H1 domain found in potassium channel tetramerization domain-containing protein 16; Potassium channel tetramerization domain-containing protein 16 (KCTD16) is a BTB/POZ domain-containing protein that is an auxiliary subunit of gamma-aminobutyric acid type B (GABA-) receptors associated with mood disorders. It interacts with amyloid beta precursor protein (APP), a type I transmembrane protein involved in a variety of cellular processes such as cell adhesion and axon guidance. KCTD16 generates largely non-desensitizing receptor responses. It consists of an N-terminal BTB domain followed by a region called the H1 domain. The BTB domain mediates interaction with the receptor. The C-terminal H1 domain, which possesses a beta-propeller-like fold, engages in interactions with G-protein beta-gamma subunits. In the related protein KCTD12, the H1 domain is also responsible for desensitization. This model corresponds to the H1 domain of KCTD16, which may not be involved in desensitization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818 160 DRKWGFITVGYRGSCTLGREGQADAKFRRVPRILVCGRISLAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDM 239
Cdd:cd22219    1 DRKWGFITVGYRGSCTMGRESQADAKFRRVPRILVCGRIALAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDM 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767937818 240 LSECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFY 277
Cdd:cd22219   81 LSECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFY 118

H1 domain found in potassium channel tetramerization domain-containing protein 16; Potassium channel tetramerization domain-containing protein 16 (KCTD16) is a BTB/POZ domain-containing protein that is an auxiliary subunit of gamma-aminobutyric acid type B (GABA-) receptors associated with mood disorders. It interacts with amyloid beta precursor protein (APP), a type I transmembrane protein involved in a variety of cellular processes such as cell adhesion and axon guidance. KCTD16 generates largely non-desensitizing receptor responses. It consists of an N-terminal BTB domain followed by a region called the H1 domain. The BTB domain mediates interaction with the receptor. The C-terminal H1 domain, which possesses a beta-propeller-like fold, engages in interactions with G-protein beta-gamma subunits. In the related protein KCTD12, the H1 domain is also responsible for desensitization. This model corresponds to the H1 domain of KCTD16, which may not be involved in desensitization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818 160 DRKWGFITVGYRGSCTLGREGQADAKFRRVPRILVCGRISLAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDM 239
Cdd:cd22219    1 DRKWGFITVGYRGSCTMGRESQADAKFRRVPRILVCGRIALAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDM 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767937818 240 LSECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFY 277
Cdd:cd22219   81 LSECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFY 118

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 767937818   27 VELNVGGQVYFTRHSTLISIPHSLLWKMFSpkrdTANDLAKDSKGRFFIDRDGFLFRYILDYLRDrQVVLPDHFPEKGR- 105
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLE----LECDDYDDDTNEYFFDRSPKHFETILNFYRT-GGKLHRPEEVCLDe 75

                          90
                  ....*....|...
gi 767937818  106 LKREAEYFQLPDL 118
Cdd:pfam02214  76 FLEEAEFYGLDEL 88

H1 domain found in potassium channel tetramerization domain-containing protein 16; Potassium channel tetramerization domain-containing protein 16 (KCTD16) is a BTB/POZ domain-containing protein that is an auxiliary subunit of gamma-aminobutyric acid type B (GABA-) receptors associated with mood disorders. It interacts with amyloid beta precursor protein (APP), a type I transmembrane protein involved in a variety of cellular processes such as cell adhesion and axon guidance. KCTD16 generates largely non-desensitizing receptor responses. It consists of an N-terminal BTB domain followed by a region called the H1 domain. The BTB domain mediates interaction with the receptor. The C-terminal H1 domain, which possesses a beta-propeller-like fold, engages in interactions with G-protein beta-gamma subunits. In the related protein KCTD12, the H1 domain is also responsible for desensitization. This model corresponds to the H1 domain of KCTD16, which may not be involved in desensitization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818 160 DRKWGFITVGYRGSCTLGREGQADAKFRRVPRILVCGRISLAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDM 239
Cdd:cd22219    1 DRKWGFITVGYRGSCTMGRESQADAKFRRVPRILVCGRIALAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDM 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767937818 240 LSECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFY 277
Cdd:cd22219   81 LSECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFY 118

H1 domain found in potassium channel tetramerization domain-containing proteins; The H1 domain is found in potassium channel tetramerization domain-containing proteins such as KCTD8, KCTD12 (also called predominantly fetal expressed T1 domain/Pfetin), KCTD12b, and KCTD16. They serve as auxiliary gamma-aminobutyric acid type B (GABA-B) receptor subunits that constitute receptor subtypes with distinct functional properties. KCTD12 and -12b generate desensitizing receptor responses while KCTD8 and -16 generate largely non-desensitizing receptor responses. They control GABA-B signaling and regulate the rise time and duration of G protein-coupled inwardly rectifying potassium (GIRK) currents, as well as enhance receptor expression levels. KCTD12 regulates agonist potency and kinetics of GABA-B 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. Members of this family consist of an N-terminal BTB domain followed by a region called the H1 domain. The BTB domain mediates interaction with the receptor. The C-terminal H1 domain, which possesses a beta-propeller-like fold, engages in interactions with G-protein beta-gamma subunits and is responsible for desensitization. This model corresponds to the H1 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818 163 WGFITVGYRGSCTLGREGQADAKFRRVPRILVCGRISLAKEVFGETLNESRDPDR-APERYTSRFYLKFKHLERAFDMLS 241
Cdd:cd22204    1 PGYITLGYRGTFAFGRDGQADVKFRKLARILVCGKVSLCREVFGDTLNESRDPDRgEPDRYTSRFFLKHNYLEQAFDQLA 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 767937818 242 ECGFHMVACNSSVTASFI-NQYTDDKIWSSYTEYVFY 277
Cdd:cd22204   81 EAGFRLVASCGSGTSGLPsAGDSEEKRWNHYTEFVFV 117

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins, KCTD8, KCTD12, KCTD16 and similar proteins; This subfamily of KCTD proteins includes KCTD8, KCTD12 (also called predominantly fetal expressed T1 domain/Pfetin), and KCTD16. They act as auxiliary subunits of GABAB receptors associated with mood disorders. KCTD8 interacts as a tetramer with GABRB1 and GABRB2. KCTD12 regulates agonist potency and kinetics of GABAB receptor signaling. It promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A-dependent G2/M transition. KCTD16 interacts with amyloid beta precursor protein (APP), a type I transmembrane protein involved in a variety of cellular processes such as cell adhesion, and axon guidance. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  23 FPEVVELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRdtANDLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPE 102
Cdd:cd18367    1 FPEIVELNVGGQVYTTSLSTLIKDPDSLLGRMFSGKN--RQELARDSKGRYFLDRDGVLFRYILDYLRNQKLVLPENFPE 78

                         90       100
                 ....*....|....*....|..
gi 767937818 103 KGRLKREAEYFQLPDLVKLLTP 124
Cdd:cd18367   79 RERLKREAEYFQLPELVKALRA 100

H1 domain found in potassium channel tetramerization domain-containing protein 8; Potassium channel tetramerization domain-containing protein 8 (KCTD8), a BTB/POZ domain-containing protein, is an auxiliary subunit of gamma-aminobutyric acid type B (GABA-B) receptors that determine the pharmacology and kinetics of the receptor response. It generates largely non-desensitizing receptor responses. KCTD8 consists of an N-terminal BTB domain followed by a region called the H1 domain. The BTB domain mediates interaction with the receptor. The C-terminal H1 domain, which possesses a beta-propeller-like fold, engages in interactions with G-protein beta-gamma subunits. In the related protein KCTD12, the H1 domain is also responsible for desensitization. This model corresponds to the H1 domain of KCTD8, which may not be involved in desensitization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818 160 DRKWGFITVGYRGSCTLGREGQADAKFRRVPRILVCGRISLAKEVFGETLNESRDPDRAPERYTSRFYLKFKHLERAFDM 239
Cdd:cd22218    4 DKRSGFITIGYRGSYTMVRDNQADAKFRRVARIMVCGRIALAKEVFGDTLNESRDPDRPPEKYTSRFYLKFTYLEQAFDR 83

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767937818 240 LSECGFHMVACNSSVTASFINQYTDDKIWSSYTEYVFY 277
Cdd:cd22218   84 LSEAGFHMVACNSTGTAAFVNQYRDDKIWSSYTEYIFF 121

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein KCTD8; KCTD8, a BTB/POZ domain-containing protein, is an auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. It interacts as a tetramer with GABRB1 and GABRB2. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  22 SFPEVVELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRdtANDLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFP 101
Cdd:cd18396    1 PFPEVVELNVGGQVYVTKHSTLLSVPDSTLASMFSRRA--ARELPRDNRGRFFIDRDGFLFRYVLDYLRDKQLALPDHFP 78

                         90       100
                 ....*....|....*....|...
gi 767937818 102 EKGRLKREAEYFQLPDLVKLLTP 124
Cdd:cd18396   79 EKERLLREAEYFQLGDLVKLLTP 101

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  25 EVVELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDTAndlaKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKG 104
Cdd:cd18365    1 DIVNLNVGGVHYTTTLATLTRFPDSMLGAMFSGSMPTT----RDDQGNYFIDRDGTLFRYILNFLRSSQLSLPEDFKEYD 76

                         90
                 ....*....|....*...
gi 767937818 105 RLKREAEYFQLPDLVKLL 122
Cdd:cd18365   77 LLLREADFYQIEPLIEAL 94

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 767937818  25 EVVELNVGGQVYFTRHSTLISIPHSLLWKMFspkrDTANDLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKG 104
Cdd:cd18375    1 ELVTLNVGGKKFTTRPSTLRRFPDSRLARML----DGKDQDFKVVNGQFFVDRDGSLFSYILDYLRTGQLTLPTEFSDYN 76

                         90       100
                 ....*....|....*....|.
gi 767937818 105 RLKREAEYFQLPDLVKLLTPD 125
Cdd:cd18375   77 RLAREAEFYGLYSLADLLSQN 97

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 767937818  26 VVELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDtandLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGR 105
Cdd:cd18364    1 LVTLNVGGYLYITQRQTLTKYPDSFLEGMVNGKIQ----CTVDADGNYFIDRDGLLFRHVLNFLRNGELLLPEGFQENQL 76

                         90
                 ....*....|
gi 767937818 106 LKREAEYFQL 115
Cdd:cd18364   77 LALEADFYQL 86

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Arabidopsis thaliana FH protein interacting protein FIP2 and similar proteins; FIP2 may act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It contains a BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  27 VELNVGGQVYFTRHSTLISIPHSLLWKMFSPKrdtaNDLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGR- 105
Cdd:cd18376    1 VKLNVGGQKFTTTLDTLTKDPDSMLAAMFSGR----HSLKKDEDGSYFIDRDGTHFRHILNYLRDGEVKIPTEDRSVLKe 76

                         90
                 ....*....|...
gi 767937818 106 LKREAEYFQLPDL 118
Cdd:cd18376   77 LLEEAEYYQLRGL 89

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins, KCTD1 and KCTD15; This subfamily of KCTD proteins includes KCTD1 and KCTD15. 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. It also functions as a novel inhibitor of the Wnt signaling pathway. Mutations in KCTD1 cause scalp-ear-nipple (SEN) syndrome. 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 form pentamers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  27 VELNVGGQVYFTRHSTLISIPHSLLWKMFspkrDTANDLAKDS-KGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGR 105
Cdd:cd18361    1 VHIDVGGHIYTSSLETLTKYPESRLGKLF----NGSIPIVLDSlKQHYFIDRDGKMFRHILNFLRTSKLLLPDDFTEFDL 76

                         90
                 ....*....|....*..
gi 767937818 106 LKREAEYFQLPDLVKLL 122
Cdd:cd18361   77 LYEEARYYELQPMVKQL 93

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 9 (KCTD9); KCTD9 is a BTB/POZ domain-containing protein that contributes to liver injury through NK cell activation during hepatitis B virus-induced acute-on-chronic liver failure. It functions as a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of target proteins, leading to their degradation by the proteasome. 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 KCTD9 BTB domain forms a pentameric structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  27 VELNVGGQVYFTRHSTLIS-IPHSLLWKMFSPKRDTANdlAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGR 105
Cdd:cd18368    3 IKLNVGGRIFTTTRSTLVKkEPDSMLARMFSDDSTWPS--SRDENGAYLIDRSPEYFEPILNYLRHGQLILNDGLNPLGV 80

                         90
                 ....*....|....*..
gi 767937818 106 LKrEAEYFQLPDLVKLL 122
Cdd:cd18368   81 LE-EAKFFGIQSLIEIL 96

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 767937818   27 VELNVGGQVYFTRHSTLISIPHSLLWKMFSpkrdTANDLAKDSKGRFFIDRDGFLFRYILDYLRDrQVVLPDHFPEKGR- 105
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLE----LECDDYDDDTNEYFFDRSPKHFETILNFYRT-GGKLHRPEEVCLDe 75

                          90
                  ....*....|...
gi 767937818  106 LKREAEYFQLPDL 118
Cdd:pfam02214  76 FLEEAEFYGLDEL 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins, KCTD10 (BACURD3), KCTD13 (BACURD1), and TNFAIP1 (BACURD2); This subfamily of KCTD proteins, also called the BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein (BACURD) subfamily, includes KCTD10 (BACURD3), KCTD13 (BACURD1), and TNFAIP1 (BACURD2). KCTD10 is a BTB/POZ domain-containing protein that interacts with proliferating cell nuclear antigen (PCNA) and polymerase delta, and participates in DNA repair, DNA replication, and cell-cycle control. Its down-regulation could inhibit cell proliferation. KCTD10 also plays crucial roles in embryonic angiogenesis and heart development in mammals by negatively regulating the Notch signaling pathway. KCTD13 is a BTB/POZ domain-containing protein that may function as a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of RhoA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. TNFAIP1, also called protein B12, is a BTB/POZ domain-containing protein that is involved in DNA replication, DNA damage repair, cell apoptosis, and is implicated in human diseases including cancer, Alzheimer's disease (AD) and type 2 diabetic nephropathy. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. KCTD10 and KCTD13 BTB domains form a novel two-fold symmetric tetramer that is distinct from the tetramer formed by voltage-gated potassium (Kv) channels.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  27 VELNVGGQVYFTRHSTLISiPHSLLWKMFSPKRDtandLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGRL 106
Cdd:cd18369    1 VKLNVGGSLHYTTIGTLTK-QDTMLRAMFSGRME----VLTDSEGWILIDRCGKHFGTILNYLRDGSVPLPESRRELAEL 75

                         90
                 ....*....|....
gi 767937818 107 KREAEYFQLPDLVK 120
Cdd:cd18369   76 LAEAKYYLVQGLVE 89

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 13 (KCTD13); KCTD13, also called BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 1 (BACURD1), or TNFAIP1-like protein, is a BTB/POZ domain-containing protein that may function as a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of RhoA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. 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 KCTD13 BTB domain forms a novel two-fold symmetric tetramer that is distinct from the tetramer formed by voltage-gated potassium (Kv) channels.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  27 VELNVGGQVYFTRHSTLiSIPHSLLWKMFSPKrdtaNDLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGRL 106
Cdd:cd18400    4 VKLNVGGSLHYTTVQTL-TKQDTMLKAMFSGR----VEVLTDSEGWVLIDRSGRHFGTILNYLRDGSVPLPESTRELEEL 78

                         90
                 ....*....|....
gi 767937818 107 KREAEYFQLPDLVK 120
Cdd:cd18400   79 LGEARYYLVQGLVE 92

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 5 (KCTD5); KCTD5 is a BTB/POZ domain-containing protein that functions as a substrate adaptor for cullin3 based ubiquitin E3 ligases. It is a negative regulator of the AKT pathway, a key signaling cascade frequently deregulated in cancer. KCTD5 does not impact the operation of Kv4.2, Kv3.4, Kv2.1, or Kv1.2 channels. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. KCTD5 forms pentamers mediated by its BTB domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  27 VELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDTANDlaKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGRL 106
Cdd:cd18390    7 VRLNVGGTYFLTTRQTLCRDPKSFLYRLCQADPDLDSD--KDETGAYLIDRDPTYFGPVLNYLRHGKLVINKDLAEEGVL 84

                         90       100
                 ....*....|....*....|...
gi 767937818 107 KrEAEYFQLPDLVKLLTpDEIKQ 129
Cdd:cd18390   85 E-EAEFYNITSLIKLVK-DKIRE 105

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing proteins KCTD2, KCTD5, and KCTD17, and similar proteins; This subfamily includes potassium channel tetramerization domain-containing proteins KCTD2, KCTD5, and KCTD17, all of which function as adaptors of Cullin3 based ubiquitin E3 ubiquitin ligases. KCTD2 suppresses gliomagenesis by destabilizing c-Myc. KCTD5 is a negative regulator of the AKT pathway, a key signaling cascade frequently deregulated in cancer. KCTD5 does not impact the operation of Kv4.2, Kv3.4, Kv2.1, or Kv1.2 channels. KCTD17 polyubiquitylates trichoplein, a protein involved in ciliogenesis down-regulation. It is a positive regulator of ciliogenesis, playing a crucial role in the initial steps of axoneme extension. A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia (M-D). The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. KCTD5 and KCTD17 BTB domains form pentamer structures.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  27 VELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDTANDlaKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGRL 106
Cdd:cd18362    2 VKLNVGGTYFLTTRTTLCRDPKSFLCRLCQEDPDLPSD--KDETGAYLIDRDPTYFGPILNYLRHGKLIIDKDLAEEGVL 79

                 ....*..
gi 767937818 107 KrEAEYF 113
Cdd:cd18362   80 E-EAEFY 85

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 767937818  27 VELNVGGQVYFTRHSTLISIPHSLLWKMfSPKRDTANDlaKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGRL 106
Cdd:cd18391    3 VRLNVGGTVFLTTRQTLCREQKSFLSRL-CQGEELQSD--RDETGAYLIDRDPTYFGPILNFLRHGKLVLDKDMAEEGVL 79

                         90
                 ....*....|....*.
gi 767937818 107 KrEAEYFQLPDLVKLL 122
Cdd:cd18391   80 E-EAEFYNIGPLIRII 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 767937818  27 VELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDTANDlakDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDHFPEKGrL 106
Cdd:cd18187    1 VVLNVSGTRFVTNRQTLTRHPDTLLGRMFKPGREFTFP---NETGEYFIDRDPTVFRTILNYYRTGKLNCPDGISIPD-L 76

                 ....*..
gi 767937818 107 KREAEYF 113
Cdd:cd18187   77 REECDFY 83

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in SH3KBP1-binding protein 1 (SHKBP1); SHKBP1, also called SETA-binding protein 1, interacts with cathepsin B and participates in tumor necrosis factor (TNF)-induced apoptosis in ovarian cancer cells. It can promote epidermal growth factor receptor (EGFR) signaling by interrupting c-Cbl-CIN85 complex and inhibiting EGFR degradation. It contains a BTB/POZ domain, also known as tetramerization (T1) domain, a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937818  25 EVVELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDTAndlaKDSKGRFFIDRDGFLFRYILDYLRDRQvvLPDHFPEKG 104
Cdd:cd18393    2 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTL----KDETGAIFIDRDPTVFAPILNFLRTKE--LDPRGIHVS 75

                         90       100
                 ....*....|....*....|....*..
gi 767937818 105 RLKREAEYFQLPDLV-KLLTPDEIKQS 130
Cdd:cd18393   76 LLLHEAQFYGITPLVrRLQLCEELDRS 102

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 19 (KCTD19); KCTD19 is a BTB/POZ domain-containing protein with unclear biological function. It may be a host factor involved in Nef-induced downregulation of MHC-I. Nef is a HIV-1-encoded protein that plays a key role in the development of AIDS. KCTD19 contains two BTB domains. This model corresponds to the first 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767937818  30 NVGGQVYFTRHSTLISIPHSLLWKmfspkrdTANDLAKDSKGRFFIDRDGFLFRYILDYLRDRQV 94
Cdd:cd18373    4 NVGGWIFSVPKSKLAQFPDSLLWK-------EASSLSESENTRLFIDRDGFTFRHVHYYLQTSKL 61

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767937818  29 LNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDTANDLAKDSK---GRFFIDRDGFLFRYILDYLR 90
Cdd:cd18424    3 INVGGSRFVLSQQVLSSHPETRLGKLAVSVRDSVLELCDDANfvdNEYFFDRSSQAFKYIMNYYK 67

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767937818  27 VELNVGGQVYFTRHSTLISIPHSLLWKMFSPKRDTANdlAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLP 97
Cdd:cd18379    1 IVINVGGVRHETYKSTLRNLPDTRLAWLTETEASAFD--YDPVTGEFFFDRHPGVFAQILNYYRTGKLHCP 69

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767937818  25 EVVELNVGGQVYFTRHSTLISIPHSLLWkmfSPKRDTANDlaKDSKGRFFiDRDGFLFRYILDYLRDRQVVLPDH 99
Cdd:cd18420   36 EKLIINVSGRRFETWRNTLEKYPDTLLG---SNEREFFYD--EETKEYFF-DRDPDIFRHILNYYRTGKLHYPKH 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767937818  26 VVELNVGGQVYFTRHSTLISIPHSLLWkmfSPKRDTandLAKDSKGRFFIDRDGFLFRYILDYLRDRQVVLPDH 99
Cdd:cd18418    1 LIVLNVSGTRFQTWRNTLERYPDTLLG---SSERDF---FYHEETQEYFFDRDPDIFRHILNFYRTGKLHYPRH 68

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily D member 3 (KCND3); KCND3, also called voltage-gated potassium channel subunit Kv4.3, is a pore-forming subunit of voltage-gated rapidly inactivating A-type potassium channels. Mutations in KCND3 cause spinocerebellar ataxia. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. KCND3 is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other Kv4/KCND alpha subunits) through its BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif. It is modulated by cytoplasmic KChIPs/KCNIPs (Kv-channel interacting proteins), which are small calcium binding proteins with EF-hand-like domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767937818  25 EVVELNVGGQVYFTRHSTLISIPHSLLWKmfSPKRDTANDLAKDskgrFFIDRDGFLFRYILDYLRDRQVVLPDH 99
Cdd:cd18419   35 ELIVLNVSGRRFQTWRTTLERYPDTLLGS--TEKEFFFNEDTKE----YFFDRDPEVFRCVLNFYRTGKLHYPRY 103