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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  18 EIRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELC 97
Cdd:cd18427   1 EISINVGGFKKRLRSHTLLRFPETRLGRLLSCRSKESILELCDDYDDTKNEFYFDRNPELFPYVLHFYNTGKLHVMGELC 80

                        90       100
                ....*....|....*....|....*..
gi 31044453  98 VFSFSQEIEYWGINEFFIDSCCSYSYH 124
Cdd:cd18427  81 VFSFSQEIEYWGINEFFIDSCCSYSYH 107

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  18 EIRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELC 97
Cdd:cd18427   1 EISINVGGFKKRLRSHTLLRFPETRLGRLLSCRSKESILELCDDYDDTKNEFYFDRNPELFPYVLHFYNTGKLHVMGELC 80

                        90       100
                ....*....|....*....|....*..
gi 31044453  98 VFSFSQEIEYWGINEFFIDSCCSYSYH 124
Cdd:cd18427  81 VFSFSQEIEYWGINEFFIDSCCSYSYH 107

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 31044453    19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHsreailelCDDYDDVQREFYFDRNPELFPYVLHFYHT-GKLHVMAELC 97
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLELE--------CDDYDDDTNEYFFDRSPKHFETILNFYRTgGKLHRPEEVC 72

                          90       100
                  ....*....|....*....|.
gi 31044453    98 VFSFSQEIEYWGINEFFIDSC 118
Cdd:pfam02214  73 LDEFLEEAEFYGLDELALELC 93

voltage-gated potassium channel protein;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  240 FELVARFAVAPDFLKFFKNALNLIDLMSI--VPFYITLVVNLVVesSPTLANLGRVAQVLRLMRIFRILKLARHSTGlrS 317
Cdd:PRK10537  31 LKPVYGMAALNLFDIWHIKALSALDLSLLanAPQFMLGVFLVLM--AIGLLFRARLAWAISILLLLAALAITLHFYP--W 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  318 LGATLKYSYKEVGLLLLY--------LSVG-----ISIFSVVAYTI------EKEENEGLATIPACWWWATVSMTTVGYG 378
Cdd:PRK10537 107 LKFLIGYCIVLLVALLIYrrdfdrssLAAGtlfavISITSLLFYSTfgalylGDGFSPPIESLSTAFYFSIVTMSTVGYG 186

                        170       180       190
                 ....*....|....*....|....*....|..
gi 31044453  379 DVVPGTTAGKLTASACILAGILVVVLPITLIF 410
Cdd:PRK10537 187 DIVPVSESARLFTISVIILGITVFATSISAIF 218

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  18 EIRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELC 97
Cdd:cd18427   1 EISINVGGFKKRLRSHTLLRFPETRLGRLLSCRSKESILELCDDYDDTKNEFYFDRNPELFPYVLHFYNTGKLHVMGELC 80

                        90       100
                ....*....|....*....|....*..
gi 31044453  98 VFSFSQEIEYWGINEFFIDSCCSYSYH 124
Cdd:cd18427  81 VFSFSQEIEYWGINEFFIDSCCSYSYH 107

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18426   1 ININVGGLKRRLSSSTLSKFPDTRLGRLLSCDSEESILQICDDYDVSAKEFYFDRNPGLFPYVLHFYQTGKLHIMEELCV 80

                        90       100
                ....*....|....*....|....*.
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYH 124
Cdd:cd18426  81 FSFSQEIEYWGINEFFLDSCCSYRYH 106

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18378   4 VLLNVGGVRHEVLWRTLDRLPRTRLGRLRECNTHESLLELCDDYDLEDNEYFFDRHPGAFTSILNFYRTGKLHMPEEMCV 83

                        90       100
                ....*....|....*....|....*.
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYH 124
Cdd:cd18378  84 LSFSQELEYWGIDEIYLESCCQHRYH 109

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster potassium voltage-gated channel protein Shab and similar proteins; Shab is a slow delayed rectifier 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. Shab 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 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18413   4 VVINVGGVKHEVLWRTLDRMPHTRLGKLRDSNTHEAIVELCDDYSLADNEYFFDRHPRSFASILNFYRTGKLHLVEEMCV 83

                        90       100
                ....*....|....*....|....*.
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYH 124
Cdd:cd18413  84 LAFSDDLEYWGVDELYLESCCQHKYH 109

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily B member 2 (KCNB2); KCNB2, also called voltage-gated potassium channel subunit Kv2.2, mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. 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. KCNB2 contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells. 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. KCNB2 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 31044453   8 DVSDTDVEDGEIRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHT 87
Cdd:cd18412   8 EIIRSKACSRRVKINVGGLNHEVLWRTLDRLPRTRLGKLRDCNTHESLLEVCDDYNLNENEYFFDRHPGAFTSILNFYRT 87

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 31044453  88 GKLHVMAELCVFSFSQEIEYWGINEFFIDSCCSYSYHGRK 127
Cdd:cd18412  88 GKLHMMEEMCALSFGQELDYWGIDEIYLESCCQARYHQKK 127

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 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18411  12 VKLNVGGLAHEVLWRTLDRLPRTRLGKLRDCNTHESLMEICDDYNLEENEYFFDRHPGAFTSILNFYRTGKLHMMEEMCA 91

                        90       100
                ....*....|....*....|....*.
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYH 124
Cdd:cd18411  92 LSFSQELDYWGIDEIYLESCCQARYH 117

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 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18382   1 VIINVGGARYSLPWSTLDRFPLTRLSRLKACRSEDDILRVCDDYDVERNEFFFDRSPEAFGVILLFLRAGKLRLLREMCA 80

                        90       100
                ....*....|....*....|....*...
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYHGR 126
Cdd:cd18382  81 LSFQEELAYWGIEEAHLERCCKRRLLRR 108

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  21 INVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILELCDDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCVFS 100
Cdd:cd18421   8 INVGGIKYRIPWTTLEEFPLTRLGQLKSCNNFDEIMDICDDYDVTCNEFFFDRNPCAFRTILTFLRAGKLRLLREMCALS 87

                        90       100
                ....*....|....*....|...
gi 31044453 101 FSQEIEYWGINEFFIDSCCSYSY 123
Cdd:cd18421  88 FQEELLYWGIEEENLEWCCRRRL 110

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAilelcdDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18379   1 IVINVGGVRHETYKSTLRNLPDTRLAWLTETEASAF------DYDPVTGEFFFDRHPGVFAQILNYYRTGKLHCPADVCG 74

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYhgRKVEPEQEKW 135
Cdd:cd18379  75 PLFEEELAFWGIDETQIEPCCWMTY--RQHRDAQETL 109

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 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRlllcHSREAIlelcddYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18380   2 IVINVSGRRFETWKNTLEKYPDTLLGS----TEKEFF------YDDDTKEYFFDRDPEIFRHILNFYRTGKLHYPRHECI 71

                        90       100       110
                ....*....|....*....|....*....|.
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYHGRKVE 129
Cdd:cd18380  72 SAYDDELAFFGILPEIIGDCCYEDYRDRKRE 102

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  15 EDGEIRINVGGFKRRLRSHTLLRFPETRLGRLLlchSREAILELcdDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMA 94
Cdd:cd18414   1 ESDRIVINVGGTRHETYRSTLRTLPGTRLAWLA---EPDAHSNF--DYDPRADEFFFDRHPGVFAHILNYYRTGKLHCPA 75

                        90       100
                ....*....|....*....|....*....
gi 31044453  95 ELCVFSFSQEIEYWGINEFFIDSCCSYSY 123
Cdd:cd18414  76 DVCGPLYEEELAFWGIDETDVEPCCWMTY 104

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 31044453  15 EDGEIRINVGGFKRRLRSHTLLRFPETRLGRlllcHSREAIlelcddYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMA 94
Cdd:cd18420  34 DDEKLIINVSGRRFETWRNTLEKYPDTLLGS----NEREFF------YDEETKEYFFDRDPDIFRHILNYYRTGKLHYPK 103

                        90       100       110
                ....*....|....*....|....*....|....*
gi 31044453  95 ELCVFSFSQEIEYWGINEFFIDSCCSYSYHGRKVE 129
Cdd:cd18420 104 HECLTAYDEELAFFGIMPDIIGDCCYEDYRDRKRE 138

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 31044453  21 INVGGFKRRLRSHTLLRFPETRLGRlllchSREAILelcddYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCVFS 100
Cdd:cd18417  39 VNVSGRRFQTWKNTLDRYPDTLLGS-----SEKEFF-----YNEDTQEYFFDRDPEMFRHILNFYRTGRLHYPRHECIQA 108

                        90       100
                ....*....|....*....|....*....
gi 31044453 101 FSQEIEYWGINEFFIDSCCSYSYHGRKVE 129
Cdd:cd18417 109 FDEELSFYGIIPEIIGDCCLEEYRDRKKE 137

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRlllcHSREAIlelcddYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18418   2 IVLNVSGTRFQTWRNTLERYPDTLLGS----SERDFF------YHEETQEYFFDRDPDIFRHILNFYRTGKLHYPRHECI 71

                        90       100       110
                ....*....|....*....|....*....|.
gi 31044453  99 FSFSQEIEYWGINEFFIDSCCSYSYHGRKVE 129
Cdd:cd18418  72 SAYDEELAFFGIIPEIIGDCCYEEYKDRRRE 102

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAilelcddyDDVQREFYFDRNPELFPYVLHFYHTGKLHV 92
Cdd:cd18316   1 VKLNVGGTLFTTSRSTLLKDPDSLLAALFSGRWPLP--------RDEDGSIFIDRDPELFRHILNFLRTGKLPL 66

Ion channel; This family includes the two membrane helix type ion channels found in bacteria.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31044453   336 LSVGISIFSVVAYTIEkeeNEGLATIPACWWWATVSMTTVGYGDVVPGTTAGKLTASACILAGILVVVLPITLIFNKFS 414
Cdd:pfam07885   2 VLLLVLIFGTVYYLLE---EGWEWSFLDALYFSFVTLTTVGYGDIVPLTDAGRLFTIFYILIGIPLFAIFLAVLGRFLT 77

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 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSReailelcdDYDDVQREFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18375   3 VTLNVGGKKFTTRPSTLRRFPDSRLARMLDGKDQ--------DFKVVNGQFFVDRDGSLFSYILDYLRTGQLTLPTEFSD 74

                        90
                ....*....|...
gi 31044453  99 FS-FSQEIEYWGI 110
Cdd:cd18375  75 YNrLAREAEFYGL 87

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 31044453  21 INVGGFKRRLRSHTLLRFPETRLG----RLLLchsreailelcddYDDVQREFYFDRNPELFPYVLHFYHT-GKLHVMAE 95
Cdd:cd18410   5 INVSGLRFETQLKTLNQFPDTLLGdpqrRNRY-------------YDPLRNEYFFDRNRPSFDAILYYYQSgGRLRRPVN 71

                        90
                ....*....|....*..
gi 31044453  96 LCVFSFSQEIEYWGINE 112
Cdd:cd18410  72 VPLDVFSEEIKFYELGE 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily A members 2 (KCNA2) and 3 (KCNA3); KCNA2 is also called NGK1, voltage-gated K(+) channel HuKIV, voltage-gated potassium channel HBK5, or voltage-gated potassium channel subunit Kv1.2. KCNA3 is also called HGK5, HLK3, HPCN3, voltage-gated K(+) channel HuKIII, or voltage-gated potassium channel subunit Kv1.3. KCNA2 and KCNA3 mediate 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. KCNA2 primarily functions in the brain and the central nervous system, but also in the cardiovascular system. It prevents aberrant action potential firing and regulates neuronal output. 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. KCNA2 and KCNA3 are alpha subunits that 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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044453  21 INVGGFKRRLRSHTLLRFPETRLG----RLLLchsreailelcddYDDVQREFYFDRNPELFPYVLHFYHT-GKLHVMAE 95
Cdd:cd18403   5 INISGLRFETQLKTLAQFPETLLGdpkkRMRY-------------FDPLRNEYFFDRNRPSFDAILYYYQSgGRLRRPVN 71

                        90
                ....*....|....*..
gi 31044453  96 LCVFSFSQEIEYWGINE 112
Cdd:cd18403  72 VPLDIFSEEIRFYELGE 88

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 31044453  21 INVGGFKRRLRSHTLLRFPETRLGrlllchSREAILELcddYDDVQREFYFDRNPELFPYVLHFYHT-GKLHVMAELCVF 99
Cdd:cd18405   5 INVSGLRFETQLKTLAQFPETLLG------DPEKRMRY---FDPLRNEYFFDRNRPSFDAILYYYQSgGRLKRPVNVPFD 75

                        90
                ....*....|...
gi 31044453 100 SFSQEIEYWGINE 112
Cdd:cd18405  76 IFSEEVKFYELGE 88

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31044453  16 DGEIRINVGGFKRRLRSHTLLRFPETRLGRLLlcHSREAILelcddYDDVQREFYFDRNPELFPYVLHFYHTGKL 90
Cdd:cd18388   1 NAPVHIDVGGHMYTSSLATLTKYPDSRISRLF--NGTEPIV-----LDSLKQHYFIDRDGEIFRYILSFLRTSKL 68

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31044453  16 DGEIRINVGGFKRRLRSHTLLRFPETRLGRLLlcHSREAILelcddYDDVQREFYFDRNPELFPYVLHFYHTGKL 90
Cdd:cd18387   2 NAPVHIDVGGHMYTSSLATLTKYPESRIGRLF--DGTEPIV-----LDSLKQHYFIDRDGQMFRYILNFLRTSKL 69

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily A member 5 (KCNA5); KCNA5, also called HPCN1, voltage-gated potassium channel HK2, or voltage-gated potassium channel subunit Kv1.5, 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. KCNA5 may play a role in regulating the secretion of insulin in normal pancreatic islets. 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. KCNA5 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 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRlllCHSREAIlelcddYDDVQREFYFDRNPELFPYVLHFYHT-GKLHVMAELC 97
Cdd:cd18406   3 VIINIAGLRFETQLGTLNQFPDTLLGD---PDKRMRY------FDPLRNEYFFDRNRPSFDGILYFYQSgGKIRRPVNVS 73

                        90
                ....*....|....*
gi 31044453  98 VFSFSQEIEYWGINE 112
Cdd:cd18406  74 IDVFADEIRFYQLGE 88

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLLCHSREAILElcddydDVQREFYFDRNPELFPYVLHFYHTGKLH 91
Cdd:cd18367   5 VELNVGGQVYTTSLSTLIKDPDSLLGRMFSGKNRQELAR------DSKGRYFLDRDGVLFRYILDYLRNQKLV 71

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 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLllCHSREaileLCDDYDDVQrEFYFDRNPELFPYVLHFYHTGKLHVMAELCV 98
Cdd:cd18391   3 VRLNVGGTVFLTTRQTLCREQKSFLSRL--CQGEE----LQSDRDETG-AYLIDRDPTYFGPILNFLRHGKLVLDKDMAE 75

                        90
                ....*....|..
gi 31044453  99 FSFSQEIEYWGI 110
Cdd:cd18391  76 EGVLEEAEFYNI 87

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins, KCTD6, KCTD21 and similar proteins; KCTD6, also called KCASH3 (KCTD containing, Cullin3 adaptor, suppressor of Hedgehog 3), is a substrate-specific adaptor of cullin-3, effectively regulating protein levels of the muscle small ankyrin-1 isoform 5 (sAnk1.5). KCTD21, also called KCASH2, 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31044453  19 IRINVGGFKRRLRSHTLLRFPETRLGRLLlchsreailelCDDYD---DVQREFYFDRNPELFPYVLHFYHTGKL 90
Cdd:cd18365   3 VNLNVGGVHYTTTLATLTRFPDSMLGAMF-----------SGSMPttrDDQGNYFIDRDGTLFRYILNFLRSSQL 66