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 442633668  12 ELVKCVLVGDTAVGKTRLICARACNKHVSLSQLLSTHVPTVWAIDQYRIYKDVLERSWEVVDGVNVSLRLWDTFGDHDKD 91
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  92 RRFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRYMYRDENYLSYFGekgtFVRAALKSDL 171
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRP----LARPIKNADI 156

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 442633668 172 VMPDEARAVAKELGVAYYETSVFTYFGVNEVFENAIRSA 210
Cdd:cd01873  157 LPPETGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

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 442633668 593 TVDHCLKLLEPVKLHNAHQLAEWCMSYLCVNYNLICKFsLKGLKALHQDNQEYLREHRWPPVWYLKDYDYYQRCLNE 669
Cdd:cd18499    1 IDEDVIDLLELAQLHNADQLAAWCLHFISTNYNAFCKH-RKEFKLLSPENQEYIEEHRWPPVWYLKELDEYEKKLKE 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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  12 ELVKCVLVGDTAVGKTRLICARACNKHVSLSQLLSTHVPTVWAIDQYRIYKDVLERSWEVVDGVNVSLRLWDTFGDHDKD 91
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  92 RRFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRYMYRDENYLSYFGekgtFVRAALKSDL 171
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRP----LARPIKNADI 156

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 442633668 172 VMPDEARAVAKELGVAYYETSVFTYFGVNEVFENAIRSA 210
Cdd:cd01873  157 LPPETGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

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 442633668    16 CVLVGDTAVGKTRLICARACNKhvslsqLLSTHVPTVwaidqYRIYKDVLErswevVDGVNVSLRLWDTFG--DHDKDRR 93
Cdd:smart00174   1 LVVVGDGAVGKTCLLIVYTTNA------FPEDYVPTV-----FENYSADVE-----VDGKPVELGLWDTAGqeDYDRLRP 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668    94 FAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRymyrdenylsyfGEKGTFVRAA-LKSDLV 172
Cdd:smart00174  65 LSYPDTDVFLICFSVDSPASFENVKEKWYPEVKHFCPNVPIILVGTKLDLR------------NDKSTLEELSkKKQEPV 132

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 442633668   173 MPDEARAVAKELG-VAYYETSVFTYFGVNEVFENAIRSAL 211
Cdd:smart00174 133 TYEQGQALAKRIGaVKYLECSALTQEGVREVFEEAIRAAL 172

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 442633668   15 KCVLVGDTAVGKTRLICARACNKHVSlsqllsTHVPTVwAIDQYRiyKDVlersweVVDGVNVSLRLWDTFG--DHDKDR 92
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPE------EYIPTI-GVDFYT--KTI------EVDGKTVKLQIWDTAGqeRFRALR 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668   93 RFAYGRSDVVLLCFSIASPISLRNCKMmWYPEIRRFCPD-VPVILVGCKNDLRymyrdenylsyfgekgtfvraalKSDL 171
Cdd:pfam00071  66 PLYYRGADGFLLVYDITSRDSFENVKK-WVEEILRHADEnVPIVLVGNKCDLE-----------------------DQRV 121

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 442633668  172 VMPDEARAVAKELGVAYYETSVFTYFGVNEVFENAIRSAL 211
Cdd:pfam00071 122 VSTEEGEALAKELGLPFMETSAKTNENVEEAFEELAREIL 161

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 442633668  481 GCFSDVTFELDDGLMKAHRAVLVGRCDVMRAMLLGDFREAHSNVIVFPGVTIYTFHKLLCYLYTDQIPPISAVkcLNLLE 560
Cdd:pfam00651   8 GELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLISEENV--DDLLA 85

                          90
                  ....*....|....*
gi 442633668  561 LANRLCLPRLLNLVE 575
Cdd:pfam00651  86 AADKLQIPSLVDKCE 100

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 442633668   485 DVTFELDDGLMKAHRAVLVGRCDVMRAMLLGDFREAHSNVIVFPGVTIYTFHKLLCYLYTDQIpPISAVKCLNLLELANR 564
Cdd:smart00225   1 DVTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYTGKL-DLPEENVEELLELADY 79

                           90
                   ....*....|....*...
gi 442633668   565 LCLPRLLNLVECRVIEDL 582
Cdd:smart00225  80 LQIPGLVELCEEFLLKLL 97

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  15 KCVLVGDTAVGKTRLICAracnkhvSLSQLLSTHVPTVwAIDqYRIYKdvlerswEVVDGVNVSLRLWDTFGDHdkdrRF 94
Cdd:PLN03118  16 KILLIGDSGVGKSSLLVS-------FISSSVEDLAPTI-GVD-FKIKQ-------LTVGGKRLKLTIWDTAGQE----RF 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  95 A------YGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCP--DVPVILVGCKNDlRYMYRDenylsyfgekgtfvraa 166
Cdd:PLN03118  76 RtltssyYRNAQGIILVYDVTRRETFTNLSDVWGKEVELYSTnqDCVKMLVGNKVD-RESERD----------------- 137

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 442633668 167 lksdlVMPDEARAVAKELGVAYYETSVFTYFGVNEVFE 204
Cdd:PLN03118 138 -----VSREEGMALAKEHGCLFLECSAKTRENVEQCFE 170

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 442633668   404 ISPQALHQCLRFIYTGTIDKDCDNIEEIREAADLLELPQLTQL 446
Cdd:smart00225  46 VSPEDFRALLNFLYTGKLDLPEENVEELLELADYLQIPGLVEL 88

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 442633668  12 ELVKCVLVGDTAVGKTRLICARACNKHVSLSQLLSTHVPTVWAIDQYRIYKDVLERSWEVVDGVNVSLRLWDTFGDHDKD 91
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  92 RRFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRYMYRDENYLSYFGekgtFVRAALKSDL 171
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRP----LARPIKNADI 156

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 442633668 172 VMPDEARAVAKELGVAYYETSVFTYFGVNEVFENAIRSA 210
Cdd:cd01873  157 LPPETGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

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 442633668 475 RHCIGDGCFSDVTFELDDGLMKAHRAVLVGRCDVMRAMLLGDFREAHSNVIVFPGVTIYTFHKLLCYLYTDQIPPISAVK 554
Cdd:cd18300    1 KLFLNKGLFSDVTFIVEDGTIPAHKALLVARCDVMAAMFGGNFRESSAKEVELPGVSKETFLALLEYLYTDQAPILEDGD 80

                         90       100
                 ....*....|....*....|....*...
gi 442633668 555 CLNLLELANRLCLPRLLNLVECRVIEDL 582
Cdd:cd18300   81 CVGLIVLANRLCLPRLVALCEQYIVKEL 108

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 442633668  14 VKCVLVGDTAVGKTRLICARACNKhvslsqLLSTHVPTVwaIDQYRiykdvleRSWEVVDGVNVSLRLWDTFG--DHDKD 91
Cdd:cd04132    4 VKIVVVGDGGCGKTCLLMVYAQGS------FPEEYVPTV--FENYV-------TTLQVPNGKIIELALWDTAGqeDYDRL 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  92 RRFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRymyRDENYLSYFGEKGTfvraalksDL 171
Cdd:cd04132   69 RPLSYPDVDVILICYSVDNPTSLDNVEDKWYPEVNHFCPGTPIVLVGLKTDLR---KDKNSVSKLRAQGL--------EP 137

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 442633668 172 VMPDEARAVAKELG-VAYYETSVFTYFGVNEVFENAIRSAL 211
Cdd:cd04132  138 VTPEQGESVAKSIGaVAYIECSAKLMENVDEVFDAAINVAL 178

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 442633668  14 VKCVLVGDTAVGKTRLICARACNKHVSlsqllsTHVPTvwAIDQYRIykDVLerswevVDGVNVSLRLWDTFG--DHDKD 91
Cdd:cd04130    1 LKCVLVGDGAVGKTSLIVSYTTNGYPT------EYVPT--AFDNFSV--VVL------VDGKPVRLQLCDTAGqdEFDKL 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  92 RRFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRYMYRDENYLSYFGEKGtfvraalksdl 171
Cdd:cd04130   65 RPLCYPDTDVFLLCFSVVNPSSFQNISEKWIPEIRKHNPKAPIILVGTQADLRTDVNVLIQLARYGEKP----------- 133

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 442633668 172 VMPDEARAVAKELG-VAYYETSVFTYFGVNEVFENAIRSA 210
Cdd:cd04130  134 VSQSRAKALAEKIGaCEYIECSALTQKNLKEVFDTAILAG 173

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 442633668  14 VKCVLVGDTAVGKTRLICARACNKhvslsqLLSTHVPTVWaiDQYriykdvlerSWEV-VDGVNVSLRLWDTFG--DHDK 90
Cdd:cd01871    2 IKCVVVGDGAVGKTCLLISYTTNA------FPGEYIPTVF--DNY---------SANVmVDGKPVNLGLWDTAGqeDYDR 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  91 DRRFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRymyRDENYLSYFGEKgtfvraalKSD 170
Cdd:cd01871   65 LRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR---DDKDTIEKLKEK--------KLT 133

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 442633668 171 LVMPDEARAVAKELG-VAYYETSVFTYFGVNEVFENAIRS 209
Cdd:cd01871  134 PITYPQGLAMAKEIGaVKYLECSALTQRGLKTVFDEAIRA 173

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 442633668 593 TVDHCLKLLEPVKLHNAHQLAEWCMSYLCVNYNLICKFsLKGLKALHQDNQEYLREHRWPPVWYLKDYDYYQRCLNE 669
Cdd:cd18499    1 IDEDVIDLLELAQLHNADQLAAWCLHFISTNYNAFCKH-RKEFKLLSPENQEYIEEHRWPPVWYLKELDEYEKKLKE 76

Rho family GTPase subfamily Rnd includes Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8; The Rnd subfamily contains Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8. These novel Rho family proteins have substantial structural differences compared to other Rho members, including N- and C-terminal extensions relative to other Rhos. Rnd3/RhoE is farnesylated at the C-terminal prenylation site, unlike most other Rho proteins that are geranylgeranylated. In addition, Rnd members are unable to hydrolyze GTP and are resistant to GAP activity. They are believed to exist only in the GTP-bound conformation, and are antagonists of RhoA activity. 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 442633668  15 KCVLVGDTAVGKTRLICARACNkhvslsQLLSTHVPTVwaidqYRIYKDVLErswevVDGVNVSLRLWDTFG--DHDKDR 92
Cdd:cd04131    3 KIVLVGDSQCGKTALLQVFAKD------SFPENYVPTV-----FENYTASFE-----VDKQRIELSLWDTSGspYYDNVR 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  93 RFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRymyrdeNYLSYFGEKGTFVRAALKSdlv 172
Cdd:cd04131   67 PLSYPDSDAVLICFDISRPETLDSVLKKWKGEVREFCPNTPVLLVGCKSDLR------TDLSTLTELSNKRQIPVSH--- 137

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 442633668 173 mpDEARAVAKELG-VAYYETSVFTY-FGVNEVFENAIRSAL 211
Cdd:cd04131  138 --EQGRNLAKQIGaAAYVECSAKTSeNSVRDVFEMATLACL 176

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 442633668 468 RIKEsmerhCIGDGCFSDVTFELDDGLMKAHRAVLVGRCDVMRAMLLGDFREAHSNVIVFPGVTIYTFHKLLCYLYTDQI 547
Cdd:cd18358   10 RIKE-----CLSKGTFSDVTFKLDDGTINAHKPLLICSCEWMAAMFGGSFIESANSEVVLPNISKVSMQAVLDYLYTKQL 84

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 442633668 548 PPISAVKCLNLLELANRLCLPRLLNLVECRVIEDLT 583
Cdd:cd18358   85 SPTADLDPLELIALANRFCLPHLVALTEQHAVQELT 120

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  14 VKCVLVGDTAVGKTRLICaRACNKhvslsQLLSTHVPTVwAIDqYRIyKDVlersweVVDGVNVSLRLWDTFGDHdkdrR 93
Cdd:cd00154    1 FKIVLIGDSGVGKTSLLL-RFVDN-----KFSENYKSTI-GVD-FKS-KTI------EVDGKKVKLQIWDTAGQE----R 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  94 FA------YGRSDVVLLCFSIASPISLRNCKmMWYPEIRRFCP-DVPVILVGCKNDLRymyrdenylsyfgekgtfvraa 166
Cdd:cd00154   62 FRsitssyYRGAHGAILVYDVTNRESFENLD-KWLNELKEYAPpNIPIILVGNKSDLE---------------------- 118

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 442633668 167 lKSDLVMPDEARAVAKELGVAYYETSVFTYFGVNEVFENAIR 208
Cdd:cd00154  119 -DERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESLAR 159

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 442633668 468 RIKEsmerhCIGDGCFSDVTFELDDGLMKAHRAVLVGRCDVMRAMLLGDFREAHSNVIVFPGVTIYTFHKLLCYLYTDQI 547
Cdd:cd18359   10 RVKE-----CLAKGTFSDVTFMLDDGTISAHKPLLISSCDWMAAMFGGPFVESSTTEVVFPYTSRSSMRAVLEYLYTGQF 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 442633668 548 PPISAVKCLNLLELANRLCLPRLLNLVECRVIEDLTLISQ 587
Cdd:cd18359   85 SSSPDLDDMKLIILANRLCLPHLVALTEQYTVTVLMEAAQ 124

Rho GTPase TC10 (Tc10); TC10 is a Rho family protein that has been shown to induce microspike formation and neurite outgrowth in vitro. Its expression changes dramatically after peripheral nerve injury, suggesting an important role in promoting axonal outgrowth and regeneration. TC10 regulates translocation of insulin-stimulated GLUT4 in adipocytes and has also been shown to bind directly to Golgi COPI coat proteins. GTP-bound TC10 in vitro can bind numerous potential effectors. Depending on its subcellular localization and distinct functional domains, TC10 can differentially regulate two types of filamentous actin in adipocytes. TC10 mRNAs are highly expressed in three types of mouse muscle tissues: leg skeletal muscle, cardiac muscle, and uterus; they were also present in brain, with higher levels in adults than in newborns. TC10 has also been shown to play a role in regulating the expression of cystic fibrosis transmembrane conductance regulator (CFTR) through interactions with CFTR-associated ligand (CAL). The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated DFTR degradation in the lysosome. 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 442633668  14 VKCVLVGDTAVGKTRLICARACNKhvslsqLLSTHVPTVWaiDQYRIYKDVlerswevvDGVNVSLRLWDTFG--DHDKD 91
Cdd:cd04135    1 LKCVVVGDGAVGKTCLLMSYANDA------FPEEYVPTVF--DHYAVSVTV--------GGKQYLLGLYDTAGqeDYDRL 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  92 RRFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLRymyRDENYLSYFGEkgtfvraaLKSDL 171
Cdd:cd04135   65 RPLSYPMTDVFLICFSVVNPASFQNVKEEWVPELKEYAPNVPYLLIGTQIDLR---DDPKTLARLND--------MKEKP 133

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 442633668 172 VMPDEARAVAKELGV-AYYETSVFTYFGVNEVFENAIRSAL 211
Cdd:cd04135  134 ITVEQGQKLAKEIGAcCYVECSALTQKGLKTVFDEAIIAIL 174

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 442633668 255 QDIYNMFLSQAYTDLVLVGAGGTKFAVHRFMLAAASSIFQRLLSTeltdmggrsssessmvsstfgeatiadfnddteal 334
Cdd:cd18299    1 EDLRNLLHSPSCADVVFILQGGVRIFAHRIVLAAASSVFADLFLM----------------------------------- 45

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668 335 iryesrtqrmwehlkrrssyqalplmeskrsndlyrelhhpvlqsirlvhvenhrgvnglQTIVTLSKLISPQALHQCLR 414
Cdd:cd18299   46 ------------------------------------------------------------MTVVTLDSDITPEAFRRVLE 65

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 442633668 415 FIYTGTIDKDCDNIEEIREAADLLELPQLTQLLSRPQT 452
Cdd:cd18299   66 FLYTGVLDENEDDLKELKDAAELLELFDLVMMCTNVLN 103

Ras homology family 3 (Rho3) of small guanosine triphosphatases (GTPases); Rho3 is a member of the Rho family found only in fungi. Rho3 is believed to regulate cell polarity by interacting with the diaphanous/formin family protein For3 to control both the actin cytoskeleton and microtubules. Rho3 is also believed to have a direct role in exocytosis that is independent of its role in regulating actin polarity. The function in exocytosis may be two-pronged: first, in the transport of post-Golgi vesicles from the mother cell to the bud, mediated by myosin (Myo2); second, in the docking and fusion of vesicles to the plasma membrane, mediated by an exocyst (Exo70) protein. 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 442633668  15 KCVLVGDTAVGKTRLICAracnkhVSLSQLLSTHVPTVWAIDQYRIYkdvlerswevVDGVNVSLRLWDTFG--DHDKDR 92
Cdd:cd04134    2 KVVVLGDGACGKTSLLNV------FTRGYFPQVYEPTVFENYIHDIF----------VDGLAVELSLWDTAGqeEFDRLR 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442633668  93 RFAYGRSDVVLLCFSIASPISLRNCKMMWYPEIRRFCPDVPVILVGCKNDLR----YMYRDENYLSYfgekgtfvraalk 168
Cdd:cd04134   66 SLSYADTHVIMLCFSVDNPDSLENVESKWLAEIRHHCPGVKLVLVALKCDLReprnERDRGTHTISY------------- 132