MALT1 (MEROPS identifier C14.026) is a paracaspase that cleaves its substrates on the C-terminal side of an arginine residue []. It is a key regulator of antigen-induced NF-kappaB activation in the adaptive immune response []. Upon antigen stimulation MALT1 acts as a scaffold for a protein complex formed with CARMA1 (also known as CARD11) and Bcl10, the CBM complex. The CBM complex links AgR (antigen receptor) triggering to NF-kappaB activation [].
This is an immunoglobulin-like domain which can be found in the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase. Malt1 is a key component of the Carma1/Bcl10/MALT1 signalosome and is critical for NF-kB signaling in multiple contexts. The MALT1 C-terminal Ig domain is suggested to recruit key factors to promote NF-kB activation. It is also proposed to undergo Lys63-linked ubiquitylation via TRAF6 in potentially nine different lysines to recruit the IKK complex [, , ].
MALT1 (MEROPS identifier C14.026) is a paracaspase that cleaves its substrates on the C-terminal side of an arginine residue []. It is a key regulator of antigen-induced NF-kappaB activation in the adaptive immune response []. Upon antigen stimulation MALT1 acts as a scaffold for a protein complex formed with CARMA1 (also known as CARD11) and Bcl10, the CBM complex. The CBM complex links AgR (antigen receptor) triggering to NF-kappaB activation [].This entry represents the death domain of MALT1.
E3 ubiquitin-protein ligase HECTD3 is an E3 ubiquitin ligase that regulates ubiquitination and degradation of Tara [], MASTL and LKB1 []. HECTD3 interacts with HSP90 and is involved in the HSP90-dependent degradation of CRAF protein []. It has been shown to interact and stabilize MALT1 (mucosa-associated lymphoid tissue 1), and may hence promote cell survival [].
This entry represents the CARD domain found in B-cell lymphoma/leukemia 10 (BCL10). BCL10 and Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1) are the integral components of CBM signalosomes. They associate with CARD9 to form M-CBM (CBM complex in myeloid immune cells) and with CARMA1 to form L-CBM (CBM complex in lymphoid immune cells), to mediate activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. Both CARMA1 and CARD9 associate with BCL10 via a CARD-CARD interaction [, ].In general, CARDs are death domains (DDs) found associated with caspases []. They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms []. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes [].
This entry represents the CARD domain found in CARD9, which is a central regulator of innate immunity and is highly expressed in dendritic cells and macrophages []. Together with BCL10 (B-cell lymphoma 10) and Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1), it forms the M-CBM signalosome (the CBM complex in myeloid immune cells), which mediates activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. CARD9 associates with BCL10 via a CARD-CARD interaction [].In general, CARDs are death domains (DDs) found associated with caspases []. They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms []. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes [].
This entry represents the CARD domain found in CARD11, also known as CARMA1. CARMA1, together with BCL10 (B-cell lymphoma 10) and Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1), form the L-CBM signalosome (CBM complex in lymphoid immune cells) which mediates activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. CARMA1 associates with BCL10 via a CARD-CARD interaction [].In general, CARDs are death domains (DDs) found associated with caspases []. They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms []. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes [].
This entry includes animal B-cell lymphoma/leukemia 10 (BCL10) and Equine herpesvirus protein E10.In lymphoid cells BCL10 plays a critical role in the activation of the transcription factor nuclear factor kappa B (NF-kB) downstream of a variety of immune receptors, including the TCR, B cell receptor, NK-cell receptors, C type family lectin receptors, Ig family receptors and G protein-coupled receptors [, , ]. Activation of NF-kB through receptor-mediated pathways requires BCL10 to form a complex (known as CBM) with the paracaspase MALT1 and with CARD-containing adaptor protein CARMA []. BCL10 is involved in the regulation of apoptosis; a BCL10 gene tanslocation is found in mucosa-associated lymphoid tissue (MALT) lymphomas [, ]. BCL10 is involved in the adaptive and innate immune response [, ]. Equine herpesvirus protein E10 (v-E10) is the viral homologue of the BCL10 protein []. It induces membrane recruitment of cellular BCL10, and this induces TRAF-mediated NF-kappaB activation [].
