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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQR 84
Cdd:cd18375   1 ELVTLNVGGKKFTTRPSTLRRFPDSRLARMLDGKDQDFKVVNGQFFVDRDGSLFSYILDYLRTGQLTLPTEFSDYNRLAR 80

                        90
                ....*....|....*.
gi 46195444  85 EALFYELDSLVDLLSQ 100
Cdd:cd18375  81 EAEFYGLYSLADLLSQ 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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQR 84
Cdd:cd18375   1 ELVTLNVGGKKFTTRPSTLRRFPDSRLARMLDGKDQDFKVVNGQFFVDRDGSLFSYILDYLRTGQLTLPTEFSDYNRLAR 80

                        90
                ....*....|....*.
gi 46195444  85 EALFYELDSLVDLLSQ 100
Cdd:cd18375  81 EAEFYGLYSLADLLSQ 96

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 46195444      7 VTLNVGGRIFTTRPSTLKQFPASRLAgMLDGRDQEFKTvDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHhrLQREA 86
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFKA-LFSSDFKESDK-SEIYLDDVSPEDFRALLNFLYTGKLDLPEENVEE--LLELA 77

                           90       100
                   ....*....|....*....|
gi 46195444     87 LFYELDSLVDLLSQFLLQSR 106
Cdd:smart00225  78 DYLQIPGLVELCEEFLLKLL 97

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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQR 84
Cdd:cd18375   1 ELVTLNVGGKKFTTRPSTLRRFPDSRLARMLDGKDQDFKVVNGQFFVDRDGSLFSYILDYLRTGQLTLPTEFSDYNRLAR 80

                        90
                ....*....|....*.
gi 46195444  85 EALFYELDSLVDLLSQ 100
Cdd:cd18375  81 EAEFYGLYSLADLLSQ 96

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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQR 84
Cdd:cd18394   3 DPVTLNVGGHLYTTSLSTLTRYPDSMLGAMFRGDFPTARDSQGNYFIDRDGPLFRYILNFLRTSELTLPVDFKEFDLLRK 82

                        90
                ....*....|....*
gi 46195444  85 EALFYELDSLVDLLS 99
Cdd:cd18394  83 EADFYQIEPLIQCLN 97

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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVD--GQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRL 82
Cdd:cd18367   3 EIVELNVGGQVYTTSLSTLIKDPDSLLGRMFSGKNRQELARDskGRYFLDRDGVLFRYILDYLRNQKLVLPENFPERERL 82

                        90
                ....*....|....*..
gi 46195444  83 QREALFYELDSLVDLLS 99
Cdd:cd18367  83 KREAEYFQLPELVKALR 99

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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQR 84
Cdd:cd18395   1 DPITLNVGGKLYTTSLATLTRYPDSMLGAMFSGKFPTKKDSQGNCFIDRDGKIFRYILNFLRTSHLDLPEDFQEMGLLKR 80

                        90
                ....*....|....*.
gi 46195444  85 EALFYELDSLVDLLSQ 100
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 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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVD--GQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRL 82
Cdd:cd18396   4 EVVELNVGGQVYVTKHSTLLSVPDSTLASMFSRRAARELPRDnrGRFFIDRDGFLFRYVLDYLRDKQLALPDHFPEKERL 83

                        90
                ....*....|....*..
gi 46195444  83 QREALFYELDSLVDLLS 99
Cdd:cd18396  84 LREAEYFQLGDLVKLLT 100

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 12 (KCTD12); KCTD12, also called predominantly fetal expressed T1 domain (Pfetin), is a BTB/POZ domain-containing protein that is an auxiliary subunit of GABAB receptors associated with mood disorders. It regulates agonist potency and kinetics of GABAB receptor signaling. It promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A-dependent G2/M transition. It also regulates colorectal cancer cell stemness through the ERK pathway. 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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVD--GQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRL 82
Cdd:cd18397   3 EIVELNVGGQVYVTRHTTLVSVPDSLLWHMFSQQKPGELARDskGRFFLDRDGFLFRYILDYLRDLQLVLPDYFPERSRL 82

                        90
                ....*....|....*..
gi 46195444  83 QREALFYELDSLVDLLS 99
Cdd:cd18397  83 QREAEFFQLPELVKRLN 99

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 7 (KCTD7); KCTD7 is a BTB/POZ domain-containing protein that has an impact on K+ fluxes, neurotransmitter synthesis, and neuronal function. It functions as a regulator of potassium conductance in neurons, and is involved in the control of excitability of cortical neurons. Mutations in KCTD7 may cause progressive myoclonus epilepsy (PME). 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 46195444   6 LVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHElLLPSDFAdhHRLQRE 85
Cdd:cd18366   5 VVPLNVGGMHFTTRLSTLRKYEDSMLAAMFSGRHHIPKDSEGRYFIDRDGSYFGYILNFLRDGD-LPPRERA--RAVYKE 81

                        90
                ....*....|.
gi 46195444  86 ALFYELDSLVD 96
Cdd:cd18366  82 AQYYGIGPLIE 92

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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSdfADHHRLQR 84
Cdd:cd18363   2 DIINLNVGGKRFSTSRQTLTWIPDSFFTSLLSGRISSLKDETGAIFIDRDPKLFSIILNYLRTKEIDLRN--VDISSLRH 79

                ....*
gi 46195444  85 EALFY 89
Cdd:cd18363  80 EAEFY 84

BTB/POZ domain; In voltage-gated K+ channels this domain is responsible for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. In KCTD1 this domain functions as a transcriptional repressor. It also mediates homomultimerization of KCTD1 and interaction of KCTD1 with the transcription factor AP-2-alpha.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444     7 VTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQREA 86
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLELECDDYDDDTNEYFFDRSPKHFETILNFYRTGGKLHRPEEVCLDEFLEEA 80

                  ....*...
gi 46195444    87 LFYELDSL 94
Cdd:pfam02214  81 EFYGLDEL 88

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLAGMLDgRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDF 76
Cdd:cd18317   1 VVLNVGGTRFELSRSTLLRFPDTRLGKLAK-ESHAYDESTNEYFFDRNPEVFEAILDYYRTGELHLPSNV 69

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein KCTD11; KCTD11 may function as an antagonist of the Hedgehog pathway of cell proliferation and differentiation by affecting the nuclear transfer of transcription factor GLI1, thus maintaining cerebellar granule cells in the undifferentiated state. It is a probable substrate-specific adapter for a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex towards HDAC1. It contains a BTB/POZ domain; in some cases the domain may be truncated. 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. Variants of the human/mouse KCTD11 appear to contain truncated BTB/POZ domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLAGMLDG--RDQEFKTVDGQ--IFVDRDGALFSFILDFLRNHELLLPSDFADHHRL 82
Cdd:cd18370   1 VTLNVGGTLYSTTLETLTRFPDSMLGAMFRAgtPIPPNLNMQGGghYFIDRDGKAFRHILNFLRLGRLDLPRGYGETALL 80

                ....*...
gi 46195444  83 QREALFYE 90
Cdd:cd18370  81 RAEADFYQ 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in SH3KBP1-binding protein 1 (SHKBP1); 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. It contains a BTB/POZ domain, also known as tetramerization (T1) domain, 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 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSdfADHHRLQR 84
Cdd:cd18393   2 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELDPRG--IHVSLLLH 79

                        90
                ....*....|.
gi 46195444  85 EALFYELDSLV 95
Cdd:cd18393  80 EAQFYGITPLV 90

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 46195444      7 VTLNVGGRIFTTRPSTLKQFPASRLAgMLDGRDQEFKTvDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHhrLQREA 86
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFKA-LFSSDFKESDK-SEIYLDDVSPEDFRALLNFLYTGKLDLPEENVEE--LLELA 77

                           90       100
                   ....*....|....*....|
gi 46195444     87 LFYELDSLVDLLSQFLLQSR 106
Cdd:smart00225  78 DYLQIPGLVELCEEFLLKLL 97

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 17 (KCTD17); KCTD17 is a BTB/POZ domain-containing protein that functions as a substrate-adaptor for cullin3-RING ubiquitin ligases that 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. The KCTD17 BTB domains form pentamers.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVD-GQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQrE 85
Cdd:cd18391   3 VRLNVGGTVFLTTRQTLCREQKSFLSRLCQGEELQSDRDEtGAYLIDRDPTYFGPILNFLRHGKLVLDKDMAEEGVLE-E 81

                        90
                ....*....|....*....
gi 46195444  86 ALFYELDSLVDLLSQFLLQ 104
Cdd:cd18391  82 AEFYNIGPLIRIIKDRMEE 100

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLAGML-DGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFA 77
Cdd:cd18187   1 VVLNVSGTRFVTNRQTLTRHPDTLLGRMFkPGREFTFPNETGEYFIDRDPTVFRTILNYYRTGKLNCPDGIS 72

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 46195444   3 GQDLVTLNVGGRIFTTRPSTLKQFPaSRLAGMLDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRL 82
Cdd:cd18401   1 GNKYVRLNVGGSLYYTTVQVLTRHD-TMLKAMFSGRMEVLTDKEGWILIDRCGKHFGTILNYLRDDTVALPKSRQEIKEL 79

                        90
                ....*....|....*
gi 46195444  83 QREALFYELDSLVDL 97
Cdd:cd18401  80 MAEAKYYLIQGLVDM 94

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLAgMLDGRDQEF---KTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADHHRLQ 83
Cdd:cd18362   2 VKLNVGGTYFLTTRTTLCRDPKSFLC-RLCQEDPDLpsdKDETGAYLIDRDPTYFGPILNYLRHGKLIIDKDLAEEGVLE 80

                ....*.
gi 46195444  84 rEALFY 89
Cdd:cd18362  81 -EAEFY 85

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel protein Shaw; Shaw, also called Shaw2, is a voltage-gated potassium channel in Drosophila. It mediates transmembrane potassium transport in excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a tetrameric 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. Shaw 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRdQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSDFADhHRLQREA 86
Cdd:cd18416   4 VVLNVGGIRHETYKATLKKIPATRLSRLTEAL-ANYDPVLNEYFFDRHPGVFAQILNYYRTGKLHYPTDVCG-PLFEEEL 81

                ....*..
gi 46195444  87 LFYELDS 93
Cdd:cd18416  82 EFWGLDA 88

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLD---GRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSD 75
Cdd:cd18414   3 DRIVINVGGTRHETYRSTLRTLPGTRLAWLAEpdaHSNFDYDPRADEFFFDRHPGVFAHILNYYRTGKLHCPAD 76

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 2 (KCND2); KCND2, also called voltage-gated potassium channel subunit Kv4.2, is a major pore-forming subunit in somatodendritic subthreshold A-type potassium current I(SA) channels. It mediates transmembrane potassium transport in excitable membranes, primarily in the brain. 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. KCND2 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46195444   6 LVTLNVGGRIFTTRPSTLKQFPASRLAGmlDGRDQEFKTVDGQIFVDRDGALFSFILDFLRNHELLLP 73
Cdd:cd18418   1 LIVLNVSGTRFQTWRNTLERYPDTLLGS--SERDFFYHEETQEYFFDRDPDIFRHILNFYRTGKLHYP 66

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily S member 3 (KCNS3); KCNS3, also called delayed-rectifier K(+) channel alpha subunit 3 or voltage-gated potassium channel subunit Kv9.3, is an alpha subunit of voltage-gated potassium channel linked to tissue oxygenation responses. It can form functional heterotetrameric channels with KCNB1 (also known as Kv2.1), and further modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1. 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. KCNS3 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQE--------FKTVDGQIFVDRDGALFSFILDF 64
Cdd:cd18428   1 ELINLNVGGFKQSVDQSTLLRFPHTRLGKLLNCHSEEailelcddYSVADKEYYFDRNPSLFRYVLNF 68

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 46195444   1 MSGQDLVTLNVGGRIFTTRPSTLKQFPASrlagMLDGRDQEF--KTVDGQIFVDRDGALFSFILDFLRNHELLLP 73
Cdd:cd18417  31 RRNDEILVVNVSGRRFQTWKNTLDRYPDT----LLGSSEKEFfyNEDTQEYFFDRDPEMFRHILNFYRTGRLHYP 101

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily C members KCNC2 and KCNC4; KCNC2, also called Shaw-like potassium channel or voltage-gated potassium channel Kv3.2, is a delayed rectifier voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. It contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system. KCNC4, also called KSHIIIC or voltage-gated potassium channel subunit Kv3.4, is a novel high-voltage-activating, tetraethylammonium (TEA)-sensitive, type-A potassium channel that mediates the voltage-dependent potassium ion permeability of excitable membranes. It plays a pivotal role in oxidative stress-related neural cell damage as an oxidation-sensitive channel. 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. KCNC2 and KCNC4 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQEFKTVDG--------------QIFVDRDGALFSFILDFLRNHEL 70
Cdd:cd18415   2 ERIILNVGGTRHETYRSTLKTLPGTRLALLASSDPQGDCLTQCsqvggsdgspgggnEFFFDRHPGVFAYVLNYYRTGKL 81

                ....*
gi 46195444  71 LLPSD 75
Cdd:cd18415  82 HCPAD 86

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in KCNB/Kv2 subfamily of Shab-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 Kv3, also known as subfamily C, contains two alpha subunit members, Kv2.1 (KCNB1) and Kv2.2 (KCNB2), which are orthologs of the Shab gene in Drosophila. They are delayed-rectifier potassium currents in various neurons, although their physiological roles often remain elusive. Kv2/KCNB subfamily alpha subunits 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLA---------GMLDGRDqEFKTVDGQIFVDRDGALFSFILDFLRNHELLLPSD 75
Cdd:cd18378   4 VLLNVGGVRHEVLWRTLDRLPRTRLGrlrecntheSLLELCD-DYDLEDNEYFFDRHPGAFTSILNFYRTGKLHMPEE 80

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in KCNG/Kv6 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 Kv6, also known as subfamily G, includes KCNG1 (Kv6.1), KCNG2 (Kv6.2 or KCNF2), KCNG3 (Kv6.3) and KCNG4 (Kv6.4), which are regulatory alpha subunits and do not form functional channels on their own. KCNG1 can form functional heterotetrameric channels with KCNB1 (also known as Kv2.1), and further modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1. KCNG2, also called cardiac potassium channel subunit, can form functional heterodimeric channels with KCNB1, and further modulates channel activity by shifting the threshold and the half-maximal activation to more negative values. KCNG3, also called voltage-gated potassium channel subunit Kv10.1, is an electrically silent modulatory subunit that can form functional heterotetrameric channels with KCNB1, and further promotes a reduction in the rate of activation and inactivation of the delayed rectifier voltage-gated potassium channel KCNB1. KCNG4 is a silent voltage-gated potassium (KvS) channel subunit that 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 46195444   7 VTLNVGGRIFTTRPSTLKQFPASRLAGMLDGRDQE--------FKTVDGQIFVDRDGALFSFILDFLRNHELLL 72
Cdd:cd18382   1 VIINVGGARYSLPWSTLDRFPLTRLSRLKACRSEDdilrvcddYDVERNEFFFDRSPEAFGVILLFLRAGKLRL 74

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46195444   8 TLNVGGRIFTTRPSTLKQFPASRLAGM-LDGRDQEFKT------VDGQIFVDRDGALFSFILDFLRNHEL 70
Cdd:cd18424   2 TINVGGSRFVLSQQVLSSHPETRLGKLaVSVRDSVLELcddanfVDNEYFFDRSSQAFKYIMNYYKTGHL 71

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in KCNA/Kv1 subfamily of Shaker-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 Kv1, also known as subfamily A, contains eight alpha subunit members, Kv1.1 (KCNA1), Kv1.2 (KCNA2), Kv1.3 (KCNA3), Kv1.4 (KCNA4), Kv1.5 (KCNA5), Kv1.6 (KCNA6), Kv1.7 (KCNA7), and Kv1.8 (KCNA10), which are orthologs of the Shaker gene in Drosophila. They are delayed rectifiers except for Kv1.4 (KCNA4), which is an A-type potassium channel. Delayed rectifiers are slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics, they play an important role in controlling action potential duration. A-type channels are fast/rapidly inactivating potassium channels. Kv1/KCNA subfamily alpha subunits form functional homo- or hetero-tetrameric channels (with other Kv1/KCNA alpha subunits) through their BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 46195444   5 DLVTLNVGGRIFTTRPSTLKQFPASrLAGMLDGRDQEFKTVDGQIFVDRDGALFSFIL 62
Cdd:cd18377   1 ERVVINVSGLRFETQLKTLAQFPNT-LLGDPNKRMRFFDPLRNEYFFDRNRPSFDAIL 57