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 15226355  11 WVINNFSFLDSDRVYSDIFVVGGCKWCLLALPEGNNNYiYDYFSLYLCVPDSEYLPSGWRRRAKVSFTMVNQVTGELSQQ 90
Cdd:cd00121   5 WKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDGES-GDYLSLYLELDKGESDLEKWSVRAEFTLKLVNQNGGKSLSK 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 15226355  91 QEGVYWFDEKNTTQGFGSMFRLLVFQSSYkgFLVNGEVDIVAEVD 135
Cdd:cd00121  84 SFTHVFFSEKGSGWGFPKFISWDDLEDSY--YLVDDSLTIEVEVK 126

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 15226355  11 WVINNFSFLDSDRVYSDIFVVGGCKWCLLALPEGNNNYiYDYFSLYLCVPDSEYLPSGWRRRAKVSFTMVNQVTGELSQQ 90
Cdd:cd00121   5 WKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDGES-GDYLSLYLELDKGESDLEKWSVRAEFTLKLVNQNGGKSLSK 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 15226355  91 QEGVYWFDEKNTTQGFGSMFRLLVFQSSYkgFLVNGEVDIVAEVD 135
Cdd:cd00121  84 SFTHVFFSEKGSGWGFPKFISWDDLEDSY--YLVDDSLTIEVEVK 126

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 15226355    13 INNFS-FLDSDRVYSDIFVVGGCKWCLLALPEGnnnyiyDYFSLYLCVPDSEYLPSGWRRRAKVSFTMVNQVTGELSQQQ 91
Cdd:pfam00917   1 IKNFSkIKEGESYYSPVEERFNIPWRLQIYRKG------GFLGLYLHCDKEEELERGWSIETEFTLKLVSSNGKSVTKTD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 15226355    92 EGVYWfdeKNTTQGFGsmfRLLVFQSSYKGFLVNGEVDIVAEVDV 136
Cdd:pfam00917  75 THVFE---KPKGWGWG---KFISWDDLEKDYLVDDSITVEAHVKI 113

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 15226355  11 WVINNFSFLDSDRVYSDIFVVGGCKWCLLALPEGNNNYiYDYFSLYLCVPDSEYLPSGWRRRAKVSFTMVNQVTGELSQQ 90
Cdd:cd00121   5 WKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDGES-GDYLSLYLELDKGESDLEKWSVRAEFTLKLVNQNGGKSLSK 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 15226355  91 QEGVYWFDEKNTTQGFGSMFRLLVFQSSYkgFLVNGEVDIVAEVD 135
Cdd:cd00121  84 SFTHVFFSEKGSGWGFPKFISWDDLEDSY--YLVDDSLTIEVEVK 126

Ubiquitin-specific protease 21 (Ubp21p) family, MATH domain; composed of fungal proteins with similarity to Ubp21p of fission yeast. Ubp21p is a deubiquitinating enzyme that may be involved in the regulation of the protein kinase Prp4p, which controls the formation of active spliceosomes. Members of this family are similar to human HAUSP (Herpesvirus-associated ubiquitin-specific protease) in that they contain an N-terminal MATH domain and a C-terminal catalytic protease (C19 family) domain. HAUSP is also an ubiquitin-specific protease that specifically catalyzes the deubiquitylation of p53 and MDM2. The MATH domain of HAUSP contains the binding site for p53 and MDM2. Similarly, the MATH domain of members in this family may be involved in substrate binding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226355  11 WVINNFSFLDsDRVYSDIFVVGGCKWCLLALPEGNNNyiYDYFSLYL----CVPDSEYLPSGWRRRAKVSFTMVNQVTGE 86
Cdd:cd03775   5 WRIKNWSELE-KKVHSPKFKCGGFEWRILLFPQGNSQ--TGGVSIYLephpEEEEKAPLDEDWSVCAQFALVISNPGDPS 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 15226355  87 LSQQQEGVYWFDEKNTTQGFGSMFRL--LVFQS--SYKGFLVNGEVDIVAEV 134
Cdd:cd03775  82 IQLSNVAHHRFNAEDKDWGFTRFIELrkLAHRTpdKPSPFLENGELNITVYV 133

Speckle-type POZ protein (SPOP) family, MATH domain; composed of proteins with similarity to human SPOP. SPOP was isolated as a novel antigen recognized by serum from a scleroderma patient, whose overexpression in COS cells results in a discrete speckled pattern in the nuclei. It contains an N-terminal MATH domain and a C-terminal BTB (also called POZ) domain. Together with Cul3, SPOP constitutes an ubiquitin E3 ligase which is able to ubiquitinate the PcG protein BMI1, the variant histone macroH2A1 and the death domain-associated protein Daxx. Therefore, SPOP may be involved in the regulation of these proteins and may play a role in transcriptional regulation, apoptosis and X-chromosome inactivation. Cul3 binds to the BTB domain of SPOP whereas Daxx and the macroH2A1 nonhistone region have been shown to bind to the MATH domain. Both MATH and BTB domains are necessary for the nuclear speckled accumulation of SPOP. There are many proteins, mostly uncharacterized, containing both MATH and BTB domains from C. elegans and plants which are excluded from this family.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226355  11 WVINNFSFLDSD---RVYSDIFVVGG---CKWCLLALPEGNNNYIYDYFSLYLCVPDSEYLPSgwrrRAKVSFTMVNqVT 84
Cdd:cd03774   9 WTISNFSFCREEmgeVIKSSTFSSGAndkLKWCLRVNPKGLDEESKDYLSLYLLLVSCPKSEV----RAKFKFSILN-AK 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15226355  85 GELSQQQEG--VYWFdEKNTTQGFGSMFRLLVFQSSYKGFLVNGEVDIVAEVDVV 137
Cdd:cd03774  84 GEETKAMESqrAYRF-VQGKDWGFKKFIRRDFLLDEANGLLPDDKLTLFCEVSVV 137

Tripartite motif containing protein 37 (TRIM37) family, MATH domain; TRIM37 is a peroxisomal protein and is a member of the tripartite motif (TRIM) protein subfamily, also known as the RING-B-box-coiled-coil (RBCC) subfamily of zinc-finger proteins. Mutations in the human TRIM37 gene (also known as MUL) cause Mulibrey (muscle-liver-brain-eye) nanism, a rare growth disorder of prenatal onset characterized by dysmorphic features, pericardial constriction and hepatomegaly. TRIM37, similar to other TRIMs, contains a cysteine-rich, zinc-binding RING-finger domain followed by another cysteine-rich zinc-binding domain, the B-box, and a coiled-coil domain. TRIM37 is autoubiquitinated in a RING domain-dependent manner, indicating that it functions as an ubiquitin E3 ligase. In addition to the tripartite motif, TRIM37 also contains a MATH domain C-terminal to the coiled-coil domain. The MATH domain of TRIM37 has been shown to interact with the TRAF domain of six known TRAFs in vitro, however, it is unclear whether this is physiologically relevant. Eleven TRIM37 mutations have been associated with Mulibrey nanism so far. One mutation, Gly322Val, is located in the MATH domain and is the only mutation that does not affect the length of the protein. It results in the incorrect subcellular localization of TRIM37.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226355   9 KLWVINNFSFLD--SDRVYSDIFVVGGCKWCLLALPEGNNNYIYDYFSLYLCVPDSEYLPSGWRRRakvsFTMVNQVTGE 86
Cdd:cd03773   7 ATFTLENFSTLRqsADPVYSDPLNVDGLCWRLKVYPDGNGEVRGNFLSVFLELCSGLGEASKYEYR----VEMVHQANPT 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 15226355  87 LSQQQEGVYWFdEKNTTQGFGSMFRLLVFQSsyKGFLvNGEVDIV 131
Cdd:cd03773  83 KNIKREFASDF-EVGECWGYNRFFRLDLLIN--EGYL-LPENDTL 123