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 18421006 215 FTWKILRFSTLEDKFYYSDDFLVGDRYWRLGFNPKGSGGGRPHaLPIFLYAQGHKANAVVTNTWGAVNLRLKNQRSSNHK 294
Cdd:cd00121   3 HTWKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDGESGDY-LSLYLELDKGESDLEKWSVRAEFTLKLVNQNGGKSL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 18421006 295 QLYSAAWYPIRSDYGVGVNNIILMSELKDasKGYMVNDAIIFEAEM 340
Cdd:cd00121  82 SKSFTHVFFSEKGSGWGFPKFISWDDLED--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 18421006  64 IVTITSFSviKDRGEPYESSIFEAAGYKWRLVLYVKGNPKGGinNHISLYARIEETETLPRGWEVNVDLKLFVHNRKLKK 143
Cdd:cd00121   4 TWKIVNFS--ELEGESIYSPPFEVGGYKWRIRIYPNGDGESG--DYLSLYLELDKGESDLEKWSVRAEFTLKLVNQNGGK 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 18421006 144 YLSVTdGTVKRYNDAKKEWGFTQLISLPTFynANEGYLVQDTASFGAEI 192
Cdd:cd00121  80 SLSKS-FTHVFFSEKGSGWGFPKFISWDDL--EDSYYLVDDSLTIEVEV 125

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18421006     66 TITSFSVIKDrGEPYESSIFEAAGYKWRLVLYVKgnpkggiNNHISLYARIEETETLPRGW--EVNVDLKLFVHNRklkK 143
Cdd:smart00061   5 TFKNVSRLEE-GESYFSPSEEHFNIPWRLKIYRK-------NGFLSLYLHCEKEECDSRKWsiEAEFTLKLVSQNG---K 73

                           90       100
                   ....*....|....*....|....*
gi 18421006    144 YLSVTDGTVKRYNdakKEWGFTQLI 168
Cdd:smart00061  74 SLSKKDKHVFEKP---SGWGFSKFI 95

Ubiquitin carboxyl-terminal hydrolase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 18421006  215 FTWKILRFSTLEDKfYYSDDFLVGDRYWRLGFNPKG 250
Cdd:COG5077   41 FTWKVKRWSELAKK-VESPPFSVGGHTWKIILFPQG 75

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 18421006  64 IVTITSFSviKDRGEPYESSIFEAAGYKWRLVLYVKGNPKGGinNHISLYARIEETETLPRGWEVNVDLKLFVHNRKLKK 143
Cdd:cd00121   4 TWKIVNFS--ELEGESIYSPPFEVGGYKWRIRIYPNGDGESG--DYLSLYLELDKGESDLEKWSVRAEFTLKLVNQNGGK 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 18421006 144 YLSVTdGTVKRYNDAKKEWGFTQLISLPTFynANEGYLVQDTASFGAEI 192
Cdd:cd00121  80 SLSKS-FTHVFFSEKGSGWGFPKFISWDDL--EDSYYLVDDSLTIEVEV 125

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18421006     66 TITSFSVIKDrGEPYESSIFEAAGYKWRLVLYVKgnpkggiNNHISLYARIEETETLPRGW--EVNVDLKLFVHNRklkK 143
Cdd:smart00061   5 TFKNVSRLEE-GESYFSPSEEHFNIPWRLKIYRK-------NGFLSLYLHCEKEECDSRKWsiEAEFTLKLVSQNG---K 73

                           90       100
                   ....*....|....*....|....*
gi 18421006    144 YLSVTDGTVKRYNdakKEWGFTQLI 168
Cdd:smart00061  74 SLSKKDKHVFEKP---SGWGFSKFI 95

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 18421006  68 TSFS-VIKD---RGEPYESSIFEAAGYKWRLVLYVKGNPKggiNNHISLY----ARIEETETLPRGWEVNVDLKLfVHNR 139
Cdd:cd03775   1 QSFTwRIKNwseLEKKVHSPKFKCGGFEWRILLFPQGNSQ---TGGVSIYlephPEEEEKAPLDEDWSVCAQFAL-VISN 76

                        90       100       110
                ....*....|....*....|....*....|.
gi 18421006 140 KLKKYLSVTDGTVKRYNDAKKEWGFTQLISL 170
Cdd:cd03775  77 PGDPSIQLSNVAHHRFNAEDKDWGFTRFIEL 107

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 18421006  61 SSKIVTITSFSVIKDRGEPYESSIFEAAGYKWRLVLYVKGNPKGGiNNHISLYarIEETETLPRG--WEVNVDLklfVHN 138
Cdd:cd03773   5 DSATFTLENFSTLRQSADPVYSDPLNVDGLCWRLKVYPDGNGEVR-GNFLSVF--LELCSGLGEAskYEYRVEM---VHQ 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18421006 139 RKLKKylsvtdgTVKRYND----AKKEWGFTQLISLPTFynANEGYLVQ--DTASF 188
Cdd:cd03773  79 ANPTK-------NIKREFAsdfeVGECWGYNRFFRLDLL--INEGYLLPenDTLIL 125