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 17534257  79 EGMLKLEIPNFSNLRSKVSTPFQYIGNLPWR-LAAKTEKTKRTSDVKFFSVYIDCNPESESTLWSCDAVVEFRLVSRNRT 157
Cdd:cd03772   2 EATFSFTVERFSRLSESVLSPPCFVRNLPWKiMVMPRNYPDRNPHQKSVGFFLQCNAESDSTSWSCHAQAVLRIINYKDD 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17534257 158 IPPFSRQFTNKFNYNSNNWGFPSFMAWEDVNNS--NYVRNEMVTVTARVV 205
Cdd:cd03772  82 EPSFSRRISHLFFSKENDWGFSNFMTWSEVTDPekGFIEDDTITLEVYVQ 131

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 17534257  79 EGMLKLEIPNFSNLRSKVSTPFQYIGNLPWR-LAAKTEKTKRTSDVKFFSVYIDCNPESESTLWSCDAVVEFRLVSRNRT 157
Cdd:cd03772   2 EATFSFTVERFSRLSESVLSPPCFVRNLPWKiMVMPRNYPDRNPHQKSVGFFLQCNAESDSTSWSCHAQAVLRIINYKDD 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17534257 158 IPPFSRQFTNKFNYNSNNWGFPSFMAWEDVNNS--NYVRNEMVTVTARVV 205
Cdd:cd03772  82 EPSFSRRISHLFFSKENDWGFSNFMTWSEVTDPekGFIEDDTITLEVYVQ 131

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 17534257    86 IPNFSNLRSKVS--TPFQYIGNLPWRLAAKTEKtkrtsdvKFFSVYIDCNPESESTL-WSCDAVVEFRLVSRNRTIppFS 162
Cdd:pfam00917   1 IKNFSKIKEGESyySPVEERFNIPWRLQIYRKG-------GFLGLYLHCDKEEELERgWSIETEFTLKLVSSNGKS--VT 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 17534257   163 RQFTNKFNyNSNNWGFPSFMAWEDVNNSnYVRNEMVTVTARVVV 206
Cdd:pfam00917  72 KTDTHVFE-KPKGWGWGKFISWDDLEKD-YLVDDSITVEAHVKI 113

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257     86 IPNFSNLRS-----KVSTPFQYIGNLPWRLAAKTEKtkrtsdvKFFSVYIDCNPESESTL-WSCDAVVEFRLVSRNRtiP 159
Cdd:smart00061   3 SHTFKNVSRleegeSYFSPSEEHFNIPWRLKIYRKN-------GFLSLYLHCEKEECDSRkWSIEAEFTLKLVSQNG--K 73

                           90       100
                   ....*....|....*....|...
gi 17534257    160 PFSRQFTNKFNYNSnNWGFPSFM 182
Cdd:smart00061  74 SLSKKDKHVFEKPS-GWGFSKFI 95

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 17534257  79 EGMLKLEIPNFSNLRSKVSTPFQYIGNLPWR-LAAKTEKTKRTSDVKFFSVYIDCNPESESTLWSCDAVVEFRLVSRNRT 157
Cdd:cd03772   2 EATFSFTVERFSRLSESVLSPPCFVRNLPWKiMVMPRNYPDRNPHQKSVGFFLQCNAESDSTSWSCHAQAVLRIINYKDD 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17534257 158 IPPFSRQFTNKFNYNSNNWGFPSFMAWEDVNNS--NYVRNEMVTVTARVV 205
Cdd:cd03772  82 EPSFSRRISHLFFSKENDWGFSNFMTWSEVTDPekGFIEDDTITLEVYVQ 131

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 17534257    86 IPNFSNLRSKVS--TPFQYIGNLPWRLAAKTEKtkrtsdvKFFSVYIDCNPESESTL-WSCDAVVEFRLVSRNRTIppFS 162
Cdd:pfam00917   1 IKNFSKIKEGESyySPVEERFNIPWRLQIYRKG-------GFLGLYLHCDKEEELERgWSIETEFTLKLVSSNGKS--VT 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 17534257   163 RQFTNKFNyNSNNWGFPSFMAWEDVNNSnYVRNEMVTVTARVVV 206
Cdd:pfam00917  72 KTDTHVFE-KPKGWGWGKFISWDDLEKD-YLVDDSITVEAHVKI 113

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger and BTB domain-containing (ZBTB) proteins, Kelch-like (KLHL) proteins, and similar proteins; This family includes a variety of BTB/POZ domain-containing proteins, such as zinc finger and BTB domain-containing (ZBTB) proteins and Kelch-like (KLHL) proteins. They 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. These special additional domains or interaction partners provide unique characteristics and functions to BTB/POZ proteins. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 228 CDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDK 307
Cdd:cd18186   2 CDVTLVVGGREFPAHRAVLAARSPYFRAMFSSGMKESSSSEIELDDVSPEAFEALLDYIYTGELELSEENVEELLAAADK 81

                .
gi 17534257 308 Y 308
Cdd:cd18186  82 L 82

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 7 (KLHL7); KLHL7 is a component of a Cul3-based E3 ubiquitin ligase complex and is involved in the ubiquitination of target proteins for proteasome-mediated degradation. Mutations in KLHL7 causes autosomal-dominant retinitis pigmentosa. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 220 FGAM-----QTNICDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPIT 294
Cdd:cd18237   9 MGVMnnmrkQKTLCDVILIVEGREIKAHRVVLAAASHFFHLMFTSNMTESKSSEVELKDAEPDIIELLVEFAYTARISVN 88

                        90       100
                ....*....|....*....|....*..
gi 17534257 295 SDNVEYLLELGDKYEIQYVMDECERFL 321
Cdd:cd18237  89 SNNVQSLLDAANQYQIEPVKKMCVDFL 115

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 28 (KLHL28); KLHL28, also called BTB/POZ domain-containing protein 5 (BTBD5), contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 227 ICDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGD 306
Cdd:cd18257  18 LCDVVLRVGDVKIHAHKVVLASCSPYFKAMFTGNLSEKENSEVEFQCIDETALQAIVEYAYTGTVFISQATVESLLPAAN 97

                        90
                ....*....|....*
gi 17534257 307 KYEIQYVMDECERFL 321
Cdd:cd18257  98 LLQIKLVLKECCDFL 112

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in intracisternal A particle-promoted polypeptide (IPP); IPP, also called Kelch-like protein 27 (KLHL27) or actin-binding protein IPP, is an actin-binding protein that may play a role in organizing the actin cytoskeleton. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 224 QTNICDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLE 303
Cdd:cd18256  17 QHEFCDVQLQVGMELFSVHRLVLAASSPYFAALFAGGMSESSKDVVQIHGVEPDIFHILLDFIYTGVVEVTVSNVQELLV 96

                        90       100
                ....*....|....*....|
gi 17534257 304 LGDKYEIQYVMDECERFLVG 323
Cdd:cd18256  97 AADMLQLTEVVEICCEFLKG 116

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like ECH-associated protein 1 (KEAP1); KEAP1, also called cytosolic inhibitor of Nrf2 (INrf2) or Kelch-like protein 19 (KLHL19), is a redox-regulated substrate adaptor protein for a Cullin3-dependent ubiquitin ligase complex that targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 227 ICDMTLVI---NKQKLFV-NKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLL 302
Cdd:cd18248  21 LCDVTLKVkyqDPKEEFMaHKVVLASSSPYFKAMFTSGLRECGMEVVPIEGVHPCVMSRLIEFAYTASISVGEKCVLHVL 100

                        90       100
                ....*....|....*....|
gi 17534257 303 ELGDKYEIQYVMDECERFLV 322
Cdd:cd18248 101 PGAVMYQMDSVVKACCDFLE 120

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in speckle-type POZ protein (SPOP) and similar proteins; This family includes speckle-type POZ protein (SPOP), speckle-type POZ protein-like (SPOPL), TD and POZ domain-containing proteins (TDPOZ), Drosophila melanogaster protein roadkill and similar proteins. Both, SPOP and SPOPL, serve as adaptors of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that mediate the ubiquitination and proteasomal degradation of target proteins. TDPOZ is a family of bipartite animal and plant proteins that contain a tumor necrosis factor receptor-associated factor (TRAF) domain (TD) and a POZ/BTB domains. TDPOZ proteins may be nuclear scaffold proteins probably involved in transcription regulation in early development and other cellular processes. Drosophila melanogaster protein roadkill, also called Hh-induced MATH and BTB domain-containing protein (HIB), is a hedgehog-induced BTB protein that modulates hedgehog signaling by degrading Ci/Gli transcription factor. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKY 308
Cdd:cd18279  20 DCCLCVGGQEFQAHKAILAARSPVFSAMFEHEMEESKKNRVEINDVDPEVFKEMMRFIYTGKAPNLDKMADDLLAAADKY 99

                        90
                ....*....|...
gi 17534257 309 EIQYVMDECERFL 321
Cdd:cd18279 100 ALERLKVMCEDAL 112

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 36 (KLHL36); KLHL36 may act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 228 CDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDK 307
Cdd:cd18266  26 CDVVLVADEQRVPAHRNLLAVCSDYFNSMFTIGMREAHQKEVELVGASYIGLKAVIDFLYSSELPLDGGNIDYVLETAHL 105

                        90       100
                ....*....|....*....|....*....
gi 17534257 308 YEIQYVMDECERFL---VGSEDILQITKL 333
Cdd:cd18266 106 LQIWKVVDFCCEYLeneVSEENYLYLQEL 134

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing proteins (RhoBTB); RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases), which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, a tandem of 2 BTB domains, and a conserved C-terminal region. In humans, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDN--VEyLLELGD 306
Cdd:cd18300  11 DVTFIVEDGTIPAHKALLVARCDVMAAMFGGNFRESSAKEVELPGVSKETFLALLEYLYTDQAPILEDGdcVG-LIVLAN 89

                        90
                ....*....|....*.
gi 17534257 307 KYEIQYVMDECERFLV 322
Cdd:cd18300  90 RLCLPRLVALCEQYIV 105

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 8 (KLHL8); KLHL8 is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for the ubiquitination and degradation of rapsyn, a postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 228 CDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDK 307
Cdd:cd18238  16 CDVTLKVGEKSIHCHRLVLACVSPYFRAMFTSEMAESKQDSITIKDIDEEAVELLVDFAYTGKLTLTVDNVQSLLYAASL 95

                        90
                ....*....|....
gi 17534257 308 YEIQYVMDECERFL 321
Cdd:cd18238  96 LQVEEVAKACCEFM 109

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 9 (BTBD9); BTBD9 is a risk factor for Restless Legs Syndrome (RLS) encoding a Cullin-3 substrate adaptor. The BTBD9 gene may be associated with antipsychotic-induced RLS in schizophrenia. Mutations in BTBD9 lead to reduced dopamine, increased locomotion and sleep fragmentation. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 219 DFGAM--QTNICDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCH---KPI 293
Cdd:cd18287  12 DIGALflNEEYSDVTFVVEEKRFPAHRVILAARSEYFRALLYGGMRESQQSEIELKDTNAEAFKALLKYIYTGRltlTDL 91

                        90
                ....*....|....*
gi 17534257 294 TSDNVEYLLELGDKY 308
Cdd:cd18287  92 KEDVLLDVLGLAHQY 106

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in plant BTB/POZ-MATH (BPM) protein family; The BPM protein family includes Arabidopsis thaliana BTB/POZ and MATH domain-containing proteins, AtBPM1-6, and similar proteins from other plants. BPM protein, also called protein BTB-POZ and MATH domain, may act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 228 CDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIY----P-CHKPITSDN----- 297
Cdd:cd18280  15 ADVTFNVDGEKFRAHKLVLAARSPVFRSMLFGPMREENEGEIVIEDVEPPVFKALLHFIYkdelPdDVEPAGSDSssldt 94

                        90       100
                ....*....|....*....|....*.
gi 17534257 298 --VEYLLELGDKYEIQYVMDECERFL 321
Cdd:cd18280  95 tmAQHLLAAADRYALERLRLLCESRL 120

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 230 MTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYpCHKPITS-DNVEYLLELGDKY 308
Cdd:cd01165   1 VVLVVEGEKFHVNKELLAQSSEYFRALFRGGFRESGQAEINLRDISPEDFRALLEFLY-GGKRDLDaSNLLELLEAANFL 79

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 21 (KLHL21); KLHL21 is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of aurora B. KLHL21 also targets IkappaB kinase-beta to regulate nuclear factor kappa-light chain enhancer of activated B cells (NF-kappaB) signaling negatively. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKY 308
Cdd:cd18250  23 DVTLCAGGREFPCHRTVLAAASSYFRAMFAGELRESRADRVVLHGVSAEILGLLLDFSYTGRVTVTQDNVEALLRAADLF 102

                        90
                ....*....|...
gi 17534257 309 EIQYVMDECERFL 321
Cdd:cd18250 103 QFPSVKEACCAYL 115

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch repeat and BTB domain-containing protein 4 (KBTBD4); KBTBD4, also called BTB and kelch domain-containing protein 4 (BKLHD4), is a BTB-BACK-Kelch domain protein belonging to a large family of cullin-RING ubiquitin ligase adaptors that facilitate the ubiquitination of target substrates. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKY 308
Cdd:cd18272  34 DVTISVEGKEFQLHRLVLSAQSCFFRSMFTSNLKEARNRVIELKDVSESVFQLLVDYIYHGTVKLRVEELQETYEVADMY 113

                        90       100
                ....*....|....*....|....*..
gi 17534257 309 EIQYVMDECERFLVGSEDILQITKLMW 335
Cdd:cd18272 114 QLTALFEECSRFLARTVQVRNCLQVMW 140

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in speckle-type POZ protein (SPOP); SPOP, also called HIB homolog 1 or Roadkill homolog 1, is a novel nuclear speckle-type protein which serves as an adaptor of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and proteasomal degradation of target proteins, such as BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKY 308
Cdd:cd18342  24 DCCLCVAGQEFQAHKAILAARSPVFSAMFEHEMEESKKNRVEINDVEPEVFKEMMCFIYTGKAPNLDKMADDLLAAADKY 103

                        90
                ....*....|...
gi 17534257 309 EIQYVMDECERFL 321
Cdd:cd18342 104 ALERLKVMCEDAL 116

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing proteins, BTBD3 and BTBD6; This family includes BTB/POZ domain-containing proteins BTBD3 and BTBD6, both of which are BTB-domain-containing Kelch-like proteins. BTBD3 controls dendrite orientation toward active axons in mammalian neocortex. BTBD6 is required for proper embryogenesis and plays an essential evolutionary conserved role during neuronal development. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 237 QKLFVNKAYLALYSPVFYAMFFSNFQErEKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKYEIQYVMDE 316
Cdd:cd18282  21 QRIPAHKYVLATGSSVFYAMFYGGLAE-NKNEIEIPDVEPAAFLNLLRYLYCDEIDLEPDTVLATLYAAKKYLVPHLARA 99

                ....*...
gi 17534257 317 CERFLVGS 324
Cdd:cd18282 100 CVQFLETS 107

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Ectoderm-neural cortex protein 1 (ENC-1); ENC-1 is also called Kelch-like protein 37 (KLHL37), nuclear matrix protein NRP/B, or p53-induced gene 10 protein. It is an actin-binding nuclear matrix protein that associates with p110(RB), and is involved in the regulation of neuronal process formation and in differentiation of neural crest cells. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELL-HVIYPCHKPITSDNVEYLLELGDK 307
Cdd:cd18267  42 DVLLHAGNRSFPCHRAVLAACSRYFEAMFSGGLKESQDSEVNFHDSIHPEVLELLlDYAYSSRVIINEENAESLLEAGDM 121

                        90
                ....*....|....
gi 17534257 308 YEIQYVMDECERFL 321
Cdd:cd18267 122 LEFQDIRDACAEFL 135

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 24 (KLHL24); KLHL24, also called kainate receptor-interacting protein for GluR6 (KRIP6) or protein DRE1, is necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity. KLHL24 is a component of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates ubiquitination of KRT14 and controls its levels during keratinocyte differentiation. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKY 308
Cdd:cd18253  20 DVIICVEGREFPCHRAILSACSSYFRAMFCNDHRESREMLVEINGILAEAMDCFLQYVYTGKVKITTENVQYLFETSSLF 99

                        90
                ....*....|...
gi 17534257 309 EIQYVMDECERFL 321
Cdd:cd18253 100 QISPLRDACAKFL 112

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 40 (KLHL40); KLHL40, also called Kelch repeat and BTB domain-containing protein 5 (KBTBD5) or sarcosynapsin, is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development. Mutations in KLHL40 may cause severe autosomal-recessive nemaline myopathy. KLHL40 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 226 NICDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELG 305
Cdd:cd18340  26 KFVDCVLKIKEKEFPCHRLVLAACSPYFRAMFLSDLEESKKREIVLEDVDPDVMGKILHYIYTSEIEITEQNVQDIFAAA 105

                        90
                ....*....|....*.
gi 17534257 306 DKYEIQYVMDECERFL 321
Cdd:cd18340 106 NMFQIPSIFTVCVSFL 121

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 4 (KLHL4); KLHL4 shares high identity and similarity with the Drosophila kelch protein, a component of ring canals. It may be associated with X-linked cleft palate (CPX) and is also a candidate gene in the impairment of mullerian duct development. In addition, it has been identified as a target of insulin-like growth factor binding protein 5 (IGFBP5). KLHL4 contains a BTB domain and kelch repeat domains, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 224 QTNICDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLE 303
Cdd:cd18336  16 HKQLCDVLLIAGNLKIPAHRLVLSAVSDYFAAMFTNDVREAKQEEIKMEGVDPDALKALVHYAYTGVLELKEDTIESLLA 95

                        90
                ....*....|....*....
gi 17534257 304 LGDKYEIQYVMDECERFLV 322
Cdd:cd18336  96 AACLLQLSQVIDVCCNFLM 114

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins, KLHL40 and KLHL41; This family includes Kelch-like proteins, KLHL40 and KLHL41. KLHL40 is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development. KLHL41 is a novel kelch related protein that is involved in pseudopod elongation in transformed cells. They both contain a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 229 DMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKY 308
Cdd:cd18269  29 DCVLKIGDKEFPCHRLVLAACSPYFRAMFLSDLEESKKKEVVLEDVDPDVMGMILKYLYTSEIDLNDQNVQDIFALASRF 108

                        90
                ....*....|...
gi 17534257 309 EIQYVMDECERFL 321
Cdd:cd18269 109 QIPSIFTVCVSYL 121

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch repeat and BTB domain-containing protein 12 (KBTBD12); KBTBD12, also called Kelch domain-containing protein 6 (KLHDC6), contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534257 227 ICDMTLVINKQKLFVNKAYLALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVE------Y 300
Cdd:cd18276  21 LTDVVLVAEGEKFPCHRLVLAAFSPYFKAMFTCGLMECSQREVVLHDITAESVSIILNYMYSSDLHLTNSNVQgvataaF 100

                        90
                ....*....|....*..
gi 17534257 301 LLELGDKYEI--QYVMD 315
Cdd:cd18276 101 FLQMEDIFSVcqKYMMD 117

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 38 (KLHL38); KLHL38 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The KLHL38 gene is significantly up-regulated during diapause, a temporary arrest of development during early ontogeny. It may also function in preadipocyte differentiation in the chicken. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17534257 246 LALYSPVFYAMFFSNFQEREKTQVELEDVVLEEFRELLHVIYPCHKPITSDNVEYLLELGDKYEIQYVMDECERFL 321
Cdd:cd18268  42 LASSSPYFRAMFCNNFRESSQAKVDLKGIDSDVLDQIVDYVYTGEILITRDNVLPLMEAASMLQYPKLFEACSLYL 117