Ion transport protein; This family contains sodium, potassium and calcium ion channels. This family is 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms as a tetramer in the membrane.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068   219 ARIIAFISIAVIALSIISFCWETVPsdieekpinnsataelldEMDEKHYSPFFWIELMCILWFTIELILRFISCPCKVT 298
Cdd:pfam00520   1 SRYFELFILLLILLNTIFLALETYF------------------QPEEPLTTVLEILDYVFTGIFTLEMLLKIIAAGFKKR 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068   299 FATSVLNIIDFVAIAPFFVNFFfadtskSNSSMSFAVLRVLRLVRVFRVFKLSRHSVGLQILGKTFRSSVQEFCLLIFFM 378
Cdd:pfam00520  63 YFRSPWNILDFVVVLPSLISLV------LSSVGSLSGLRVLRLLRLLRLLRLIRRLEGLRTLVNSLIRSLKSLGNLLLLL 136

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068   379 AIALVLFASGMY---------FAEQGEPNSKFTSIPASFWFVLVTMTTVGYGDLVPLSPFGKVVGGMCAM-------IGV 442
Cdd:pfam00520 137 LLFLFIFAIIGYqlfggklktWENPDNGRTNFDNFPNAFLWLFQTMTTEGWGDIMYDTIDGKGEFWAYIYfvsfiilGGF 216

                         250       260
                  ....*....|....*....|..
gi 32564068   443 LTLALPVPIIVANFKHFYRQEN 464
Cdd:pfam00520 217 LLLNLFIAVIIDNFQELTERTE 238

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 32564068    92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKR-QHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKEM 170
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLELeCDDYDDDTNEYFFDRSPKHFETILNFYRTGGKLHRPEEVCLDEFLEEA 80

                          90
                  ....*....|...
gi 32564068   171 RFFQMGDDLLEEF 183
Cdd:pfam02214  81 EFYGLDELALELC 93

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 32564068     92 VTINVSGMRFQTFESTLSRYPNSLLgDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSgGRVKRPEiVPIDIFLKEMR 171
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFK-ALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYT-GKLDLPE-ENVEELLELAD 78

                           90
                   ....*....|....
gi 32564068    172 FFQMGD--DLLEEF 183
Cdd:smart00225  79 YLQIPGlvELCEEF 92

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily A member 6 (KCNA6); KCNA6, also called voltage-gated potassium channel HBK2 or voltage-gated potassium channel subunit Kv1.6, 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. KCNA6 is distributed primarily in neurons of central and peripheral nervous systems. 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. KCNA6 is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other Kv1/KCNA 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKEMR 171
Cdd:cd18407   3 LVINISGLRFETQLRTLSIFPDTLLGDPSRRVRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVHVPLDIFLEEIR 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 32564068 172 FFQMGDDLLEEFWIAEGYEKPKEVMMPNNKTQRKIWELMEYPDSS 216
Cdd:cd18407  83 FYQLGQEAIETFREDEGFIPEEEKPLPSHHFQRQVWLLFEYPESS 127

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily A member 7 (KCNA7); KCNA7, also called voltage-gated potassium channel subunit Kv1.7, 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. KCNA7 plays an important role in the repolarization of cell 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. KCNA7 is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other Kv1/KCNA 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKEMR 171
Cdd:cd18408   8 VVLNVAGLRFETRARTLGRFPDTLLGDPARRGRFYDDRRREYFFDRHRPSFDAVLYYYQSGGRLRRPAHVPLDVFLEEVA 87

                        90       100
                ....*....|....*....|....*..
gi 32564068 172 FFQMGDDLLEEFWIAEGYEKPKEVMMP 198
Cdd:cd18408  88 FYGLGAAALARLREDEGCPVPPERPLP 114

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster potassium voltage-gated channel protein Shaker and similar proteins; Shaker, also termed protein minisleep, represents a family of putative potassium channel proteins in the nervous system of Drosophila. It is a voltage-gated potassium channel that 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. Shaker plays a role in the regulation of sleep need or efficiency. 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. Shaker 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKEMR 171
Cdd:cd18410   3 VVINVSGLRFETQLKTLNQFPDTLLGDPQRRNRYYDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDVFSEEIK 82

                        90
                ....*....|....*...
gi 32564068 172 FFQMGDDLLEEFWIAEGY 189
Cdd:cd18410  83 FYELGENAFEKYREDEGF 100

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily A member 10 (KCNA10); KCNA10, also called voltage-gated potassium channel subunit Kv1.8, is a cyclic nucleotide-gated, voltage-activated potassium channel that 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. KCNA10 is expressed in proximal tubular cells, glomerular and vascular endothelial cells, as well as in vascular smooth muscle cells. It may facilitate proximal tubular sodium absorption by stabilizing cell membrane voltage. The channel activity is up-regulated by cAMP. 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. KCNA10 is an alpha subunit that forms functional homotetrameric channels 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 32564068  90 QIVTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKE 169
Cdd:cd18409   1 QKVIINIAGLRFETQLKTLDQFPDTLLGDPEKRMKYFDSMRNEYFFDRNRPSFDGILYYYQSGGKIRRPANVPLDVFADE 80

                ....*..
gi 32564068 170 MRFFQMG 176
Cdd:cd18409  81 IIFYELG 87

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily A member 4 (KCNA4); KCNA4 is also called HPCN2, or voltage-gated K(+) channel HuKII, voltage-gated potassium channel HBK4, voltage-gated potassium channel HK1, or voltage-gated potassium channel subunit Kv1.4. 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. KCNA4 is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other Kv1/KCNA 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKEMR 171
Cdd:cd18405   3 VVINVSGLRFETQLKTLAQFPETLLGDPEKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLKRPVNVPFDIFSEEVK 82

                        90
                ....*....|..
gi 32564068 172 FFQMGDDLLEEF 183
Cdd:cd18405  83 FYELGEEALLKF 94

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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNK--RQHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVkRPEIVPIDIFLKE 169
Cdd:cd18187   1 VVLNVSGTRFVTNRQTLTRHPDTLLGRMFKpgREFTFPNETGEYFIDRDPTVFRTILNYYRTGKLN-CPDGISIPDLREE 79

                ....
gi 32564068 170 MRFF 173
Cdd:cd18187  80 CDFY 83

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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSgGRVKRPEIVPIDIFLKEMR 171
Cdd:cd18317   1 VVLNVGGTRFELSRSTLLRFPDTRLGKLAKESHAYDESTNEYFFDRNPEVFEAILDYYRT-GELHLPSNVCPASFKEELE 79

                .
gi 32564068 172 F 172
Cdd:cd18317  80 F 80

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDrNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSgGRVKRPEIVPIDIFLKEMR 171
Cdd:cd18380   2 IVINVSGRRFETWKNTLEKYPDTLLGS-TEKEFFYDDDTKEYFFDRDPEIFRHILNFYRT-GKLHYPRHECISAYDDELA 79

                ....*....
gi 32564068 172 FFQMGDDLL 180
Cdd:cd18380  80 FFGILPEII 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068  89 DQIVTINVSGMRFQTFESTLSRYPNSLLGDrNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSgGRVKRPEIVPIDIFLK 168
Cdd:cd18420  35 DEKLIINVSGRRFETWRNTLEKYPDTLLGS-NEREFFYDEETKEYFFDRDPDIFRHILNYYRT-GKLHYPKHECLTAYDE 112

                        90
                ....*....|..
gi 32564068 169 EMRFFQMGDDLL 180
Cdd:cd18420 113 ELAFFGIMPDII 124

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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGD-RNKRQHF--------FVSDTNEFFFDRHRTTFESILYIYQSG 152
Cdd:cd18378   4 VLLNVGGVRHEVLWRTLDRLPRTRLGRlRECNTHEsllelcddYDLEDNEYFFDRHPGAFTSILNFYRTG 73

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 32564068     92 VTINVSGMRFQTFESTLSRYPNSLLgDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSgGRVKRPEiVPIDIFLKEMR 171
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFK-ALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYT-GKLDLPE-ENVEELLELAD 78

                           90
                   ....*....|....
gi 32564068    172 FFQMGD--DLLEEF 183
Cdd:smart00225  79 YLQIPGlvELCEEF 92

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in KCNC/Kv3 subfamily of Shaw-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 four alpha subunit members, Kv3.1 (KCNC1), Kv3.2 (KCNC2), Kv3.3 (KCNC3), and Kv3.4 (KCNC4), which are orthologs of the Shaw gene in Drosophila. Unlike other Kv subfamilies, Kv3 channels typically open only at positive potentials and both, activation and deactivation, in response to changes in voltage are very rapid. They are uniquely associated with the ability of certain neurons to fire action potentials and to release neurotransmitter at high rates of up to 1,000 Hz. Kv3/KCNC 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32564068  92 VTINVSGMRFQTFESTLSRYPN---SLLGDRNKRQHFFVSDTNEFFFDRHRTTFESILYIYQSG 152
Cdd:cd18379   1 IVINVGGVRHETYKSTLRNLPDtrlAWLTETEASAFDYDPVTGEFFFDRHPGVFAQILNYYRTG 64

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068  88 TDQIVtINVSGMRFQTFESTLSRYPN---SLLGDRNKRQHF-FVSDTNEFFFDRHRTTFESILYIYQSgGRVKRPEIVPI 163
Cdd:cd18414   2 SDRIV-INVGGTRHETYRSTLRTLPGtrlAWLAEPDAHSNFdYDPRADEFFFDRHPGVFAHILNYYRT-GKLHCPADVCG 79

                        90
                ....*....|
gi 32564068 164 DIFLKEMRFF 173
Cdd:cd18414  80 PLYEEELAFW 89

voltage-gated potassium channel protein;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 32564068  381 ALVLFASGMYFAEQG------EPNSKFTSIPASFWFVLVTMTTVGYGDLVPLSP 428
Cdd:PRK10537 140 AVISITSLLFYSTFGalylgdGFSPPIESLSTAFYFSIVTMSTVGYGDIVPVSE 193

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 4 (KCTD4); KCTD4 is a BTB/POZ domain-containing protein with an unknown biological function. 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 32564068  91 IVTINVSGMRFQTFESTLSRYPNSLLGDR-NKRQHFFVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKE 169
Cdd:cd18364   1 LVTLNVGGYLYITQRQTLTKYPDSFLEGMvNGKIQCTVDADGNYFIDRDGLLFRHVLNFLRNGELLLPEGFQENQLLALE 80

                ....*.
gi 32564068 170 MRFFQM 175
Cdd:cd18364  81 ADFYQL 86

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 32564068  91 IVTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTN-EFFFDRHRTTFESILYIYQSGGRVKRPEIVPIdifLKE 169
Cdd:cd18366   5 VVPLNVGGMHFTTRLSTLRKYEDSMLAAMFSGRHHIPKDSEgRYFIDRDGSYFGYILNFLRDGDLPPRERARAV---YKE 81

                        90
                ....*....|..
gi 32564068 170 MRFFQMGdDLLE 181
Cdd:cd18366  82 AQYYGIG-PLIE 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 32564068  90 QIVTINVSGMRFQTFESTLSRYPNSLLGD--RNKRQHFFVSDtNEFFFDRHRTTFESIL 146
Cdd:cd18375   1 ELVTLNVGGKKFTTRPSTLRRFPDSRLARmlDGKDQDFKVVN-GQFFVDRDGSLFSYIL 58

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily B member 1 (KCNB1); KCNB1, also called delayed rectifier potassium channel 1 (DRK1) or voltage-gated potassium channel subunit Kv2.1, mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. 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. KCNB1 is involved in the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout 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. KCNB1 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGD-RNKRQHF--------FVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVP 162
Cdd:cd18411  12 VKLNVGGLAHEVLWRTLDRLPRTRLGKlRDCNTHEslmeicddYNLEENEYFFDRHPGAFTSILNFYRTGKLHMMEEMCA 91

                        90
                ....*....|....*....
gi 32564068 163 IDiFLKEMRFFQMGDDLLE 181
Cdd:cd18411  92 LS-FSQELDYWGIDEIYLE 109

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGD----RNKRQHFFVSD-----TNEFFFDRHRTTFESILYIYQSGGRVKRPEIVP 162
Cdd:cd18382   1 VIINVGGARYSLPWSTLDRFPLTRLSRlkacRSEDDILRVCDdydveRNEFFFDRSPEAFGVILLFLRAGKLRLLREMCA 80

                        90
                ....*....|....*....
gi 32564068 163 IDiFLKEMRFFQMGDDLLE 181
Cdd:cd18382  81 LS-FQEELAYWGIEEAHLE 98

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily S member 1 (KCNS1); KCNS1, also called delayed-rectifier K(+) channel alpha subunit 1 or voltage-gated potassium channel subunit Kv9.1, is a modulatory alpha subunit of voltage-gated potassium channel that mediates neuropathic pain following nerve injury. It 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. 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. KCNS1 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGD----RNKRQHFFVSD-----TNEFFFDRHRTTFESILYIYQSG 152
Cdd:cd18426   1 ININVGGLKRRLSSSTLSKFPDTRLGRllscDSEESILQICDdydvsAKEFYFDRNPGLFPYVLHFYQTG 70

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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTN-EFFFDRHRTTFESILYIYQSGGRVKRPEIVPIDIFLKEM 170
Cdd:cd18395   3 ITLNVGGKLYTTSLATLTRYPDSMLGAMFSGKFPTKKDSQgNCFIDRDGKIFRYILNFLRTSHLDLPEDFQEMGLLKREA 82

                ....*
gi 32564068 171 RFFQM 175
Cdd:cd18395  83 DFYQI 87

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily S member 2 (KCNS2); KCNS2, also called delayed-rectifier K(+) channel alpha subunit 2 or voltage-gated potassium channel subunit Kv9.2, is a modulatory alpha subunit of voltage-gated potassium channel 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. 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. KCNS2 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGD----RNKRQHFFVSD-----TNEFFFDRHRTTFESILYIYQSG 152
Cdd:cd18427   2 ISINVGGFKKRLRSHTLLRFPETRLGRllscRSKESILELCDdyddtKNEFYFDRNPELFPYVLHFYNTG 71

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily G members, KCNG1 and KCNG2; KCNG1, also called voltage-gated potassium channel subunit Kv6.1 or kH2, functions as a regulatory alpha-subunit of voltage-gated potassium channel that 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 or voltage-gated potassium channel subunit Kv6.2, is a new gamma-subunit of voltage-gated potassium channels that 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. 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. KCNG1 and KCNG2 are regulatory alpha subunits and do not form homomultimers. They form heteromultimers (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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHF---------FVSDTNEFFFDRHRTTFESILYIYQSG 152
Cdd:cd18421   6 VIINVGGIKYRIPWTTLEEFPLTRLGQLKSCNNFdeimdicddYDVTCNEFFFDRNPCAFRTILTFLRAG 75

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily G member 4 (KCNG4); KCNG4, also called voltage-gated potassium channel subunit Kv6.4, is a silent voltage-gated potassium (KvS) channel subunit that 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. KCNG4 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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHF---------FVSDTNEFFFDRHRTTFESILYIYQSGGRVKRPEIVP 162
Cdd:cd18423   4 IIINVGGIKYLMPWSTLDEFPLTRLGKLKFCSSYeeivqicddYDEDTNEFFFDRNPCAFRMIVSFLAAGKLRLLREMCA 83

                        90
                ....*....|....*....
gi 32564068 163 IDiFLKEMRFFQMGDDLLE 181
Cdd:cd18423  84 LS-FQEELTYWGIEEANLE 101

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 32564068  92 VTINVSGMRFQTFESTLSRYPNSLLGDRNKRQHFFVSDTNE---FFFDRHRTTFESILYIYQSGGRVKRPEIvPIDIFLK 168
Cdd:cd18362   2 VKLNVGGTYFLTTRTTLCRDPKSFLCRLCQEDPDLPSDKDEtgaYLIDRDPTYFGPILNYLRHGKLIIDKDL-AEEGVLE 80

                ....*
gi 32564068 169 EMRFF 173
Cdd:cd18362  81 EAEFY 85