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 453232540  16 TLVFNIYNFEHLDG-SYTSDLKEHNGIYWCVRIQSNKAAKSqKRRVSIYLVCNPN-NSSPDWSVTTSFGFRIINSWGKsR 93
Cdd:cd00121    2 KHTWKIVNFSELEGeSIYSPPFEVGGYKWRIRIYPNGDGES-GDYLSLYLELDKGeSDLEKWSVRAEFTLKLVNQNGG-K 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 453232540  94 NKISTLFNHTFTSNETSKGTSGYCTWDELTaaNSGFLVEGRFQIEFDL 141
Cdd:cd00121   80 SLSKSFTHVFFSEKGSGWGFPKFISWDDLE--DSYYLVDDSLTIEVEV 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 453232540  16 TLVFNIYNFEHLDG-SYTSDLKEHNGIYWCVRIQSNKAAKSqKRRVSIYLVCNPN-NSSPDWSVTTSFGFRIINSWGKsR 93
Cdd:cd00121    2 KHTWKIVNFSELEGeSIYSPPFEVGGYKWRIRIYPNGDGES-GDYLSLYLELDKGeSDLEKWSVRAEFTLKLVNQNGG-K 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 453232540  94 NKISTLFNHTFTSNETSKGTSGYCTWDELTaaNSGFLVEGRFQIEFDL 141
Cdd:cd00121   80 SLSKSFTHVFFSEKGSGWGFPKFISWDDLE--DSYYLVDDSLTIEVEV 125

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 453232540    19 FNIYNFEHL-----DGSYTSDLKEHNGIYWCVRIQSNkaaksqKRRVSIYLVCNP-NNSSPDWSVTTSFGFRIINSWGKS 92
Cdd:smart00061   1 VLSHTFKNVsrleeGESYFSPSEEHFNIPWRLKIYRK------NGFLSLYLHCEKeECDSRKWSIEAEFTLKLVSQNGKS 74

                           90
                   ....*....|....*...
gi 453232540    93 rnkISTLFNHTFTSNETS 110
Cdd:smart00061  75 ---LSKKDKHVFEKPSGW 89

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain superfamily; Proteins in this superfamily are characterized by the presence of a common protein-protein interaction motif of about 100 amino acids, known as the BTB/POZ domain. Members include transcription factors, oncogenic proteins, ion channel proteins, and potassium channel tetramerization domain (KCTD) proteins. They have been identified in poxviruses and many eukaryotes, and have diverse functions, such as transcriptional regulation, chromatin remodeling, protein degradation and cytoskeletal regulation. Many BTB/POZ proteins contain one or two additional domains, such as kelch repeats, zinc-finger domains, FYVE (Fab1, YOTB, Vac1, and EEA1) fingers, or ankyrin repeats, among others. These special additional domains or interaction partners provide unique characteristics and functions to BTB/POZ proteins. In ion channel proteins and KCTD proteins, the BTB/POZ domain is also called the tetramerization (T1) domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 453232540 168 LITDGKTVKVCLALLADNSPILYNLFYV--EKPGQTTFHIFDFTYEA--ILGMVsiLQLDSFEVSVYNYRDLLELGQRY 242
Cdd:cd01165    3 LVVEGEKFHVNKELLAQSSEYFRALFRGgfRESGQAEINLRDISPEDfrALLEF--LYGGKRDLDASNLLELLEAANFL 79

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 453232540  16 TLVFNIYNFEHLDG-SYTSDLKEHNGIYWCVRIQSNKAAKSqKRRVSIYLVCNPN-NSSPDWSVTTSFGFRIINSWGKsR 93
Cdd:cd00121    2 KHTWKIVNFSELEGeSIYSPPFEVGGYKWRIRIYPNGDGES-GDYLSLYLELDKGeSDLEKWSVRAEFTLKLVNQNGG-K 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 453232540  94 NKISTLFNHTFTSNETSKGTSGYCTWDELTaaNSGFLVEGRFQIEFDL 141
Cdd:cd00121   80 SLSKSFTHVFFSEKGSGWGFPKFISWDDLE--DSYYLVDDSLTIEVEV 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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 453232540  16 TLVFNIYNFEHLDGSYTSDLKEHNGIYWcvRI----QSNKAAKSQKRRVSIYLVCNPNNSSPDWSVTTSFGFRIINsWGK 91
Cdd:cd03772    4 TFSFTVERFSRLSESVLSPPCFVRNLPW--KImvmpRNYPDRNPHQKSVGFFLQCNAESDSTSWSCHAQAVLRIIN-YKD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 453232540  92 SRNKISTLFNHTFTSNETSKGTSGYCTWDELTAANSGFLVEGRFQIEFDLNVNSSTG 148
Cdd:cd03772   81 DEPSFSRRISHLFFSKENDWGFSNFMTWSEVTDPEKGFIEDDTITLEVYVQADAPHG 137

BTB/POZ domain; The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is present near the N-terminus of a fraction of zinc finger (pfam00096) proteins and in proteins that contain the pfam01344 motif such as Kelch and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerization and in some instances heteromeric dimerization. The structure of the dimerized PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 453232540  168 LITDGKTVKVCLALLADNSPILYNLFY--VEKPGQTTFHIFDFTYEAILGMVSIL---QLDSFEvsvyNYRDLLELGQRY 242
Cdd:pfam00651  15 LVVGDKEFRAHKAVLAACSPYFKALFSgqESESSVSEITLDDVSPEDFEALLEFMytgKLISEE----NVDDLLAAADKL 90

                          90
                  ....*....|....*.
gi 453232540  243 QIPSVTDKCEEFLLKT 258
Cdd:pfam00651  91 QIPSLVDKCEEFLIKS 106

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 453232540   21 IYNFEHLD--GSYTSDLKEHNGIYWCVRIqsnkaaKSQKRRVSIYLVCNPNN-SSPDWSVTTSFGFRIINSWGKSRNKIS 97
Cdd:pfam00917   1 IKNFSKIKegESYYSPVEERFNIPWRLQI------YRKGGFLGLYLHCDKEEeLERGWSIETEFTLKLVSSNGKSVTKTD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 453232540   98 TlfnHTFtSNETSKGTSGYCTWDELtaaNSGFLVEGRFQIE 138
Cdd:pfam00917  75 T---HVF-EKPKGWGWGKFISWDDL---EKDYLVDDSITVE 108