Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991    4 SYYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPE-IPCIVVANKIDADiNVTQKSFN----FAKKFSLPLYFVSAAD 78
Cdd:smart00175  68 SYYRGAVGALLVYDITNRESFENLENWLKELREYASPnVVIMLVGNKSDLE-EQRQVSREeaeaFAEEHGLPFFETSAKT 146

                           90
                   ....*....|....*....
gi 1237937991   79 GTNVVKVWLtaEVASKLFN 97
Cdd:smart00175 147 NTNVEEAFE--ELAREILK 163

GTP-binding nuclear protein Ran; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPEIPCIVVANKID-ADINVTQKSFNFAKKFSLPLYFVSAADGTNVV 83
Cdd:PTZ00132   78 YYIKGQCAIIMFDVTSRITYKNVPNWHRDIVRVCENIPIVLVGNKVDvKDRQVKARQITFHRKKNLQYYDISAKSNYNFE 157

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1237937991  84 K--VWLtaevASKLFND-------AIRLAVSYKQNSQDFMDEIFQELE---NFSLEQEEED 132
Cdd:PTZ00132  158 KpfLWL----ARRLTNDpnlvfvgAPALAPEEIQIDPELVAQAEKELQaaaNVPLPDDDDD 214

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 1237937991   1 MHASYYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPE-IPCIVVANKIDADIN---VTQKSFNFAKKFSLPLYFVSA 76
Cdd:cd00154    65 ITSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPPnIPIILVGNKSDLEDErqvSTEEAQQFAKENGLLFFETSA 144

                  ....*.
gi 1237937991  77 ADGTNV 82
Cdd:cd00154   145 KTGENV 150

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1237937991   1 MHASYYHKAHACIMVFDIQrkvTYRNLSTWYTELREFRPEIPCIVVANKID 51
Cdd:pfam08477  67 LHPFYYRGAAAALLVYDSR---TFSNLKYWLRELKKYAGNSPVILVGNKID 114

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 1237937991   4 SYYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPE-IPCIVVANKIDADINV---TQKSFNFAKKFSLPLYFVSAADG 79
Cdd:pfam00071  67 LYYRGADGFLLVYDITSRDSFENVKKWVEEILRHADEnVPIVLVGNKCDLEDQRvvsTEEGEALAKELGLPFMETSAKTN 146

                          90
                  ....*....|
gi 1237937991  80 TNVVKVWLTA 89
Cdd:pfam00071 147 ENVEEAFEEL 156

Ras-related nuclear proteins (Ran)/TC4 family of small GTPases; Ran GTPase is involved in diverse biological functions, such as nuclear transport, spindle formation during mitosis, DNA replication, and cell division. Among the Ras superfamily, Ran is a unique small G protein. It does not have a lipid modification motif at the C-terminus to bind to the membrane, which is often observed within the Ras superfamily. Ran may therefore interact with a wide range of proteins in various intracellular locations. Like other GTPases, Ran exists in GTP- and GDP-bound conformations that interact differently with effectors. Conversion between these forms and the assembly or disassembly of effector complexes requires the interaction of regulator proteins. The intrinsic GTPase activity of Ran is very low, but it is greatly stimulated by a GTPase-activating protein (RanGAP1) located in the cytoplasm. By contrast, RCC1, a guanine nucleotide exchange factor that generates RanGTP, is bound to chromatin and confined to the nucleus. Ran itself is mobile and is actively imported into the nucleus by a mechanism involving NTF-2. Together with the compartmentalization of its regulators, this is thought to produce a relatively high concentration of RanGTP in the nucleus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPEIPCIVVANKIDA-DINVTQKSFNFAKKFSLPLYFVSAADGTNVV 83
Cdd:cd00877    69 YYIQGQCAIIMFDVTSRVTYKNVPNWHRDLVRVCENIPIVLCGNKVDIkDRKVKPKQITFHRKKNLQYYEISAKSNYNFE 148

                          90
                  ....*....|....*..
gi 1237937991  84 K--VWLtaevASKLFND 98
Cdd:cd00877   149 KpfLWL----ARKLLGN 161

Rab GTPase family 11 (Rab11)-like includes Rab11a, Rab11b, and Rab25; Rab11a, Rab11b, and Rab25 are closely related, evolutionary conserved Rab proteins that are differentially expressed. Rab11a is ubiquitously synthesized, Rab11b is enriched in brain and heart and Rab25 is only found in epithelia. Rab11/25 proteins seem to regulate recycling pathways from endosomes to the plasma membrane and to the trans-Golgi network. Furthermore, Rab11a is thought to function in the histamine-induced fusion of tubulovesicles containing H+, K+ ATPase with the plasma membrane in gastric parietal cells and in insulin-stimulated insertion of GLUT4 in the plasma membrane of cardiomyocytes. Overexpression of Rab25 has recently been observed in ovarian cancer and breast cancer, and has been correlated with worsened outcomes in both diseases. In addition, Rab25 overexpression has also been observed in prostate cancer, transitional cell carcinoma of the bladder, and invasive breast tumor cells. 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 1237937991   4 SYYHKAHACIMVFDIQRKVTYRNLSTWYTELREF-RPEIPCIVVANKID--ADINV-TQKSFNFAKKFSLPLYFVSAADG 79
Cdd:cd01868    71 AYYRGAVGALLVYDITKKSTFENVERWLKELRDHaDSNIVIMLVGNKSDlrHLRAVpTEEAKAFAEKNGLSFIETSALDG 150

                  ...
gi 1237937991  80 TNV 82
Cdd:cd01868   151 TNV 153

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. 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 1237937991   1 MHASYYHKAHACIMVFDIQRKVTYRNLSTWYTELR------EFRPEIpcIVVANKIDADINVT---QKSFNFAKKFSLPL 71
Cdd:cd04109    66 MLDKYIYGAQAVCLVYDITNSQSFENLEDWLSVVKkvneesETKPKM--VLVGNKTDLEHNRQvtaEKHARFAQENDMES 143

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991  72 YFVSAADGTNVVKVWltAEVASKLfndairLAVSYKQNSQDFMDEIFQelenfsleqeeEDVPDQEQSSSIETPSEEVAS 151
Cdd:cd04109   144 IFVSAKTGDRVFLCF--QRIAAEL------LGVKLSQAELEQSQRVVK-----------ADVSRYSERTLREPVSRSVNK 204

                  ...
gi 1237937991 152 PHS 154
Cdd:cd04109   205 RSN 207

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991   2 HASYYHK---AHACIMVFDIQRKVTYRNLSTWYTELREFRPEIPCIVVANKIDADINVTQKSFNFAKKF-----SLPLYF 73
Cdd:COG1100    70 RQFYARQltgASLYLFVVDGTREETLQSLYELLESLRRLGKKSPIILVLNKIDLYDEEEIEDEERLKEAlsednIVEVVA 149

                  ....*....
gi 1237937991  74 VSAADGTNV 82
Cdd:COG1100   150 TSAKTGEGV 158

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 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPE-IPCIVVANKIDADIN--VT-QKSFNFAKKFSLPLYFVSAADGT 80
Cdd:cd04123    69 YYRDADGAILVYDITDADSFQKVKKWIKELKQMRGNnISLVIVGNKIDLERQrvVSkSEAEEYAKSVGAKHFETSAKTGK 148

                  ..
gi 1237937991  81 NV 82
Cdd:cd04123   149 GI 150

Rab GTPase family 30 (Rab30); Rab30 subfamily. Rab30 appears to be associated with the Golgi stack. It is expressed in a wide variety of tissue types and in humans maps to chromosome 11. 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 1237937991   4 SYYHKAHACIMVFDIQRKVTYRNLSTWYTELREF-RPEIPCIVVANKIDADIN---VTQKSFNFAKKFSLPLYFVSAADG 79
Cdd:cd04114    75 SYYRSANALILTYDITCEESFRCLPEWLREIEQYaNNKVITILVGNKIDLAERrevSQQRAEEFSDAQDMYYLETSAKES 154

                          90
                  ....*....|....*.
gi 1237937991  80 TNVVKVWLtaEVASKL 95
Cdd:cd04114   155 DNVEKLFL--DLACRL 168

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. 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 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPEIPCIVVANKID---ADINVTQKSFNFAKKFSLPLYFVSAADGTN 81
Cdd:cd04106    71 YYRGAQACILVFSTTDRESFEAIESWKEKVEAECGDIPMVLVQTKIDlldQAVITNEEAEALAKRLQLPLFRTSVKDDFN 150

                  ....*
gi 1237937991  82 VVKVW 86
Cdd:cd04106   151 VTELF 155

GTPase CgtA; Reviewed

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991  33 ELREFRPEI---PCIVVANKID---ADINVTQksfnFAKKFSLPLYFVSAADGTNVVKvwLTAEVASKLfnDAIRLAVSY 106
Cdd:PRK12297  264 ELKLYNPRLlerPQIVVANKMDlpeAEENLEE----FKEKLGPKVFPISALTGQGLDE--LLYAVAELL--EETPEFPLE 335

                          90       100
                  ....*....|....*....|....*...
gi 1237937991 107 KQNSQDFMDEIFQELEN-FSLEQEEEDV 133
Cdd:PRK12297  336 EEEVEEEVYYKFEEEEKdFTITRDEDGV 363

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 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYtELREFRPEIPCIVVANKID----ADINVTQKSFNFAKKFSLPLYFVSAADGT 80
Cdd:cd00882    72 LLRGADLILLVVDSTDRESEEDAKLLI-LRRLRKEGIPIILVGNKIDlleeREVEELLRLEELAKILGVPVFEVSAKTGE 150

                  ..
gi 1237937991  81 NV 82
Cdd:cd00882   151 GV 152

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 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYTELRE-FRPEIPCIVVANKIDADiNVTQKSFNFAKKF--SLPLYFV--SAADG 79
Cdd:cd01860    70 YYRGAAAAIVVYDITSEESFEKAKSWVKELQEhGPPNIVIALAGNKADLE-SKRQVSTEEAQEYadENGLLFMetSAKTG 148

                          90
                  ....*....|....*.
gi 1237937991  80 TNVVKVWLtaEVASKL 95
Cdd:cd01860   149 ENVNELFT--EIARKL 162

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. 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 1237937991   4 SYYHKAHACIMVFDIQRKVTYRNLSTWYTELREF-RPEIPCIVVANKID--ADINVTQ-KSFNFAKKFSLPLYFVSAADG 79
Cdd:cd04113    68 SYYRGAAGALLVYDITSRESFNALTNWLTDARTLaSPDIVIILVGNKKDleDDREVTFlEASRFAQENGLLFLETSALTG 147

                  ...
gi 1237937991  80 TNV 82
Cdd:cd04113   148 ENV 150

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
                   ....*....|....*....|....*....|....*....|....*..
gi 1237937991    6 YHKAHACIMVFDIQRKVTYRNLST-WYTELREFRPEIPCIVVANKID 51
Cdd:smart00174  67 YPDTDVFLICFSVDSPASFENVKEkWYPEVKHFCPNVPIILVGTKLD 113

Rab GTPase family 12 (Rab12); Rab12 was first identified in canine cells, where it was localized to the Golgi complex. The specific function of Rab12 remains unknown, and inconsistent results about its cellular localization have been reported. More recent studies have identified Rab12 associated with post-Golgi vesicles, or with other small vesicle-like structures but not with the Golgi complex. 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. 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 1237937991   3 ASYYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPE-IPCIVVANKID--ADINVT-QKSFNFAKKFS-LPLYFVSAA 77
Cdd:cd04120    67 SAYYRSAKGIILVYDITKKETFDDLPKWMKMIDKYASEdAELLLVGNKLDceTDREITrQQGEKFAQQITgMRFCEASAK 146

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991  78 DGTNVVKVWLtaevasKLFNDAIrlavsykqnSQDFMDEIFQELEN--FSLEQEEEDVPD 135
Cdd:cd04120   147 DNFNVDEIFL------KLVDDIL---------KKMPLDILRNELSNsiLSLQPEPEIPPE 191

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 1237937991  13 IMVFDIQRKVTYRNLST-WYTELREFRPEIPCIVVANKID-------ADINVTQKSF-------NFAKKFSLPLYF-VSA 76
Cdd:cd00157    76 LLCFSVDSPSSFENVKTkWYPEIKHYCPNVPIILVGTKIDlrddgntLKKLEKKQKPitpeegeKLAKEIGAVKYMeCSA 155

                          90       100
                  ....*....|....*....|....*.
gi 1237937991  77 ADGTNVVKVwltaevasklFNDAIRL 102
Cdd:cd00157   156 LTQEGLKEV----------FDEAIRA 171

Obg GTPase; The Obg nucleotide binding protein subfamily has been implicated in stress response, chromosome partitioning, replication initiation, mycelium development, and sporulation. Obg proteins are among a large group of GTP binding proteins conserved from bacteria to humans. The E. coli homolog, ObgE is believed to function in ribosomal biogenesis. Members of the subfamily contain two equally and highly conserved domains, a C-terminal GTP binding domain and an N-terminal glycine-rich domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991  13 IMVFDIQRKV----TYRNLSTwytELREFRPEI---PCIVVANKIDA--DINVTQKSFNFAKKF-SLPLYFVSAADGTNV 82
Cdd:cd01898    83 LHVIDLSGEDdpveDYETIRN---ELEAYNPGLaekPRIVVLNKIDLldAEERFEKLKELLKELkGKKVFPISALTGEGL 159

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991   4 SYYHKAHACIMVFDIQRKVTYRNLSTWYTELREF-RPEIPCIVVANKIDADIN---VTQKSFNFAKKFSLPLYFVSAADG 79
Cdd:PLN03108   74 SYYRGAAGALLVYDITRRETFNHLASWLEDARQHaNANMTIMLIGNKCDLAHRravSTEEGEQFAKEHGLIFMEASAKTA 153

                  ...
gi 1237937991  80 TNV 82
Cdd:PLN03108  154 QNV 156

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYTELREF------RPEIPCIVVANKID----ADINVTQ-KSFNFAKKFslpLYF 73
Cdd:cd04119    69 FYKDTQGVLLVYDVTDRQSFEALDSWLKEMKQEggphgnMENIVVVVCANKIDltkhRAVSEDEgRLWAESKGF---KYF 145

                          90       100
                  ....*....|....*....|....*....
gi 1237937991  74 -VSAADGTNVvkvwltAEVASKLFNDAIR 101
Cdd:cd04119   146 eTSACTGEGV------NEMFQTLFSSIVD 168

Rab GTPase family 19 (Rab19); Rab19 subfamily. Rab19 proteins are associated with Golgi stacks. Similarity analysis indicated that Rab41 is closely related to Rab19. However, the function of these Rabs is not yet characterized. 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
                  ....*....|....*....|....*....|....*....|....*....
gi 1237937991   4 SYYHKAHACIMVFDIQRKVTYRNLSTWYTELREF-RPEIPCIVVANKID 51
Cdd:cd01864    71 SYYRSANGAIIAYDITRRSSFESVPHWIEEVEKYgASNVVLLLIGNKCD 119

Rab GTPase family 15 (Rab15); Rab15 colocalizes with the transferrin receptor in early endosome compartments, but not with late endosomal markers. It codistributes with Rab4 and Rab5 on early/sorting endosomes, and with Rab11 on pericentriolar recycling endosomes. It is believed to function as an inhibitory GTPase that regulates distinct steps in early endocytic trafficking. 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 1237937991   5 YYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRPE-IPCIVVANKIDADIN---VTQKSFNFAKKFSLPLYFVSAADGT 80
Cdd:cd04117    69 YYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEgVQKILIGNKADEEQKrqvGDEQGNKLAKEYGMDFFETSACTNK 148

                  ..
gi 1237937991  81 NV 82
Cdd:cd04117   149 NI 150

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1237937991   6 YHKAHACIMVFDIQRKVTYRNLST-WYTELREFRPEIPCIVVANKID 51
Cdd:cd04133    70 YRGADVFLLAFSLISKASYENVLKkWIPELRHYAPGVPIVLVGTKLD 116

Rab GTPase-like family 4 (Rab-like4); RabL4 (Rab-like4) subfamily. RabL4s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL4 lacks a prenylation site at the C-terminus. The specific function of RabL4 remains unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937991   1 MHASYYHKAHACIMVFDIQRKVTYRNLSTWYTELREFRP--EIPCIVVANKID----ADINVTQKSfNFAKKFSLPLYFV 74
Cdd:cd04101    69 MVENVWEQPAVVCVVYDVTNEVSFNNCSRWINRVRTHSHglHTPGVLVGNKCDltdrREVDAAQAQ-ALAQANTLKFYET 147

                  ....*...
gi 1237937991  75 SAADGTNV 82
Cdd:cd04101   148 SAKEGVGY 155

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 1237937991   6 YHKAHACIMVFDIQRKVTYRN-LSTWYTELREFRPEIPCIVVANKID--ADINVTQKsfnFAKKFSLPlyfVSAADGTNV 82
Cdd:cd04131    70 YPDSDAVLICFDISRPETLDSvLKKWKGEVREFCPNTPVLLVGCKSDlrTDLSTLTE---LSNKRQIP---VSHEQGRNL 143

                  ..
gi 1237937991  83 VK 84
Cdd:cd04131   144 AK 145

Ribosome biogenesis GTPase RbgA [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1237937991  27 LSTWYTELREFRPEIPCIVVANKID-ADINVTQKSFNFAKKFSLPLYFVSAADGTNV 82
Cdd:COG1161    37 LSSRNPMLDELVGNKPRLLVLNKADlADPSVTKQWLKYFEKQGVDALAISAKKGKGI 93