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 17534631   141 SEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPVIDDDDVEGILH 220
Cdd:pfam00651   6 EQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLISEENVDDLLA 85

                          90       100
                  ....*....|....*....|..
gi 17534631   221 LAHMYDVPVAIRKCEEFLIEKS 242
Cdd:pfam00651  86 AADKLQIPSLVDKCEEFLIKSL 107

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 17534631   141 SEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPVIDDDDVEGILH 220
Cdd:pfam00651   6 EQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLISEENVDDLLA 85

                          90       100
                  ....*....|....*....|..
gi 17534631   221 LAHMYDVPVAIRKCEEFLIEKS 242
Cdd:pfam00651  86 AADKLQIPSLVDKCEEFLIKSL 107

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534631      8 LTHTFKNVSKLEDGKTLYGPEEEHFNIPWQLSFCRKEEFVGVFLRCLRPTDGIVPWEINADCILKLTSSAGKCLSHSSTY 87
Cdd:smart00061   2 LSHTFKNVSRLEEGESYFSPSEEHFNIPWRLKIYRKNGFLSLYLHCEKEECDSRKWSIEAEFTLKLVSQNGKSLSKKDKH 81

                           90
                   ....*....|....
gi 17534631     88 IFQSIGGFGRRKFV 101
Cdd:smart00061  82 VFEKPSGWGFSKFI 95

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 17534631   8 LTHTFKNVSKLE-DGKTLYGPEEEHFNIPWQLSFCRK-----EEFVGVFLRCLRPTDGIVPWEINADCILKLTS-SAGKC 80
Cdd:cd00121   1 GKHTWKIVNFSElEGESIYSPPFEVGGYKWRIRIYPNgdgesGDYLSLYLELDKGESDLEKWSVRAEFTLKLVNqNGGKS 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 17534631  81 LSHSSTYIFQS--IGGFGRRKFVSWDTLVKD-HLVNDSIIMEATV 122
Cdd:cd00121  81 LSKSFTHVFFSekGSGWGFPKFISWDDLEDSyYLVDDSLTIEVEV 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 17534631   141 SEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPVIDDDDVEGILH 220
Cdd:pfam00651   6 EQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLISEENVDDLLA 85

                          90       100
                  ....*....|....*....|..
gi 17534631   221 LAHMYDVPVAIRKCEEFLIEKS 242
Cdd:pfam00651  86 AADKLQIPSLVDKCEEFLIKSL 107

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534631      8 LTHTFKNVSKLEDGKTLYGPEEEHFNIPWQLSFCRKEEFVGVFLRCLRPTDGIVPWEINADCILKLTSSAGKCLSHSSTY 87
Cdd:smart00061   2 LSHTFKNVSRLEEGESYFSPSEEHFNIPWRLKIYRKNGFLSLYLHCEKEECDSRKWSIEAEFTLKLVSQNGKSLSKKDKH 81

                           90
                   ....*....|....
gi 17534631     88 IFQSIGGFGRRKFV 101
Cdd:smart00061  82 VFEKPSGWGFSKFI 95

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 17534631   8 LTHTFKNVSKLE-DGKTLYGPEEEHFNIPWQLSFCRK-----EEFVGVFLRCLRPTDGIVPWEINADCILKLTS-SAGKC 80
Cdd:cd00121   1 GKHTWKIVNFSElEGESIYSPPFEVGGYKWRIRIYPNgdgesGDYLSLYLELDKGESDLEKWSVRAEFTLKLVNqNGGKS 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 17534631  81 LSHSSTYIFQS--IGGFGRRKFVSWDTLVKD-HLVNDSIIMEATV 122
Cdd:cd00121  81 LSKSFTHVFFSekGSGWGFPKFISWDDLEDSyYLVDDSLTIEVEV 125

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 17534631 148 VVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPVIDD-DDVEGILHLAHMY 225
Cdd:cd01165   1 VVLVVEGEKFHVNKELLAQSSEYFRALFRGGFRESGQAEINLRDISPEDFRALLEFLYGGKRDLDaSNLLELLEAANFL 79

BTB (Broad-Complex, Tramtrack and Bric a brac) /POZ (poxvirus and zinc finger) domain found in Dictyostelium discoideum trishanku and similar proteins; Trishanku is a novel regulator required for normal morphogenesis and cell-type stability in Dictyostelium discoideum. It contains a 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 17534631 143 EQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDDVEGILHL 221
Cdd:cd18314   4 SEFSDVVLCVGDRKFFAHRIVLCARSPVFRSMLTGSMIESNLKEVTLEDVEPEIFETVLKYMYtGQVTLSEENVLDLLML 83

                        90
                ....*....|...
gi 17534631 222 AHMYDVPVAIRKC 234
Cdd:cd18314  84 ASKYQVPDLEKLC 96

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 35 (KLHL35); KLHL35 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. Significant differences in DNA methylation of the KLHL35 gene in abdominal aortic aneurysm (AAA) patients compared to non-AAA controls suggest a potential role in AAA pathology. Hypermethylation of the KLHL35 gene has also been associated with the development of 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 17534631 145 FSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPV-IDDDDVEGILHLAH 223
Cdd:cd18265  23 FTDVVLLVDGKDFPCHRATLSANSAYFRAMFGGHLKESRQAVVEIQKVSAAAMEVLLDYMYGGGLrIQEDNVESVLEASD 102

                        90
                ....*....|....*...
gi 17534631 224 MYDVPVAIRKCEEFLIEK 241
Cdd:cd18265 103 LLQVSKLREACVRFLEGQ 120

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 17534631 140 KSEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPV-IDDDDVEGI 218
Cdd:cd18255  13 RAKGQLLDVTLIADGQRFQAHKVVLASCSDYFRAMFTGGMRESSQDEIELKGVSAKGLKHILDFAYTSELtLDLDCIQDV 92

                        90       100
                ....*....|....*....|.
gi 17534631 219 LHLA-HMYDVPVaIRKCEEFL 238
Cdd:cd18255  93 LGAAvHLQMLPV-VELCEEFL 112

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch repeat and BTB domain-containing protein 2 (KBTBD2); KBTBD2, also called BTB and kelch domain-containing protein 1 (BKLHD1), plays an essential role in the regulation of insulin-signaling pathway. It is a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase, which targets p85alpha, the regulatory subunit of the phosphoinositol-3-kinase (PI3K) heterodimer, causing p85alpha ubiquitination and proteasome-mediated degradation. 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 17534631 142 EEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDDVEGILH 220
Cdd:cd18270  23 QQLLTDIVLIVEGTEFPCHKMVLATCSSYFRAMFMSGLSESKQTHVHLRNVDAATLQIIITYAYtGNLAINDSTVEQLYE 102

                        90       100
                ....*....|....*....|.
gi 17534631 221 LAHMYDVPVAIRKCEEFLIEK 241
Cdd:cd18270 103 TACFLQVEDVLQRCREYLIKK 123

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 17534631 142 EEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYG--EPVIDDDDVEGIL 219
Cdd:cd18286  14 NGEDSDITIKVDGKTFKAHRCILCARSSYFAAMLSGSWAESNSSEITLTGVSHAAVSFVLLFIYGgvLDLPDDVNLGELL 93

                ....*....
gi 17534631 220 HLAHMYDVP 228
Cdd:cd18286  94 SLADMYGLD 102

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 17534631 144 QFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDDVEGILHLA 222
Cdd:cd18340  26 KFVDCVLKIKEKEFPCHRLVLAACSPYFRAMFLSDLEESKKREIVLEDVDPDVMGKILHYIYtSEIEITEQNVQDIFAAA 105

                        90
                ....*....|....*....
gi 17534631 223 HMYDVPVAIRKCEEFLIEK 241
Cdd:cd18340 106 NMFQIPSIFTVCVSFLQKR 124

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 17534631 142 EEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKheaINSID---FQNFLEVLY-GEPVIDDDDVEG 217
Cdd:cd18297   9 NPEMSDVTFLVEGRPFYAHKIVLVTASDRFKSMLSSGSTEAQTPVIE---IPDIRydiFQLMMQYLYtGGVESLDVAQDD 85

                        90       100
                ....*....|....*....|....
gi 17534631 218 ILHL---AHMYDVPVAIRKCEEFL 238
Cdd:cd18297  86 ALELlraASFFQLDGLKRHCEILL 109

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 17534631 140 KSEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAE--ADKSEIkHEAINSIdFQNFLEVLY-GEPVIDDDDVE 216
Cdd:cd18250  16 RAERKFFDVTLCAGGREFPCHRTVLAAASSYFRAMFAGELREsrADRVVL-HGVSAEI-LGLLLDFSYtGRVTVTQDNVE 93

                        90       100
                ....*....|....*....|..
gi 17534631 217 GILHLAHMYDVPVAIRKCEEFL 238
Cdd:cd18250  94 ALLRAADLFQFPSVKEACCAYL 115

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster protein germ cell-less (GCL) and similar proteins; GCL proteins are nuclear envelope proteins highly conserved between the mammalian and Drosophila orthologs. Drosophila melanogaster GCL is a key regulator required for the specification of pole cells and primordial germ cell formation in embryos. Both, human germ cell-less protein-like 1 (GMCL1) and germ cell-less protein-like 2 (GMCL2), also called germ cell-less protein-like 1-like (GMCL1P1 or GMCL1L), may function in spermatogenesis. They may also be substrate-specific adaptors of E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. They contain BTB and BACK domains. 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 17534631 142 EEQFSDVVLAVEDKKFfVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAIN-SIDfQNFLEVLYG-----EPVIDDDDV 215
Cdd:cd18305  12 NGENSDITICALGREW-KLHKIYLCQSGYFASMFSGSWKESKETVINLEIPDdNIT-VEALNVVFGslyrdEIEIKPSRV 89

                        90       100
                ....*....|....*....|....*
gi 17534631 216 EGILHLAHMYDVPVAIRKCEEFLIE 240
Cdd:cd18305  90 VSILAAATLLQLDGLIQQCSEVMKE 114

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 17534631 145 FSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDDVEGILHLAH 223
Cdd:cd18253  18 FTDVIICVEGREFPCHRAILSACSSYFRAMFCNDHRESREMLVEINGILAEAMDCFLQYVYtGKVKITTENVQYLFETSS 97

                        90       100
                ....*....|....*....|
gi 17534631 224 MYDVPVAIRKCEEFLIEKSE 243
Cdd:cd18253  98 LFQISPLRDACAKFLEEQLD 117

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 1 (KLHL1); KLHL1 is a neuronal actin-binding protein that modulates voltage-gated CaV2.1 (P/Q-type) and CaV3.2 (alpha1H T-type) calcium channels. It may play a role in organizing the actin cytoskeleton the brain cells. KLHL1 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 17534631 133 KKLRSFEKsEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVID 211
Cdd:cd18335   8 RKMESYLK-QQQLCDVILIAGNRKIPAHRLVLSAVSDYFAAMFTSDVCEAKQEEIKMEGIDPNALWDLVQFAYtGCLELK 86

                        90       100
                ....*....|....*....|....*....
gi 17534631 212 DDDVEGILHLAHMYDVPVAIRKCEEFLIE 240
Cdd:cd18335  87 EDTIENLLAAACLLQLSQVVEVCCHFLMK 115

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 17534631 140 KSEEQFSDVVLAVE----DKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDD 214
Cdd:cd18248  16 RLSQQLCDVTLKVKyqdpKEEFMAHKVVLASSSPYFKAMFTSGLRECGMEVVPIEGVHPCVMSRLIEFAYtASISVGEKC 95

                        90       100
                ....*....|....*....|....*..
gi 17534631 215 VEGILHLAHMYDVPVAIRKCEEFLIEK 241
Cdd:cd18248  96 VLHVLPGAVMYQMDSVVKACCDFLEQQ 122

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 17534631 140 KSEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPV-IDDDDVEGI 218
Cdd:cd18237  16 RKQKTLCDVILIVEGREIKAHRVVLAAASHFFHLMFTSNMTESKSSEVELKDAEPDIIELLVEFAYTARIsVNSNNVQSL 95

                        90       100
                ....*....|....*....|...
gi 17534631 219 LHLAHMYDVPVAIRKCEEFLIEK 241
Cdd:cd18237  96 LDAANQYQIEPVKKMCVDFLKEQ 118

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins KLHL9 and KLHL13; KLHL9 and KLHL13 (also called BTB and kelch domain-containing protein 2, or BKLHD2) are substrate-specific adaptors of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes, thereby coordinating faithful mitotic progression and completion of cytokinesis. They 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 17534631 140 KSEEQFSDVVLAVED--KKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDDVE 216
Cdd:cd18239  18 RGEGLLCDVTLVPGDgdETFPVHRAMMASASDYFKAMFTGGMKEQELMCIKLHGVSKIGLKNIIDFIYtAKLSLNMDNLQ 97

                        90       100
                ....*....|....*....|...
gi 17534631 217 GILHLAHMYDVPVAIRKCEEFLI 239
Cdd:cd18239  98 DTLEAASFLQILPVLDFCKVLLI 120

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 17534631 133 KKLRSFEKSEEqFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVID 211
Cdd:cd18238   4 KVLHQFYENGE-LCDVTLKVGEKSIHCHRLVLACVSPYFRAMFTSEMAESKQDSITIKDIDEEAVELLVDFAYtGKLTLT 82

                        90       100
                ....*....|....*....|....*..
gi 17534631 212 DDDVEGILHLAHMYDVPVAIRKCEEFL 238
Cdd:cd18238  83 VDNVQSLLYAASLLQVEEVAKACCEFM 109

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch repeat and BTB domain-containing protein 8 (KBTBD8); KBTBD8, also called T-cell activation kelch repeat protein (TA-KRP), is a BTB-kelch family protein that is located in the Golgi apparatus and translocates to the spindle apparatus during mitosis. It acts as a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification. The BCR(KBTBD8) complex monoubiquitylates NOLC1 and its paralog TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. 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 17534631 142 EEQFSDVVLAVEDKKFFVL-RKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPVI-DDDDVEGIL 219
Cdd:cd18274  19 EGQLTDIVVEVDHGKTFSChRNVLAAISPYFRSMFTSGLTESTQKEVRIVGVEAESMHLVLDYAYTSRVTlTEANVQALF 98

                        90       100
                ....*....|....*....|..
gi 17534631 220 HLAHMYDVPVAIRKCEEFLIEK 241
Cdd:cd18274  99 TAASIFQIPSLQDQCAQFMISR 120

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins KLHL1, KLHL4 and KLHL5; This family contains the Kelch-like proteins: KLHL1, KLHL4 and KLHL5, all of which share high identity and similarity with the Drosophila kelch protein, a component of ring canals. KLHL1 is a neuronal actin-binding protein that modulates voltage-gated CaV2.1 (P/Q-type) and CaV3.2 (alpha1H T-type) calcium channels. Family members 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17534631 146 SDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDDVEGILHLAHM 224
Cdd:cd18234   2 CDVILIAGDRRIPAHRLVLSAVSDYFAAMFTNDVREATEEEIKLKDVDPDALWTLVQYCYtGRLELKEDNVESLLATACL 81

                        90
                ....*....|....*
gi 17534631 225 YDVPVAIRKCEEFLI 239
Cdd:cd18234  82 LQLSEVVEACCGFLM 96

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 12 (KLHL12); KLHL12, also called CUL3-interacting protein 1 (C3IP1) or DKIR homolog, is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of the Wnt signaling pathway and ER-Golgi transport. 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 17534631 133 KKLRSFEKsEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLYGEPV-ID 211
Cdd:cd18242  10 NTMNSLRK-SNTLCDVTLRVEGKEFPAHRIVLAACSDYFCAMFTSEMSEKGKSEVELQGLTASTMEILLDFVYTETVhVT 88

                        90       100
                ....*....|....*....|....*..
gi 17534631 212 DDDVEGILHLAHMYDVPVAIRKCEEFL 238
Cdd:cd18242  89 VENVQELLPAACLLQLKGVKQACCEFL 115

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 30 (KLHL30); KLHL30 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 17534631 140 KSEEQFSDVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVLY-GEPVIDDDDVEGI 218
Cdd:cd18259  27 RSNPKLSDVTLLVGGREFPCHRSVLALCSHYFNAMFTGDFVESISARVEIKDVDPAVMESLIDFAYtGKLTINQGNVEAL 106

                        90       100
                ....*....|....*....|
gi 17534631 219 LHLAHMYDVPVAIRKCEEFL 238
Cdd:cd18259 107 IRTSNRLQFPTVRKVCSRYL 126

first 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, tandem BTB domains, and a conserved C-terminal region. In vertebrates, 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 first 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 17534631 143 EQFSDVVLAVEDK-KFFVLRKFLASHSSYFKSLLLG-TFAEADKSeIKHEAinsidFQNFLEVLY-GEPVIDDDDVEGIL 219
Cdd:cd18299  10 PSCADVVFILQGGvRIFAHRIVLAAASSVFADLFLMmTVVTLDSD-ITPEA-----FRRVLEFLYtGVLDENEDDLKELK 83

                        90
                ....*....|....*....
gi 17534631 220 HLAHMYDVPVAIRKCEEFL 238
Cdd:cd18299  84 DAAELLELFDLVMMCTNVL 102

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 15 (KLHL15); KLHL15 is a substrate-specific adaptor for the Cullin3 E3 ubiquitin-protein ligase complex that targets the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits. It also plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR), by targeting the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. KLHL15 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 17534631 147 DVVLAVEDKKFFVLRKFLASHSSYFKSLLLGTFAEADKSEIKHEAINSIDFQNFLEVL-YGEPVIDDDDVEGILHLAHMY 225
Cdd:cd18244  32 DVTLVIEDHQFQAHKALLATQSDYFRIMFTADMRERDQDKIHLKGLTATGFSHVLQFMyYGTIELSMLTVHEILQAAMYV 111

                        90
                ....*....|....*.
gi 17534631 226 DVPVAIRKCEEFLIEK 241
Cdd:cd18244 112 QLTEVVKFCCSFLLAK 127