Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 40255182 280 GEEYSQILYS--SKLYRFfkyieNRDVAKtvLKERGLKNIRI 319
Cdd:cd13176   2 GEEDEEVLFShrAKLYRF-----DKDVKQ--WKERGVGDIKI 36

BTB/POZ domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40255182   118 KVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNEKGEYEIAEGISATVFRTVLDYYKTGIINCPDGISIPD 197
Cdd:pfam16017   1 RLTLVVDGTRFVVDPSLFTAHPDTMLGRMFGSSMERNFTRPNEKGEYEIAEGISSTVFRAILDYYKTGVIRCPPSVSIPE 80

                          90       100
                  ....*....|....*....|....*.
gi 40255182   198 LRDTCDYLCINFDFNTIRCQDLSALL 223
Cdd:pfam16017  81 LREACDYLLIPFDATTIKCQNLRALL 106

Ran-binding protein 2, Ran binding domains; RanBP2 (also called E3 SUMO-protein ligase RanBP2, 358 kDa nucleoporin, and nuclear pore complex (NPC) protein Nup358) is a giant nucleoporin that localizes to the cytosolic face of the NPC. RanBP2 contains a leucine-rich region, 8 zinc-finger motifs, a cyclophilin A homologous domain, and 4 RanBDs. Ran is a Ras-like nuclear small GTPase, which regulates receptor-mediated transport between the nucleus and the cytoplasm. RanGTP hydrolysis is stimulated by RanGAP together with the Ran-binding domain containing acessory proteins RanBP1 and RanBP2. These accessory proteins stabilize the active GTP-bound form of Ran. All eukaryotic cells contain RanBP1, but in vertebrates however, the main RanBP seems to be RanBP2. There is no RanBP2 ortholog in yeast. Transport complex disassembly is accomplished by a small ubiquitin-related modifier-1 (SUMO-1)-modified version of RanGAP that is bound to RanBP2. RanBP1 acts as a second line of defense against exported RanGTP-importin complexes which have escaped from dissociation by RanBP2. RanBP2 also interacts with the importin subunit beta-1. RabBD shares structural similarity to the PH domain, but lacks detectable sequence similarity. The members here include human, chicken, frog, tunicates, sea urchins, ticks, sea anemones, and sponges. RanBD repeats 1 and 3 are present in this hierarchy.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 40255182 280 GEEYSQILYS--SKLYRFfkyieNRDVAKtvLKERGLKNIRI 319
Cdd:cd13176   2 GEEDEEVLFShrAKLYRF-----DKDVKQ--WKERGVGDIKI 36

BTB/POZ domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40255182   118 KVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNEKGEYEIAEGISATVFRTVLDYYKTGIINCPDGISIPD 197
Cdd:pfam16017   1 RLTLVVDGTRFVVDPSLFTAHPDTMLGRMFGSSMERNFTRPNEKGEYEIAEGISSTVFRAILDYYKTGVIRCPPSVSIPE 80

                          90       100
                  ....*....|....*....|....*.
gi 40255182   198 LRDTCDYLCINFDFNTIRCQDLSALL 223
Cdd:pfam16017  81 LREACDYLLIPFDATTIKCQNLRALL 106

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 10 (BTBD10); BTBD10, also called glucose metabolism-related protein 1 (GMRP1), plays a major role as an activator of AKT family members. It binds to Akt and protein phosphatase 2A (PP2A) and inhibits the PP2A-mediated dephosphorylation of Akt, thereby keeping Akt activated. It also plays a role in preventing motor neuronal death and accelerating the growth of pancreatic beta cells. BTBD10 contains a BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids. 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 40255182 117 EKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNEKGEYEIAEGISATVFRTVLDYYKTGIINCPDGISIP 196
Cdd:cd18385   3 ERVTLIVDNTRFVVDPSIFTAQPNTMLGRMFGSGREHNFTRPNEKGEYEVAEGISSTVFRAILDYYKTGIIRCPDGISIP 82

                        90       100
                ....*....|....*....|....*...
gi 40255182 197 DLRDTCDYLCINFDFNTIRCQDLSALLH 224
Cdd:cd18385  83 ELREACDYLCISFDYSTIKCRDLSALMH 110

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 40255182    119 VTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREynftrpNEKGEYEIaEGISATVFRTVLDYYKTGIINCPDGiSIPDL 198
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKE------SDKSEIYL-DDVSPEDFRALLNFLYTGKLDLPEE-NVEEL 73

                   ....*....
gi 40255182    199 RDTCDYLCI 207
Cdd:smart00225  74 LELADYLQI 82

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 40255182 116 PEKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNeKGEYEI-AEGIsatVFRTVLDYYKTGIINCPDG 192
Cdd:cd18367   2 PEIVELNVGGQVYTTSLSTLIKDPDSLLGRMFSGKNRQELARDS-KGRYFLdRDGV---LFRYILDYLRNQKLVLPEN 75

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 40255182 119 VTLLVDGTRFVVNPQIFTAHPDTMLGRMFgpgREYNFTRPNEKGEYEIAEgiSATVFRTVLDYYKTGIINCP-DGISIPD 197
Cdd:cd18316   1 VKLNVGGTLFTTSRSTLLKDPDSLLAALF---SGRWPLPRDEDGSIFIDR--DPELFRHILNFLRTGKLPLPsDFVELEE 75

                ....*...
gi 40255182 198 LRDTCDYL 205
Cdd:cd18316  76 LLAEAEFY 83

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40255182 109 SNSHSQAPEKVTLLVDGTRFVVNPQIFTAHPDTMLGRmfgPGREYNFTrpNEKGEYEIAEgiSATVFRTVLDYYKTGIIN 188
Cdd:cd18419  27 ADKNKRQDELIVLNVSGRRFQTWRTTLERYPDTLLGS---TEKEFFFN--EDTKEYFFDR--DPEVFRCVLNFYRTGKLH 99

                ..
gi 40255182 189 CP 190
Cdd:cd18419 100 YP 101

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 40255182 117 EKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFgPGREYNFTRPNekGEYEIAEgiSATVFRTVLDYYKTGIINCPDGIS 194
Cdd:cd18375   1 ELVTLNVGGKKFTTRPSTLRRFPDSRLARML-DGKDQDFKVVN--GQFFVDR--DGSLFSYILDYLRTGQLTLPTEFS 73

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 40255182 120 TLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGR---------------EYNFTRpnekgeyeiaegiSATVFRTVLDYYKT 184
Cdd:cd18424   2 TINVGGSRFVLSQQVLSSHPETRLGKLAVSVRdsvlelcddanfvdnEYFFDR-------------SSQAFKYIMNYYKT 68

                .
gi 40255182 185 G 185
Cdd:cd18424  69 G 69

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 40255182 117 EKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREynfTRPNEKGEYEIAEgiSATVFRTVLDYYKTGIINCPD 191
Cdd:cd18395   1 DPITLNVGGKLYTTSLATLTRYPDSMLGAMFSGKFP---TKKDSQGNCFIDR--DGKIFRYILNFLRTSHLDLPE 70

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 40255182 116 PEKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNEKGEYEIAEgiSATVFRTVLDYYKTGIINCPDGISI 195
Cdd:cd18414   2 SDRIVINVGGTRHETYRSTLRTLPGTRLAWLAEPDAHSNFDYDPRADEFFFDR--HPGVFAHILNYYRTGKLHCPADVCG 79

                .
gi 40255182 196 P 196
Cdd:cd18414  80 P 80

Ran-binding protein 2, Ran binding domains; RanBP2 (also called E3 SUMO-protein ligase RanBP2, 358 kDa nucleoporin, and nuclear pore complex (NPC) protein Nup358) is a giant nucleoporin that localizes to the cytosolic face of the NPC. RanBP2 contains a leucine-rich region, 8 zinc-finger motifs, a cyclophilin A homologous domain, and 4 RanBDs. Ran is a Ras-like nuclear small GTPase, which regulates receptor-mediated transport between the nucleus and the cytoplasm. RanGTP hydrolysis is stimulated by RanGAP together with the Ran-binding domain containing acessory proteins RanBP1 and RanBP2. These accessory proteins stabilize the active GTP-bound form of Ran. All eukaryotic cells contain RanBP1, but in vertebrates however, the main RanBP seems to be RanBP2. There is no RanBP2 ortholog in yeast. Transport complex disassembly is accomplished by a small ubiquitin-related modifier-1 (SUMO-1)-modified version of RanGAP that is bound to RanBP2. RanBP1 acts as a second line of defense against exported RanGTP-importin complexes which have escaped from dissociation by RanBP2. RanBP2 also interacts with the importin subunit beta-1. RabBD shares structural similarity to the PH domain, but lacks detectable sequence similarity. The members here include human, chicken, frog, tunicates, sea urchins, ticks, sea anemones, and sponges. RanBD repeats 1 and 3 are present in this hierarchy.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 40255182 280 GEEYSQILYS--SKLYRFfkyieNRDVAKtvLKERGLKNIRI 319
Cdd:cd13176   2 GEEDEEVLFShrAKLYRF-----DKDVKQ--WKERGVGDIKI 36