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 1622963190 128 CPSMGTSEAACLLDNPLCADVLFILQDQEHIFAHRIYLATSSSKFYDLFLMECEESpnwsegacekekqsrdfqeqilsv 207
Cdd:cd18355     1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190 208 dseeereegpprtpqaeqwkssnkslvealgleaegavpetqtLADWSKGFIGMHREMQVNPISKRVGPVTVVRMDASVQ 287
Cdd:cd18355    57 -------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQ 93

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1622963190 288 PGPFRTLLQFLYTGQLDEKEKDLVGLAQIAEVLEMFDLRMMVENIMNKEAFMN 340
Cdd:cd18355    94 HGPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190   1 MWYPEIKHFCPRTPVVLVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPEKGREVAKELGIPYYETSVFDQFGIKDVF 80
Cdd:cd01873   109 MWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPETGRAVAKELGIPYYETSVVTQFGVKDVF 188

                  ....*..
gi 1622963190  81 DNAIRAA 87
Cdd:cd01873   189 DNAIRAA 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 1622963190 128 CPSMGTSEAACLLDNPLCADVLFILQDQEHIFAHRIYLATSSSKFYDLFLMECEESpnwsegacekekqsrdfqeqilsv 207
Cdd:cd18355     1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190 208 dseeereegpprtpqaeqwkssnkslvealgleaegavpetqtLADWSKGFIGMHREMQVNPISKRVGPVTVVRMDASVQ 287
Cdd:cd18355    57 -------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQ 93

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1622963190 288 PGPFRTLLQFLYTGQLDEKEKDLVGLAQIAEVLEMFDLRMMVENIMNKEAFMN 340
Cdd:cd18355    94 HGPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190   1 MWYPEIKHFCPRTPVVLVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPEKGREVAKELGIPYYETSVFDQFGIKDVF 80
Cdd:cd01873   109 MWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPETGRAVAKELGIPYYETSVVTQFGVKDVF 188

                  ....*..
gi 1622963190  81 DNAIRAA 87
Cdd:cd01873   189 DNAIRAA 195

BTB/POZ domain; The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is present near the N-terminus of a fraction of zinc finger (pfam00096) proteins and in proteins that contain the pfam01344 motif such as Kelch and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerization and in some instances heteromeric dimerization. The structure of the dimerized PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190 356 KECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNLDLD 435
Cdd:pfam00651   2 NELREQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLISEENVD 81

                          90       100
                  ....*....|....*....|....*.
gi 1622963190 436 plELIALANRFCLPHLVALAEQHAVQ 461
Cdd:pfam00651  82 --DLLAAADKLQIPSLVDKCEEFLIK 105

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 1622963190   2 WYPEIKHFCP-RTPVVLVGCQLDLRyaDLEAVnrarrplarpikrgdilPPEKGREVAKELGIPYYETSVFDQFGIKDVF 80
Cdd:pfam00071  93 WVEEILRHADeNVPIVLVGNKCDLE--DQRVV-----------------STEEGEALAKELGLPFMETSAKTNENVEEAF 153

                  ....*...
gi 1622963190  81 DNAIRAAL 88
Cdd:pfam00071 154 EELAREIL 161

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 1622963190 128 CPSMGTSEAACLLDNPLCADVLFILQDQEHIFAHRIYLATSSSKFYDLFLMECEESpnwsegacekekqsrdfqeqilsv 207
Cdd:cd18355     1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190 208 dseeereegpprtpqaeqwkssnkslvealgleaegavpetqtLADWSKGFIGMHREMQVNPISKRVGPVTVVRMDASVQ 287
Cdd:cd18355    57 -------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQ 93

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1622963190 288 PGPFRTLLQFLYTGQLDEKEKDLVGLAQIAEVLEMFDLRMMVENIMNKEAFMN 340
Cdd:cd18355    94 HGPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 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 1622963190 345 KAFHVRKANRIKECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLY 424
Cdd:cd18359     1 KAFHVRRTNRVKECLAKGTFSDVTFMLDDGTISAHKPLLISSCDWMAAMFGGPFVESSTTEVVFPYTSRSSMRAVLEYLY 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1622963190 425 TKQLSPNLDLDPLELIALANRFCLPHLVALAEQHAVQELTKAAM 468
Cdd:cd18359    81 TGQFSSSPDLDDMKLIILANRLCLPHLVALTEQYTVTVLMEAAQ 124

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 1622963190 356 KECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNLDLD 435
Cdd:cd18300     1 KLFLNKGLFSDVTFIVEDGTIPAHKALLVARCDVMAAMFGGNFRESSAKEVELPGVSKETFLALLEYLYTDQAPILEDGD 80

                          90       100
                  ....*....|....*....|....*...
gi 1622963190 436 PLELIALANRFCLPHLVALAEQHAVQEL 463
Cdd:cd18300    81 CVGLIVLANRLCLPRLVALCEQYIVKEL 108

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190   1 MWYPEIKHFCPRTPVVLVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPEKGREVAKELGIPYYETSVFDQFGIKDVF 80
Cdd:cd01873   109 MWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPETGRAVAKELGIPYYETSVVTQFGVKDVF 188

                  ....*..
gi 1622963190  81 DNAIRAA 87
Cdd:cd01873   189 DNAIRAA 195

first 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, tandem BTB domains, and a conserved C-terminal region. In vertebrates, 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 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 1622963190 134 SEAACLLDNPLCADVLFILQDQEHIFAHRIYLATSSSKFYDLFLMEceespnwsegacekekqsrdfqeqilsvdseeer 213
Cdd:cd18299     1 EDLRNLLHSPSCADVVFILQGGVRIFAHRIVLAAASSVFADLFLMM---------------------------------- 46

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190 214 eegpprtpqaeqwkssnkslvealgleaegavpetqtladwskgfigmhremqvnpiskrvgpvTVVRMDASVQPGPFRT 293
Cdd:cd18299    47 ----------------------------------------------------------------TVVTLDSDITPEAFRR 62

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1622963190 294 LLQFLYTGQLDEKEKDLVGLAQIAEVLEMFDLRMMVENIMN 334
Cdd:cd18299    63 VLEFLYTGVLDENEDDLKELKDAAELLELFDLVMMCTNVLN 103

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 1622963190   1 MWYPEIKHFCPRTPVVLVGCQLDLRYADLeavnrarrPLARPIKRGDILPPEKGREVAKELG-IPYYETSVFDQFGIKDV 79
Cdd:cd00157    93 KWYPEIKHYCPNVPIILVGTKIDLRDDGN--------TLKKLEKKQKPITPEEGEKLAKEIGaVKYMECSALTQEGLKEV 164

                  ....*..
gi 1622963190  80 FDNAIRA 86
Cdd:cd00157   165 FDEAIRA 171

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger and BTB domain-containing (ZBTB) proteins, Kelch-like (KLHL) proteins, and similar proteins; This family includes a variety of BTB/POZ domain-containing proteins, such as zinc finger and BTB domain-containing (ZBTB) proteins and Kelch-like (KLHL) proteins. They 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. These special additional domains or interaction partners provide unique characteristics and functions to BTB/POZ proteins. 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 1622963190 364 FSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNLDlDPLELIALA 443
Cdd:cd18186     1 LCDVTLVVGGREFPAHRAVLAARSPYFRAMFSSGMKESSSSEIELDDVSPEAFEALLDYIYTGELELSEE-NVEELLAAA 79

                  ...
gi 1622963190 444 NRF 446
Cdd:cd18186    80 DKL 82

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 1622963190   2 WYPEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKGREVAKELG-IPYYETSVFDQFGIKDVF 80
Cdd:cd01874    95 WVPEITHHCPKTPFLLVGTQIDLR-DDPSTIEKLAKNKQKPIT------PETGEKLARDLKaVKYVECSALTQKGLKNVF 167

                  ....*...
gi 1622963190  81 DNAIRAAL 88
Cdd:cd01874   168 DEAILAAL 175

Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)-like consists of Rac1, Rac2 and Rac3; The Rac1-like subfamily consists of Rac1, Rac2, and Rac3 proteins, plus the splice variant Rac1b that contains a 19-residue insertion near switch II relative to Rac1. While Rac1 is ubiquitously expressed, Rac2 and Rac3 are largely restricted to hematopoietic and neural tissues respectively. Rac1 stimulates the formation of actin lamellipodia and membrane ruffles. It also plays a role in cell-matrix adhesion and cell anoikis. In intestinal epithelial cells, Rac1 is an important regulator of migration and mediates apoptosis. Rac1 is also essential for RhoA-regulated actin stress fiber and focal adhesion complex formation. In leukocytes, Rac1 and Rac2 have distinct roles in regulating cell morphology, migration, and invasion, but are not essential for macrophage migration or chemotaxis. Rac3 has biochemical properties that are closely related to Rac1, such as effector interaction, nucleotide binding, and hydrolysis; Rac2 has a slower nucleotide association and is more efficiently activated by the RacGEF Tiam1. Both Rac1 and Rac3 have been implicated in the regulation of cell migration and invasion in human metastatic breast cancer. 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 1622963190   2 WYPEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKRgdilppEKGREVAKELG-IPYYETSVFDQFGIKDVF 80
Cdd:cd01871    95 WYPEVRHHCPNTPIILVGTKLDLR-DDKDTIEKLKEKKLTPITY------PQGLAMAKEIGaVKYLECSALTQRGLKTVF 167

                  ....*.
gi 1622963190  81 DNAIRA 86
Cdd:cd01871   168 DEAIRA 173

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 1622963190   2 WYPEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKGREVAKELG-IPYYETSVFDQFGIKDVF 80
Cdd:cd01870    95 WTPEVKHFCPNVPIILVGNKKDLR-NDEHTIRELAKMKQEPVK------PEEGRAMAEKIGaFGYLECSAKTKEGVREVF 167

                  ....*...
gi 1622963190  81 DNAIRAAL 88
Cdd:cd01870   168 EMATRAAL 175

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 1622963190 361 KGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNLDLDPLELI 440
Cdd:cd18286    14 NGEDSDITIKVDGKTFKAHRCILCARSSYFAAMLSGSWAESNSSEITLTGVSHAAVSFVLLFIYGGVLDLPDDVNLGELL 93

                          90
                  ....*....|....*...
gi 1622963190 441 ALANRFCLPHLVALAEQH 458
Cdd:cd18286    94 SLADMYGLDGLKDVVAYT 111

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 1622963190   2 WYPEIKHFCP-RTPVVLVGCQLDLRyaDLEAVnrarrplarpikrgdilPPEKGREVAKELGIPYYETSVFDQFGIKDVF 80
Cdd:pfam00071  93 WVEEILRHADeNVPIVLVGNKCDLE--DQRVV-----------------STEEGEALAKELGLPFMETSAKTNENVEEAF 153

                  ....*...
gi 1622963190  81 DNAIRAAL 88
Cdd:pfam00071 154 EELAREIL 161

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 1622963190 477 VLSYLELAQFHNAHQLAAWCLHHICTNYNSVCSKfrKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKRER 550
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 1622963190 364 FSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNLDLDpLELIALA 443
Cdd:cd18314     6 FSDVVLCVGDRKFFAHRIVLCARSPVFRSMLTGSMIESNLKEVTLEDVEPEIFETVLKYMYTGQVTLSEENV-LDLLMLA 84

                          90
                  ....*....|.
gi 1622963190 444 NRFCLPHLVAL 454
Cdd:cd18314    85 SKYQVPDLEKL 95

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 19 (BTBD19); BTBD19 is a BTB domain-containing 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622963190 355 IKECLSKGTFSDVTFKLDDGA--ISAHKPLLICSCEWMAAMFGGSFV-ESANSEVYLPNINKISMQAVLDYLYTKQLSpn 431
Cdd:cd18294     5 MKSLINNPEFSDVKFLVGPERqeIFAHKCILAARCEVFRAMFLTGPQkESTQSPLVLSDIEPEVFRAVLEFIYTNCVT-- 82

                          90       100
                  ....*....|....*....|....*....
gi 1622963190 432 ldLDP---LELIALANRFCLPHLVALAEQ 457
Cdd:cd18294    83 --LSNhtvIEVLAAAVEYGLDELRKLCER 109

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 1622963190 360 SKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSpnLDLDPLE- 438
Cdd:cd18255    14 AKGQLLDVTLIADGQRFQAHKVVLASCSDYFRAMFTGGMRESSQDEIELKGVSAKGLKHILDFAYTSELT--LDLDCIQd 91

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1622963190 439 LIALANrfclpHLVALAEQHAVQELTKAAMS 469
Cdd:cd18255    92 VLGAAV-----HLQMLPVVELCEEFLKSAMS 117

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 1622963190   2 WYPEIKHFCPRTPVVLVGCQLDLR-----YADleavnrarRPLARPIKRGdilppeKGREVAKELGIPYY-ETSVFDQFG 75
Cdd:cd04133    95 WIPELRHYAPGVPIVLVGTKLDLRddkqfFAD--------HPGAVPITTA------QGEELRKQIGAAAYiECSSKTQQN 160

                          90
                  ....*....|...
gi 1622963190  76 IKDVFDNAIRAAL 88
Cdd:cd04133   161 VKAVFDAAIKVVL 173

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 1622963190 363 TFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSpNLDLDP---LEL 439
Cdd:cd18297    11 EMSDVTFLVEGRPFYAHKIVLVTASDRFKSMLSSGSTEAQTPVIEIPDIRYDIFQLMMQYLYTGGVE-SLDVAQddaLEL 89

                          90
                  ....*....|....*..
gi 1622963190 440 IALANRFCLPHLVALAE 456
Cdd:cd18297    90 LRAASFFQLDGLKRHCE 106

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 1622963190 362 GTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNLD 433
Cdd:cd18251    21 GILFDVVLVVEGKPIEAHRILLAASCDYFRGMFAGGLREMQQTEVLIHGVSYNAMCKILDFIYTSELELSLD 92

BTB (Broad-Complex, Tramtrack and Bric a brac) /POZ (poxvirus and zinc finger) domain found in plant ARM repeat protein interacting with ABF2 (ARIA) and similar proteins; 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, a transcription factor which controls ABA-dependent gene expression via the G-box-type ABA-responsive elements. ARIA is a novel abscisic acid signaling component. It negatively regulates seed germination and young seedling growth. 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 1622963190 363 TFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNLDLdPLELIAL 442
Cdd:cd18352    12 TLSDVTFLVEGRRFYAHRIALLASSDAFRAMFDGGYREKEARDIEIPNIRWEVFELMMRFIYTGSVDITNDI-AKDLLRA 90

                          90       100
                  ....*....|....*....|..
gi 1622963190 443 ANRFCLPHLVALAEQHAVQELT 464
Cdd:cd18352    91 ADQYLLEGLKRLCEYTIAQDLT 112

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 1622963190 360 SKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQ--LSPNLDLDpl 437
Cdd:cd18261    24 NDGILCDITLVAEEQKFHAHKAVLAACSDYFRAMFSLCMVESEADEVNLHGVTSLGLKQALDFAYTGQilLEPGVIQD-- 101

                          90       100
                  ....*....|....*....|....*...
gi 1622963190 438 eLIALANRFCLPHLVALAEQHAVQELTK 465
Cdd:cd18261   102 -VLAAGSHLQLLELLSLCSHYLIQELNS 128

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 28 (KLHL28); KLHL28, also called BTB/POZ domain-containing protein 5 (BTBD5), 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 1622963190 366 DVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYT 425
Cdd:cd18257    20 DVVLRVGDVKIHAHKVVLASCSPYFKAMFTGNLSEKENSEVEFQCIDETALQAIVEYAYT 79

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 1622963190 354 RIKECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLS 429
Cdd:cd18266    15 GLNEQRQRGLFCDVVLVADEQRVPAHRNLLAVCSDYFNSMFTIGMREAHQKEVELVGASYIGLKAVIDFLYSSELP 90

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 1622963190 354 RIKECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQL 428
Cdd:cd18247     9 VMEEIRRQGKLCDVTLKVGDQKFSAHRIVLAATIPYFHAMFTHDMVESKQDEITMQGIEPSALEALINFAYSGRI 83

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 1622963190 361 KGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQ 427
Cdd:cd18242    18 SNTLCDVTLRVEGKEFPAHRIVLAACSDYFCAMFTSEMSEKGKSEVELQGLTASTMEILLDFVYTET 84

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 41 (KLHL41); KLHL41 is also called Kel-like protein 23, Kelch repeat and BTB domain-containing protein 10 (KBTBD10), Kelch-related protein 1 (Krp1), or sarcosine. It is a novel kelch-related protein that is involved in pseudopod elongation in transformed cells. It is also involved in skeletal muscle development and differentiation. It regulates proliferation and differentiation of myoblasts and plays a role in myofibril assembly by promoting lateral fusion of adjacent thin fibrils into mature, wide myofibrils. 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 1622963190 355 IKECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSEVYLPNINKISMQAVLDYLYTKQLSPNlDL 434
Cdd:cd18341    18 LKELLDENKFVDCTLKAGDKSLPCHRLILAACSPYFREYFLSEESEEKKKEVVLDNVDPNIMDMILKYLYSAEIDLN-DG 96