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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRT--KELDPRGVHGSSLLHEA 98
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLELECDDYDDDTNEYFFDRSPKHFETILNFYRTggKLHRPEEVCLDEFLEEA 80

                  ....*...
gi 1039777626  99 QFYGLTPL 106
Cdd:pfam02214  81 EFYGLDEL 88

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 1039777626  18 GEVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELDPRGVHGSSLLHE 97
Cdd:cd18363     1 GDIINLNVGGKRFSTSRQTLTWIPDSFFTSLLSGRISSLKDETGAIFIDRDPKLFSIILNYLRTKEIDLRNVDISSLRHE 80

                  ....*.
gi 1039777626  98 AQFYGL 103
Cdd:cd18363    81 AEFYGI 86

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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELD--PRGVHGSSLLHEA 98
Cdd:cd18316     1 VKLNVGGTLFTTSRSTLLKDPDSLLAALFSGRWPLPRDEDGSIFIDRDPELFRHILNFLRTGKLPlpSDFVELEELLAEA 80

                  ...
gi 1039777626  99 QFY 101
Cdd:cd18316    81 EFY 83

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Arabidopsis thaliana FH protein interacting protein FIP2 and similar proteins; FIP2 may act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. 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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLR---TKELDPRGVHGSSLLHE 97
Cdd:cd18376     1 VKLNVGGQKFTTTLDTLTKDPDSMLAAMFSGRHSLKKDEDGSYFIDRDGTHFRHILNYLRdgeVKIPTEDRSVLKELLEE 80

                  ....*....
gi 1039777626  98 AQFYGLTPL 106
Cdd:cd18376    81 AEYYQLRGL 89

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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSSLL-HEA 98
Cdd:cd18395     3 ITLNVGGKLYTTSLATLTRYPDSMLGAMFSGKFPTKKDSQGNCFIDRDGKIFRYILNFLRTSHLDlPEDFQEMGLLkREA 82

                          90
                  ....*....|....*.
gi 1039777626  99 QFYGLTPLVRRLQVRE 114
Cdd:cd18395    83 DFYQIQPLIEALQEKE 98

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 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELDPRGVhGSSLLHEA 98
Cdd:cd18366     4 EVVPLNVGGMHFTTRLSTLRKYEDSMLAAMFSGRHHIPKDSEGRYFIDRDGSYFGYILNFLRDGDLPPRER-ARAVYKEA 82

                  ....*....
gi 1039777626  99 QFYGLTPLV 107
Cdd:cd18366    83 QYYGIGPLI 91

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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGR-ISTLKDETGAIFIDRDPTVFAPILNFLR------TKELDPRGVhgss 93
Cdd:cd18391     3 VRLNVGGTVFLTTRQTLCREQKSFLSRLCQGEeLQSDRDETGAYLIDRDPTYFGPILNFLRhgklvlDKDMAEEGV---- 78

                          90       100
                  ....*....|....*....|..
gi 1039777626  94 lLHEAQFYGLTPLVRRLQVREE 115
Cdd:cd18391    79 -LEEAEFYNIGPLIRIIKDRME 99

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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLS-GRISTLKDETGAIFIDRDPTVFAPILNFLRT-KELDPRGVHGSSLLHEA 98
Cdd:cd18187     1 VVLNVSGTRFVTNRQTLTRHPDTLLGRMFKpGREFTFPNETGEYFIDRDPTVFRTILNYYRTgKLNCPDGISIPDLREEC 80

                  ...
gi 1039777626  99 QFY 101
Cdd:cd18187    81 DFY 83

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 5 (KCTD5); KCTD5 is a BTB/POZ domain-containing protein that functions as a substrate adaptor for cullin3 based ubiquitin E3 ligases. It 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. 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 forms pentamers mediated by its BTB domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGR--ISTLKDETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSSLLHE 97
Cdd:cd18390     7 VRLNVGGTYFLTTRQTLCRDPKSFLYRLCQADpdLDSDKDETGAYLIDRDPTYFGPVLNYLRHGKLViNKDLAEEGVLEE 86

                          90       100
                  ....*....|....*....|....*
gi 1039777626  98 AQFYGLTPLVRRLQ--VREELDRSS 120
Cdd:cd18390    87 AEFYNITSLIKLVKdkIRERDSKTS 111

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 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSG--RISTLKDETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSS-L 94
Cdd:cd18367     3 EIVELNVGGQVYTTSLSTLIKDPDSLLGRMFSGknRQELARDSKGRYFLDRDGVLFRYILDYLRNQKLVlPENFPERErL 82

                          90
                  ....*....|....*..
gi 1039777626  95 LHEAQFYGLTPLVRRLQ 111
Cdd:cd18367    83 KREAEYFQLPELVKALR 99

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 1039777626   23 LNVGGKRFSTSRQTLTWIPDsFFSSLLSGRIStLKDETGAIFIDRDPTVFAPILNFLRTKELDPRGVHGSSLLHEAQFYG 102
Cdd:smart00225   4 LVVGGKKFHAHKAVLAAHSP-YFKALFSSDFK-ESDKSEIYLDDVSPEDFRALLNFLYTGKLDLPEENVEELLELADYLQ 81

                   ....*.
gi 1039777626  103 LTPLVR 108
Cdd:smart00225  82 IPGLVE 87

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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLkDETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSSLLHEAQ 99
Cdd:cd18317     1 VVLNVGGTRFELSRSTLLRFPDTRLGKLAKESHAYD-ESTNEYFFDRNPEVFEAILDYYRTGELHlPSNVCPASFKEELE 79

                  ...
gi 1039777626 100 FYG 102
Cdd:cd18317    80 FWG 82

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3); KCND3, also called voltage-gated potassium channel subunit Kv4.3, is a pore-forming subunit of voltage-gated rapidly inactivating A-type potassium channels. Mutations in KCND3 cause spinocerebellar ataxia. 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. KCND3 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777626   2 AVATTAVEGVPSRGAPG-------EVIHLNVGGKRFSTSRQTLTWIPDSFFSSllSGRISTLKDETGAIFIDRDPTVFAP 74
Cdd:cd18419    11 AIGWMPVANCPMPLAPAdknkrqdELIVLNVSGRRFQTWRTTLERYPDTLLGS--TEKEFFFNEDTKEYFFDRDPEVFRC 88

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1039777626  75 ILNFLRTKELD-PRGVHGSSLLHEAQFYGLTP 105
Cdd:cd18419    89 VLNFYRTGKLHyPRYECISAYDEELAFYGILP 120

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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGA-IFIDRDPTVFAPILNFLRT-KELDPRGVHGSSLLH-E 97
Cdd:cd18388     4 VHIDVGGHMYTSSLATLTKYPDSRISRLFNGTEPIVLDSLKQhYFIDRDGEIFRYILSFLRTsKLLLPEDFKDFNLLYeE 83

                          90
                  ....*....|....
gi 1039777626  98 AQFYGLTPLVRRLQ 111
Cdd:cd18388    84 AKYYQLQPMVKELE 97

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 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSG----RISTLKDETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSSLL 95
Cdd:cd18370     1 VTLNVGGTLYSTTLETLTRFPDSMLGAMFRAgtpiPPNLNMQGGGHYFIDRDGKAFRHILNFLRLGRLDlPRGYGETALL 80

                  ....*..
gi 1039777626  96 H-EAQFY 101
Cdd:cd18370    81 RaEADFY 87

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSllSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSSLLHE 97
Cdd:cd18417    35 EILVVNVSGRRFQTWKNTLDRYPDTLLGS--SEKEFFYNEDTQEYFFDRDPEMFRHILNFYRTGRLHyPRHECIQAFDEE 112

                  ....*...
gi 1039777626  98 AQFYGLTP 105
Cdd:cd18417   113 LSFYGIIP 120

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 1039777626  21 IHLNVGGKRFSTSRQTLTwIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLR---------TKELdprgvhg 91
Cdd:cd18369     1 VKLNVGGSLHYTTIGTLT-KQDTMLRAMFSGRMEVLTDSEGWILIDRCGKHFGTILNYLRdgsvplpesRREL------- 72

                          90
                  ....*....|....*.
gi 1039777626  92 SSLLHEAQFYGLTPLV 107
Cdd:cd18369    73 AELLAEAKYYLVQGLV 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 18 (KCTD18); KCTD18 is a BTB/POZ domain-containing protein with with unknown biological function. A duplication of the KCTD18 gene has been found in a patient with epilepsy, developmental delay, and autistic behavior, which may contribute to the phenotype. 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. 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 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELDPR-GVHGSSLLHE 97
Cdd:cd18372     1 DVLRLNVGGCIYTARRESLCRFKDSMLSSMFSGRFPLKLDESGACVIDRDGRLFKYLLDYLHGELQIPEdEQTRLALQEE 80

                  ....*.
gi 1039777626  98 AQFYGL 103
Cdd:cd18372    81 ADYFGI 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTL----KDETGAIFIDRDPTVFAPILNFLRTKE--LDPRGVHGS 92
Cdd:cd18398     3 EVVELNVGGQVYFTRHATLVSIPHSLLWKMFSPKRDTAndlaKDSKGRFFIDRDGFLFRYILDYLRDRQvvLPDHFPEKG 82

                          90
                  ....*....|....*...
gi 1039777626  93 SLLHEAQFYGLTPLVRRL 110
Cdd:cd18398    83 RLKREAEYFQLPDLVKLL 100

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 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSllSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSSLLHE 97
Cdd:cd18420    36 EKLIINVSGRRFETWRNTLEKYPDTLLGS--NEREFFYDEETKEYFFDRDPDIFRHILNYYRTGKLHyPKHECLTAYDEE 113

                  ....*...
gi 1039777626  98 AQFYGLTP 105
Cdd:cd18420   114 LAFFGIMP 121

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGA-IFIDRDPTVFAPILNFLRT-KELDPRGVHGSSLLH-E 97
Cdd:cd18387     5 VHIDVGGHMYTSSLATLTKYPESRIGRLFDGTEPIVLDSLKQhYFIDRDGQMFRYILNFLRTsKLLIPDDFKDYSLLYeE 84

                          90
                  ....*....|....
gi 1039777626  98 AQFYGLTPLVRRLQ 111
Cdd:cd18387    85 AKYFQLQPMLLELE 98

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 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKD---ETGAIFIDRDPTVFAPILNFLRTKELD-PRGVHGSSL 94
Cdd:cd18414     3 DRIVINVGGTRHETYRSTLRTLPGTRLAWLAEPDAHSNFDydpRADEFFFDRHPGVFAHILNYYRTGKLHcPADVCGPLY 82

                  ....*....
gi 1039777626  95 LHEAQFYGL 103
Cdd:cd18414    83 EEELAFWGI 91

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 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDS----FFSSLLSGRISTLKDETGA----------IFIDRDPTVFAPILNFLRTKEL 84
Cdd:cd18415     2 ERIILNVGGTRHETYRSTLKTLPGTrlalLASSDPQGDCLTQCSQVGGsdgspgggneFFFDRHPGVFAYVLNYYRTGKL 81

                          90       100
                  ....*....|....*....|
gi 1039777626  85 D-PRGVHGSSLLHEAQFYGL 103
Cdd:cd18415    82 HcPADVCGPLFEEELAFWGI 101

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily V member 2 (KCNV2); KCNV2, also called voltage-gated potassium channel subunit Kv8.2, is a modulatory voltage-gated potassium channel alpha subunit that modulates channel activity by shifting the threshold and the half-maximal activation to more negative values. KCNV2 is essential for visual function and cone survival. 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. KCNV2 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777626  21 IHLNVGGKRFSTSRQTLTWIPDSFFssllsGRISTLKD-------------ETGAIFIDRDPTVFAPILNFLRT------ 81
Cdd:cd18425     1 LNINVGGTSYQISYRVAASYPKTRI-----GRLATYTDrsrkldlcddynvQNDEYFFDRDPAVFHHIYNFYRTgvlwvk 75

                          90       100
                  ....*....|....*....|..
gi 1039777626  82 KELDPRgvhgsSLLHEAQFYGL 103
Cdd:cd18425    76 DELCPR-----NFLEEINYWGV 92

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039777626  19 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGR----ISTLKDETGAI----FIDRDPTVFAPILNFLRTKEL 84
Cdd:cd18428     1 ELINLNVGGFKQSVDQSTLLRFPHTRLGKLLNCHseeaILELCDDYSVAdkeyYFDRNPSLFRYVLNFYYTGKL 74

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039777626  23 LNVGGKRFSTSRQTLTWIPDSFFSSLLSGR----ISTLKD----ETGAIFIDRDPTVFAPILNFLRTKEL 84
Cdd:cd18382     3 INVGGARYSLPWSTLDRFPLTRLSRLKACRseddILRVCDdydvERNEFFFDRSPEAFGVILLFLRAGKL 72