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CARD11

Domain

The linker region, also named autoinhibitory interface, is less inhibitory on its own than that of CARD9 (PubMed:31296852). The linker region together with the inhibitory domain (ID) are required to prevent constitutive activation and maintain CARD11 in an autoinhibitory state (PubMed:31296852). Disruption of the inhibitory domain (ID) region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments (PubMed:31296852).

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 (PubMed:11278692, PubMed:11356195, PubMed:12356734). 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 (PubMed:11356195). 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 (PubMed:24074955). Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). Stimulates the phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1 signaling pathway (PubMed:28628108).

Involvement in disease

B-cell expansion with NFKB and T-cell anergy

BENTA

An autosomal dominant condition characterized by onset in infancy of splenomegaly and polyclonal expansion of B cells, resulting in peripheral lymphocytosis. Affected individuals also show mild immune dysfunction, including some defective antibody responses and T-cell anergy. There may be a predisposition to the development of B-cell malignancy.

None

The disease is caused by variants affecting the gene represented in this entry.

Immunodeficiency 11 A

IMD11A

An autosomal recessive primary immunodeficiency characterized by normal numbers of T and B-lymphocytes, but defective intracellular signaling. There is a block in B-cell differentiation with increased numbers of transitional B-cells and hypogammaglobulinemia, as well as decreased numbers of regulatory T-cells and defects in T-cell function.

None

The disease is caused by variants affecting the gene represented in this entry.

Immunodeficiency 11B with atopic dermatitis

IMD11B

An autosomal dominant disorder of immune dysfunction characterized by onset of moderate to severe atopic dermatitis in early childhood. Some patients may have recurrent infections and other variable immune abnormalities. Laboratory studies show defects in T-cell activation, increased IgE, and eosinophilia.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylation at Ser-559, Ser-644 and Ser-652 by PRKCB and PRKCQ leads to a shift from an inactive to an active form that activates the NF-kappa-B signaling.

Tissue specificity

Detected in adult peripheral blood leukocytes, thymus, spleen and liver. Also found in promyelocytic leukemia HL-60 cells, chronic myelogenous leukemia K-562 cells, Burkitt's lymphoma Raji cells and colorectal adenocarcinoma SW480 cells. Not detected in HeLaS3, MOLT-4, A-549 and G431 cells.

Cellular localization

  • Cytoplasm
  • Membrane raft
  • Colocalized with DPP4 in membrane rafts.

Alternative names

  • Caspase recruitment domain-containing protein 11
  • CARD-containing MAGUK protein 1
  • Carma 1
  • CARD11
  • CARMA1

Target type

Proteins

Primary research area

Immuno-oncology

Molecular weight

133284Da