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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  10 MSDPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLL 89
Cdd:cd18394    1 MTDPVTLNVGGHLYTTSLSTLTRYPDSMLGAMFRGDFPTARDSQGNYFIDRDGPLFRYILNFLRTSELTLPVDFKEFDLL 80

                         90       100
                 ....*....|....*....|....
gi 806638758  90 RKEADFYQIEPLIQCLNDPRPLYP 113
Cdd:cd18394   81 RKEADFYQIEPLIQCLNDPKPLYP 104

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 6 (KCTD6); KCTD6, also called KCTD containing, Cullin3 adaptor, suppressor of Hedgehog 3 (KCASH3), is a BTB/POZ domain-containing protein that functions as a substrate-specific adaptor of cullin-3, regulating protein levels of the muscle small ankyrin-1 isoform 5 (sAnk1.5) as well as suppressing histone deacetylase and Hedgehog activity in medulloblastoma. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  10 MSDPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLL 89
Cdd:cd18394    1 MTDPVTLNVGGHLYTTSLSTLTRYPDSMLGAMFRGDFPTARDSQGNYFIDRDGPLFRYILNFLRTSELTLPVDFKEFDLL 80

                         90       100
                 ....*....|....*....|....
gi 806638758  90 RKEADFYQIEPLIQCLNDPRPLYP 113
Cdd:cd18394   81 RKEADFYQIEPLIQCLNDPKPLYP 104

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758    14 VTLNVGGHLYTTSLTTLTRYPDSMLgAMFGGDFPTArDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDfkEFDLLRKEA 93
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFK-ALFSSDFKES-DKSEIYLDDVSPEDFRALLNFLYTGKLDLPEE--NVEELLELA 77

                           90
                   ....*....|.
gi 806638758    94 DFYQIEPLIQC 104
Cdd:smart00225  78 DYLQIPGLVEL 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 6 (KCTD6); KCTD6, also called KCTD containing, Cullin3 adaptor, suppressor of Hedgehog 3 (KCASH3), is a BTB/POZ domain-containing protein that functions as a substrate-specific adaptor of cullin-3, regulating protein levels of the muscle small ankyrin-1 isoform 5 (sAnk1.5) as well as suppressing histone deacetylase and Hedgehog activity in medulloblastoma. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  10 MSDPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLL 89
Cdd:cd18394    1 MTDPVTLNVGGHLYTTSLSTLTRYPDSMLGAMFRGDFPTARDSQGNYFIDRDGPLFRYILNFLRTSELTLPVDFKEFDLL 80

                         90       100
                 ....*....|....*....|....
gi 806638758  90 RKEADFYQIEPLIQCLNDPRPLYP 113
Cdd:cd18394   81 RKEADFYQIEPLIQCLNDPKPLYP 104

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 21 (KCTD21); KCTD21, also calledz KCTD containing, Cullin3 adaptor, suppressor of Hedgehog 2 (KCASH2), is a BTB/POZ domain-containing protein that functions as a substrate-specific adaptor of cullin-3, promoting the ubiquitination and degradation of histone deacetylase HDAC1, thereby inhibiting the deacetylation-mediated transcriptional activation of the Hedgehog effectors Gli1 and Gli2. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  12 DPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRK 91
Cdd:cd18395    1 DPITLNVGGKLYTTSLATLTRYPDSMLGAMFSGKFPTKKDSQGNCFIDRDGKIFRYILNFLRTSHLDLPEDFQEMGLLKR 80

                         90
                 ....*....|....*.
gi 806638758  92 EADFYQIEPLIQCLND 107
Cdd:cd18395   81 EADFYQIQPLIEALQE 96

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins, KCTD8, KCTD12, KCTD16 and similar proteins; This subfamily of KCTD proteins includes KCTD8, KCTD12 (also called predominantly fetal expressed T1 domain/Pfetin), and KCTD16. They act as auxiliary subunits of GABAB receptors associated with mood disorders. KCTD8 interacts as a tetramer with GABRB1 and GABRB2. KCTD12 regulates agonist potency and kinetics of GABAB receptor signaling. It promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A-dependent G2/M transition. KCTD16 interacts with amyloid beta precursor protein (APP), a type I transmembrane protein involved in a variety of cellular processes such as cell adhesion, and axon guidance. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPT--ARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRK 91
Cdd:cd18367    5 VELNVGGQVYTTSLSTLIKDPDSLLGRMFSGKNRQelARDSKGRYFLDRDGVLFRYILDYLRNQKLVLPENFPERERLKR 84

                         90
                 ....*....|....*
gi 806638758  92 EADFYQIEPLIQCLN 106
Cdd:cd18367   85 EAEYFQLPELVKALR 99

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins; The potassium channel tetramerization domain (KCTD) family proteins contain the BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD proteins play crucial roles in a variety of fundamental biological processes, such as protein ubiquitination and degradation, suppression of proliferation or transcription, cytoskeleton regulation, tetramerization and gating of ion channels and others. Some KCTD proteins are involved in protein ubiquitination as part of the CRL (Cullin RING Ligase) E3 ligases. Some others show Cullin-independent functions including binding and regulation of GABA (gamma-aminobutyric acid) receptors (KCTD8, KCTD12 and KCTD16) and inhibition of AP-2 function (KCTD15). KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRKEA 93
Cdd:cd18316    1 VKLNVGGTLFTTSRSTLLKDPDSLLAALFSGRWPLPRDEDGSIFIDRDPELFRHILNFLRTGKLPLPSDFVELEELLAEA 80

                 ...
gi 806638758  94 DFY 96
Cdd:cd18316   81 EFY 83

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 15 (KCTD15); KCTD15 is a BTB/POZ domain-containing protein that plays a role in the regulation of neural crest (NC) formation and other steps in embryonic development. It inhibits AP2 transcriptional activity by interaction with its activation domain. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. The KCTD1 BTB domains, closely related to KCTD15, form pentamers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  13 PVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDP-QGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRK 91
Cdd:cd18388    3 PVHIDVGGHMYTSSLATLTKYPDSRISRLFNGTEPIVLDSlKQHYFIDRDGEIFRYILSFLRTSKLLLPEDFKDFNLLYE 82

                         90
                 ....*....|....
gi 806638758  92 EADFYQIEPLIQCL 105
Cdd:cd18388   83 EAKYYQLQPMVKEL 96

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel regulatory protein (KCNRG); KCNRG, also called potassium channel regulator or protein CLLD4, is an endoplasmic reticulum (ER)-associated tumor suppressor that regulates Kv1 family potassium channel proteins by retaining a fraction of the channels in endomembranes. It contains a BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRKEA 93
Cdd:cd18375    3 VTLNVGGKKFTTRPSTLRRFPDSRLARMLDGKDQDFKVVNGQFFVDRDGSLFSYILDYLRTGQLTLPTEFSDYNRLAREA 82

                         90
                 ....*....|...
gi 806638758  94 DFYQIEPLIQCLN 106
Cdd:cd18375   83 EFYGLYSLADLLS 95

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 1 (KCTD1); KCTD1 is a nuclear BTB/POZ domain-containing protein that acts as a transcriptional repressor and mediates protein-protein interactions through a BTB domain. It represses the transcriptional activity of AP-2 family members, including TFAP2A, TFAP2B and TFAP2C to various extent. It also functions as a novel inhibitor of the Wnt signaling pathway. Mutations in KCTD1 cause scalp-ear-nipple (SEN) syndrome. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. The KCTD1 BTB domains form pentamers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  13 PVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDP-QGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRK 91
Cdd:cd18387    4 PVHIDVGGHMYTSSLATLTKYPESRIGRLFDGTEPIVLDSlKQHYFIDRDGQMFRYILNFLRTSKLLIPDDFKDYSLLYE 83

                         90
                 ....*....|.
gi 806638758  92 EADFYQIEPLI 102
Cdd:cd18387   84 EAKYFQLQPML 94

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 16 (KCTD16); KCTD16 is a BTB/POZ domain-containing protein that is an auxiliary subunit of GABAB receptors associated with mood disorders. It interacts with amyloid beta precursor protein (APP), a type I transmembrane protein involved in a variety of cellular processes such as cell adhesion and axon guidance. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  12 DPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPT----ARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFD 87
Cdd:cd18398    3 EVVELNVGGQVYFTRHATLVSIPHSLLWKMFSPKRDTandlAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKG 82

                         90
                 ....*....|....*...
gi 806638758  88 LLRKEADFYQIEPLIQCL 105
Cdd:cd18398   83 RLKREAEYFQLPDLVKLL 100

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein KCTD8; KCTD8, a BTB/POZ domain-containing protein, is an auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. It interacts as a tetramer with GABRB1 and GABRB2. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPT--ARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRK 91
Cdd:cd18396    6 VELNVGGQVYVTKHSTLLSVPDSTLASMFSRRAARelPRDNRGRFFIDRDGFLFRYVLDYLRDKQLALPDHFPEKERLLR 85

                         90
                 ....*....|....
gi 806638758  92 EADFYQIEPLIQCL 105
Cdd:cd18396   86 EAEYFQLGDLVKLL 99

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 3 (KCTD3) and SH3KBP1-binding protein 1 (SHKBP1); The group of KCTD proteins includes KCTD3 and SHKBP1. KCTD3, also called renal carcinoma antigen NY-REN-45, is a BTB/POZ domain-containing protein that is an accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3), upregulating its cell-surface expression and current density without affecting its voltage dependence and kinetics. SHKBP1, also called SETA-binding protein 1, interacts with cathepsin B and participates in tumor necrosis factor (TNF)-induced apoptosis in ovarian cancer cells. It can promote epidermal growth factor receptor (EGFR) signaling by interrupting c-Cbl-CIN85 complex and inhibiting EGFR degradation. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  11 SDPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSEltlpLDFKEFDL-- 88
Cdd:cd18363    1 GDIINLNVGGKRFSTSRQTLTWIPDSFFTSLLSGRISSLKDETGAIFIDRDPKLFSIILNYLRTKE----IDLRNVDIss 76

                         90
                 ....*....|
gi 806638758  89 LRKEADFYQI 98
Cdd:cd18363   77 LRHEAEFYGI 86

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in voltage-gated potassium (Kv) channels and potassium channel tetramerization domain-containing (KCTD) proteins; This family includes two protein groups: voltage-gated potassium (Kv) channels and potassium channel tetramerization domain-containing (KCTD) proteins. Kv channels are membrane proteins with fundamental physiological roles. They are responsible for a variety of electrical phenomena, such as the repolarization of the action potential, spike frequency adaptation, synaptic repolarization, and smooth muscle contraction. KCTD proteins play crucial roles in a variety of fundamental biological processes, such as protein ubiquitination and degradation, suppression of proliferation or transcription, cytoskeleton regulation, tetramerization and gating of ion channels, and others. All family members contain the BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQ-GNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEfDLLRKE 92
Cdd:cd18187    1 VVLNVSGTRFVTNRQTLTRHPDTLLGRMFKPGREFTFPNEtGEYFIDRDPTVFRTILNYYRTGKLNCPDGISI-PDLREE 79

                 ....
gi 806638758  93 ADFY 96
Cdd:cd18187   80 CDFY 83

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 3 (KCTD3); KCTD3, also called renal carcinoma antigen NY-REN-45, is a BTB/POZ domain-containing protein that is an accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3), upregulating its cell-surface expression and current density without affecting its voltage dependence and kinetics. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  12 DPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTlpLDFKEFDLLRK 91
Cdd:cd18392    2 EIIQLNVGGTRFSTSRQTLMWIPDSFFSSLLSGRISSLKDETGAIFIDRDPTAFVPILNFLRTKELD--LRGVNINVLRH 79

                 ....*....
gi 806638758  92 EADFYQIEP 100
Cdd:cd18392   80 EAEFYGITP 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins, KCTD10 (BACURD3), KCTD13 (BACURD1), and TNFAIP1 (BACURD2); This subfamily of KCTD proteins, also called the BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein (BACURD) subfamily, includes KCTD10 (BACURD3), KCTD13 (BACURD1), and TNFAIP1 (BACURD2). KCTD10 is a BTB/POZ domain-containing protein that interacts with proliferating cell nuclear antigen (PCNA) and polymerase delta, and participates in DNA repair, DNA replication, and cell-cycle control. Its down-regulation could inhibit cell proliferation. KCTD10 also plays crucial roles in embryonic angiogenesis and heart development in mammals by negatively regulating the Notch signaling pathway. KCTD13 is a BTB/POZ domain-containing protein that may function as a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of RhoA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. TNFAIP1, also called protein B12, is a BTB/POZ domain-containing protein that is involved in DNA replication, DNA damage repair, cell apoptosis, and is implicated in human diseases including cancer, Alzheimer's disease (AD) and type 2 diabetic nephropathy. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. KCTD10 and KCTD13 BTB domains form a novel two-fold symmetric tetramer that is distinct from the tetramer formed by voltage-gated potassium (Kv) channels.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYpDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRKEA 93
Cdd:cd18369    1 VKLNVGGSLHYTTIGTLTKQ-DTMLRAMFSGRMEVLTDSEGWILIDRCGKHFGTILNYLRDGSVPLPESRRELAELLAEA 79

                         90
                 ....*....|..
gi 806638758  94 DFYQIEPLI-QC 104
Cdd:cd18369   80 KYYLVQGLVeQC 91

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in tumor necrosis factor, alpha-induced protein 1, endothelial (TNFAIP1); TNFAIP1, also called BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 2 (BACURD2), or protein B12, is a BTB/POZ domain-containing protein that is involved in DNA replication, DNA damage repair and cell apoptosis, and is implicated in human diseases including cancer, Alzheimer's disease (AD) and type 2 diabetic nephropathy. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. The BTB domains of other BACURD subfamily members, KCTD10 and KCTD13, form a novel two-fold symmetric tetramer that is distinct from the tetramer formed by voltage-gated potassium (Kv) channels.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYpDSMLGAMFGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLRKEA 93
Cdd:cd18401    5 VRLNVGGSLYYTTVQVLTRH-DTMLKAMFSGRMEVLTDKEGWILIDRCGKHFGTILNYLRDDTVALPKSRQEIKELMAEA 83

                 ....*....
gi 806638758  94 DFYQIEPLI 102
Cdd:cd18401   84 KYYLIQGLV 92

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in voltage-gated potassium (Kv) channels; Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. This family includes several groups of alpha subunits such as KCNA/Kv1 family of Shaker-type Kv channels, KCNB/Kv2 family of Shab-type Kv channels, KCNC/Kv3 family of Shaw-type Kv channels, KCND/Kv4 family of Shal-type Kv channels, KCNF/Kv5 subfamily of Kv channels, KCNG/Kv6 subfamily of Kv channels, KCNV/Kv8 subfamily of Kv channels, and KCNS/Kv9 subfamily of Kv channels. Kv alpha subunits form functional homo- or hetero-tetrameric channels (typically with other alpha subunits from the same subfamily) through their BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif. KCNQ/Kv7 channels are not included in this family, since they do not contain a BTB/POZ domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMfGGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEfDLLRKEA 93
Cdd:cd18317    1 VVLNVGGTRFELSRSTLLRFPDTRLGKL-AKESHAYDESTNEYFFDRNPEVFEAILDYYRTGELHLPSNVCP-ASFKEEL 78

                 ...
gi 806638758  94 DFY 96
Cdd:cd18317   79 EFW 81

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins KCTD2, KCTD5, and KCTD17, and similar proteins; This subfamily includes potassium channel tetramerization domain-containing proteins KCTD2, KCTD5, and KCTD17, all of which function as adaptors of Cullin3 based ubiquitin E3 ubiquitin ligases. KCTD2 suppresses gliomagenesis by destabilizing c-Myc. KCTD5 is a negative regulator of the AKT pathway, a key signaling cascade frequently deregulated in cancer. KCTD5 does not impact the operation of Kv4.2, Kv3.4, Kv2.1, or Kv1.2 channels. KCTD17 polyubiquitylates trichoplein, a protein involved in ciliogenesis down-regulation. It is a positive regulator of ciliogenesis, playing a crucial role in the initial steps of axoneme extension. A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia (M-D). The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. KCTD5 and KCTD17 BTB domains form pentamer structures.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGD--FPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLrK 91
Cdd:cd18362    2 VKLNVGGTYFLTTRTTLCRDPKSFLCRLCQEDpdLPSDKDETGAYLIDRDPTYFGPILNYLRHGKLIIDKDLAEEGVL-E 80

                 ....*
gi 806638758  92 EADFY 96
Cdd:cd18362   81 EAEFY 85

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 2 (KCTD2); KCTD2 is a BTB/POZ domain-containing protein that functions as an adaptor of Cullin3 E3 ubiquitin ligase. It suppresses gliomagenesis by destabilizing c-Myc. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. KCTD5 and KCTD17 BTB domain, highly similar to KCTD2, form pentamer structures.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMF--GGDFPTARDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDFKEFDLLrK 91
Cdd:cd18389    3 VRLNVGGTYFVSTKQTLCRDPKSFLYRLCqeDPDLDSDKDETGAYLIDRDPTYFGPILNYLRHGKLIINKELAEEGVL-E 81

                         90
                 ....*....|....*.
gi 806638758  92 EADFYQIEPLIQCLND 107
Cdd:cd18389   82 EAEFYNIASLVRLVKE 97

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 1 (KCND1); KCND1, also called voltage-gated potassium channel subunit Kv4.1, is a pore-forming subunit of voltage-gated rapidly inactivating A-type potassium channels. It may contribute to I (To) current in heart and I (Sa) current in neurons. Its properties are modulated by interactions with other alpha subunits and with regulatory subunits. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. KCND1 is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other Kv4/KCND alpha subunits) through its BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif. It is modulated by cytoplasmic KChIPs/KCNIPs (Kv-channel interacting proteins), which are small calcium binding proteins with EF-hand-like domains.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  16 LNVGGHLYTTSLTTLTRYPDSMLGAMfGGDFPTARDPQgNYFIDRDGPLFRYVLNFLRTSELTLPLD--FKEFDllrKEA 93
Cdd:cd18417   39 VNVSGRRFQTWKNTLDRYPDTLLGSS-EKEFFYNEDTQ-EYFFDRDPEMFRHILNFYRTGRLHYPRHecIQAFD---EEL 113

                         90
                 ....*....|....*....
gi 806638758  94 DFYQIEPLIQ---CLNDPR 109
Cdd:cd18417  114 SFYGIIPEIIgdcCLEEYR 132

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in KCND/Kv4 subfamily of Shal-type voltage-dependent potassium channels; Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. The potassium voltage-gated channel subfamily Kv4, also known as subfamily D, contains three alpha subunit members, Kv4.1 (KCND1), Kv4.2 (KCND2), and Kv4.3 (KCND3), which are orthologs of the Shal gene in Drosophila. They are A-type potassium channels that mediate the native, fast inactivating (A-type) K+ current (IA) described both in the nervous system (A currents) and the heart (transient outward current). Kv4/KCND subfamily alpha subunits form functional homo- or hetero-tetrameric channels through their BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif. They are modulated by cytoplasmic KChIPs/KCNIPs (Kv-channel interacting proteins), which are small calcium binding proteins with EF-hand-like domains.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFptARDPQGNYFIDRDGPLFRYVLNFLRTSELTLP 80
Cdd:cd18380    2 IVINVSGRRFETWKNTLEKYPDTLLGSTEKEFF--YDDDTKEYFFDRDPEIFRHILNFYRTGKLHYP 66

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758    14 VTLNVGGHLYTTSLTTLTRYPDSMLgAMFGGDFPTArDPQGNYFIDRDGPLFRYVLNFLRTSELTLPLDfkEFDLLRKEA 93
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFK-ALFSSDFKES-DKSEIYLDDVSPEDFRALLNFLYTGKLDLPEE--NVEELLELA 77

                           90
                   ....*....|.
gi 806638758    94 DFYQIEPLIQC 104
Cdd:smart00225  78 DYLQIPGLVEL 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster potassium voltage-gated channel protein Shal and similar proteins; Drosophila melanogaster Shal, also called Shaker cognate l or Shal2, is a transient potassium current (I(A)) channel, which is required for maintaining excitability during repetitive firing and normal locomotion in Drosophila. It may play a role in the nervous system and in the regulation of beating frequency in pacemaker cells. Shal mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. Shal is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other alpha subunits) through its BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMfGGDFPTARDPQgNYFIDRDGPLFRYVLNFLRTSELTLP 80
Cdd:cd18420   38 LIINVSGRRFETWRNTLEKYPDTLLGSN-EREFFYDEETK-EYFFDRDPDIFRHILNYYRTGKLHYP 102

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily C members KCNC1 and KCNC3; KCNC1 (also called NGK2, voltage-gated potassium channel subunit Kv3.1, or voltage-gated potassium channel subunit Kv4) and KCNC3 (also called KSHIIID or voltage-gated potassium channel subunit Kv3.3) play important roles in the rapid repolarization of fast-firing brain neurons. Assuming opened or closed conformations in response to the voltage difference across the membrane, the proteins form tetrameric potassium-selective channels through which potassium ions may pass in accordance with their electrochemical gradient. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. KCNC1 and KCNC3 are alpha subunit that form functional homo- or hetero-tetrameric channels (with other alpha subunits) through their BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 806638758  11 SDPVTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTA--RDPQ-GNYFIDRDGPLFRYVLNFLRTSELTLPLD 82
Cdd:cd18414    2 SDRIVINVGGTRHETYRSTLRTLPGTRLAWLAEPDAHSNfdYDPRaDEFFFDRHPGVFAHILNYYRTGKLHCPAD 76

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily V member 1 (KCNV1); KCNV1, also called neuronal potassium channel alpha subunit HNKA or voltage-gated potassium channel subunit Kv8.1, is a new neuronal voltage-gated potassium channel alpha subunit with specific inhibitory properties towards Shab and Shaw channels. It modulates KCNB1 (also known as Kv2.1) and KCNB2 (also known as Kv2.2) channel activity by shifting the threshold for inactivation to more negative values and by slowing the rate of inactivation. It can also down-regulate the channel activity of KCNB1, KCNB2, KCNC4 (also known as Kv3.4) and KCND1 (also known as Kv4.1), possibly by trapping them in intracellular membranes. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. KCNV1 is a regulatory alpha subunit that cannot form a functional homo-tetrameric channel. It forms hetero-tetrameric channels (with other functional alpha subunits) through its BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 806638758  15 TLNVGGHLYTTSLTTLTRYPDSMLG--AMFGGDFPTARDPQGN-----YFIDRDGPLFRYVLNFLRTSEL 77
Cdd:cd18424    2 TINVGGSRFVLSQQVLSSHPETRLGklAVSVRDSVLELCDDANfvdneYFFDRSSQAFKYIMNYYKTGHL 71

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in KCNS/Kv9 subfamily of potassium voltage-gated channels; Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. The potassium voltage-gated channel subfamily Kv9, also known as subfamily S, includes KCNS1 (Kv9.1), KCNS2 (Kv9.2) and KCNS3 (Kv9.3). They are regulatory alpha subunits that cannot form functional homo-tetrameric channels. Both KCNS1 and KCNS2 are delayed-rectifier K(+) channel alpha subunits that can form functional heterotetrameric channels with KCNB1 (also known as Kv2.1) and KCNB2 (also known as Kv2.2), and further modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 and KCNB2. KCNS3 is a delayed-rectifier K(+) channel alpha subunit linked to tissue oxygenation responses. It can form functional heterotetrameric channels with KCNB1, and further modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 806638758  14 VTLNVGGHLYTTSLTTLTRYPDSMLGAMFGGDFPTA--------RDPQGNYFIDRDGPLFRYVLNFLRTSEL 77
Cdd:cd18384    1 IRINVGGFRRRLSASALLRFPGTRLGRLLACHSEEAilelcddyDVAAREFYFDRNPGFFLYVLHFYRTGKL 72