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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622934106   1 MRESQpEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEVLLDFLSLAHKYGFPELEDSTSEYL 65
Cdd:cd18287    56 MRESQ-QSEIELKDTNAEAFKALLKYIYTGRLTLTDLKEDVLLDVLGLAHQYGFEELEAAISDYL 119

F5/8 type C domain; This domain is also known as the discoidin (DS) domain family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106 377 NALLNGDTKNYdWdsgytcHQLGSGA---IVVQLAQPYMIGSIRLLLW--DCDDRSYSYYVEVSTNQQQWTMVADRTKVS 451
Cdd:pfam00754  15 AAALDGDPNTA-W------SAWSGDDpqwIQVDLGKPKKITGVVTQGRqdGSNGYVTSYKIEYSLDGENWTTVKDEKIPG 87

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1622934106 452 C---KSWQSVSFErQP--ASFIRIVGTHNTAN 478
Cdd:pfam00754  88 NndnNTPVTNTFD-PPikARYVRIVPTSWNGG 118

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622934106   1 MRESQpEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEVLLDFLSLAHKYGFPELEDSTSEYL 65
Cdd:cd18287    56 MRESQ-QSEIELKDTNAEAFKALLKYIYTGRLTLTDLKEDVLLDVLGLAHQYGFEELEAAISDYL 119

BTB And C-terminal Kelch; The BACK domain is found juxtaposed to the BTB domain; they are separated by as little as two residues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106   81 ASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAP-EKDIFLALLNWCKHNSKENH---AEIMQA 156
Cdd:smart00875   8 ADAHGLEELAEKALRFILQNFSEVSSSEEFLELPLEQLLELLSSDDLNVSsEEEVFEAVLRWVKHDPEKRRehlPELLEH 87

                           90
                   ....*....|....
gi 1622934106  157 VRLPLMSLTELLNV 170
Cdd:smart00875  88 VRLPLLSPDYLLEV 101

Broad-Complex, Tramtrack and Bric a brac; Domain in Broad-Complex, Tramtrack and Bric a brac. Also known as POZ (poxvirus and zinc finger) domain. Known to be a protein-protein interaction motif found at the N-termini of several C2H2-type transcription factors as well as Shaw-type potassium channels. Known structure reveals a tightly intertwined dimer formed via interactions between N-terminal strand and helix structures. However in a subset of BTB/POZ domains, these two secondary structures appear to be missing. Be aware SMART predicts BTB/POZ domains without the beta1- and alpha1-secondary structures.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622934106    6 PEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKeevLLDFLSLAHKYGFPELEDSTSEYLCTIL 69
Cdd:smart00225  37 DKSEIYLDDVSPEDFRALLNFLYTGKLDLPEEN---VEELLELADYLQIPGLVELCEEFLLKLL 97

F5/8 type C domain; This domain is also known as the discoidin (DS) domain family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106 224 KSALLDGDTQNYdldhgfsRHPIDDDCRSGIEIKLGQPSIINHVRILLWDRDSRSY--SYFIEVSMDELDWVRVIDHS-- 299
Cdd:pfam00754  14 AAAALDGDPNTA-------WSAWSGDDPQWIQVDLGKPKKITGVVTQGRQDGSNGYvtSYKIEYSLDGENWTTVKDEKip 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1622934106 300 -QYLCRSWQKLYFPARV-CRYIRIVGTH-NTVNKIFHIVAF 337
Cdd:pfam00754  87 gNNDNNTPVTNTFDPPIkARYVRIVPTSwNGGNGIALRAEL 127

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622934106   1 MRESQpEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEVLLDFLSLAHKYGFPELEDSTSEYL 65
Cdd:cd18287    56 MRESQ-QSEIELKDTNAEAFKALLKYIYTGRLTLTDLKEDVLLDVLGLAHQYGFEELEAAISDYL 119

BTB And C-terminal Kelch; The BACK domain is found juxtaposed to the BTB domain; they are separated by as little as two residues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106   81 ASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAP-EKDIFLALLNWCKHNSKENH---AEIMQA 156
Cdd:smart00875   8 ADAHGLEELAEKALRFILQNFSEVSSSEEFLELPLEQLLELLSSDDLNVSsEEEVFEAVLRWVKHDPEKRRehlPELLEH 87

                           90
                   ....*....|....
gi 1622934106  157 VRLPLMSLTELLNV 170
Cdd:smart00875  88 VRLPLLSPDYLLEV 101

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622934106   9 EIPLQDTTAEAFTMLLKYIYTGRAtltdEKEEVLLDFLSLAHKYGFPELEDSTSEYLCTIL 69
Cdd:pfam00651  51 EITLDDVSPEDFEALLEFMYTGKL----ISEENVDDLLAAADKLQIPSLVDKCEEFLIKSL 107

BACK (BTB and C-terminal Kelch) domain found in BTB/POZ domain-containing proteins, BTBD3 and BTBD6; This subfamily 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 evolutionarily-conserved role during neuronal development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  69 LNIQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAPEKDIFLALLNW----CKH 144
Cdd:cd18488     1 LSARNACVLLSQSRLFEEPELMQRCWEVIDAQAELALKSEGFTEIDYKTLESILRRETLNAKESVVFEAALRWaeaeCQR 80

                          90
                  ....*....|...
gi 1622934106 145 NSKENHAEIMQAV 157
Cdd:cd18488    81 RGLEPTPENKRKV 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622934106   1 MRESQpEAEIPLQDTTAEAFTMLLKYIYTGRATLTdekEEVLLDFLSLAHKYGFPELE 58
Cdd:cd18314    40 MIESN-LKEVTLEDVEPEIFETVLKYMYTGQVTLS---EENVLDLLMLASKYQVPDLE 93

BACK (BTB and C-terminal Kelch) domain found in BTB/POZ domain-containing protein 3 (BTBD3); BTBD3 is a BTB-domain-containing Kelch-like protein that controls dendrite orientation toward active axons in mammalian neocortex.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622934106  69 LNIQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAPEKDIFLALLNWCK 143
Cdd:cd18524     1 LSAKNACVLLSQSCLFEEPDLTQRCWEVIDAQAELALKSEGFCDIDFQTLESILRRETLNAKEIVVFEAALNWAE 75

BACK (BTB and C-terminal Kelch) domain found in BTB/POZ domain-containing proteins, BTBD1 and BTBD2; This subfamily includes BTB/POZ domain-containing proteins BTBD1 and BTBD2, both of which are BTB-domain-containing Kelch-like proteins that interact with DNA topoisomerase 1 (Topo1), a key enzyme in cell survival. BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622934106  69 LNIQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAPEKDIFLALLNWCKH 144
Cdd:cd18487     1 LSSDNAFMLLTQARLFDEPQLASLCLETIDKNTAEALAAEGFTDIDLDTLCVVLERDTLGIRECKLFQAVLRWAEA 76

BACK (BTB and C-terminal Kelch) domain found in BTB/POZ domain-containing protein 19 (BTBD19); BTBD19 is a BTB-domain-containing Kelch-like protein. Its function remains unclear.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622934106  71 IQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAPEKDIFLALLNW 141
Cdd:cd18494     2 VETACEALQAAVTYGQDELKERCLAFIEEHTEEVFKTKGFHELSDEALSVILRSDKLRIDELDILKAVREW 72

BACK (BTB and C-terminal Kelch) domain found in Kelch-like proteins, KLHL2 and KLHL3; This subfamily includes Kelch-like proteins, KLHL2 and KLHL3. KLHL2 is a novel actin-binding protein predominantly expressed in the brain. It plays a role in the reorganization of the actin cytoskeleton, and promotes growth of cell projections in oligodendrocyte precursors. Both KLHL2 and KLHL3 function as a component of an E3 ubiquitin ligase complex that mediates the ubiquitination of target proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622934106 103 EVLSSEGFLSLSKTALLNIVLRDSFAAP-EKDIFLALLNWCKHNSKENH---AEIMQAVRLPLMS 163
Cdd:cd18445    35 EVVKGEEFLLLSKEQVCELISSDDLTVPsEEKVFEAVMSWVNHDPENRKehlAELLEHVRLPLLS 99

kelch-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  18 EAFTMLLKYIYTGRATLTDEKEEvllDFLSLAHKYGFPELEDSTSEYLCTILNIQNVCMTFDVASLYSLPKLTCMCCMFM 97
Cdd:PHA03098   57 DSFNEVIKYIYTGKINITSNNVK---DILSIANYLIIDFLINLCINYIIKIIDDNNCIDIYRFSFFYGCKKLYSAAYNYI 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  98 DRNAQEVLSSEGFLSLSKTALLNIvLRDS--FAAPEKDIFLALLNWCKHNSKENHAEImqavrlplmslTELLNVVRPSg 175
Cdd:PHA03098  134 RNNIELIYNDPDFIYLSKNELIKI-LSDDklNVSSEDVVLEIIIKWLTSKKNNKYKDI-----------CLILKVLRIT- 200

                  ....*..
gi 1622934106 176 LLSPDAI 182
Cdd:PHA03098  201 FLSEEGI 207

BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 2 (KLHL2); KLHL2, also called actin-binding protein Mayven, is a novel actin-binding protein predominantly expressed in the brain. It plays a role in the reorganization of the actin cytoskeleton, and promotes growth of cell projections in oligodendrocyte precursors. KLHL2 is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  81 ASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAP-EKDIFLALLNWCKHNS---KENHAEIMQA 156
Cdd:cd18512    13 ADMHACTELLNQANTYAEQHFSDVVLSEEFLNLGIEQVCSLIASDKLTISsEEKVFEAVIAWVNHDKevrQEHMAHLMEH 92

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622934106 157 VRLPLMSLTELLNVVRPSGLLS-----PDAILDAIK 187
Cdd:cd18512    93 VRLPLLSREYLVQRVEEETLVKnssacKDYLIEAMK 128

BACK (BTB and C-terminal Kelch) domain found in Drosophila melanogaster serine-enriched protein (GPRS) and similar proteins; The family includes uncharacterized Drosophila melanogaster serine-enriched protein (GPRS) and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  70 NIQNVCMTFDVASLYSLPK----LTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAPEKDIFLALLNWCKHN 145
Cdd:cd18507     1 NVDTVCALLASAERYDQYKctktLVQKVLEFVDKHGTDVLNLPEFLLLPEHVVRLILSRDSLGADEMTKFQAALAWSRKY 80

BACK (BTB and C-terminal Kelch) domain found in BTB/POZ domain-containing protein 1 (BTBD1); BTBD1, also called Hepatitis C virus NS5A-transactivated protein 8 or HCV NS5A-transactivated protein 8, is a BTB-domain-containing Kelch-like protein specifically expressed in skeletal muscle. It interacts with DNA topoisomerase 1 (Topo1), a key enzyme in cell survival. BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta. It may serve as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  69 LNIQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAPEKDIFLALLNW----CKH 144
Cdd:cd18522     1 LRADNAFMLLTQARLFDEPQLASLCLDTIDKSTMDAISAEGFTDIDLDTLCAVLERDTLSIRESRLFGAVVRWaeaeCQR 80

                          90       100
                  ....*....|....*....|....*..
gi 1622934106 145 --------NSKENHAEIMQAVRLPLMS 163
Cdd:cd18522    81 qqlpvtseNKQKVLGKALSLIRFPLMT 107

BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 12 (KLHL12); KLHL12, also termed CUL3-interacting protein 1 (C3IP1), or DKIR, is a substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  96 FMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAP-EKDIFLALLNWCKHNSKENH---AEIMQAVRLPLMSLTELLNVV 171
Cdd:cd18452    28 FSQKHFPEVVQHEEFMLLSQEEVEKLIKSDEIQVDsEEPVFEAVLNWVKHDKEEREdylPELLQYVRLPLLSPRYITDVV 107

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in leucine-zipper-like transcriptional regulator 1 (LZTR-1); LZTR-1 is a golgi BTB-kelch protein that is degraded upon induction of apoptosis. It may also function as a transcriptional regulator that plays a crucial role in embryogenesis. Germline loss-of-function mutations in LZTR-1 predispose to an inherited disorder of multiple schwannomas. LZTR-1 contains two BTB domains. This model corresponds to the first domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106   4 SQPEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEE------VLL--DFLSLAHKYGFPELEDSTSEYL 65
Cdd:cd18308    86 DSPMLEVRLPEADPEAFELILSFIYTDKIDPTRKGQDpgsnevVLLmmDVYRLALQFQMSRLEQLCVQYL 155

BACK (BTB and C-terminal Kelch) domain found in Kelch-like proteins KLHL1, KLHL4 and KLHL5; This subfamily contains 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. Members of this subfamily contain a BTB domain and kelch repeat domains, characteristics of a kelch family protein. KLHL1 is a neuronal actin-binding protein that modulates voltage-gated CaV2.1 (P/Q-type) and CaV3.2 (alpha1H T-type) calcium channels.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622934106 103 EVLSSEGFLSLSKTALLNIVLRDSFAAP-EKDIFLALLNWCKH---NSKENHAEIMQAVRLPLMS 163
Cdd:cd18444    36 EVIQNQEFLLLPAEEVAKLLASDDLNVPsEETIFHALLLWVKHdlpERKKHLAKLLALIRLPLLT 100

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622934106   1 MRESQpEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEVLldfLSLAHKYGFPELEDSTSEYLCTILNIQN 73
Cdd:cd18343    55 MEESK-KNRVEINDVDPEVFKEMMRFIYTGKAPNLDKMADNL---LAAADKYALERLKVMCEEALCNNLSVEN 123

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster protein roadkill and similar proteins; 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622934106   3 ESQPEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEvllDFLSLAHKYGFPELEDSTSEYLCTILNIQNV 74
Cdd:cd18345    53 EERKQNRVEITDVDHEVMREMLRFIYTGKAPNLDKMAD---DLLAAADKYALERLKVMCEEALCSNLSVENV 121

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1622934106   1 MRESQPeAEIPLQDTTAEAFTMLLKYIYTGRATLtdeKEEVLLDFLSLAHKY 52
Cdd:cd01165    32 FRESGQ-AEINLRDISPEDFRALLEFLYGGKRDL---DASNLLELLEAANFL 79

BACK (BTB and C-terminal Kelch) domain found in ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1); ABTB1, also called elongation factor 1A-binding protein, or Bood POZ containing gene type 1 (BPOZ-1), is an anti-proliferative factor that may act as a mediator of the phosphatase and tensin homologue (PTEN) growth-suppressive signaling pathway. It may play a role in developmental processes.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1622934106  69 LNIQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSL 113
Cdd:cd18497     1 LDEDNVIDVLRTARLFNLPRLEDQCTEFMAKNLEELVDDEEFAEL 45

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622934106   2 RESQPEaEIPLQDTTAEAFTMLLKYIYTGRATLTDekEEVLLDFLSLAHKYGFPELEDSTSEYL 65
Cdd:cd18286    52 AESNSS-EITLTGVSHAAVSFVLLFIYGGVLDLPD--DVNLGELLSLADMYGLDGLKDVVAYTL 112

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622934106   4 SQPEAEIPLQDTTAEAFTMLLKYIYTGRATLTdekEEVLLDFLSLAHKYGFPELEDSTSEYLCTIL 69
Cdd:cd18282    46 AENKNEIEIPDVEPAAFLNLLRYLYCDEIDLE---PDTVLATLYAAKKYLVPHLARACVQFLETSL 108

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.

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                  ....*....|....*....|....*....|....*....|...
gi 1622934106   1 MRESQpEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEVLL 43
Cdd:cd18234    35 VREAT-EEEIKLKDVDPDALWTLVQYCYTGRLELKEDNVESLL 76

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622934106   3 ESQPEAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEvllDFLSLAHKYGFPELEDSTSEYLCTILNIQN 73
Cdd:cd18342    57 EESKKNRVEINDVEPEVFKEMMCFIYTGKAPNLDKMAD---DLLAAADKYALERLKVMCEDALCSNLSVEN 124

BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 6 (KLHL6); KLHL6 is a BTB-kelch protein with a lymphoid tissue-restricted expression pattern. It belongs to the KLHL gene family, which is composed of an N-terminal BTB-POZ domain and four to six Kelch motifs in tandem. It is involved in B-lymphocyte antigen receptor signaling and germinal center formation.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106  69 LNIQNVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDS-FAAPEKDIFLALLNWCKHNSK 147
Cdd:cd18446     1 LHPENCVGILRLADAHSLESLKKQVQNYIIQNFSQVLNHEEFLELPVDILCHILKSDDlYVTEEEQVFETVMRWVRYKES 80

                          90
                  ....*....|....*...
gi 1622934106 148 ENHA---EIMQAVRLPLM 162
Cdd:cd18446    81 ERLPllpRVLENVRLPLL 98

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622934106   7 EAEIPLQDTTAEAFTMLLKYIYTGRATLTDEKEEVLLDFLSLahkYGFPELEDSTSEYLCTILNIQN 73
Cdd:cd18274    62 QKEVRIVGVEAESMHLVLDYAYTSRVTLTEANVQALFTAASI---FQIPSLQDQCAQFMISRLDPQN 125

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing proteins, BTBD1 and BTBD2; This family includes BTB/POZ domain-containing proteins BTBD1 and BTBD2, both of which are BTB-domain-containing Kelch-like proteins that interact with DNA topoisomerase 1 (Topo1), a key enzyme of cell survival. BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622934106   7 EAEIPLQDTTAEAFTMLLKYIYtgratlTDEKE---EVLLDFLSLAHKYGFPELEDSTSEYLCTILNIQN 73
Cdd:cd18281    64 SAEIELPDVEPAAFLALLRFLY------SDEVQigpETVMTTLYTAKKYAVPALESACVEFLKKNLSSDN 127

BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 35 (KLHL35); KLHL35 belongs to the KLHL family. Its function remains unclear. Hypermethylation of KLHL35 is associated with hepatocellular carcinoma and abdominal aortic aneurysm.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622934106  73 NVCMTFDVASLYSLPKLTCMCCMFMDRNAQEVLSSEGFLSLSKTALLNIVLRDSFAAPEKDIFL-ALLNWCKH 144
Cdd:cd18474     5 NCLALLAAADALHCAPLQEHCIRVLLRDFAQAARHPSFLKLELQLVLELLADDSLAVRSEEVVLeAALRWVDA 77

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622934106   3 ESQPEAEIPLQDTTAEAFTMLLKYIYTGRATLTdekEEVLLDFLSLAHKYGFPELEDSTSEY 64
Cdd:cd18292    55 SKQSEIELVEDPECAAVFEKFLRYLYTGQISVN---LETALPLLMLADKYNVTDLKQLCVDF 113