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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748  99 CPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECEESpcwgggageevpcrdfqgrtqslg 178
Cdd:cd18355     1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 179 saeegkegpqrtpqadpgassgqdlpeslalqmeasgseghaLSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSMQS 258
Cdd:cd18355    57 ------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQH 94

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907077748 259 GPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 310
Cdd:cd18355    95 GPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 146

P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1907077748  10 FKRPIKRGDILPPEKGREVAKELGIPYYETSVFDQFGIKDVFDNAIRAA 58
Cdd:cd01873   147 LARPIKNADILPPETGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB1 functions as a tumor suppressor that regulates the integrity of the Golgi complex through the methyltransferase METTL7B. It also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748  99 CPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECEESpcwgggageevpcrdfqgrtqslg 178
Cdd:cd18355     1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 179 saeegkegpqrtpqadpgassgqdlpeslalqmeasgseghaLSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSMQS 258
Cdd:cd18355    57 ------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQH 94

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907077748 259 GPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 310
Cdd:cd18355    95 GPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 146

RhoBTB protein is an atypical member of the Rho family of small GTPases; Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila, and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric a brac) domains, and a C-terminal region of unknown function. RhoBTB proteins may act as docking points for multiple components participating in signal transduction cascades. RhoBTB genes appeared upregulated in some cancer cell lines, suggesting a participation of RhoBTB proteins in the pathogenesis of particular tumors. Note that the Dictyostelium RacA GTPase domain is more closely related to Rac proteins than to RhoBTB proteins, where RacA actually belongs. Thus, the Dictyostelium RacA is not included here. Most Rho proteins contain a lipid modification site at the C-terminus; however, RhoBTB is one of few Rho subfamilies that lack this feature.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1907077748  10 FKRPIKRGDILPPEKGREVAKELGIPYYETSVFDQFGIKDVFDNAIRAA 58
Cdd:cd01873   147 LARPIKNADILPPETGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

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 1907077748  336 DVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLDpLELIALANR 415
Cdd:smart00225   1 DVTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYTGKLDLPEENV-EELLELADY 79

                           90
                   ....*....|....*...
gi 1907077748  416 FCLTHLVALVEQHAVQEL 433
Cdd:smart00225  80 LQIPGLVELCEEFLLKLL 97

Rho (Ras homology) subfamily of Ras-like small GTPases; Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1907077748   22 PEKGREVAKELG-IPYYETSVFDQFGIKDVFDNAIRAAL 59
Cdd:smart00174 134 YEQGQALAKRIGaVKYLECSALTQEGVREVFEEAIRAAL 172

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB1 functions as a tumor suppressor that regulates the integrity of the Golgi complex through the methyltransferase METTL7B. It also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748  99 CPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECEESpcwgggageevpcrdfqgrtqslg 178
Cdd:cd18355     1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 179 saeegkegpqrtpqadpgassgqdlpeslalqmeasgseghaLSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSMQS 258
Cdd:cd18355    57 ------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQH 94

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907077748 259 GPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 310
Cdd:cd18355    95 GPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 146

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 2 (RhoBTB2); RhoBTB2, also called Deleted in breast cancer 2 gene protein (DBC2) or p83, is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB2 functions as a tumor suppressor that regulates the expression of the methyltransferase METTL7A. It also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 315 KAFHVRKANRIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLY 394
Cdd:cd18359     1 KAFHVRRTNRVKECLAKGTFSDVTFMLDDGTISAHKPLLISSCDWMAAMFGGPFVESSTTEVVFPYTSRSSMRAVLEYLY 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907077748 395 TKQLSPNLDLDPLELIALANRFCLTHLVALVEQHAVQELTKAA 437
Cdd:cd18359    81 TGQFSSSPDLDDMKLIILANRLCLPHLVALTEQYTVTVLMEAA 123

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing proteins (RhoBTB); RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases), which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, a tandem of 2 BTB domains, and a conserved C-terminal region. In humans, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 326 KECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLD 405
Cdd:cd18300     1 KLFLNKGLFSDVTFIVEDGTIPAHKALLVARCDVMAAMFGGNFRESSAKEVELPGVSKETFLALLEYLYTDQAPILEDGD 80

                          90       100
                  ....*....|....*....|....*...
gi 1907077748 406 PLELIALANRFCLTHLVALVEQHAVQEL 433
Cdd:cd18300    81 CVGLIVLANRLCLPRLVALCEQYIVKEL 108

BACK (BTB and C-terminal Kelch) domain found in Rho-related BTB domain-containing proteins (RhoBTB); RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases), which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline rich region, a tandem of 2 BTB domains, and a C-terminal BACK domain. In humans, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907077748 443 IDGEVLSYLELAQFHNANQLAAWCLHHICTNYNSVCsKFRKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKRE 519
Cdd:cd18499     1 IDEDVIDLLELAQLHNADQLAAWCLHFISTNYNAFC-KHRKEFKLLSPENQEYIEEHRWPPVWYLKELDEYEKKLKE 76

RhoBTB protein is an atypical member of the Rho family of small GTPases; Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila, and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric a brac) domains, and a C-terminal region of unknown function. RhoBTB proteins may act as docking points for multiple components participating in signal transduction cascades. RhoBTB genes appeared upregulated in some cancer cell lines, suggesting a participation of RhoBTB proteins in the pathogenesis of particular tumors. Note that the Dictyostelium RacA GTPase domain is more closely related to Rac proteins than to RhoBTB proteins, where RacA actually belongs. Thus, the Dictyostelium RacA is not included here. Most Rho proteins contain a lipid modification site at the C-terminus; however, RhoBTB is one of few Rho subfamilies that lack this feature.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1907077748  10 FKRPIKRGDILPPEKGREVAKELGIPYYETSVFDQFGIKDVFDNAIRAA 58
Cdd:cd01873   147 LARPIKNADILPPETGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 9 (BTBD9); BTBD9 is a risk factor for Restless Legs Syndrome (RLS) encoding a Cullin-3 substrate adaptor. The BTBD9 gene may be associated with antipsychotic-induced RLS in schizophrenia. Mutations in BTBD9 lead to reduced dopamine, increased locomotion and sleep fragmentation. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 325 IKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLS-PNLD 403
Cdd:cd18287    13 IGALFLNEEYSDVTFVVEEKRFPAHRVILAARSEYFRALLYGGMRESQQSEIELKDTNAEAFKALLKYIYTGRLTlTDLK 92

                          90       100
                  ....*....|....*....|....*.
gi 1907077748 404 LDP-LELIALANRFCLTHLVALVEQH 428
Cdd:cd18287    93 EDVlLDVLGLAHQYGFEELEAAISDY 118

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 8 (BTBD8); BTBD8 is a BTB-domain-containing Kelch-like protein that may play a role in developmental processes. It may also act as a protein-protein adaptor in a transcription complex and thus be involved in brain development. BTBD8 contains two BTB domains. This model corresponds to the second domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 331 KGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLDPLELI 410
Cdd:cd18286    14 NGEDSDITIKVDGKTFKAHRCILCARSSYFAAMLSGSWAESNSSEITLTGVSHAAVSFVLLFIYGGVLDLPDDVNLGELL 93

                          90
                  ....*....|....*...
gi 1907077748 411 ALANRFCLTHLVALVEQH 428
Cdd:cd18286    94 SLADMYGLDGLKDVVAYT 111

BACK (BTB and C-terminal Kelch) domain found in Rho-related BTB domain-containing protein 3 (RhoBTB3); RhoBTB3 is an atypical member of the Rho GTPase family of signaling proteins, which is characterized by containing a carboxyl terminal extension that harbors two BTB domains and a BACK domain and is capable of assembling cullin 3-dependent ubiquitin ligase complexes. It is a Golgi-associated Rho-related ATPase that regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. RhoBTB3 is involved in vesicle trafficking and in targeting proteins for degradation in the proteasome. It binds directly to Rab9 GTPase and functions with Rab9 in protein transport from endosomes to the trans Golgi network. It also promotes proteasomal degradation of Hypoxia-inducible factor alpha (HIFalpha) by facilitating hydroxylation and ubiquitination.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907077748 447 VLSYLELAQFHNANQLAAWCLHHICTNYNSVCSKfrKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKRER 520
Cdd:cd18532     5 VVSLLRKAKFHNADQLSTWLLHFIASNYLIFSQK--PEFQDLSAEERDFVETHRWPSSMYLQELAEYRQHIHSR 76

BTB (Broad-Complex, Tramtrack and Bric a brac) /POZ (poxvirus and zinc finger) domain found in Dictyostelium discoideum trishanku and similar proteins; Trishanku is a novel regulator required for normal morphogenesis and cell-type stability in Dictyostelium discoideum. It contains a BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 334 FSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLDpLELIALA 413
Cdd:cd18314     6 FSDVVLCVGDRKFFAHRIVLCARSPVFRSMLTGSMIESNLKEVTLEDVEPEIFETVLKYMYTGQVTLSEENV-LDLLMLA 84

                          90
                  ....*....|.
gi 1907077748 414 NRFCLTHLVAL 424
Cdd:cd18314    85 SKYQVPDLEKL 95

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Ankyrin repeat and BTB/POZ domain-containing protein 2 (ABTB2) and similar proteins; This family includes ABTB2, BTBD11, plant ARM repeat protein interacting with ABF2 (ARIA), and similar proteins. ABTB2, also called bood POZ containing gene type 2 (BPOZ-2), is a scaffold protein that controls the degradation of many biological proteins ranging from embryonic development to tumor progression. It may be involved in the initiation of hepatocyte growth. ABTB2 functions as an adaptor protein for the E3 ubiquitin ligase scaffold protein Cullin-3. It directly binds to eukaryotic elongation factor 1A1 (eEF1A1) to promote eEF1A1 ubiquitylation and degradation, and prevent translation. The BTBD11 gene has been recently identified as an all-trans retinoic acid (atRA)-responsive gene that lies downstream of atRA and its receptors in the regulation of neurite outgrowth and cell adhesion in neural as well as non-neural tissues. ARIA is an armadillo (ARM) repeat and BTB domain-containing protein that acts as a positive regulator of ABA response via the modulation of the transcriptional activity of ABF2. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 333 TFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSpNLDLDP---LEL 409
Cdd:cd18297    11 EMSDVTFLVEGRPFYAHKIVLVTASDRFKSMLSSGSTEAQTPVIEIPDIRYDIFQLMMQYLYTGGVE-SLDVAQddaLEL 89

                          90
                  ....*....|....*..
gi 1907077748 410 IALANRFCLTHLVALVE 426
Cdd:cd18297    90 LRAASFFQLDGLKRHCE 106

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 26 (KLHL26); KLHL26 is encoded by the klhl26 gene, which is regulated by p53 via fuzzy tandem repeats. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 330 SKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSpnLDLDPLE- 408
Cdd:cd18255    14 AKGQLLDVTLIADGQRFQAHKVVLASCSDYFRAMFTGGMRESSQDEIELKGVSAKGLKHILDFAYTSELT--LDLDCIQd 91

                          90       100
                  ....*....|....*....|....*.
gi 1907077748 409 LIALANRFCLTHLVALVEQHAVQELT 434
Cdd:cd18255    92 VLGAAVHLQMLPVVELCEEFLKSAMS 117

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 337 VTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDlDPLELIALANRF 416
Cdd:cd01165     1 VVLVVEGEKFHVNKELLAQSSEYFRALFRGGFRESGQAEINLRDISPEDFRALLEFLYGGKRDLDAS-NLLELLEAANFL 79

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3); KLHL3 is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. It contains a BTB domain and kelch repeat domains, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 318 HVRKANRI-KECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTK 396
Cdd:cd18339     4 HMKKAFKVmNELRSKQLLCDVTIVAEDVEIEAHRVVLAACSPYFCAMFTGDMSESKAKKIEIKDVDGQTLSKLIDYIYTA 83

                  ..
gi 1907077748 397 QL 398
Cdd:cd18339    84 EI 85

Ras homology family (Rho) of small guanosine triphosphatases (GTPases); Members of the Rho (Ras homology) family include RhoA, Cdc42, Rac, Rnd, Wrch1, RhoBTB, and Rop. There are 22 human Rho family members identified currently. These proteins are all involved in the reorganization of the actin cytoskeleton in response to external stimuli. They also have roles in cell transformation by Ras in cytokinesis, in focal adhesion formation and in the stimulation of stress-activated kinase. These various functions are controlled through distinct effector proteins and mediated through a GTP-binding/GTPase cycle involving three classes of regulating proteins: GAPs (GTPase-activating proteins), GEFs (guanine nucleotide exchange factors), and GDIs (guanine nucleotide dissociation inhibitors). Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Since crystal structures often lack C-terminal residues, this feature is not available for annotation in many of the CDs in the hierarchy.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907077748   6 KGKVFKRPIKRGDILPPEKGREVAKELG-IPYYETSVFDQFGIKDVFDNAIRA 57
Cdd:cd00157   119 DGNTLKKLEKKQKPITPEEGEKLAKEIGaVKYMECSALTQEGLKEVFDEAIRA 171

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 7 (KLHL7); KLHL7 is a component of a Cul3-based E3 ubiquitin ligase complex and is involved in the ubiquitination of target proteins for proteasome-mediated degradation. Mutations in KLHL7 causes autosomal-dominant retinitis pigmentosa. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 331 KGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNlDLDPLELI 410
Cdd:cd18237    18 QKTLCDVILIVEGREIKAHRVVLAAASHFFHLMFTSNMTESKSSEVELKDAEPDIIELLVEFAYTARISVN-SNNVQSLL 96

                  ....*.
gi 1907077748 411 ALANRF 416
Cdd:cd18237    97 DAANQY 102

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 32 (KLHL32); KLHL32, also called BTB and kelch domain-containing protein 5 (BKLHD5), contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. Deletion of KLHL32 may be ssociated with Tourette syndrome and obsessive-compulsive disorder. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 330 SKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQ--LSPNLDLDpl 407
Cdd:cd18261    24 NDGILCDITLVAEEQKFHAHKAVLAACSDYFRAMFSLCMVESEADEVNLHGVTSLGLKQALDFAYTGQilLEPGVIQD-- 101

                          90       100
                  ....*....|....*....|....*...
gi 1907077748 408 eLIALANRFCLTHLVALVEQHAVQELTK 435
Cdd:cd18261   102 -VLAAGSHLQLLELLSLCSHYLIQELNS 128

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 18 (KLHL18); KLHL18 acts as a substrate-specific adaptor for a Cullin3 E3 ubiquitin-protein ligase complex that regulates mitotic entry and ubiquitylates Aurora-A. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907077748 324 RIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQL 398
Cdd:cd18247     9 VMEEIRRQGKLCDVTLKVGDQKFSAHRIVLAATIPYFHAMFTHDMVESKQDEITMQGIEPSALEALINFAYSGRI 83

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in rabankyrin-5 (Rank-5); Rank-5, also called ankyrin repeat and FYVE domain-containing protein 1 (ANKFY1) or ankyrin repeats hooked to a zinc finger motif (ANKHZN), is a Rab5 effector that regulates and coordinates different endocytic mechanisms. It contains an N-terminal BTB domain, followed by a BACK domain, several ankyrin (ANK) repeats and a C-terminal FYVE domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 325 IKECLSKGTFSDVTFTLDDGAISAHKPLLIC-SCEWmaamfggSFVESAN-REVHLPNINKMSMQAVLEYLYTKQLSPNL 402
Cdd:cd18303     9 VASLFDKELYSDITIKLADKSIPAHKFVLAArSEKW-------SNENLAStNELDLSDISYEVVLALLRWLYTDELDLTL 81

                          90       100
                  ....*....|....*....|....*.
gi 1907077748 403 DLDPL-ELIALANRFCLTHLVALVEQ 427
Cdd:cd18303    82 DDEFLlELMKAAKRFQLTDLVERCER 107

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins KLHL9 and KLHL13; KLHL9 and KLHL13 (also called BTB and kelch domain-containing protein 2, or BKLHD2) are substrate-specific adaptors of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes, thereby coordinating faithful mitotic progression and completion of cytokinesis. They contain a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 330 SKGTFSDVTFTLDDG--AISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLD--LD 405
Cdd:cd18239    19 GEGLLCDVTLVPGDGdeTFPVHRAMMASASDYFKAMFTGGMKEQELMCIKLHGVSKIGLKNIIDFIYTAKLSLNMDnlQD 98

                  ...
gi 1907077748 406 PLE 408
Cdd:cd18239    99 TLE 101

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 36 (KLHL36); KLHL36 may act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907077748 324 RIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLS 399
Cdd:cd18266    15 GLNEQRQRGLFCDVVLVADEQRVPAHRNLLAVCSDYFNSMFTIGMREAHQKEVELVGASYIGLKAVIDFLYSSELP 90

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins, KLHL40 and KLHL41; This family includes Kelch-like proteins, KLHL40 and KLHL41. KLHL40 is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development. KLHL41 is a novel kelch related protein that is involved in pseudopod elongation in transformed cells. They both contain a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 325 IKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNlDL 404
Cdd:cd18269    18 LKDLLDENKFVDCVLKIGDKEFPCHRLVLAACSPYFRAMFLSDLEESKKKEVVLEDVDPDVMGMILKYLYTSEIDLN-DQ 96

                          90
                  ....*....|..
gi 1907077748 405 DPLELIALANRF 416
Cdd:cd18269    97 NVQDIFALASRF 108

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins KLHL1, KLHL4 and KLHL5; This family contains the Kelch-like proteins: KLHL1, KLHL4 and KLHL5, all of which share high identity and similarity with the Drosophila kelch protein, a component of ring canals. KLHL1 is a neuronal actin-binding protein that modulates voltage-gated CaV2.1 (P/Q-type) and CaV3.2 (alpha1H T-type) calcium channels. Family members contain a BTB domain and kelch repeat domains, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 335 SDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLspNLDLDPLE-LIALA 413
Cdd:cd18234     2 CDVILIAGDRRIPAHRLVLSAVSDYFAAMFTNDVREATEEEIKLKDVDPDALWTLVQYCYTGRL--ELKEDNVEsLLATA 79

                          90
                  ....*....|...
gi 1907077748 414 nrfCLTHLVALVE 426
Cdd:cd18234    80 ---CLLQLSEVVE 89

BTB (Broad-Complex, Tramtrack and Bric a brac) /POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster proteins bric-a-brac 1 (BAB1), bric-a-brac 2 (BAB2), modifier of mdg4 (doom), and similar proteins; BAB1 and BAB2 probably act as transcriptional regulators that are required for specification of the tarsal segment and are involved in antenna development. Doom is a product of the Drosophila mod(mdg4) gene. It induces apoptosis and binds to baculovirus inhibitor-of-apoptosis proteins. This subfamily also includes Drosophila melanogaster sex determination protein fruitless (FRU), protein jim lovell (LOV), zinc finger protein chinmo, transcription factor GAGA, transcription factor Ken, and longitudinals lacking proteins (LOLA). FRU probably acts as a transcriptional regulator that plays a role in male courtship behavior and sexual orientation, and enhances male-specific expression of takeout in brain-associated fat body. LOV, also called tyrosine kinase-related (TKR), has a regulatory role during midline cell development. Chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila. GAGA is a transcriptional activator that functions by regulating chromatin structure. Ken, also termed protein Ken and Barbie, is a transcription factor required for Terminalia development. LOLA proteins are putative transcription factors required for axon growth and guidance in the central and peripheral nervous systems. Proteins in this subfamily contain a BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 334 FSDVTFTLDDGAISAHKPLLI-CSCeWMAAMFGgSFVESANREVHLPNINKMSMQAVLEYLYTKQLS-PNLDLDPLELIA 411
Cdd:cd18315     1 LVDVTLACEGGSLKAHKLVLAaASP-YFAALLK-ETPPDEHPVIILPDVPYSELKALLDFIYTGEVNvSQEQLESLLKLA 78

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in inhibitor of Bruton tyrosine kinase (IBtk); IBtk is an inhibitor or negative regulator of Bruton tyrosine kinase (Btk), which is required for B-cell differentiation and development. IBtk binds to the PH domain of Btk and down-regulates the Btk kinase activity. It contains two BTB domains. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 334 FSDVTFTLDDG-AISAHKPLLICSCEWMAAMFGGSFVE-SANREVHLPnINKMSMQAVLEYLYTKQLSP---NLDLDPL- 407
Cdd:cd18302     5 LYDVTIVSEDGkEFPCHKCVLVARLEYFHSMLSSSWIEaSSCSALTMP-IPSDILEIILDYLYTDEASAvkeSQNVEFLc 83

                          90       100
                  ....*....|....*....|....*..
gi 1907077748 408 ELIALANRFCLTHLVALVEQHAVQELT 434
Cdd:cd18302    84 NVLVIADQLLITRLKEICEVALVELLS 110

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 30 (KLHL30); KLHL30 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907077748 334 FSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPN 401
Cdd:cd18259    32 LSDVTLLVGGREFPCHRSVLALCSHYFNAMFTGDFVESISARVEIKDVDPAVMESLIDFAYTGKLTIN 99

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in RCC1 and BTB domain-containing protein 1 (RCBTB1); RCBTB1 is also called chronic lymphocytic leukemia deletion region gene 7 protein (CLLD7), CLL deletion region gene 7 protein, regulator of chromosome condensation and BTB domain-containing protein 1, or E4.5. It is a novel chromosome condensation regulator-like guanine nucleotide exchange factor that may be involved in cell cycle regulation by chromatin remodeling. It may also function as a tumor suppressor that regulates pathways of DNA damage/repair and apoptosis. RCBTB1 may also be a substrate adaptor for a cullin3 (CUL3) E3 ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Biallelic mutations in RCBTB1 may cause isolated and syndromic retinal dystrophy. It contains an RCC1 repeat, a BTB domain, and a BACK domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907077748 318 HVRKANRIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKq 397
Cdd:cd18353     4 FLTVAESLKKEFDSPETSDLKFRVDGKYIHVHKAVLKIRCEHFRTMFQSHWNEDMKEVIEIDQFSYPVYRAFLEYLYTD- 82

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1907077748 398 lspNLDLDP---LELIALANRFCLTHLVALVEQ 427
Cdd:cd18353    83 ---SVDLPPedaIGLLDLATSYCENRLKKLCQH 112

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 12 (KLHL12); KLHL12, also called CUL3-interacting protein 1 (C3IP1) or DKIR homolog, is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of the Wnt signaling pathway and ER-Golgi transport. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907077748 331 KGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQ 397
Cdd:cd18242    18 SNTLCDVTLRVEGKEFPAHRIVLAACSDYFCAMFTSEMSEKGKSEVELQGLTASTMEILLDFVYTET 84

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 38 (KLHL38); KLHL38 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The KLHL38 gene is significantly up-regulated during diapause, a temporary arrest of development during early ontogeny. It may also function in preadipocyte differentiation in the chicken. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907077748 334 FSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDL 404
Cdd:cd18268    23 LTDVILCTGDKEIPCHRNVLASSSPYFRAMFCNNFRESSQAKVDLKGIDSDVLDQIVDYVYTGEILITRDN 93