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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680526    6 ATWLPFARAAAVGWLPLAQQPLPPAPEVKASRGDEVLVVNVSGRRFETWKNTLDRYPDTLLGSSEKEFFYDAESGEYFFD 85
Cdd:cd18417   1 ATWLPFARAAAVGWLPLAKKPMPKPPSDKKRRNDEILVVNVSGRRFQTWKNTLDRYPDTLLGSSEKEFFYNEDTQEYFFD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6680526   86 RDPDMFRHVLNFYRTGRLHCPRQECIQAFDEELAFYGLVPELVGDCCLEEYRDRKKEN 143
Cdd:cd18417  81 RDPEMFRHILNFYRTGRLHYPRHECIQAFDEELSFYGIIPEIIGDCCLEEYRDRKKEN 138

Domain of unknown function (DUF3399); This domain is functionally uncharacterized. This domain is found in eukaryotes. This presumed domain is about 100 amino acids in length. This domain is found associated with pfam02214, pfam00520.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680526    470 SRSAFEQQHHHLLHCLEKTTCHEFTDELTFSEALGAVSLGGRTSRSTSVSSQPmgpgSLFSSCCSRRvNRRAIRLANSTA 549
Cdd:pfam11879   1 STSLFESQHHHLLHCLEKTTNHEFVDEQTYEQNCLEVSLQNRPSRSPSLSSQD----GLTSSCCSRR-AKRNTRLPNSSV 75

                  .
gi 6680526    550 S 550
Cdd:pfam11879  76 P 76

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 6680526    6 ATWLPFARAAAVGWLPLAQQPLPPAPEVKASRGDEVLVVNVSGRRFETWKNTLDRYPDTLLGSSEKEFFYDAESGEYFFD 85
Cdd:cd18417   1 ATWLPFARAAAVGWLPLAKKPMPKPPSDKKRRNDEILVVNVSGRRFQTWKNTLDRYPDTLLGSSEKEFFYNEDTQEYFFD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6680526   86 RDPDMFRHVLNFYRTGRLHCPRQECIQAFDEELAFYGLVPELVGDCCLEEYRDRKKEN 143
Cdd:cd18417  81 RDPEMFRHILNFYRTGRLHYPRHECIQAFDEELSFYGIIPEIIGDCCLEEYRDRKKEN 138

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 6680526     42 LVVNVSGRRFETWKNTLDRYPDTLLGSSEKE--FFYDAESGEYFFDRDPDMFRHVLNFYRT-GRLHCPRQECIQAFDEEL 118
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLELecDDYDDDTNEYFFDRSPKHFETILNFYRTgGKLHRPEEVCLDEFLEEA 80

                          90
                  ....*....|...
gi 6680526    119 AFYGLVPELVGDC 131
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 6680526      42 LVVNVSGRRFETWKNTLDRYPDTLLGSSEKEFFYDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPrQECIQAFDEELAFY 121
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYTGKLDLP-EENVEELLELADYL 80

                           90
                   ....*....|.
gi 6680526     122 gLVPELVGDCC 132
Cdd:smart00225  81 -QIPGLVELCE 90

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 6680526    6 ATWLPFARAAAVGWLPLAQQPLPPAPEVKASRGDEVLVVNVSGRRFETWKNTLDRYPDTLLGSSEKEFFYDAESGEYFFD 85
Cdd:cd18417   1 ATWLPFARAAAVGWLPLAKKPMPKPPSDKKRRNDEILVVNVSGRRFQTWKNTLDRYPDTLLGSSEKEFFYNEDTQEYFFD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6680526   86 RDPDMFRHVLNFYRTGRLHCPRQECIQAFDEELAFYGLVPELVGDCCLEEYRDRKKEN 143
Cdd:cd18417  81 RDPEMFRHILNFYRTGRLHYPRHECIQAFDEELSFYGIIPEIIGDCCLEEYRDRKKEN 138

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 6680526    8 WLPFARAAAVGWLPLAQQPLPPAPEVKASR--GDEVLVVNVSGRRFETWKNTLDRYPDTLLGSSEKEFFYDAESGEYFFD 85
Cdd:cd18420   2 WLPFARAAAIGWVPIANNPLPPPPVDQERRrtDDEKLIINVSGRRFETWRNTLEKYPDTLLGSNEREFFYDEETKEYFFD 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6680526   86 RDPDMFRHVLNFYRTGRLHCPRQECIQAFDEELAFYGLVPELVGDCCLEEYRDRKKEN 143
Cdd:cd18420  82 RDPDIFRHILNYYRTGKLHYPKHECLTAYDEELAFFGIMPDIIGDCCYEDYRDRKREN 139

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 6680526   41 VLVVNVSGRRFETWKNTLDRYPDTLLGSSEKEFFYDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECIQAFDEELAF 120
Cdd:cd18418   1 LIVLNVSGTRFQTWRNTLERYPDTLLGSSERDFFYHEETQEYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELAF 80

                        90       100
                ....*....|....*....|...
gi 6680526  121 YGLVPELVGDCCLEEYRDRKKEN 143
Cdd:cd18418  81 FGIIPEIIGDCCYEEYKDRRREN 103

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 6680526     42 LVVNVSGRRFETWKNTLDRYPDTLLGSSEKE--FFYDAESGEYFFDRDPDMFRHVLNFYRT-GRLHCPRQECIQAFDEEL 118
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLELecDDYDDDTNEYFFDRSPKHFETILNFYRTgGKLHRPEEVCLDEFLEEA 80

                          90
                  ....*....|...
gi 6680526    119 AFYGLVPELVGDC 131
Cdd:pfam02214  81 EFYGLDELALELC 93

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 6680526   42 LVVNVSGRRFETWKNTLDRYPDTLLGSSEK---EFFYDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECIQAFDEEL 118
Cdd:cd18187   1 VVLNVSGTRFVTNRQTLTRHPDTLLGRMFKpgrEFTFPNETGEYFIDRDPTVFRTILNYYRTGKLNCPDGISIPDLREEC 80

                ...
gi 6680526  119 AFY 121
Cdd:cd18187  81 DFY 83

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 6680526   40 EVLVVNVSGRRFETWKNTLDRYPDT-LLGSSEKE----FFYDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECIQAF 114
Cdd:cd18414   3 DRIVINVGGTRHETYRSTLRTLPGTrLAWLAEPDahsnFDYDPRADEFFFDRHPGVFAHILNYYRTGKLHCPADVCGPLY 82

                        90       100       110
                ....*....|....*....|....*....|.
gi 6680526  115 DEELAFYGLVPELVGDCCLEEYRD-RKKENA 144
Cdd:cd18414  83 EEELAFWGIDETDVEPCCWMTYRQhRDAEEA 113

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel protein Shaw; Shaw, also called Shaw2, is a voltage-gated potassium channel in Drosophila. It mediates transmembrane potassium transport in excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a tetrameric potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. Shaw is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other alpha subunits) through its BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680526   39 DEVLVVNVSGRRFETWKNTLDRYPDTLLGS-SEKEFFYDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECIQAFDEE 117
Cdd:cd18416   1 ENRVVLNVGGIRHETYKATLKKIPATRLSRlTEALANYDPVLNEYFFDRHPGVFAQILNYYRTGKLHYPTDVCGPLFEEE 80

                        90
                ....*....|....*....
gi 6680526  118 LAFYGLVPELVGDCCLEEY 136
Cdd:cd18416  81 LEFWGLDANQVEPCCWMTY 99

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 6680526   39 DEVLVVNVSGRRFETWKNTLDRYPDT---LLGSSEKE-------------FFYDAESGEYFFDRDPDMFRHVLNFYRTGR 102
Cdd:cd18415   1 NERIILNVGGTRHETYRSTLKTLPGTrlaLLASSDPQgdcltqcsqvggsDGSPGGGNEFFFDRHPGVFAYVLNYYRTGK 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 6680526  103 LHCPRQECIQAFDEELAFYGLVPELVGDCCLEEYRD-RKKENA 144
Cdd:cd18415  81 LHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQhRDAEEA 123

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680526   42 LVVNVSGRRFETWKNTLDRYPDTLLG---SSEKEFFY----DAE--SGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECIQ 112
Cdd:cd18424   1 FTINVGGSRFVLSQQVLSSHPETRLGklaVSVRDSVLelcdDANfvDNEYFFDRSSQAFKYIMNYYKTGHLHVMEELCAI 80

                        90       100
                ....*....|....*....|....*...
gi 6680526  113 AFDEELAFYGLVPELVGDCCLEEYRDRK 140
Cdd:cd18424  81 SFLQEIEYWGIDELSIDSCCRERYYRRK 108

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 6680526   40 EVLVVNVSGRRFETWKNTLDRYPDTLLGS-SEKEFFYDAESGEYFFDRDPDMFRHVLNFYRT-GRLHCPRQECIQAFDEE 117
Cdd:cd18408   6 ERVVLNVAGLRFETRARTLGRFPDTLLGDpARRGRFYDDRRREYFFDRHRPSFDAVLYYYQSgGRLRRPAHVPLDVFLEE 85

                        90
                ....*....|..
gi 6680526  118 LAFYGLVPELVG 129
Cdd:cd18408  86 VAFYGLGAAALA 97

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 6680526   42 LVVNVSGRRFETWKNTLDRYPDTLLGS--SEKEFFYDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQEC-IQAFDEEL 118
Cdd:cd18316   1 VKLNVGGTLFTTSRSTLLKDPDSLLAAlfSGRWPLPRDEDGSIFIDRDPELFRHILNFLRTGKLPLPSDFVeLEELLAEA 80

                ...
gi 6680526  119 AFY 121
Cdd:cd18316  81 EFY 83

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 6680526   42 LVVNVSGRRFETWKNTLDRYPDTLLG----SSEKEFF------YDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECI 111
Cdd:cd18413   4 VVINVGGVKHEVLWRTLDRMPHTRLGklrdSNTHEAIvelcddYSLADNEYFFDRHPRSFASILNFYRTGKLHLVEEMCV 83

                        90       100
                ....*....|....*....|....*
gi 6680526  112 QAFDEELAFYGLVPELVGDCCLEEY 136
Cdd:cd18413  84 LAFSDDLEYWGVDELYLESCCQHKY 108

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 6680526   44 VNVSGRRFETWKNTLDRYPDT----LLGSSEKEFF------YDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECIQA 113
Cdd:cd18427   4 INVGGFKKRLRSHTLLRFPETrlgrLLSCRSKESIlelcddYDDTKNEFYFDRNPELFPYVLHFYNTGKLHVMGELCVFS 83

                        90       100
                ....*....|....*....|....
gi 6680526  114 FDEELAFYGLVPELVGDCCLEEYR 137
Cdd:cd18427  84 FSQEIEYWGINEFFIDSCCSYSYH 107

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680526   40 EVLVVNVSGRRFETWKNTLDRYPDTLLG-----SSEKEFF-----YDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQE 109
Cdd:cd18428   1 ELINLNVGGFKQSVDQSTLLRFPHTRLGkllncHSEEAILelcddYSVADKEYYFDRNPSLFRYVLNFYYTGKLHVMEEL 80

                        90       100
                ....*....|....*....|....*...
gi 6680526  110 CIQAFDEELAFYGLVPELVGDCCLEEYR 137
Cdd:cd18428  81 CVFSFCQEIEYWGINELFIDSCCSNRYQ 108

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 6680526   40 EVLVVNVSGRRFETWKNTLDRYPDTLLGSSEKEF-FYDAESGEYFFDRDPDMFRHVLNFYRT-GRLHCPRQECIQAFDEE 117
Cdd:cd18406   1 ERVIINIAGLRFETQLGTLNQFPDTLLGDPDKRMrYFDPLRNEYFFDRNRPSFDGILYFYQSgGKIRRPVNVSIDVFADE 80

                        90       100
                ....*....|....*....|.
gi 6680526  118 LAFYGLvpelvGDCCLEEYRD 138
Cdd:cd18406  81 IRFYQL-----GEEAMERFRE 96

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 6680526   27 LPPAPE--VKASRGDEVLVVNVSGRRFETWKNTLDRYPDTLLG-----SSEKEFF-----YDAESGEYFFDRDPDMFRHV 94
Cdd:cd18412   2 LPPEPVeiIRSKACSRRVKINVGGLNHEVLWRTLDRLPRTRLGklrdcNTHESLLevcddYNLNENEYFFDRHPGAFTSI 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 6680526   95 LNFYRTGRLHCPRQECIQAFDEELAFYGLVPELVGDCCLEEYRDRK 140
Cdd:cd18412  82 LNFYRTGKLHMMEEMCALSFGQELDYWGIDEIYLESCCQARYHQKK 127

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 6680526   40 EVLVVNVSGRRFETWKNTLDRYPDTLLGSSEKEF-FYDAESGEYFFDRDPDMFRHVLNFYRT-GRLHCPRQECIQAFDEE 117
Cdd:cd18405   1 ERVVINVSGLRFETQLKTLAQFPETLLGDPEKRMrYFDPLRNEYFFDRNRPSFDAILYYYQSgGRLKRPVNVPFDIFSEE 80

                        90       100
                ....*....|....*....|.
gi 6680526  118 LAFYGLvpelvGDCCLEEYRD 138
Cdd:cd18405  81 VKFYEL-----GEEALLKFRE 96

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 6680526   44 VNVSGRRFETWKNTLDRYPDTLLG-----SSEKEFF-----YDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECIQA 113
Cdd:cd18411  14 LNVGGLAHEVLWRTLDRLPRTRLGklrdcNTHESLMeicddYNLEENEYFFDRHPGAFTSILNFYRTGKLHMMEEMCALS 93

                        90       100
                ....*....|....*....|...
gi 6680526  114 FDEELAFYGLVPELVGDCCLEEY 136
Cdd:cd18411  94 FSQELDYWGIDEIYLESCCQARY 116

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 6680526   42 LVVNVSGRRFETWKNTLDRYPDTLLG-----SSEKEFF-----YDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECI 111
Cdd:cd18423   4 IIINVGGIKYLMPWSTLDEFPLTRLGklkfcSSYEEIVqicddYDEDTNEFFFDRNPCAFRMIVSFLAAGKLRLLREMCA 83

                        90       100
                ....*....|....*....|..
gi 6680526  112 QAFDEELAFYGLVPELVGDCCL 133
Cdd:cd18423  84 LSFQEELTYWGIEEANLERCCL 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680526    333 LTMAIIIFATVmFYAEKGTSKTNFTSipaAFWYTIVTMTTLGYGDMVPSTIAGKIFGSICSLSGVLVIALPVPVIVSNFS 412
Cdd:pfam07885   2 VLLLVLIFGTV-YYLLEEGWEWSFLD---ALYFSFVTLTTVGYGDIVPLTDAGRLFTIFYILIGIPLFAIFLAVLGRFLT 77

                  .
gi 6680526    413 R 413
Cdd:pfam07885  78 E 78

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 6680526   42 LVVNVSGRRFETWKNTLDRYPDTLLGS-------SEKEFF---YDAESGEYFFDRDPDMFRHVLNFYRTGRLHCPRQECI 111
Cdd:cd18425   1 LNINVGGTSYQISYRVAASYPKTRIGRlatytdrSRKLDLcddYNVQNDEYFFDRDPAVFHHIYNFYRTGVLWVKDELCP 80

                        90       100
                ....*....|....*....|....*...
gi 6680526  112 QAFDEELAFYGLVPELVGDCCLEEYRDR 139
Cdd:cd18425  81 RNFLEEINYWGVRIKNTPRCCRISFEER 108

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 6680526   39 DEVLVVNVSGRRFETWKNTLDRYPDTLLGS--SEKEFFYDAESGEYFFDRDPDMFRHVLNFYRTGRLHcPRQECIQAFDE 116
Cdd:cd18363   1 GDIINLNVGGKRFSTSRQTLTWIPDSFFTSllSGRISSLKDETGAIFIDRDPKLFSIILNYLRTKEID-LRNVDISSLRH 79

                ....*..
gi 6680526  117 ELAFYGL 123
Cdd:cd18363  80 EAEFYGI 86

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680526   42 LVVNVSGRRFETWKNTLDRYPDTLLGSSEKEFFYDAE--SGEYFFDRDPDMFRHVLNFYRTGRLHCPRQecIQAFD---E 116
Cdd:cd18394   5 VTLNVGGHLYTTSLSTLTRYPDSMLGAMFRGDFPTARdsQGNYFIDRDGPLFRYILNFLRTSELTLPVD--FKEFDllrK 82

                ....*....
gi 6680526  117 ELAFYGLVP 125
Cdd:cd18394  83 EADFYQIEP 91