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 1958758824 279 GEEYSQILYS--SKLYRFfkyieNRDVAKtvLKERGLKNIRI 318
Cdd:cd13176     2 GEEDEEVLFShrAKLYRF-----DKDVKQ--WKERGVGDIKI 36

BTB/POZ domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958758824 117 KVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNEKGEYEIAEGISATVFRTVLDYYKTGIINCPDGISIPD 196
Cdd:pfam16017   1 RLTLVVDGTRFVVDPSLFTAHPDTMLGRMFGSSMERNFTRPNEKGEYEIAEGISSTVFRAILDYYKTGVIRCPPSVSIPE 80

                          90       100
                  ....*....|....*....|....*.
gi 1958758824 197 LRDTCDYLCINFDFNTIRCQDLSALL 222
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 1958758824 279 GEEYSQILYS--SKLYRFfkyieNRDVAKtvLKERGLKNIRI 318
Cdd:cd13176     2 GEEDEEVLFShrAKLYRF-----DKDVKQ--WKERGVGDIKI 36

BTB/POZ domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958758824 117 KVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNEKGEYEIAEGISATVFRTVLDYYKTGIINCPDGISIPD 196
Cdd:pfam16017   1 RLTLVVDGTRFVVDPSLFTAHPDTMLGRMFGSSMERNFTRPNEKGEYEIAEGISSTVFRAILDYYKTGVIRCPPSVSIPE 80

                          90       100
                  ....*....|....*....|....*.
gi 1958758824 197 LRDTCDYLCINFDFNTIRCQDLSALL 222
Cdd:pfam16017  81 LREACDYLLIPFDATTIKCQNLRALL 106

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 20 (KCTD20) and BTB/POZ domain-containing protein 10 (BTBD10); KCTD20, also termed potassium channel tetramerization domain containing 20, is a positive regulator of Akt signaling. It may play an important role in regulating the death and growth of some non-nervous and nervous cells. BTBD10, also termed 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958758824 116 EKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNEKGEYEIAEGISATVFRTVLDYYKTGIINCPDGISIP 195
Cdd:cd18318     1 EKVTLVVDGTRFVVDPSLFTAHPDTMLGRMFGSGLENNFTRPNERGEYEVADGISATVFRAILDYYKTGIIRCPPSVSVA 80

                          90
                  ....*....|..
gi 1958758824 196 DLRDTCDYLCIN 207
Cdd:cd18318    81 ELREACDYLLIP 92

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 1958758824  118 VTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREynftrpNEKGEYEIaEGISATVFRTVLDYYKTGIINCPDGiSIPDL 197
Cdd:smart00225   2 VTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKE------SDKSEIYL-DDVSPEDFRALLNFLYTGKLDLPEE-NVEEL 73

                   ....*....
gi 1958758824  198 RDTCDYLCI 206
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; 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 1958758824 118 VTLLVDGTRFVVNPQIFTAHPDTMLGRMFgpgREYNFTRPNEKGEYEIAEgiSATVFRTVLDYYKTGIINCP-DGISIPD 196
Cdd:cd18316     1 VKLNVGGTLFTTSRSTLLKDPDSLLAALF---SGRWPLPRDEDGSIFIDR--DPELFRHILNFLRTGKLPLPsDFVELEE 75

                  ....*...
gi 1958758824 197 LRDTCDYL 204
Cdd:cd18316    76 LLAEAEFY 83

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 1958758824 115 PEKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREYNFTRPNeKGEYEI-AEGIsatVFRTVLDYYKTGIINCPDG 191
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 protein 6 (KCTD6); KCTD6, also called KCTD containing, Cullin3 adaptor, suppressor of Hedgehog 3 (KCASH3), is a BTB/POZ domain-containing protein that functions as a substrate-specific adaptor of cullin-3, regulating protein levels of the muscle small ankyrin-1 isoform 5 (sAnk1.5) as well as suppressing histone deacetylase and Hedgehog activity in medulloblastoma. The BTB/POZ domain, also known as tetramerization (T1) domain, is a versatile protein-protein interaction motif that facilitates homodimerization or heterodimerization. KCTD family BTB domains can adopt a wide range of oligomerization geometries, including homodimerization, tetramerization, and pentamerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958758824 118 VTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGREynfTRPNEKGEYEIAEgiSATVFRTVLDYYKTGIINCPDGISIPD- 196
Cdd:cd18394     5 VTLNVGGHLYTTSLSTLTRYPDSMLGAMFRGDFP---TARDSQGNYFIDR--DGPLFRYILNFLRTSELTLPVDFKEFDl 79

                          90
                  ....*....|
gi 1958758824 197 LRDTCDYLCI 206
Cdd:cd18394    80 LRKEADFYQI 89

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 1958758824 118 VTLLVDGTRFVVNPQIFTAHPDTMLGrmfgpGREYNFTRPNEKGEYEIAEgiSATVFRTVLDYYKTGIINCP 189
Cdd:cd18418     2 IVLNVSGTRFQTWRNTLERYPDTLLG-----SSERDFFYHEETQEYFFDR--DPDIFRHILNFYRTGKLHYP 66

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 1958758824 116 EKVTLLVDGTRFVVNPQIFTAHPDTMLGRmfgPGREYNFTrpNEKGEYEIAEgiSATVFRTVLDYYKTGIINCP 189
Cdd:cd18419    35 ELIVLNVSGRRFQTWRTTLERYPDTLLGS---TEKEFFFN--EDTKEYFFDR--DPEVFRCVLNFYRTGKLHYP 101

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 16 (KCTD16); KCTD16 is a BTB/POZ domain-containing protein that is an auxiliary subunit of GABAB 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. 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 1958758824 115 PEKVTLLVDGTRFVVNPQIFTAHPDTMLGRMFGPGRE-YNFTRPNEKGEYEIAEgiSATVFRTVLDYYKTGIINCPD 190
Cdd:cd18398     2 PEVVELNVGGQVYFTRHATLVSIPHSLLWKMFSPKRDtANDLAKDSKGRFFIDR--DGFLFRYILDYLRDRQVVLPD 76

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 1958758824 117 KVTLLVDGTRFVVNPQIFTAHPDTMLGrmfGPGREYNFTrpNEKGEYEIAEgiSATVFRTVLDYYKTGIINCPDGISI 194
Cdd:cd18380     1 RIVINVSGRRFETWKNTLEKYPDTLLG---STEKEFFYD--DDTKEYFFDR--DPEIFRHILNFYRTGKLHYPRHECI 71

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 1958758824 279 GEEYSQILYS--SKLYRFfkyieNRDVAKtvLKERGLKNIRI 318
Cdd:cd13176     2 GEEDEEVLFShrAKLYRF-----DKDVKQ--WKERGVGDIKI 36