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 2000186055  16 SVQKFCYEWTISNFSFCMDGIRENVTSPRFSLEASEEMQWCLRIFPNGVDEESKDYLSVYLGLLSCPKSPVWAKVQFWII 95
Cdd:cd03774     1 KVVKFCYMWTISNFSFCREEMGEVIKSSTFSSGANDKLKWCLRVNPKGLDEESKDYLSLYLLLVSCPKSEVRAKFKFSIL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2000186055  96 NAQGEKYLITKMSNVLRFLPNQYWGYKKFILRDFLLSHRHRLLPEDQFTLCCKVSIVER 154
Cdd:cd03774    81 NAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEANGLLPDDKLTLFCEVSVVQD 139

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 2000186055  16 SVQKFCYEWTISNFSFCMDGIRENVTSPRFSLEASEEMQWCLRIFPNGVDEESKDYLSVYLGLLSCPKSPVWAKVQFWII 95
Cdd:cd03774     1 KVVKFCYMWTISNFSFCREEMGEVIKSSTFSSGANDKLKWCLRVNPKGLDEESKDYLSLYLLLVSCPKSEVRAKFKFSIL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2000186055  96 NAQGEKYLITKMSNVLRFLPNQYWGYKKFILRDFLLSHRHRLLPEDQFTLCCKVSIVER 154
Cdd:cd03774    81 NAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEANGLLPDDKLTLFCEVSVVQD 139

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 2000186055 179 GELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKAPhlhSRS 258
Cdd:pfam00651   2 NELREQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLI---SEE 78

                          90       100
                  ....*....|....*....|....*....
gi 2000186055 259 MATGLLAAADKYDLQGLKGMCEDALCRNL 287
Cdd:pfam00651  79 NVDDLLAAADKLQIPSLVDKCEEFLIKSL 107

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000186055   24 WTISNFSFCMDGirENVTSPRFsleASEEMQWCLRIFPNGvdeeskDYLSVYLGLLSCPKS----PVWAKVQFWIINaQG 99
Cdd:smart00061   4 HTFKNVSRLEEG--ESYFSPSE---EHFNIPWRLKIYRKN------GFLSLYLHCEKEECDsrkwSIEAEFTLKLVS-QN 71

                           90       100
                   ....*....|....*....|....*.
gi 2000186055  100 EKYLITKMSNVlrFLPNQYWGYKKFI 125
Cdd:smart00061  72 GKSLSKKDKHV--FEKPSGWGFSKFI 95

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 2000186055  16 SVQKFCYEWTISNFSFCMDGIRENVTSPRFSLEASEEMQWCLRIFPNGVDEESKDYLSVYLGLLSCPKSPVWAKVQFWII 95
Cdd:cd03774     1 KVVKFCYMWTISNFSFCREEMGEVIKSSTFSSGANDKLKWCLRVNPKGLDEESKDYLSLYLLLVSCPKSEVRAKFKFSIL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2000186055  96 NAQGEKYLITKMSNVLRFLPNQYWGYKKFILRDFLLSHRHRLLPEDQFTLCCKVSIVER 154
Cdd:cd03774    81 NAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEANGLLPDDKLTLFCEVSVVQD 139

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in speckle-type POZ protein-like (SPOPL); SPOPL, also called HIB homolog 2 or Roadkill homolog 2, is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The complexes may contain homodimeric SPOPL or the heterodimers formed by speckle-type POZ protein (SPOP) and SPOPL, which are less efficient than ubiquitin ligase complexes containing only SPOP. 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 2000186055 167 IKDPRQMLVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFI 246
Cdd:cd18343     1 LKVPECRLAEDLGNLWENSRFTDCSLFVGGQEFKAHKSILAARSPVFNAMFEHEMEESKKNRVEINDVDPEVFKEMMRFI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2000186055 247 YTGKAPHLHsrSMATGLLAAADKYDLQGLKGMCEDALCRNLSVKN 291
Cdd:cd18343    81 YTGKAPNLD--KMADNLLAAADKYALERLKVMCEEALCNNLSVEN 123

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 2000186055 167 IKDPRQMLVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFI 246
Cdd:cd18342     2 VKVPECRLADELGGLWENSRFTDCCLCVAGQEFQAHKAILAARSPVFSAMFEHEMEESKKNRVEINDVEPEVFKEMMCFI 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2000186055 247 YTGKAPHLHsrSMATGLLAAADKYDLQGLKGMCEDALCRNLSVKNA 292
Cdd:cd18342    82 YTGKAPNLD--KMADDLLAAADKYALERLKVMCEDALCSNLSVENA 125

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 2000186055 179 GELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKAPhlhSRS 258
Cdd:pfam00651   2 NELREQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLI---SEE 78

                          90       100
                  ....*....|....*....|....*....
gi 2000186055 259 MATGLLAAADKYDLQGLKGMCEDALCRNL 287
Cdd:pfam00651  79 NVDDLLAAADKLQIPSLVDKCEEFLIKSL 107

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 2000186055 187 FTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKAPhlHSRSMATGLLAA 266
Cdd:cd18186     1 LCDVTLVVGGREFPAHRAVLAARSPYFRAMFSSGMKESSSSEIELDDVSPEAFEALLDYIYTGELE--LSEENVEELLAA 78

                  ....
gi 2000186055 267 ADKY 270
Cdd:cd18186    79 ADKL 82

BACK (BTB and C-terminal Kelch) 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 complex that mediates 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 domain. TDPOZ proteins may be nuclear scaffold proteins involved in transcription regulation in early development and other cellular processes. Drosophila melanogaster protein roadkill, also termed 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2000186055 287 LSVKNAVPTLILADLHKTEHLKTRAMDFIILHASEVSDTVGWKSMVESHPHLVEEAFYS 345
Cdd:cd14821     1 LSVENAAEVLVLADLHSAEQLKTHAIDFINSHATDVMETEGWKSMVRSHPHLVAEAFRA 59

BACK (BTB and C-terminal Kelch) domain found in speckle-type POZ protein-like (SPOPL); SPOPL, also termed HIB homolog 2, or Roadkill homolog 2, is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The complexes containing homodimeric SPOPL or the heterodimer formed by speckle-type POZ protein (SPOP) and SPOPL are less efficient than ubiquitin ligase complexes containing only SPOP.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2000186055 287 LSVKNAVPTLILADLHKTEHLKTRAMDFI------------------ILHASEVSDTVGWKSMVESHPHLVEEAFYSLSS 348
Cdd:cd18519     1 LSVENVADTLILADLHSAEQLKAQAIDFInrcsvlrqlgckdgknwnSNHATDIMETAGWKSMIHSHPHLVAEAFRALAS 80

                  ....*...
gi 2000186055 349 IQCPGFEP 356
Cdd:cd18519    81 AQCPPFGI 88

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 2000186055 172 QMLVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKA 251
Cdd:cd18287     7 HFLSEDIGALFLNEEYSDVTFVVEEKRFPAHRVILAARSEYFRALLYGGMRESQQSEIELKDTNAEAFKALLKYIYTGRL 86

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2000186055 252 pHLHSRSMATGL--LAAADKYDLQGLkgmcEDALCRNL 287
Cdd:cd18287    87 -TLTDLKEDVLLdvLGLAHQYGFEEL----EAAISDYL 119

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Ankyrin repeat and BTB/POZ domain-containing protein 2 (ABTB2) and similar proteins; This family includes ABTB2, BTBD11, plant ARM repeat protein interacting with ABF2 (ARIA), and similar proteins. ABTB2, also called bood POZ containing gene type 2 (BPOZ-2), is a scaffold protein that controls the degradation of many biological proteins ranging from embryonic development to tumor progression. It may be involved in the initiation of hepatocyte growth. ABTB2 functions as an adaptor protein for the E3 ubiquitin ligase scaffold protein Cullin-3. It directly binds to eukaryotic elongation factor 1A1 (eEF1A1) to promote eEF1A1 ubiquitylation and degradation, and prevent translation. The BTBD11 gene has been recently identified as an all-trans retinoic acid (atRA)-responsive gene that lies downstream of atRA and its receptors in the regulation of neurite outgrowth and cell adhesion in neural as well as non-neural tissues. ARIA is an armadillo (ARM) repeat and BTB domain-containing protein that acts as a positive regulator of ABA response via the modulation of the transcriptional activity of ABF2. 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 2000186055 179 GELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKAPHLH-SR 257
Cdd:cd18297     4 PHYVNNPEMSDVTFLVEGRPFYAHKIVLVTASDRFKSMLSSGSTEAQTPVIEIPDIRYDIFQLMMQYLYTGGVESLDvAQ 83

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2000186055 258 SMATGLLAAADKYDLQGLKGMCEDALCRNLSVKN 291
Cdd:cd18297    84 DDALELLRAASFFQLDGLKRHCEILLSQQIDLDN 117

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 2000186055  20 FCYEWTISNFSFCMDgirENVTSPRFSleaSEEMQWCLRIFPNGvDEESKDYLSVYLGLLSC----PKSPVWAKVQFWII 95
Cdd:cd00121     1 GKHTWKIVNFSELEG---ESIYSPPFE---VGGYKWRIRIYPNG-DGESGDYLSLYLELDKGesdlEKWSVRAEFTLKLV 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2000186055  96 NAQGEKYLITKMSNVLRFLPNQYWGYKKFILRDFLLSHRHrlLPEDQFTLCCKV 149
Cdd:cd00121    74 NQNGGKSLSKSFTHVFFSEKGSGWGFPKFISWDDLEDSYY--LVDDSLTIEVEV 125

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 2000186055 174 LVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKAPH 253
Cdd:cd18250     8 LLRGLSELRAERKFFDVTLCAGGREFPCHRTVLAAASSYFRAMFAGELRESRADRVVLHGVSAEILGLLLDFSYTGRVTV 87

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2000186055 254 LHSRsmATGLLAAADKYDLQGLKGMCEDALCRNLSVKNA 292
Cdd:cd18250    88 TQDN--VEALLRAADLFQFPSVKEACCAYLQQRLDVSNC 124

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 2000186055 180 ELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKApHLHSRSM 259
Cdd:cd18237    14 NMRKQKTLCDVILIVEGREIKAHRVVLAAASHFFHLMFTSNMTESKSSEVELKDAEPDIIELLVEFAYTARI-SVNSNNV 92

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2000186055 260 ATgLLAAADKYDLQGLKGMCEDALCRNLSVKN 291
Cdd:cd18237    93 QS-LLDAANQYQIEPVKKMCVDFLKEQLDASN 123

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 17 (BTBD17); BTBD17, also called galectin-3-binding protein-like, is a BTB domain-containing protein. Its function remains unclear. It may be associated with hepatocellular carcinoma. 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 2000186055 172 QMLVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMF-EHEMLESLTNRIEIH--DIHLQVFKEMMAFIYT 248
Cdd:cd18292     2 REFLQDIAQLYNNEELSDIVLRVGGKVFHAHRLILAKSSDVFRVMLsNDWWSESKQSEIELVedPECAAVFEKFLRYLYT 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2000186055 249 GkapHLH-SRSMATGLLAAADKYDLQGLKGMCED 281
Cdd:cd18292    82 G---QISvNLETALPLLMLADKYNVTDLKQLCVD 112

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 8 (BTBD8); BTBD8 is a BTB-domain-containing Kelch-like protein that may play a role in developmental processes. It may also act as a protein-protein adaptor in a transcription complex and thus be involved in brain development. BTBD8 contains two BTB domains. This model corresponds to the second 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 2000186055 173 MLVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKAP 252
Cdd:cd18286     3 RLGKDLLQLFLNGEDSDITIKVDGKTFKAHRCILCARSSYFAAMLSGSWAESNSSEITLTGVSHAAVSFVLLFIYGGVLD 82

                          90       100
                  ....*....|....*....|....
gi 2000186055 253 HLHSRSMaTGLLAAADKYDLQGLK 276
Cdd:cd18286    83 LPDDVNL-GELLSLADMYGLDGLK 105

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 23 (KLHL23); KLHL23 overexpression is associated with increased cell proliferation and invasion in gastric cancer. Downregulation of KLHL23 is associated with invasion, metastasis, and poor prognosis of hepatocellular carcinoma and pancreatic cancer. KLHL23 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 2000186055 180 ELWENSLFTDCSLV-VAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKApHLHSRS 258
Cdd:cd18252    14 TFYLDGLFTDITLQcASGQIFHCHKAALAACSSYFKVMFTADMKEKSNNVIKLSGIDHDILEALVNYVYTSQI-CITERN 92

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2000186055 259 MATgLLAAADKYDLQGLKGMCEDALCRNLSVKNAV 293
Cdd:cd18252    93 VQS-LLEAADLLQFISVKKACEQFLVRHLDIDNCL 126

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3); KLHL3 is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. It 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 2000186055 178 IGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKAPHLHSR 257
Cdd:cd18339    12 MNELRSKQLLCDVTIVAEDVEIEAHRVVLAACSPYFCAMFTGDMSESKAKKIEIKDVDGQTLSKLIDYIYTAEIEVTEEN 91

                          90       100       110
                  ....*....|....*....|....*....|
gi 2000186055 258 SMAtgLLAAADKYDLQGLKGMCEDALCRNL 287
Cdd:cd18339    92 VQV--LLPAASLLQLMDVRQNCCDFLQSQL 119

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 25 (KLHL25); KLHL25, also called ectoderm-neural cortex protein 2 (ENC-2), is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that is required for translational homeostasis. The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated EIF4EBP1 (4E-BP1). Cullin3-KLHL25 ubiquitin ligase also targets ATP-citrate lyase (ACLY), a key enzyme for lipid synthesis, for degradation to inhibit lipid synthesis and tumor progression. KLHL25 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 2000186055 174 LVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHD-IHLQVFKEMMAFIYTGKAp 252
Cdd:cd18254     9 VLTHLNTLRKQCMFTDVTLWAGNRSFPCHRAVLAACSRYFEAMFSNGLRESLDSTVNFHDsLHPEVLELLLDFAYSSRI- 87

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2000186055 253 hLHSRSMATGLLAAADKYDLQGLKGMCEDALCRNLSVKN 291
Cdd:cd18254    88 -IINEENAESLLEAGDMLQFHDVRDAAAEFLEKNLYPSN 125

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins, KLHL2 and KLHL3; The family includes Kelch-like proteins, KLHL2 and KLHL3. KLHL2 is a novel actin-binding protein predominantly expressed in brain. It plays a role in the reorganization of the actin cytoskeleton, and promotes growth of cell projections in oligodendrocyte precursors. KLHL2 and KLHL3 each functions as a component of an E3 ubiquitin ligase complex that mediates the ubiquitination of target proteins. They contain 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2000186055 180 ELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYT 248
Cdd:cd18235    14 ELRKQNLLCDVILVADGVEIPAHRVVLASCSPYFHAMFTGDLSESRANRVTLQDVDGKALLLLIDYVYT 82

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in gigaxonin; Gigaxonin, also called Kelch-like protein 16 (KLHL16), may be a cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. It may also act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, including tubulin folding cofactor B (TBCB), microtubule-associated protein MAP1B, and glial fibrillary acidic protein (GFAP). Gigaxonin is mutated in giant axonal neuropathy. 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 2000186055 174 LVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHE--MLESLTNRIEIHDIHLQVFKEMMAFIYTGKA 251
Cdd:cd18245     1 LLRALNSFREEPHLCDATLVVGGEEIPVQKNVLAAASPYFRAKLNYNppKDDGSTYKIELEGISVEVMEEILDYIYTGQI 80

                          90       100
                  ....*....|....*....|....*...
gi 2000186055 252 PhlHSRSMATGLLAAADKYDLQGLKGMC 279
Cdd:cd18245    81 K--LSEDNIQDIVQAADLLLMTDLKDLC 106

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2000186055 180 ELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGKA 251
Cdd:cd18253    11 EFRDSRLFTDVIICVEGREFPCHRAILSACSSYFRAMFCNDHRESREMLVEINGILAEAMDCFLQYVYTGKV 82

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 26 (KLHL26); KLHL26 is encoded by the klhl26 gene, which is regulated by p53 via fuzzy tandem repeats. 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 2000186055 181 LWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTgkaphlhSRSMA 260
Cdd:cd18255    12 LRAKGQLLDVTLIADGQRFQAHKVVLASCSDYFRAMFTGGMRESSQDEIELKGVSAKGLKHILDFAYT-------SELTL 84

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2000186055 261 TG-----LLAAADKYDLQGLKGMCEDALCRNLSVKN 291
Cdd:cd18255    85 DLdciqdVLGAAVHLQMLPVVELCEEFLKSAMSVEN 120

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 18 (KLHL18); KLHL18 acts as a substrate-specific adaptor for a Cullin3 E3 ubiquitin-protein ligase complex that regulates mitotic entry and ubiquitylates Aurora-A. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2000186055 178 IGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGK 250
Cdd:cd18247    10 MEEIRRQGKLCDVTLKVGDQKFSAHRIVLAATIPYFHAMFTHDMVESKQDEITMQGIEPSALEALINFAYSGR 82

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 33 (KLHL33); KLHL33 contains BTB domains and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. KLHL33 gene expression in normal and tumor tissue suggest a significant association with prostate cancer risk. KLHL33 contains two BTB domains. 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 2000186055 178 IGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLTNRIEIHDIHLQVFKEMMAFIYTGkAPHLhSR 257
Cdd:cd18263     4 IEGLWEKGVGCDVQLEADGSIFRVHRVILAAGSDYFRAMFTSGMKESTQSVVQLPTIPAKDLRLLISFAYSG-ILHL-SW 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2000186055 258 SMATGLLAAADKYDLQGLKGMCEDALCRNLS 288
Cdd:cd18263    82 ENLFEATCTALQLQISGALALCLDFLQREIS 112

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger protein 131 (ZNF131); ZNF131, also called zinc finger and BTB domain-containing protein 35 (ZBTB35), is a transcriptional activator implicated as a regulator of Kaiso-mediated biological processes. It regulates cell growth of developing and mature T cells. It inhibits estrogen signaling by suppressing estrogen receptor alpha homo-dimerization, and plays a role in breast cancer cell proliferation. It contains a BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2000186055 172 QMLVNDIGELWENSLFTDCSLVVAGQEFRSHKAILAACSPVFRAMFEHEMLESLtnrIEIHDIHLQVFKEMMAFIYTGK 250
Cdd:cd18221     3 KVMLDRLNEQRELDQFTDITLIVDGHQFKAHKAVLAACSQFFYKFFQDFTQEPL---VEIEGVSNMAFRHLIEFTYTAK 78