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 40807368     7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQREA 86
Cdd:pfam02214   1 VKLNVGGTRFETLKSTLTRFPDTRLGRLLELECDDYDDDTNEYFFDRSPKHFETILNFYRTGGKLHRPEEVCLDEFLEEA 80

                  ....*...
gi 40807368    87 LFYELRSL 94
Cdd:pfam02214  81 EFYGLDEL 88

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing 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 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQREA 86
Cdd:cd18316   1 VKLNVGGTLFTTSRSTLLKDPDSLLAALFSGRWPLPRDEDGSIFIDRDPELFRHILNFLRTGKLPLPSDFVELEELLAEA 80

                ...
gi 40807368  87 LFY 89
Cdd:cd18316  81 EFY 83

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 40807368   5 ELVTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQR 84
Cdd:cd18365   1 DIVNLNVGGVHYTTTLATLTRFPDSMLGAMFSGSMPTTRDDQGNYFIDRDGTLFRYILNFLRSSQLSLPEDFKEYDLLLR 80

                        90
                ....*....|....
gi 40807368  85 EALFYELRSLVDLL 98
Cdd:cd18365  81 EADFYQIEPLIEAL 94

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 21 (KCTD21); KCTD21, also calledz KCTD containing, Cullin3 adaptor, suppressor of Hedgehog 2 (KCASH2), is a BTB/POZ domain-containing protein that functions as a substrate-specific adaptor of cullin-3, promoting the ubiquitination and degradation of histone deacetylase HDAC1, thereby inhibiting the deacetylation-mediated transcriptional activation of the Hedgehog effectors Gli1 and Gli2. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQREA 86
Cdd:cd18395   3 ITLNVGGKLYTTSLATLTRYPDSMLGAMFSGKFPTKKDSQGNCFIDRDGKIFRYILNFLRTSHLDLPEDFQEMGLLKREA 82

                        90
                ....*....|..
gi 40807368  87 LFYELRSLVDLL 98
Cdd:cd18395  83 DFYQIQPLIEAL 94

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 12 (KCTD12); KCTD12, also called predominantly fetal expressed T1 domain (Pfetin), is a BTB/POZ domain-containing protein that is an auxiliary subunit of GABAB receptors associated with mood disorders. It regulates agonist potency and kinetics of GABAB receptor signaling. It promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A-dependent G2/M transition. It also regulates colorectal cancer cell stemness through the ERK pathway. 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 40807368   5 ELVTLNVGGKIFTTRFSTIKQFPASRLARMLD-------GRDQEfkmvgGQIFVDRDGDLFSFILDFLRTHQLLLPTEFS 77
Cdd:cd18397   3 EIVELNVGGQVYVTRHTTLVSVPDSLLWHMFSqqkpgelARDSK-----GRFFLDRDGFLFRYILDYLRDLQLVLPDYFP 77

                        90       100
                ....*....|....*....|...
gi 40807368  78 DYLRLQREALFYELRSLVDLLNP 100
Cdd:cd18397  78 ERSRLQREAEFFQLPELVKRLNP 100

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 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARM--------LDGRDQEFkmvggqiFVDRDGDLFSFILDFLRTHQLLLPTEFSD 78
Cdd:cd18361   1 VHIDVGGHIYTSSLETLTKYPESRLGKLfngsipivLDSLKQHY-------FIDRDGKMFRHILNFLRTSKLLLPDDFTE 73

                        90       100
                ....*....|....*....|
gi 40807368  79 YLRLQREALFYELRSLVDLL 98
Cdd:cd18361  74 FDLLYEEARYYELQPMVKQL 93

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 40807368   6 LVTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQRE 85
Cdd:cd18364   1 LVTLNVGGYLYITQRQTLTKYPDSFLEGMVNGKIQCTVDADGNYFIDRDGLLFRHVLNFLRNGELLLPEGFQENQLLALE 80

                ....*.
gi 40807368  86 ALFYEL 91
Cdd:cd18364  81 ADFYQL 86

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 15 (KCTD15); KCTD15 is a BTB/POZ domain-containing protein that plays a role in the regulation of neural crest (NC) formation and other steps in embryonic development. It inhibits AP2 transcriptional activity by interaction with its activation domain. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. The KCTD1 BTB domains, closely related to KCTD15, form pentamers.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQ-EFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQRE 85
Cdd:cd18388   4 VHIDVGGHMYTSSLATLTKYPDSRISRLFNGTEPiVLDSLKQHYFIDRDGEIFRYILSFLRTSKLLLPEDFKDFNLLYEE 83

                        90
                ....*....|...
gi 40807368  86 ALFYELRSLVDLL 98
Cdd:cd18388  84 AKYYQLQPMVKEL 96

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 7 (KCTD7); KCTD7 is a BTB/POZ domain-containing protein that has an impact on K+ fluxes, neurotransmitter synthesis, and neuronal function. It functions as a regulator of potassium conductance in neurons, and is involved in the control of excitability of cortical neurons. Mutations in KCTD7 may cause progressive myoclonus epilepsy (PME). The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   5 ELVTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRtHQLLLPTEFSdyLRLQR 84
Cdd:cd18366   4 EVVPLNVGGMHFTTRLSTLRKYEDSMLAAMFSGRHHIPKDSEGRYFIDRDGSYFGYILNFLR-DGDLPPRERA--RAVYK 80

                        90
                ....*....|..
gi 40807368  85 EALFYELRSLVD 96
Cdd:cd18366  81 EAQYYGIGPLIE 92

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 40807368   5 ELVTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTefSDYLRLQR 84
Cdd:cd18363   2 DIINLNVGGKRFSTSRQTLTWIPDSFFTSLLSGRISSLKDETGAIFIDRDPKLFSIILNYLRTKEIDLRN--VDISSLRH 79

                ....*
gi 40807368  85 EALFY 89
Cdd:cd18363  80 EAEFY 84

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein KCTD11; KCTD11 may function as an antagonist of the Hedgehog pathway of cell proliferation and differentiation by affecting the nuclear transfer of transcription factor GLI1, thus maintaining cerebellar granule cells in the undifferentiated state. It is a probable substrate-specific adapter for a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex towards HDAC1. It contains a BTB/POZ domain; in some cases the domain may be truncated. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization. Variants of the human/mouse KCTD11 appear to contain truncated BTB/POZ domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMV----GGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRL 82
Cdd:cd18370   1 VTLNVGGTLYSTTLETLTRFPDSMLGAMFRAGTPIPPNLnmqgGGHYFIDRDGKAFRHILNFLRLGRLDLPRGYGETALL 80

                ....*...
gi 40807368  83 QREALFYE 90
Cdd:cd18370  81 RAEADFYQ 88

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 40807368   5 ELVTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQllLPTEFSDYLRLQR 84
Cdd:cd18393   2 EVIHLNVGGKRFSTSRQTLTWIPDSFFSSLLSGRISTLKDETGAIFIDRDPTVFAPILNFLRTKE--LDPRGIHVSLLLH 79

                        90
                ....*....|.
gi 40807368  85 EALFYELRSLV 95
Cdd:cd18393  80 EAQFYGITPLV 90

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 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQ--EFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTE 75
Cdd:cd18379   1 IVINVGGVRHETYKSTLRNLPDTRLAWLTETEASafDYDPVTGEFFFDRHPGVFAQILNYYRTGKLHCPAD 71

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 40807368   7 VTLNVGGKIFTTRFST-IKQfpASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQRE 85
Cdd:cd18369   1 VKLNVGGSLHYTTIGTlTKQ--DTMLRAMFSGRMEVLTDSEGWILIDRCGKHFGTILNYLRDGSVPLPESRRELAELLAE 78

                        90
                ....*....|.
gi 40807368  86 ALFYELRSLVD 96
Cdd:cd18369  79 AKYYLVQGLVE 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 40807368   7 VTLNVGGKIFTTRFSTIKQfPASRLARMLDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQREA 86
Cdd:cd18400   4 VKLNVGGSLHYTTVQTLTK-QDTMLKAMFSGRVEVLTDSEGWVLIDRSGRHFGTILNYLRDGSVPLPESTRELEELLGEA 82

                        90
                ....*....|
gi 40807368  87 LFYELRSLVD 96
Cdd:cd18400  83 RYYLVQGLVE 92

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 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGrDQEF---KMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQ 83
Cdd:cd18362   2 VKLNVGGTYFLTTRTTLCRDPKSFLCRLCQE-DPDLpsdKDETGAYLIDRDPTYFGPILNYLRHGKLIIDKDLAEEGVLE 80

                ....*.
gi 40807368  84 rEALFY 89
Cdd:cd18362  81 -EAEFY 85

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   6 LVTLNVGGKIFTTRFSTIKQFPASrlarMLDGRDQEF--KMVGGQIFVDRDGDLFSFILDFLRTHQLLLP 73
Cdd:cd18380   1 RIVINVSGRRFETWKNTLEKYPDT----LLGSTEKEFfyDDDTKEYFFDRDPEIFRHILNFYRTGKLHYP 66

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 40807368   6 LVTLNVGGKIFTTRFSTIKQFPASRLARmlDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLP 73
Cdd:cd18418   1 LIVLNVSGTRFQTWRNTLERYPDTLLGS--SERDFFYHEETQEYFFDRDPDIFRHILNFYRTGKLHYP 66

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 2 (KCTD2); KCTD2 is a BTB/POZ domain-containing protein that functions as an adaptor of Cullin3 E3 ubiquitin ligase. It suppresses gliomagenesis by destabilizing c-Myc. 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 domain, highly similar to KCTD2, form pentamer structures.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDgRDQEF---KMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFSDYLRLQ 83
Cdd:cd18389   3 VRLNVGGTYFVSTKQTLCRDPKSFLYRLCQ-EDPDLdsdKDETGAYLIDRDPTYFGPILNYLRHGKLIINKELAEEGVLE 81

                        90
                ....*....|....*
gi 40807368  84 rEALFYELRSLVDLL 98
Cdd:cd18389  82 -EAEFYNIASLVRLV 95

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 40807368   5 ELVTLNVGGKIFTTRFSTIKQFPASRLARmlDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLP 73
Cdd:cd18419  35 ELIVLNVSGRRFQTWRTTLERYPDTLLGS--TEKEFFFNEDTKEYFFDRDPEVFRCVLNFYRTGKLHYP 101

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 40807368   1 MSSQELVTLNVGGKIFTTRFSTIKQFPASrlarMLDGRDQEF--KMVGGQIFVDRDGDLFSFILDFLRTHQLLLP 73
Cdd:cd18417  31 RRNDEILVVNVSGRRFQTWKNTLDRYPDT----LLGSSEKEFfyNEDTQEYFFDRDPEMFRHILNFYRTGRLHYP 101

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQE--------FKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTE 75
Cdd:cd18378   4 VLLNVGGVRHEVLWRTLDRLPRTRLGRLRECNTHEsllelcddYDLEDNEYFFDRHPGAFTSILNFYRTGKLHMPEE 80

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster potassium voltage-gated channel protein Shal and similar proteins; Drosophila melanogaster Shal, also called Shaker cognate l or Shal2, is a transient potassium current (I(A)) channel, which is required for maintaining excitability during repetitive firing and normal locomotion in Drosophila. It may play a role in the nervous system and in the regulation of beating frequency in pacemaker cells. Shal mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. Shal is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other alpha subunits) through its BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   4 QELVTLNVGGKIFTTRFSTIKQFPASRLARmlDGRDQEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLP 73
Cdd:cd18420  35 DEKLIINVSGRRFETWRNTLEKYPDTLLGS--NEREFFYDEETKEYFFDRDPDIFRHILNYYRTGKLHYP 102

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 40807368   9 LNVGGKIFTTRFSTIKQFPASRLARMLDGRDQEFKM--------VGGQIFVDRDGDLFSFILDFLRTHQLLLPTEF 76
Cdd:cd18425   3 INVGGTSYQISYRVAASYPKTRIGRLATYTDRSRKLdlcddynvQNDEYFFDRDPAVFHHIYNFYRTGVLWVKDEL 78

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARMLDGRDQE--------FKMVGGQIFVDRDGDLFSFILDFLRTHQL 70
Cdd:cd18427   2 ISINVGGFKKRLRSHTLLRFPETRLGRLLSCRSKEsilelcddYDDTKNEFYFDRNPELFPYVLHFYNTGKL 73

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily G member 3 (KCNG3); KCNG3, also called voltage-gated potassium channel subunit Kv6.3 or voltage-gated potassium channel subunit Kv10.1, is an electrically silent modulatory subunit that can form functional heterotetrameric channels with KCNB1 (also known as Kv2.1), and further promotes a reduction in the rate of activation and inactivation of the delayed rectifier voltage-gated potassium channel 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. KCNG3 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARM------------LDGRDQEfkmvGGQIFVDRDGDLFSFILDFLRTHQL 70
Cdd:cd18422   1 VTLNVGGTRYSFSREVIKDFPLRRVSRLhgclseqdvlevCDDYDRE----RNEYFFDRHSEAFGFIMLYVKYGKL 72

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 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARM---------------LDGRDQEFkmvggqiFVDRDGDLFSFILDFLRTHQLL 71
Cdd:cd18423   4 IIINVGGIKYLMPWSTLDEFPLTRLGKLkfcssyeeivqicddYDEDTNEF-------FFDRNPCAFRMIVSFLAAGKLR 76

                ....
gi 40807368  72 LPTE 75
Cdd:cd18423  77 LLRE 80

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40807368   7 VTLNVGGKIFTTRFSTIKQFPASRLARM---------LDGRDqEFKMVGGQIFVDRDGDLFSFILDFLRTHQLLLPTEFS 77
Cdd:cd18421   6 VIINVGGIKYRIPWTTLEEFPLTRLGQLkscnnfdeiMDICD-DYDVTCNEFFFDRNPCAFRTILTFLRAGKLRLLREMC 84

                        90
                ....*....|..
gi 40807368  78 dYLRLQREALFY 89
Cdd:cd18421  85 -ALSFQEELLYW 95