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 1958794369   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd01870     1 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  85 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTK 164
Cdd:cd01870    81 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTIRELAKMKQEPVKPEEGRAMAEKIGAFGYLECSAKTK 160

                         170
                  ....*....|....*
gi 1958794369 165 DGVREVFEMATRAAL 179
Cdd:cd01870   161 EGVREVFEMATRAAL 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 1958794369   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd01870     1 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  85 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTK 164
Cdd:cd01870    81 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTIRELAKMKQEPVKPEEGRAMAEKIGAFGYLECSAKTK 160

                         170
                  ....*....|....*
gi 1958794369 165 DGVREVFEMATRAAL 179
Cdd:cd01870   161 EGVREVFEMATRAAL 175

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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTV-FENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFS 85
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIgVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  86 IDSPDSLENIPeKWTPEVKHFCP-NVPIILVGNKKDLRNdehtrrelakmkQEPVKPEEGRDMANRIGAFgYMECSAKTK 164
Cdd:pfam00071  81 ITSRDSFENVK-KWVEEILRHADeNVPIVLVGNKCDLED------------QRVVSTEEGEALAKELGLP-FMETSAKTN 146

                         170
                  ....*....|....*.
gi 1958794369 165 DGVREVFEMATRAALQ 180
Cdd:pfam00071 147 ENVEEAFEELAREILK 162

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369   4 IRKKLVIVGDGACGKTCLLIVFSKDQF-PEVYVPTV-FENYVADIEVDGKQVELALWDTAGQEDYDRLRPL---SYPDTD 78
Cdd:COG1100     2 GEKKIVVVGTGGVGKTSLVNRLVGDIFsLEKYLSTNgVTIDKKELKLDGLDVDLVIWDTPGQDEFRETRQFyarQLTGAS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  79 VILMCFSIDSPDSLENIPEkWTPEVKHFCPNVPIILVGNKKDLRNDEhtrrelakmkqEPVKPEEGRDMANRIGAFGYME 158
Cdd:COG1100    82 LYLFVVDGTREETLQSLYE-LLESLRRLGKKSPIILVLNKIDLYDEE-----------EIEDEERLKEALSEDNIVEVVA 149

                         170
                  ....*....|....
gi 1958794369 159 CSAKTKDGVREVFE 172
Cdd:COG1100   150 TSAKTGEGVEELFA 163

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 1958794369   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd01870     1 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  85 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTK 164
Cdd:cd01870    81 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTIRELAKMKQEPVKPEEGRAMAEKIGAFGYLECSAKTK 160

                         170
                  ....*....|....*
gi 1958794369 165 DGVREVFEMATRAAL 179
Cdd:cd01870   161 EGVREVFEMATRAAL 175

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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSI 86
Cdd:cd00157     2 KIVVVGDGAVGKTCLLISYTTNKFPTEYVPTVFDNYSANVTVDGKQVNLGLWDTAGQEEYDRLRPLSYPQTDVFLLCFSV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  87 DSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKmKQEPVKPEEGRDMANRIGAFGYMECSAKTKDG 166
Cdd:cd00157    82 DSPSSFENVKTKWYPEIKHYCPNVPIILVGTKIDLRDDGNTLKKLEK-KQKPITPEEGEKLAKEIGAVKYMECSALTQEG 160

                         170
                  ....*....|.
gi 1958794369 167 VREVFEMATRA 177
Cdd:cd00157   161 LKEVFDEAIRA 171

Ras homology family 2 (Rho2) of small guanosine triphosphatases (GTPases); Rho2 is a fungal GTPase that plays a role in cell morphogenesis, control of cell wall integrity, control of growth polarity, and maintenance of growth direction. Rho2 activates the protein kinase C homolog Pck2, and Pck2 controls Mok1, the major (1-3) alpha-D-glucan synthase. Together with Rho1 (RhoA), Rho2 regulates the construction of the cell wall. Unlike Rho1, Rho2 is not an essential protein, but its overexpression is lethal. 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 proper intracellular localization via membrane attachment. As with other Rho family GTPases, the GDP/GTP cycling is regulated by GEFs (guanine nucleotide exchange factors), GAPs (GTPase-activating proteins) and GDIs (guanine nucleotide dissociation inhibitors).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd04129     1 RRKLVIVGDGACGKTSLLYVFTLGEFPEEYHPTVFENYVTDCRVDGKPVQLALWDTAGQEEYERLRPLSYSKAHVILIGF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  85 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAkmKQEPVKPEEGRDMANRIGAFGYMECSAKTK 164
Cdd:cd04129    81 AIDTPDSLENVRTKWIEEVRRYCPNVPVILVGLKKDLRQEAVAKGNYA--TDEFVPIQQAKLVARAIGAKKYMECSALTG 158

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1958794369 165 DGVREVFEMATRAALQARRG---KKKSGCLIL 193
Cdd:cd04129   159 EGVDDVFEAATRAALLVRKSgkeEPGANCCII 190

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 1958794369   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd04131     1 RCKIVLVGDSQCGKTALLQVFAKDSFPENYVPTVFENYTASFEVDKQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  85 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTK 164
Cdd:cd04131    81 DISRPETLDSVLKKWKGEVREFCPNTPVLLVGCKSDLRTDLSTLTELSNKRQIPVSHEQGRNLAKQIGAAAYVECSAKTS 160

                         170
                  ....*....|....*.
gi 1958794369 165 D-GVREVFEMATRAAL 179
Cdd:cd04131   161 EnSVRDVFEMATLACL 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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTV-FENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFS 85
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIgVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  86 IDSPDSLENIPeKWTPEVKHFCP-NVPIILVGNKKDLRNdehtrrelakmkQEPVKPEEGRDMANRIGAFgYMECSAKTK 164
Cdd:pfam00071  81 ITSRDSFENVK-KWVEEILRHADeNVPIVLVGNKCDLED------------QRVVSTEEGEALAKELGLP-FMETSAKTN 146

                         170
                  ....*....|....*.
gi 1958794369 165 DGVREVFEMATRAALQ 180
Cdd:pfam00071 147 ENVEEAFEELAREILK 162

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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSI 86
Cdd:cd01874     3 KCVVVGDGAVGKTCLLISYTTNKFPSEYVPTVFDNYAVTVMIGGEPYTLGLFDTAGQEDYDRLRPLSYPQTDVFLVCFSV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  87 DSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTKDG 166
Cdd:cd01874    83 VSPSSFENVKEKWVPEITHHCPKTPFLLVGTQIDLRDDPSTIEKLAKNKQKPITPETGEKLARDLKAVKYVECSALTQKG 162

                         170
                  ....*....|...
gi 1958794369 167 VREVFEMATRAAL 179
Cdd:cd01874   163 LKNVFDEAILAAL 175

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 1958794369   5 RKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCF 84
Cdd:cd04173     1 RCKIVVVGDTQCGKTALLHVFAKDNYPESYVPTVFENYTASFEIDKHRIELNMWDTSGSSYYDNVRPLAYPDSDAVLICF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  85 SIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAK-T 163
Cdd:cd04173    81 DISRPETLDSVLKKWQGETQEFCPNAKLVLVGCKLDMRTDLSTLRELSKQRLIPVTHEQGSLLARQLGAVAYVECSSRmS 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1958794369 164 KDGVREVFEMATRAALQ----------ARRGKKKS 188
Cdd:cd04173   161 ENSVRDVFHVTTLASVRrehpslkrstSRRGLKRI 195

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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSI 86
Cdd:cd04135     2 KCVVVGDGAVGKTCLLMSYANDAFPEEYVPTVFDHYAVSVTVGGKQYLLGLYDTAGQEDYDRLRPLSYPMTDVFLICFSV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  87 DSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTKDG 166
Cdd:cd04135    82 VNPASFQNVKEEWVPELKEYAPNVPYLLIGTQIDLRDDPKTLARLNDMKEKPITVEQGQKLAKEIGACCYVECSALTQKG 161

                         170
                  ....*....|...
gi 1958794369 167 VREVFEMATRAAL 179
Cdd:cd04135   162 LKTVFDEAIIAIL 174

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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSI 86
Cdd:cd04133     3 KCVTVGDGAVGKTCMLISYTSNTFPTDYVPTVFDNFSANVVVDGNTVNLGLWDTAGQEDYNRLRPLSYRGADVFLLAFSL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  87 DSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLRNDEHTRRELAKMKqePVKPEEGRDMANRIGAFGYMECSAKTKDG 166
Cdd:cd04133    83 ISKASYENVLKKWIPELRHYAPGVPIVLVGTKLDLRDDKQFFADHPGAV--PITTAQGEELRKQIGAAAYIECSSKTQQN 160

                         170
                  ....*....|...
gi 1958794369 167 VREVFEMATRAAL 179
Cdd:cd04133   161 VKAVFDAAIKVVL 173

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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVA-DIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFS 85
Cdd:cd00154     2 KIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSkTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVYD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  86 IDSPDSLENIpEKWTPEVKHFCP-NVPIILVGNKKDLRNDehtrRElakmkqepVKPEEGRDMANRIGAFgYMECSAKTK 164
Cdd:cd00154    82 VTNRESFENL-DKWLNELKEYAPpNIPIILVGNKSDLEDE----RQ--------VSTEEAQQFAKENGLL-FFETSAKTG 147

                         170
                  ....*....|..
gi 1958794369 165 DGVREVFEMATR 176
Cdd:cd00154   148 ENVDEAFESLAR 159

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras 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 Ras 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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSI 86
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDSYRKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYSI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  87 DSPDSLEnipekwtpEVKHF---------CPNVPIILVGNKKDLrndEHTRRelakmkqepVKPEEGRDMANRIGAfGYM 157
Cdd:cd00876    81 TSRESFE--------EIKNIreqilrvkdKEDVPIVLVGNKCDL---ENERQ---------VSTEEGEALAEEWGC-PFL 139

                         170
                  ....*....|....*....
gi 1958794369 158 ECSAKTKDGVREVFEMATR 176
Cdd:cd00876   140 ETSAKTNINIDELFNTLVR 158

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369    7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSI 86
Cdd:smart00173   2 KLVVLGSGGVGKSALTIQFIQGHFVDDYDPTIEDSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYSI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369   87 DSPDSLENIPEKWTP--EVKHfCPNVPIILVGNKKDLRNDehtrRElakmkqepVKPEEGRDMANRIGAfGYMECSAKTK 164
Cdd:smart00173  82 TDRQSFEEIKKFREQilRVKD-RDDVPIVLVGNKCDLESE----RV--------VSTEEGKELARQWGC-PFLETSAKER 147

                   ....*...
gi 1958794369  165 DGVREVFE 172
Cdd:smart00173 148 VNVDEAFY 155

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. 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. 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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTV---FENYVadIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMC 83
Cdd:cd01860     3 KLVLLGDSSVGKSSIVLRFVKNEFSENQESTIgaaFLTQT--VNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  84 FSIDSPDSLENIpEKWTPEVK-HFCPNVPIILVGNKKDLRNDehtrRElakmkqepVKPEEGRDMANRIGAFgYMECSAK 162
Cdd:cd01860    81 YDITSEESFEKA-KSWVKELQeHGPPNIVIALAGNKADLESK----RQ--------VSTEEAQEYADENGLL-FMETSAK 146

                         170
                  ....*....|....*
gi 1958794369 163 TKDGVREVFEMATRA 177
Cdd:cd01860   147 TGENVNELFTEIARK 161

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. 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. 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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVAD-IEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFS 85
Cdd:cd04123     2 KVVLLGEGRVGKTSLVLRYVENKFNEKHESTTQASFFQKtVNIGGKRIDLAIWDTAGQERYHALGPIYYRDADGAILVYD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  86 IDSPDSLENIpEKWTPEVKHFC-PNVPIILVGNKKDLRNDEHtrrelakmkqepVKPEEGRDMANRIGAfGYMECSAKTK 164
Cdd:cd04123    82 ITDADSFQKV-KKWIKELKQMRgNNISLVIVGNKIDLERQRV------------VSKSEAEEYAKSVGA-KHFETSAKTG 147

                  ....*...
gi 1958794369 165 DGVREVFE 172
Cdd:cd04123   148 KGIEELFL 155

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. 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. 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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENY-VADIEVDGKQVELALWDTAGQEdydRLRPLS---YPDTDVILM 82
Cdd:cd01869     4 KLLLIGDSGVGKSCLLLRFADDTYTESYISTIGVDFkIRTIELDGKTVKLQIWDTAGQE---RFRTITssyYRGAHGIII 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  83 CFSIDSPDSLENIPEkWTPEVKHF-CPNVPIILVGNKKDLRNdehtrrelakmkQEPVKPEEGRDMANRIGaFGYMECSA 161
Cdd:cd01869    81 VYDVTDQESFNNVKQ-WLQEIDRYaSENVNKLLVGNKCDLTD------------KKVVDYTEAKEFADELG-IPFLETSA 146

                         170
                  ....*....|....*.
gi 1958794369 162 KTKDGVREVFEMATRA 177
Cdd:cd01869   147 KNATNVEEAFMTMARE 162

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. Most Ras 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 Ras 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 1958794369   7 KLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDTAGQEDYDRLRPLSYPDTDVILMCFSI 86
Cdd:cd04139     2 KVIMVGSGGVGKSALTLQFMYDEFVEDYEPTKADSYRKKVVLDGEEVQLNILDTAGQEDYAAIRDNYFRSGEGFLLVFSI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958794369  87 DSPDSLENIPEKWTPEVKH-FCPNVPIILVGNKKDLrndEHTRRelakmkqepVKPEEGRDMANRIGAfGYMECSAKTKD 165
Cdd:cd04139    82 TDMESFTALAEFREQILRVkEDDNVPLLLVGNKCDL---EDKRQ---------VSVEEAANLAEQWGV-NYVETSAKTRA 148