MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 405133769 114 GIYIWKIENFSGLQKAQEEERPVVMHSPGFYTGKPGYKLCLRLHIQLPNAqRCANFISLFVHT 176
Cdd:cd03776    1 GIYVWKIKNFSNLRRSMEAGSPVVIHSPGFYTSPPGYKLCARLNLSLPEA-RCPNYISLFVHL 62

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF6 is the most divergent in its TRAF domain among the mammalian TRAFs. In addition to mediating TNFR family signaling, it is also an essential signaling molecule of the interleukin-1/Toll-like receptor superfamily. Whereas other TRAF molecules display similar and overlapping TNFR-binding specificities, TRAF6 binds completely different sites on receptors such as CD40 and RANK. TRAF6 serves as a molecular bridge between innate and adaptive immunity and plays a central role in osteoimmunology. DTRAF2, as an activator of nuclear factor-kappaB, plays a pivotal role in Drosophila development and innate immunity. TRAF6 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 405133769 114 GIYIWKIENFSGLQKAQEEERPVVMHSPGFYTGKPGYKLCLRLHIQLPNAqRCANFISLFVHT 176
Cdd:cd03776    1 GIYVWKIKNFSNLRRSMEAGSPVVIHSPGFYTSPPGYKLCARLNLSLPEA-RCPNYISLFVHL 62

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF6 is the most divergent in its TRAF domain among the mammalian TRAFs. In addition to mediating TNFR family signaling, it is also an essential signaling molecule of the interleukin-1/Toll-like receptor superfamily. Whereas other TRAF molecules display similar and overlapping TNFR-binding specificities, TRAF6 binds completely different sites on receptors such as CD40 and RANK. TRAF6 serves as a molecular bridge between innate and adaptive immunity and plays a central role in osteoimmunology. DTRAF2, as an activator of nuclear factor-kappaB, plays a pivotal role in Drosophila development and innate immunity. TRAF6 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 405133769 114 GIYIWKIENFSGLQKAQEEERPVVMHSPGFYTGKPGYKLCLRLHIQLPNAqRCANFISLFVHT 176
Cdd:cd03776    1 GIYVWKIKNFSNLRRSMEAGSPVVIHSPGFYTSPPGYKLCARLNLSLPEA-RCPNYISLFVHL 62

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF2 associates with the receptors TNFR-1, TNFR-2, RANK (which mediates differentiation and maturation of osteoclasts) and CD40 (which is important for the proliferation and activation of B cells), among others. It regulates distinct pathways that lead to the activation of nuclear factor-kappaB and Jun NH2-terminal kinases. TRAF2 also indirectly associates with death receptors through its interaction with TRADD (TNFR-associated death domain protein). It is involved in regulating oxidative stress or ROS-induced cell death and in the preconditioning of cells by sublethal stress for protection from subsequent injury. TRAF2 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 405133769  99 NLEGKITEMEAQQCNGIYIWKIENFSGLQKAQEEERPVVMHSPGFYTGKPGYKLCLRLHIQLPNAQRCANFISLFV 174
Cdd:cd03778    4 DLEQKVLE*EASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFV 79

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF3 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF3 was first described as a molecule that binds the cytoplasmic tail of CD40. However, it is not required for CD40 signaling. More recently, TRAF3 has been identified as a key regulator of type I interferon (IFN) production and the mammalian innate antiviral immunity. It mediates IFN responses in Toll-like receptor (TLR)-dependent as well as TLR-independent viral recognition pathways. It is also a key element in immunological homeostasis through its regulation of the anti-inflammatory cytokine interleukin-10. TRAF3 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 405133769  62 IQQLEGRLVRQDHQIreliakmetqNTHMVELKrtirNLEGKITEMEAQQCNGIYIWKIENFSGLQKAQEEERPVVMHSP 141
Cdd:cd03777    1 TGLLESQLSRHDQML----------SVHDIRLA----DMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQ 66

                         90
                 ....*....|....*..
gi 405133769 142 GFYTGKPGYKLCLRLHI 158
Cdd:cd03777   67 PFYTGYFGYKMCARVYL 83

MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 405133769 114 GIYIWKIENFSglqkaqeEERPVVMHSPGFYTGkpGYKLCLRLHiqlPNAQR-CANFISLFVH 175
Cdd:cd00121    1 GKHTWKIVNFS-------ELEGESIYSPPFEVG--GYKWRIRIY---PNGDGeSGDYLSLYLE 51

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 405133769  54 EVENFKETIQQLEGRLVRQDHQIRELIAKMETQNTHMVELKRTIRNLEGKITEMEAQ 110
Cdd:COG4942   28 ELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAE 84