CARD11 in resting as well as activated T cells in the context of the active CBM complex))
  • PRKCQ and CARD11 form a signalosome with TNFRSF4 in the immune synapse and play a major role in promoting maximum and prolonged NFKB activity mediated by TNFRSF4
  • FYB regulating T cell receptor-mediated activation of integrins via association with the SKAP1 adapter and the NFKB1 pathway through interactions with both the CARD11 adapter and MAP3K7
  • CARD11 serves as a scaffold for BCL10, MALT1 and other effector proteins and regulates various signaling pathways related to the immune response
  • STUB1 is a CARD11 associated protein, and ubiquitination of CARD11 by STUB1 promotes TCR-induced NFKB1 signaling
  • interaction mode between CARD11 CARD and BCL10 CARD based on a structure-based modeling study
  • SMO activates trimeric G proteins and CARD11-associated signaling complex, leading to NFKB1 activation, contributing to the survival of DLBCL
  • PLEKHO1 interacts with CARD11 and has an inhibitory effect on PKCQ-CBM-NFKB1 signaling
  • is a novel target for AKT1 phosphorylation, suggesting that AKT1-mediated phosphorylation of CARD11 is an additional regulatory mechanism tuning the NFKB1 response downstream of antigen receptor and co-stimulatory signaling
  • AIP augments CARMA1-BCL10-MALT1 complex formation to facilitate NFKB1 signaling upon T cell activation
  • has a noncanonical function as a negative regulator of the AKT1-FOXO1 signal axis, independent of NFKB1 activation
  • cell & other
    REGULATION
    inhibited by KIF13B, the kinesin-3 family member GAKIN that is a CARD11 inhibitor
    Other regulated by MAP4K1(MAP4K1-mediated phosphorylation of CARD11 as an additional regulatory mechanism tuning the NF-KB response upon TCR stimulation
    ASSOCIATED DISORDERS
    corresponding disease(s) PPBL , IMD11 , CADINS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in diffuse large B cell lymphoma, that enhance activity and that are mostly found in the coiled-coil domain
    tumoral somatic mutation      
    frequently found in Non-Hodgkin lymphoma
    tumoral germinal mutation     gain of function
    CARD11 gain-of-function mutations are recurrently detected in human diffuse large B-cell lymphoma (DLBCL)
    tumoral     --over  
    in cutaneous squamous cell carcinoma (cSCC)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS