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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715207 181 PVFTWSLPNFSTLTLDSYTSDPFSSGDRNWVLKVYPNGDGVGKDN-----SLSLYLLSESNEKNYVRATLRVLNQIGSDN 255
Cdd:cd00121     1 GKHTWKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDGESGDYlslylELDKGESDLEKWSVRAEFTLKLVNQNGGKS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1063715207 256 VEKPVEGWP-NAAENGWGYQEFIPLADLQDatKGFVVDDLLEVEVEI 301
Cdd:cd00121    81 LSKSFTHVFfSEKGSGWGFPKFISWDDLED--SYYLVDDSLTIEVEV 125

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715207 181 PVFTWSLPNFSTLTLDSYTSDPFSSGDRNWVLKVYPNGDGVGKDN-----SLSLYLLSESNEKNYVRATLRVLNQIGSDN 255
Cdd:cd00121     1 GKHTWKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDGESGDYlslylELDKGESDLEKWSVRAEFTLKLVNQNGGKS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1063715207 256 VEKPVEGWP-NAAENGWGYQEFIPLADLQDatKGFVVDDLLEVEVEI 301
Cdd:cd00121    81 LSKSFTHVFfSEKGSGWGFPKFISWDDLED--SYYLVDDSLTIEVEV 125

MATH domain; This motif has been called the Meprin And TRAF-Homology (MATH) domain. This domain is hugely expanded in the nematode C. elegans.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715207 188 PNFSTLTL-DSYTSDPFSSGDRNWVLKVYPNGDGVGKDNSLSLYLLSESNEKNYVRATLRVLNQIGSdNVEKPvEGWPNA 266
Cdd:pfam00917   2 KNFSKIKEgESYYSPVEERFNIPWRLQIYRKGGFLGLYLHCDKEEELERGWSIETEFTLKLVSSNGK-SVTKT-DTHVFE 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1063715207 267 AENGWGYQEFIPLADLQdatKGFVVDDLLEVEVEI 301
Cdd:pfam00917  80 KPKGWGWGKFISWDDLE---KDYLVDDSITVEAHV 111

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715207 181 PVFTWSLPNFSTLTLDSYTSDPFSSGDRNWVLKVYPNGDGVGKDN-----SLSLYLLSESNEKNYVRATLRVLNQIGSDN 255
Cdd:cd00121     1 GKHTWKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDGESGDYlslylELDKGESDLEKWSVRAEFTLKLVNQNGGKS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1063715207 256 VEKPVEGWP-NAAENGWGYQEFIPLADLQDatKGFVVDDLLEVEVEI 301
Cdd:cd00121    81 LSKSFTHVFfSEKGSGWGFPKFISWDDLED--SYYLVDDSLTIEVEV 125

Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7) family, N-terminal MATH (TRAF-like) domain; composed of proteins similar to human HAUSP, an enzyme that specifically catalyzes the deubiquitylation of p53 and MDM2, hence playing an important role in the p53-MDM2 pathway. It contains an N-terminal TRAF-like domain and a C-terminal catalytic protease (C19 family) domain. The tumor suppressor p53 protein is a transcription factor that responds to many cellular stress signals and is regulated primarily through ubiquitylation and subsequent degradation. MDM2 is a RING-finger E3 ubiquitin ligase that promotes p53 ubiquitinylation. p53 and MDM2 bind to the same site in the N-terminal TRAF-like domain of HAUSP in a mutually exclusive manner. HAUSP also interacts with the Epstein-Barr nuclear antigen 1 (EBNA1) protein of the Epstein-Barr virus (EBV), which efficiently immortalizes infected cells predisposing the host to a variety of cancers. EBNA1 plays several important roles in EBV latent infection and cellular transformation. It binds the same pocket as p53 in the HAUSP TRAF-like domain. Through interactions with p53, MDM2 and EBNA1, HAUSP plays a role in cell proliferation, apoptosis and EBV-mediated immortalization.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1063715207 268 ENGWGYQEFIPLADLQDATKGFVVDDLLEVEVEIMA 303
Cdd:cd03772    97 ENDWGFSNFMTWSEVTDPEKGFIEDDTITLEVYVQA 132