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 767964444  13 ETIKCVVVGDNAVGKTRLICARACNTTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDEVSVSLRLWDTFGDHHKD 92
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPE 172
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767964444 173 KGREVAKELGLPYYETSVFDQFGIKDVFDNAIRAA 207
Cdd:cd01873  161 TGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767964444 465 KAFHVRKANRIKECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSE 525
Cdd:cd18358    1 KAFHVRKANRIKECLSKGTFSDVTFKLDDGTINAHKPLLICSCEWMAAMFGGSFIESANSE 61

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 767964444  13 ETIKCVVVGDNAVGKTRLICARACNTTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDEVSVSLRLWDTFGDHHKD 92
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPE 172
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767964444 173 KGREVAKELGLPYYETSVFDQFGIKDVFDNAIRAA 207
Cdd:cd01873  161 TGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 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 767964444    17 CVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDEVSVSLRLWDTFG--DHHKDRR 94
Cdd:smart00174   1 LVVVGDGAVGKTCLLIVYTTNAFPEDY------VPTVF--ENYSADVEV--------DGKPVELGLWDTAGqeDYDRLRP 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444    95 FAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKG 174
Cdd:smart00174  65 LSYPDTDVFLICFSVDSPASFENVKEKWYPEVKHFCPNVPIILVGTKLDLR-NDKSTLEELSKKKQEPVT------YEQG 137

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 767964444   175 REVAKELG-LPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:smart00174 138 QALAKRIGaVKYLECSALTQEGVREVFEEAIRAAL 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 767964444   16 KCVVVGDNAVGKTRLICaracntTLTQYQLLATHVPTVwAIDQYRvcqevlersRDV-VDEVSVSLRLWDTFG--DHHKD 92
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLI------RFTQNKFPEEYIPTI-GVDFYT---------KTIeVDGKTVKLQIWDTAGqeRFRAL 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444   93 RRFAYGRSDVVVLCFSIANPNSLNHVKSmWYPEIKHFCP-RTPVILVGCQLDLRyaDLEAVnrarrplarpikrgdilPP 171
Cdd:pfam00071  65 RPLYYRGADGFLLVYDITSRDSFENVKK-WVEEILRHADeNVPIVLVGNKCDLE--DQRVV-----------------ST 124

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 767964444  172 EKGREVAKELGLPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:pfam00071 125 EEGEALAKELGLPFMETSAKTNENVEEAFEELAREIL 161

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444   396 PMTVVRMDaSVQPGPFRTLLQFLYTGQLDEKEKDLVGLAQIAEVLEMFDLRMMVENIMNK 455
Cdd:smart00225  37 DKSEIYLD-DVSPEDFRALLNFLYTGKLDLPEENVEELLELADYLQIPGLVELCEEFLLK 95

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 767964444  476 KECLSKGTFSDVTFKLDDGAISAHKPLLICSCEWMAAMFGGSFVESANSE 525
Cdd:pfam00651   2 NELREQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSE 51

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 767964444  13 ETIKCVVVGDNAVGKTRLICARACNTTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDEVSVSLRLWDTFGDHHKD 92
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPE 172
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767964444 173 KGREVAKELGLPYYETSVFDQFGIKDVFDNAIRAA 207
Cdd:cd01873  161 TGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

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 767964444  15 IKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDEVSVSLRLWDTFGDHHKD-- 92
Cdd:cd00157    1 IKIVVVGDGAVGKTCLLISYTTNKFPTEY------VPTVF--DNYSANVTV--------DGKQVNLGLWDTAGQEEYDrl 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRYADLeavnrarrPLARPIKRGDILPPE 172
Cdd:cd00157   65 RPLSYPQTDVFLLCFSVDSPSSFENVKTKWYPEIKHYCPNVPIILVGTKIDLRDDGN--------TLKKLEKKQKPITPE 136

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767964444 173 KGREVAKELGL-PYYETSVFDQFGIKDVFDNAIRA 206
Cdd:cd00157  137 EGEKLAKEIGAvKYMECSALTQEGLKEVFDEAIRA 171

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 767964444    17 CVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDEVSVSLRLWDTFG--DHHKDRR 94
Cdd:smart00174   1 LVVVGDGAVGKTCLLIVYTTNAFPEDY------VPTVF--ENYSADVEV--------DGKPVELGLWDTAGqeDYDRLRP 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444    95 FAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKG 174
Cdd:smart00174  65 LSYPDTDVFLICFSVDSPASFENVKEKWYPEVKHFCPNVPIILVGTKLDLR-NDKSTLEELSKKKQEPVT------YEQG 137

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 767964444   175 REVAKELG-LPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:smart00174 138 QALAKRIGaVKYLECSALTQEGVREVFEEAIRAAL 172

Ras homolog family, member G (RhoG) of small guanosine triphosphatases (GTPases); RhoG is a GTPase with high sequence similarity to members of the Rac subfamily, including the regions involved in effector recognition and binding. However, RhoG does not bind to known Rac1 and Cdc42 effectors, including proteins containing a Cdc42/Rac interacting binding (CRIB) motif. Instead, RhoG interacts directly with Elmo, an upstream regulator of Rac1, in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1. The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor. Thus RhoG activates Rac1 through Elmo and Dock180 to control cell morphology. RhoG has also been shown to play a role in caveolar trafficking and has a novel role in signaling the neutrophil respiratory burst stimulated by G protein-coupled receptor (GPCR) agonists. 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 767964444  12 VETIKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRvcqevlerSRDVVDEVSVSLRLWDTFGDHHK 91
Cdd:cd01875    1 MQSIKCVVVGDGAVGKTCLLICYTTNAFPKEY------IPTVF--DNYS--------AQTAVDGRTVSLNLWDTAGQEEY 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  92 DR--RFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVNRARRPLARPIKrgdil 169
Cdd:cd01875   65 DRlrTLSYPQTNVFIICFSIASPSSYENVRHKWHPEVCHHCPNVPILLVGTKKDLR-NDADTLKKLKEQGQAPIT----- 138

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 767964444 170 pPEKGREVAKELG-LPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:cd01875  139 -PQQGGALAKQIHaVKYLECSALNQDGVKEVFAEAVRAVL 177

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 767964444  15 IKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYrvcqevlerSRDV-VDEVSVSLRLWDTFG--DHHK 91
Cdd:cd01871    2 IKCVVVGDGAVGKTCLLISYTTNAFPGEY------IPTVF--DNY---------SANVmVDGKPVNLGLWDTAGqeDYDR 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  92 DRRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVNRARRPLARPIKRgdilpp 171
Cdd:cd01871   65 LRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR-DDKDTIEKLKEKKLTPITY------ 137

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 767964444 172 EKGREVAKELG-LPYYETSVFDQFGIKDVFDNAIRA 206
Cdd:cd01871  138 PQGLAMAKEIGaVKYLECSALTQRGLKTVFDEAIRA 173

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 767964444  14 TIKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQevlersrdVVDEVSVSLRLWDTFG--DHHK 91
Cdd:cd01874    1 TIKCVVVGDGAVGKTCLLISYTTNKFPSEY------VPTVF--DNYAVTV--------MIGGEPYTLGLFDTAGqeDYDR 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  92 DRRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVNRARRPLARPIKrgdilpP 171
Cdd:cd01874   65 LRPLSYPQTDVFLVCFSVVSPSSFENVKEKWVPEITHHCPKTPFLLVGTQIDLR-DDPSTIEKLAKNKQKPIT------P 137

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 767964444 172 EKGREVAKELG-LPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:cd01874  138 ETGEKLARDLKaVKYVECSALTQKGLKNVFDEAILAAL 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 767964444  16 KCVVVGDNAVGKTRLIcaracnTTLTQYQLLATHVPTVWaiDQYrvcqevlerSRDV-VDEVSVSLRLWDTFG--DHHKD 92
Cdd:cd01870    3 KLVIVGDGACGKTCLL------IVFSKDQFPEVYVPTVF--ENY---------VADIeVDGKQVELALWDTAGqeDYDRL 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPE 172
Cdd:cd01870   66 RPLSYPDTDVILMCFSIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLR-NDEHTIRELAKMKQEPVK------PE 138

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767964444 173 KGREVAKELG-LPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:cd01870  139 EGRAMAEKIGaFGYLECSAKTKEGVREVFEMATRAAL 175

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 767964444  15 IKCVVVGDNAVGKTRLICARACNttltqyQLLATHVPTVWaiDQYRVCQEVlersrdvvDEVSVSLRLWDTFGDHHKD-- 92
Cdd:cd04131    2 CKIVLVGDSQCGKTALLQVFAKD------SFPENYVPTVF--ENYTASFEV--------DKQRIELSLWDTSGSPYYDnv 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVnrarRPLArpIKRGDILPPE 172
Cdd:cd04131   66 RPLSYPDSDAVLICFDISRPETLDSVLKKWKGEVREFCPNTPVLLVGCKSDLR-TDLSTL----TELS--NKRQIPVSHE 138

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 767964444 173 KGREVAKELG-LPYYETSVFD-QFGIKDVFDNAIRAAL 208
Cdd:cd04131  139 QGRNLAKQIGaAAYVECSAKTsENSVRDVFEMATLACL 176

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 767964444   16 KCVVVGDNAVGKTRLICaracntTLTQYQLLATHVPTVwAIDQYRvcqevlersRDV-VDEVSVSLRLWDTFG--DHHKD 92
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLI------RFTQNKFPEEYIPTI-GVDFYT---------KTIeVDGKTVKLQIWDTAGqeRFRAL 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444   93 RRFAYGRSDVVVLCFSIANPNSLNHVKSmWYPEIKHFCP-RTPVILVGCQLDLRyaDLEAVnrarrplarpikrgdilPP 171
Cdd:pfam00071  65 RPLYYRGADGFLLVYDITSRDSFENVKK-WVEEILRHADeNVPIVLVGNKCDLE--DQRVV-----------------ST 124

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 767964444  172 EKGREVAKELGLPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:pfam00071 125 EEGEALAKELGLPFMETSAKTNENVEEAFEELAREIL 161

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 767964444  15 IKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRvcqevlerSRDVVDEVSVSLRLWDTFG--DHHKD 92
Cdd:cd04133    2 IKCVTVGDGAVGKTCMLISYTSNTFPTDY------VPTVF--DNFS--------ANVVVDGNTVNLGLWDTAGqeDYNRL 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLR-----YADleavnrarRPLARPIKRGd 167
Cdd:cd04133   66 RPLSYRGADVFLLAFSLISKASYENVLKKWIPELRHYAPGVPIVLVGTKLDLRddkqfFAD--------HPGAVPITTA- 136

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 767964444 168 ilppeKGREVAKELGLPYY-ETSVFDQFGIKDVFDNAIRAAL 208
Cdd:cd04133  137 -----QGEELRKQIGAAAYiECSSKTQQNVKAVFDAAIKVVL 173

Rnd1/Rho6 GTPases; Rnd1/Rho6 is a member of the novel Rho subfamily Rnd, together with Rnd2/Rho7 and Rnd3/RhoE/Rho8. Rnd1/Rho6 binds GTP but does not hydrolyze it to GDP, indicating that it is constitutively active. In rat, Rnd1/Rho6 is highly expressed in the cerebral cortex and hippocampus during synapse formation, and plays a role in spine formation. Rnd1/Rho6 is also expressed in the liver and in endothelial cells, and is upregulated in uterine myometrial cells during pregnancy. Like Rnd3/RhoE/Rho8, Rnd1/Rho6 is believed to function as an antagonist to RhoA. 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 767964444   9 RPNVETIKCVVVGDNAVGKTRL--ICARACNTTltqyqllaTHVPTVWaiDQYRVCQEVlersrdvvDEVSVSLRLWDTF 86
Cdd:cd04174    8 QPLVVRCKLVLVGDVQCGKTAMlqVLAKDCYPE--------TYVPTVF--ENYTACLET--------EEQRVELSLWDTS 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  87 GDHHKD--RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVNRARRPLARPIK 164
Cdd:cd04174   70 GSPYYDnvRPLCYSDSDAVLLCFDISRPEIFDSALKKWRAEILDYCPSTRILLIGCKTDLR-TDLSTLMELSNQKQAPIS 148

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767964444 165 RgdilppEKGREVAKELGLP-YYETSVF-DQFGIKDVFDNAiRAALISRRHLQFWKSHLKKVQKPLLQ 230
Cdd:cd04174  149 Y------EQGCAMAKQLGAEaYLECSAFtSEKSIHSIFRTA-SLLCINKLSPLAKKSPVRSLSKRLLH 209

Rnd2/Rho7 GTPases; Rnd2/Rho7 is a member of the novel Rho subfamily Rnd, together with Rnd1/Rho6 and Rnd3/RhoE/Rho8. Rnd2/Rho7 is transiently expressed in radially migrating cells in the brain while they are within the subventricular zone of the hippocampus and cerebral cortex. These migrating cells typically develop into pyramidal neurons. Cells that exogenously expressed Rnd2/Rho7 failed to migrate to upper layers of the brain, suggesting that Rnd2/Rho7 plays a role in the radial migration and morphological changes of developing pyramidal neurons, and that Rnd2/Rho7 degradation is necessary for proper cellular migration. The Rnd2/Rho7 GEF Rapostlin is found primarily in the brain and together with Rnd2/Rho7 induces dendrite branching. Unlike Rnd1/Rho6 and Rnd3/RhoE/Rho8, which are RhoA antagonists, Rnd2/Rho7 binds the GEF Pragmin and significantly stimulates RhoA activity and Rho-A mediated cell contraction. Rnd2/Rho7 is also found to be expressed in spermatocytes and early spermatids, with male-germ-cell Rac GTPase-activating protein (MgcRacGAP), where it localizes to the Golgi-derived pro-acrosomal vesicle. 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 767964444  16 KCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDEVSVSLRLWDTFGDHHKD--R 93
Cdd:cd04173    3 KIVVVGDTQCGKTALLHVFAKDNYPESY------VPTVF--ENYTASFEI--------DKHRIELNMWDTSGSSYYDnvR 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  94 RFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRyADLEAVnrarrplaRPIKRGDILP--P 171
Cdd:cd04173   67 PLAYPDSDAVLICFDISRPETLDSVLKKWQGETQEFCPNAKLVLVGCKLDMR-TDLSTL--------RELSKQRLIPvtH 137

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767964444 172 EKGREVAKELG-LPYYE-TSVFDQFGIKDVFDNAIRAALiSRRHLQFWKSHLKKVQK 226
Cdd:cd04173  138 EQGSLLARQLGaVAYVEcSSRMSENSVRDVFHVTTLASV-RREHPSLKRSTSRRGLK 193

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 767964444  16 KCVVVGDNAVGKTRLIcaracnTTLTQYQLLATHVPTV---WAIDQYrvcqevlersrdvVDEVSVSLRLWDTFGDHHKD 92
Cdd:cd04134    2 KVVVLGDGACGKTSLL------NVFTRGYFPQVYEPTVfenYIHDIF-------------VDGLAVELSLWDTAGQEEFD 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  93 --RRFAYGRSDVVVLCFSIANPNSLNHVKSMWYPEIKHFCPRTPVILVGCQLDLRYADLEAVNRARrplarpikrgdILP 170
Cdd:cd04134   63 rlRSLSYADTHVIMLCFSVDNPDSLENVESKWLAEIRHHCPGVKLVLVALKCDLREPRNERDRGTH-----------TIS 131

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 767964444 171 PEKGREVAKELG-LPYYETSVFDQFGIKDVFDNAIRAALISR 211
Cdd:cd04134  132 YEEGLAVAKRINaCRYLECSAKLNRGVNEAFTEAARVALNAR 173

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  18 VVVGDNAVGKTRLIcaracNTTLTQYQLL--ATHVPTVWaIDQYRVcqevlersrdVVDEVSVSLRLWDTFG-------D 88
Cdd:cd00882    1 VVVGRGGVGKSSLL-----NALLGGEVGEvsDVPGTTRD-PDVYVK----------ELDKGKVKLVLVDTPGldefgglG 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  89 HHKDRRFAYGRSDVVVLCFSIANPNSLNHVKSMWypEIKHFCPRTPVILVGCQLDLRYADleavnrarrplarpikrgDI 168
Cdd:cd00882   65 REELARLLLRGADLILLVVDSTDRESEEDAKLLI--LRRLRKEGIPIILVGNKIDLLEER------------------EV 124

                        170       180       190
                 ....*....|....*....|....*....|...
gi 767964444 169 LPPEKGREVAKELGLPYYETSVFDQFGIKDVFD 201
Cdd:cd00882  125 EELLRLEELAKILGVPVFEVSAKTGEGVDELFE 157

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. 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 facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  18 VVVGDNAVGKTRLIcaracnTTLTQYQLLATHVPTVwAIDQYrvcqevlERSRDVVDEVSVSLRLWDTFGdhhkDRRF-- 95
Cdd:cd04111    6 IVIGDSTVGKSSLL------KRFTEGRFAEVSDPTV-GVDFF-------SRLIEIEPGVRIKLQLWDTAG----QERFrs 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767964444  96 ---AYGRSDV-VVLCFSIANPNSLNHVKSmWYPEIK-HFCPRTPV-ILVGCQLDLRyaDLEAVNRarrplarpikrgdil 169
Cdd:cd04111   68 itrSYYRNSVgVLLVFDITNRESFEHVHD-WLEEARsHIQPHRPVfILVGHKCDLE--SQRQVTR--------------- 129