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 568968408 344 KAFHVRKANRIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLY 423
Cdd:cd18358    1 KAFHVRKANRIKECLSKGTFSDVTFKLDDGTINAHKPLLICSCEWMAAMFGGSFIESANSEVVLPNISKVSMQAVLDYLY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568968408 424 TKQLSPNLDLDPLELIALANRFCLTHLVALVEQHAVQELTKAAVSG 469
Cdd:cd18358   81 TKQLSPTADLDPLELIALANRFCLPHLVALTEQHAVQELTKASKSG 126

BACK (BTB and C-terminal Kelch) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 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 functions as a tumor suppressor that regulates the integrity of the Golgi complex through the methyltransferase METTL7B. RhoBTB1 also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408 472 IDGEVLSYLELAQFHNANQLAAWCLHHICTNYNSVCSKFRKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKREREK 551
Cdd:cd18530    1 IDGEVLTYLELAQFHNAHQLAAWCLHHICTNYNSVCSKFRKEIKSKSPENQEYFERHRWPPVWYLKEEDHYQRVKKEREK 80

                         90       100
                 ....*....|....*....|
gi 568968408 552 EDLALNKHHSRRKWCFWHSS 571
Cdd:cd18530   81 EDVALHKHHSKRKWCFWNSS 100

second 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 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 568968408 344 KAFHVRKANRIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLY 423
Cdd:cd18358    1 KAFHVRKANRIKECLSKGTFSDVTFKLDDGTINAHKPLLICSCEWMAAMFGGSFIESANSEVVLPNISKVSMQAVLDYLY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568968408 424 TKQLSPNLDLDPLELIALANRFCLTHLVALVEQHAVQELTKAAVSG 469
Cdd:cd18358   81 TKQLSPTADLDPLELIALANRFCLPHLVALTEQHAVQELTKASKSG 126

BACK (BTB and C-terminal Kelch) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 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 functions as a tumor suppressor that regulates the integrity of the Golgi complex through the methyltransferase METTL7B. RhoBTB1 also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408 472 IDGEVLSYLELAQFHNANQLAAWCLHHICTNYNSVCSKFRKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKREREK 551
Cdd:cd18530    1 IDGEVLTYLELAQFHNAHQLAAWCLHHICTNYNSVCSKFRKEIKSKSPENQEYFERHRWPPVWYLKEEDHYQRVKKEREK 80

                         90       100
                 ....*....|....*....|
gi 568968408 552 EDLALNKHHSRRKWCFWHSS 571
Cdd:cd18530   81 EDVALHKHHSKRKWCFWNSS 100

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        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408     1 MWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKGREVAKELG-IPYYETSVFDQFGIKDV 79
Cdd:smart00174  91 KWYPEVKHFCPNVPIILVGTKLDLR-NDKSTLEELSKKKQEPVT------YEQGQALAKRIGaVKYLECSALTQEGVREV 163

                   ....*....
gi 568968408    80 FDNAIRAAL 88
Cdd:smart00174 164 FEEAIRAAL 172

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 568968408   365 DVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLDpLELIALANR 444
Cdd:smart00225   1 DVTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYTGKLDLPEENV-EELLELADY 79

                           90
                   ....*....|....*...
gi 568968408   445 FCLTHLVALVEQHAVQEL 462
Cdd:smart00225  80 LQIPGLVELCEEFLLKLL 97

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
                   ....*....|....*....|....*....|....*....|....*
gi 568968408   290 FRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNK 334
Cdd:smart00225  51 FRALLNFLYTGKLDLPEENVEELLELADYLQIPGLVELCEEFLLK 95

second 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 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 568968408 344 KAFHVRKANRIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLY 423
Cdd:cd18358    1 KAFHVRKANRIKECLSKGTFSDVTFKLDDGTINAHKPLLICSCEWMAAMFGGSFIESANSEVVLPNISKVSMQAVLDYLY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568968408 424 TKQLSPNLDLDPLELIALANRFCLTHLVALVEQHAVQELTKAAVSG 469
Cdd:cd18358   81 TKQLSPTADLDPLELIALANRFCLPHLVALTEQHAVQELTKASKSG 126

BACK (BTB and C-terminal Kelch) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 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 functions as a tumor suppressor that regulates the integrity of the Golgi complex through the methyltransferase METTL7B. RhoBTB1 also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408 472 IDGEVLSYLELAQFHNANQLAAWCLHHICTNYNSVCSKFRKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKREREK 551
Cdd:cd18530    1 IDGEVLTYLELAQFHNAHQLAAWCLHHICTNYNSVCSKFRKEIKSKSPENQEYFERHRWPPVWYLKEEDHYQRVKKEREK 80

                         90       100
                 ....*....|....*....|
gi 568968408 552 EDLALNKHHSRRKWCFWHSS 571
Cdd:cd18530   81 EDVALHKHHSKRKWCFWNSS 100

BACK (BTB and C-terminal Kelch) 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 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 functions as a tumor suppressor that regulates the expression of the methyltransferase METTL7A. RhoBTB2 also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408 472 IDGEVLSYLELAQFHNANQLAAWCLHHICTNYNSVCSKFRKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKREREK 551
Cdd:cd18531    1 IDGQVLVYLELAQFHNAKQLADWCLHHICTNYNSVCRKFPRDMKAMSPENQEHFEKHRWPPVWYLKEEDRYLRSKKEREK 80

                         90
                 ....*....|....*..
gi 568968408 552 EDLALNKHHSRRKWCFW 568
Cdd:cd18531   81 EEELLRKQHPKRKWCFW 97

first 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 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 568968408 126 PECPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECeespcwgggageevpcrdfqgrtqs 205
Cdd:cd18356    1 PDPPTKSEEHPAHLLEDPLCADVILVLQERIRIYAHKIYLSTSSSKFYDLFLMDR------------------------- 55

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408 206 lgsaeegkegpqrtpqadpgassgqdlpeslalqmeasgseGHALSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSM 285
Cdd:cd18356   56 -----------------------------------------GRDLSSWSRAFVSIQEEVAEDPLTYKSRLMVVVKMDSSI 94

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568968408 286 QSGPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 339
Cdd:cd18356   95 QPGPFRAVLKYLYTGELDENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 148

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 568968408 472 IDGEVLSYLELAQFHNANQLAAWCLHHICTNYNSVCsKFRKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKRE 548
Cdd:cd18499    1 IDEDVIDLLELAQLHNADQLAAWCLHFISTNYNAFC-KHRKEFKLLSPENQEYIEEHRWPPVWYLKELDEYEKKLKE 76

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408   1 MWYQEIKHFCPRTPVVLVGCQLDLRYADLeavnrarrPLARPIKRGDILPPEKGREVAKELG-IPYYETSVFDQFGIKDV 79
Cdd:cd00157   93 KWYPEIKHYCPNVPIILVGTKIDLRDDGN--------TLKKLEKKQKPITPEEGEKLAKEIGaVKYMECSALTQEGLKEV 164

                 ....*..
gi 568968408  80 FDNAIRA 86
Cdd:cd00157  165 FDEAIRA 171

Ras homology family 4 (Rho4) of small guanosine triphosphatases (GTPases)-like; Rho4 is a GTPase that controls septum degradation by regulating secretion of Eng1 or Agn1 during cytokinesis. Rho4 also plays a role in cell morphogenesis. Rho4 regulates septation and cell morphology by controlling the actin cytoskeleton and cytoplasmic microtubules. The localization of Rho4 is modulated by Rdi1, which may function as a GDI, and by Rga9, which is believed to function as a GAP. In S. pombe, both Rho4 deletion and Rho4 overexpression result in a defective cell wall, suggesting a role for Rho4 in maintaining cell wall integrity. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408   1 MWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKGREVAKELG-IPYYETSVFDQFGIKDV 79
Cdd:cd04132   97 KWYPEVNHFCPGTPIVLVGLKTDLR-KDKNSVSKLRAQGLEPVT------PEQGESVAKSIGaVAYIECSAKLMENVDEV 169

                         90       100
                 ....*....|....*....|....
gi 568968408  80 FDNAIRAALiSRRHLQFWKSHLKK 103
Cdd:cd04132  170 FDAAINVAL-SKSGRAARKKKKKK 192

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 568968408 354 IKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLS-PNLD 432
Cdd:cd18287   13 IGALFLNEEYSDVTFVVEEKRFPAHRVILAARSEYFRALLYGGMRESQQSEIELKDTNAEAFKALLKYIYTGRLTlTDLK 92

                         90       100
                 ....*....|....*....|....*.
gi 568968408 433 LDP-LELIALANRFCLTHLVALVEQH 457
Cdd:cd18287   93 EDVlLDVLGLAHQYGFEELEAAISDY 118

cell division cycle 42 (Cdc42) is a small GTPase of the Rho family; Cdc42 is an essential GTPase that belongs to the Rho family of Ras-like GTPases. These proteins act as molecular switches by responding to exogenous and/or endogenous signals and relaying those signals to activate downstream components of a biological pathway. Cdc42 transduces signals to the actin cytoskeleton to initiate and maintain polarized growth and to mitogen-activated protein morphogenesis. In the budding yeast Saccharomyces cerevisiae, Cdc42 plays an important role in multiple actin-dependent morphogenetic events such as bud emergence, mating-projection formation, and pseudohyphal growth. In mammalian cells, Cdc42 regulates a variety of actin-dependent events and induces the JNK/SAPK protein kinase cascade, which leads to the activation of transcription factors within the nucleus. Cdc42 mediates these processes through interactions with a myriad of downstream effectors, whose number and regulation we are just starting to understand. In addition, Cdc42 has been implicated in a number of human diseases through interactions with its regulators and downstream effectors. 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. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408   2 WYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKGREVAKELG-IPYYETSVFDQFGIKDVF 80
Cdd:cd01874   95 WVPEITHHCPKTPFLLVGTQIDLR-DDPSTIEKLAKNKQKPIT------PETGEKLARDLKaVKYVECSALTQKGLKNVF 167

                 ....*...
gi 568968408  81 DNAIRAAL 88
Cdd:cd01874  168 DEAILAAL 175

Ras homology family A (RhoA)-like includes RhoA, RhoB and RhoC; The RhoA subfamily consists of RhoA, RhoB, and RhoC. RhoA promotes the formation of stress fibers and focal adhesions, regulating cell shape, attachment, and motility. RhoA can bind to multiple effector proteins, thereby triggering different downstream responses. In many cell types, RhoA mediates local assembly of the contractile ring, which is necessary for cytokinesis. RhoA is vital for muscle contraction; in vascular smooth muscle cells, RhoA plays a key role in cell contraction, differentiation, migration, and proliferation. RhoA activities appear to be elaborately regulated in a time- and space-dependent manner to control cytoskeletal changes. 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. RhoA and RhoC are observed only in geranylgeranylated forms; however, RhoB can be present in palmitoylated, farnesylated, and geranylgeranylated forms. RhoA and RhoC are highly relevant for tumor progression and invasiveness; however, RhoB has recently been suggested to be a tumor suppressor. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408   2 WYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKGREVAKELG-IPYYETSVFDQFGIKDVF 80
Cdd:cd01870   95 WTPEVKHFCPNVPIILVGNKKDLR-NDEHTIRELAKMKQEPVK------PEEGRAMAEKIGaFGYLECSAKTKEGVREVF 167

                 ....*...
gi 568968408  81 DNAIRAAL 88
Cdd:cd01870  168 EMATRAAL 175

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 568968408   365 DVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLDpLELIALANR 444
Cdd:smart00225   1 DVTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYTGKLDLPEENV-EELLELADY 79

                           90
                   ....*....|....*...
gi 568968408   445 FCLTHLVALVEQHAVQEL 462
Cdd:smart00225  80 LQIPGLVELCEEFLLKLL 97

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408    2 WYQEIKHFCP-RTPVVLVGCQLDLRyaDLEAVnrarrplarpikrgdilPPEKGREVAKELGIPYYETSVFDQFGIKDVF 80
Cdd:pfam00071  93 WVEEILRHADeNVPIVLVGNKCDLE--DQRVV-----------------STEEGEALAKELGLPFMETSAKTNENVEEAF 153

                  ....*...
gi 568968408   81 DNAIRAAL 88
Cdd:pfam00071 154 EELAREIL 161

Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 responsive Cdc42 homolog) is a Rho family GTPase that shares significant sequence and functional similarity with Cdc42. Wrch-1 was first identified in mouse mammary epithelial cells, where its transcription is upregulated in Wnt-1 transformation. Wrch-1 contains N- and C-terminal extensions relative to cdc42, suggesting potential differences in cellular localization and function. The Wrch-1 N-terminal extension contains putative SH3 domain-binding motifs and has been shown to bind the SH3 domain-containing protein Grb2, which increases the level of active Wrch-1 in cells. Unlike Cdc42, which localizes to the cytosol and perinuclear membranes, Wrch-1 localizes extensively with the plasma membrane and endosomes. The membrane association, localization, and biological activity of Wrch-1 indicate an atypical model of regulation distinct from other Rho family GTPases. 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. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408   2 WYQEIKHFCPRTPVVLVGCQLDLRYaDLEAVNRARRPLARPIkrgdilPPEKGREVAKELG-IPYYETSVFDQFGIKDVF 80
Cdd:cd04130   94 WIPEIRKHNPKAPIILVGTQADLRT-DVNVLIQLARYGEKPV------SQSRAKALAEKIGaCEYIECSALTQKNLKEVF 166

                 ....*..
gi 568968408  81 DNAIRAA 87
Cdd:cd04130  167 DTAILAG 173

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 3 (RhoBTB3); RhoBTB3 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. RhoBTB3 is a Golgi-associated Rho-related ATPase that regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. It 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) through facilitating hydroxylation and suppresses the Warburg effect. 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 568968408 363 FSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLDPLELIALA 442
Cdd:cd18360   10 LADVVFKIQGTTVPAHRAVLVARCEVMAAMFNGNYAEAKSFLVPIYGVSKDTFLSFLEYLYTDSCCPASILQAMALLICA 89

                         90       100
                 ....*....|....*....|
gi 568968408 443 NRFCLTHLVALVEQHAVQEL 462
Cdd:cd18360   90 EMYQVSRLQHICELYIITQL 109

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 568968408 363 FSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLDpLELIALA 442
Cdd:cd18314    6 FSDVVLCVGDRKFFAHRIVLCARSPVFRSMLTGSMIESNLKEVTLEDVEPEIFETVLKYMYTGQVTLSEENV-LDLLMLA 84

                         90
                 ....*....|.
gi 568968408 443 NRFCLTHLVAL 453
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 568968408 362 TFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSpNLDLDP---LEL 438
Cdd:cd18297   11 EMSDVTFLVEGRPFYAHKIVLVTASDRFKSMLSSGSTEAQTPVIEIPDIRYDIFQLMMQYLYTGGVE-SLDVAQddaLEL 89

                         90
                 ....*....|....*..
gi 568968408 439 IALANRFCLTHLVALVE 455
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 568968408 359 SKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSpnLDLDPLE- 437
Cdd:cd18255   14 AKGQLLDVTLIADGQRFQAHKVVLASCSDYFRAMFTGGMRESSQDEIELKGVSAKGLKHILDFAYTSELT--LDLDCIQd 91

                         90       100
                 ....*....|....*....|....*.
gi 568968408 438 LIALANRFCLTHLVALVEQHAVQELT 463
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 568968408 366 VTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDlDPLELIALANRF 445
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 568968408 347 HVRKANRI-KECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTK 425
Cdd:cd18339    4 HMKKAFKVmNELRSKQLLCDVTIVAEDVEIEAHRVVLAACSPYFCAMFTGDMSESKAKKIEIKDVDGQTLSKLIDYIYTA 83

                 ..
gi 568968408 426 QL 427
Cdd:cd18339   84 EI 85

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 2 (KLHL2); KLHL2, also called actin-binding protein Mayven, is a novel actin-binding protein predominantly expressed in the brain. It plays a role in the reorganization of the actin cytoskeleton, and promotes growth of cell projections in oligodendrocyte precursors. KLHL2 is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal 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 568968408 347 HVRKANRI-KECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTK 425
Cdd:cd18338    4 HMKKAFKVmNELRSQNLLCDVTIVAEDVEIAAHRVVLAACSPYFHAMFTGEMSESRAKRVRIKEVDGWTLKMLIDYVYTA 83

                 ..
gi 568968408 426 QL 427
Cdd:cd18338   84 EI 85

Rho-related protein from plants (Rop)-like; The Rop (Rho-related protein from plants) subfamily plays a role in diverse cellular processes, including cytoskeletal organization, pollen and vegetative cell growth, hormone responses, stress responses, and pathogen resistance. Rops are able to regulate several downstream pathways to amplify a specific signal by acting as master switches early in the signaling cascade. They transmit a variety of extracellular and intracellular signals. Rops are involved in establishing cell polarity in root-hair development, root-hair elongation, pollen-tube growth, cell-shape formation, responses to hormones such as abscisic acid (ABA) and auxin, responses to abiotic stresses such as oxygen deprivation, and disease resistance and disease susceptibility. An individual Rop can have a unique function or an overlapping function shared with other Rop proteins; in addition, a given Rop-regulated function can be controlled by one or multiple Rop proteins. For example, Rop1, Rop3, and Rop5 are all involved in pollen-tube growth; Rop2 plays a role in response to low-oxygen environments, cell-morphology, and root-hair development; root-hair development is also regulated by Rop4 and Rop6; Rop6 is also responsible for ABA response, and ABA response is also regulated by Rop10. Plants retain some of the regulatory mechanisms that are shared by other members of the Rho family, but have also developed a number of unique modes for regulating Rops. Unique RhoGEFs have been identified that are exclusively active toward Rop proteins, such as those containing the domain PRONE (plant-specific Rop nucleotide exchanger). 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. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968408   2 WYQEIKHFCPRTPVVLVGCQLDLR-----YADleavnrarRPLARPIKRGdilppeKGREVAKELGIPYY-ETSVFDQFG 75
Cdd:cd04133   95 WIPELRHYAPGVPIVLVGTKLDLRddkqfFAD--------HPGAVPITTA------QGEELRKQIGAAAYiECSSKTQQN 160

                         90
                 ....*....|...
gi 568968408  76 IKDVFDNAIRAAL 88
Cdd:cd04133  161 VKAVFDAAIKVVL 173

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 22 (KLHL22); KLHL22 is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for chromosome alignment and localization of polo-like kinase 1 (PLK1) at kinetochores. The BCR(KLHL22) ubiquitin ligase complex mediates mono-ubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. 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 568968408 361 GTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLD 432
Cdd:cd18251   21 GILFDVVLVVEGKPIEAHRILLAASCDYFRGMFAGGLREMQQTEVLIHGVSYNAMCKILDFIYTSELELSLD 92

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 568968408 353 RIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQL 427
Cdd:cd18247    9 VMEEIRRQGKLCDVTLKVGDQKFSAHRIVLAATIPYFHAMFTHDMVESKQDEITMQGIEPSALEALINFAYSGRI 83

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1); ABTB1, also called elongation factor 1A-binding protein or bood POZ containing gene type 1 (BPOZ-1), is an anti-proliferative factor that may act as a mediator of the phosphatase and tensin homolog (PTEN) growth-suppressive signaling pathway. It may play a role in developmental processes. ABTB1 contains an ankyrin repeat and two BTB domains. 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 568968408 357 CLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFveSANREVHL--PNINKMSMQAVLEYLYTKQLspNLDLD 434
Cdd:cd18295   13 LLEQGSYSDVTFNVHGESFPAHRCILSARSPYFAEMFETKW--KDKREINLkhPLVNPDAFRALLQYLYTGRL--EIHVD 88

                 ....*....
gi 568968408 435 PLE-LIALA 442
Cdd:cd18295   89 DVEdCKRLA 97

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 568968408 359 SKGTFSDVTFTLDDG--AISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLD--LD 434
Cdd:cd18239   19 GEGLLCDVTLVPGDGdeTFPVHRAMMASASDYFKAMFTGGMKEQELMCIKLHGVSKIGLKNIIDFIYTAKLSLNMDnlQD 98

                 ...
gi 568968408 435 PLE 437
Cdd:cd18239   99 TLE 101