Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. 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 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAF 89
Cdd:cd01862   1 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVTVDDRLVTLQIWDTAGQERFQSLGVAFYRGADCCVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  90 DVTNAASFKSLDSWRDEFLIQASPRDPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGNIPYYEVSAKEALNVEAAFL 169
Cdd:cd01862  81 DVTNPKSFESLDSWRDEFLIQASPRDPENFPFVVLGNKIDLEEKRQVSTKKAQQWCKSKGNIPYFETSAKEAINVDQAFE 160

                       170
                ....*....|..
gi 17536699 170 AIARDALARESQ 181
Cdd:cd01862 161 TIARLALEQEKE 172

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. 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 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAF 89
Cdd:cd01862   1 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVTVDDRLVTLQIWDTAGQERFQSLGVAFYRGADCCVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  90 DVTNAASFKSLDSWRDEFLIQASPRDPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGNIPYYEVSAKEALNVEAAFL 169
Cdd:cd01862  81 DVTNPKSFESLDSWRDEFLIQASPRDPENFPFVVLGNKIDLEEKRQVSTKKAQQWCKSKGNIPYFETSAKEAINVDQAFE 160

                       170
                ....*....|..
gi 17536699 170 AIARDALARESQ 181
Cdd:cd01862 161 TIARLALEQEKE 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 17536699    11 KVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAFD 90
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699    91 VTNAASFKSLDSWRDEFLIQAsprdPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGnIPYYEVSAKEALNVEAAFLA 170
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHA----DENVPIVLVGNKCDLEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEEAFEE 155

                  ....*.
gi 17536699   171 IARDAL 176
Cdd:pfam00071 156 LAREIL 161

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSN-QYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLG---VAFYRGADCC 85
Cdd:COG1100   4 KKIVVVGTGGVGKTSLVNRLVGDIFSLeKYLSTNGVTIDKKELKLDGLDVDLVIWDTPGQDEFRETRqfyARQLTGASLY 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  86 VLAFDVTNAASFKSLDSWRdEFLIQASPrdpdHFPFVLLGNKVDLESQRAVSSK-RAQSWCQTKGNIPYYEVSAKEALNV 164
Cdd:COG1100  84 LFVVDGTREETLQSLYELL-ESLRRLGK----KSPIILVLNKIDLYDEEEIEDEeRLKEALSEDNIVEVVATSAKTGEGV 158

                       170
                ....*....|....*....
gi 17536699 165 EAAFLAIARDALARESQET 183
Cdd:COG1100 159 EELFAALAEILRGEGDSLD 177

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. 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 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAF 89
Cdd:cd01862   1 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVTVDDRLVTLQIWDTAGQERFQSLGVAFYRGADCCVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  90 DVTNAASFKSLDSWRDEFLIQASPRDPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGNIPYYEVSAKEALNVEAAFL 169
Cdd:cd01862  81 DVTNPKSFESLDSWRDEFLIQASPRDPENFPFVVLGNKIDLEEKRQVSTKKAQQWCKSKGNIPYFETSAKEAINVDQAFE 160

                       170
                ....*....|..
gi 17536699 170 AIARDALARESQ 181
Cdd:cd01862 161 TIARLALEQEKE 172

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 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAF 89
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  90 DVTNAASFKSLDSWRDEFLIQAsprdPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQtKGNIPYYEVSAKEALNVEAAFL 169
Cdd:cd00154  81 DVTNRESFENLDKWLNELKEYA----PPNIPIILVGNKSDLEDERQVSTEEAQQFAK-ENGLLFFETSAKTGENVDEAFE 155

                ....
gi 17536699 170 AIAR 173
Cdd:cd00154 156 SLAR 159

Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. 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 17536699   6 KKALLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCC 85
Cdd:cd04116   2 KSSLLKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERFRSLRTPFYRGSDCC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  86 VLAFDVTNAASFKSLDSWRDEFLIQASPRDPDHFPFVLLGNKVDLEsQRAVSSKRAQSWCQTKGNIPYYEVSAKEALNVE 165
Cdd:cd04116  82 LLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFVILGNKIDIP-ERQVSTEEAQAWCRDNGDYPYFETSAKDATNVA 160

                ....*...
gi 17536699 166 AAFLAIAR 173
Cdd:cd04116 161 AAFEEAVR 168

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 17536699   9 LLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLA 88
Cdd:cd01868   3 LFKIVLIGDSGVGKSNLLSRFTRNEFNLDSKSTIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGALLV 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  89 FDVTNAASFKSLDSWRDEFliqaspRD--PDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGnIPYYEVSAKEALNVEA 166
Cdd:cd01868  83 YDITKKSTFENVERWLKEL------RDhaDSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNG-LSFIETSALDGTNVEE 155

                ....*
gi 17536699 167 AFLAI 171
Cdd:cd01868 156 AFKQL 160

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 17536699   9 LLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLA 88
Cdd:cd01869   2 LFKLLLIGDSGVGKSCLLLRFADDTYTESYISTIGVDFKIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  89 FDVTNAASFKSLDSWRDEFLIQASprdpDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKgNIPYYEVSAKEALNVEAAF 168
Cdd:cd01869  82 YDVTDQESFNNVKQWLQEIDRYAS----ENVNKLLVGNKCDLTDKKVVDYTEAKEFADEL-GIPFLETSAKNATNVEEAF 156

                       170
                ....*....|
gi 17536699 169 LAIARDALAR 178
Cdd:cd01869 157 MTMAREIKKR 166

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 17536699  11 KVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAFD 90
Cdd:cd04123   2 KVVLLGEGRVGKTSLVLRYVENKFNEKHESTTQASFFQKTVNIGGKRIDLAIWDTAGQERYHALGPIYYRDADGAILVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  91 VTNAASFKSLDSWRDEfLIQASprdPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGnIPYYEVSAKEALNVEAAFLA 170
Cdd:cd04123  82 ITDADSFQKVKKWIKE-LKQMR---GNNISLVIVGNKIDLERQRVVSKSEAEEYAKSVG-AKHFETSAKTGKGIEELFLS 156

                ....
gi 17536699 171 IARD 174
Cdd:cd04123 157 LAKR 160

Rab GTPase family 2 (Rab2); Rab2 is localized on cis-Golgi membranes and interacts with Golgi matrix proteins. Rab2 is also implicated in the maturation of vesicular tubular clusters (VTCs), which are microtubule-associated intermediates in transport between the ER and Golgi apparatus. In plants, Rab2 regulates vesicle trafficking between the ER and the Golgi bodies and is important to pollen tube growth. 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 17536699   9 LLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLA 88
Cdd:cd01866   4 LFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGALLV 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  89 FDVTNAASFKSLDSWRDEFLIQASPrdpdHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGNIpYYEVSAKEALNVEAAF 168
Cdd:cd01866  84 YDITRRETFNHLTSWLEDARQHSNS----NMTIMLIGNKCDLESRREVSYEEGEAFAREHGLI-FMETSAKTASNVEEAF 158

                ....*
gi 17536699 169 LAIAR 173
Cdd:cd01866 159 INTAK 163

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 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAF 89
Cdd:cd04113   1 FKFLIIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  90 DVTNAASFKSLDSWRDEFLIQASPrdpdHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGnIPYYEVSAKEALNVEAAFL 169
Cdd:cd04113  81 DITSRESFNALTNWLTDARTLASP----DIVIILVGNKKDLEDDREVTFLEASRFAQENG-LLFLETSALTGENVEEAFL 155

                ....
gi 17536699 170 AIAR 173
Cdd:cd04113 156 KCAR 159

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699   9 LLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLA 88
Cdd:cd01864   3 LFKIILIGDSNVGKTCVVQRFKSGTFSERQGNTIGVDFTMKTLEIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAIIA 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  89 FDVTNAASFKSLDSWRDEFLIQASPrdpdHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGNIPYYEVSAKEALNVEAAF 168
Cdd:cd01864  83 YDITRRSSFESVPHWIEEVEKYGAS----NVVLLLIGNKCDLEEQREVLFEEACTLAEHYGILAVLETSAKESSNVEEAF 158

                ....*.
gi 17536699 169 LAIARD 174
Cdd:cd01864 159 LLMATE 164

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. 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 17536699   9 LLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLA 88
Cdd:cd04110   6 LFKLLIIGDSGVGKSSLLLRFADNTFSGSYITTIGVDFKIRTVEINGERVKLQIWDTAGQERFRTITSTYYRGTHGVIVV 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  89 FDVTNAASFKSLDSWRDEflIQAsprDPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKgNIPYYEVSAKEALNVEAAF 168
Cdd:cd04110  86 YDVTNGESFVNVKRWLQE--IEQ---NCDDVCKVLVGNKNDDPERKVVETEDAYKFAGQM-GISLFETSAKENINVEEMF 159

                       170
                ....*....|....*
gi 17536699 169 LAIARDALARESQET 183
Cdd:cd04110 160 NCITELVLRAKKDNL 174

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. 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 17536699   9 LLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRT----------VTLQIWDTAGQERFQSLGVAF 78
Cdd:cd04127   4 LIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYNSQGpdgtsgkafrVHLQLWDTAGQERFRSLTTAF 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  79 YRGADCCVLAFDVTNAASFKSLDSWRDEFLIQASPRDPDhfpFVLLGNKVDLESQRAVSSKRAQSWCQTKGnIPYYEVSA 158
Cdd:cd04127  84 FRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAYCENPD---IVLIGNKADLPDQREVSERQARELADKYG-IPYFETSA 159

                ....*....
gi 17536699 159 KEALNVEAA 167
Cdd:cd04127 160 ATGQNVEKA 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 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDR--TVTLQIWDTAGQERFQSLGVAFYRGADCCVL 87
Cdd:cd04106   1 IKVIVVGNGNVGKSSMIQRFVKGIFTKDYKKTIGVDFLEKQIFLRQSdeDVRLMLWDTAGQEEFDAITKAYYRGAQACIL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  88 AFDVTNAASFKSLDSWRdefliQASPRDPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQtKGNIPYYEVSAKEALNVEAA 167
Cdd:cd04106  81 VFSTTDRESFEAIESWK-----EKVEAECGDIPMVLVQTKIDLLDQAVITNEEAEALAK-RLQLPLFRTSVKDDFNVTEL 154

                .
gi 17536699 168 F 168
Cdd:cd04106 155 F 155

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of 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 17536699   9 LLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLA 88
Cdd:cd04122   2 IFKYIIIGDMGVGKSCLLHQFTEKKFMADCPHTIGVEFGTRIIEVNGQKIKLQIWDTAGQERFRAVTRSYYRGAAGALMV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  89 FDVTNAASFKSLDSWrdefLIQASPRDPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGnIPYYEVSAKEALNVEAAF 168
Cdd:cd04122  82 YDITRRSTYNHLSSW----LTDARNLTNPNTVIFLIGNKADLEAQRDVTYEEAKQFADENG-LLFLECSAKTGENVEDAF 156

                ....*
gi 17536699 169 LAIAR 173
Cdd:cd04122 157 LETAK 161

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 17536699  10 LKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAF 89
Cdd:cd04119   1 IKVISMGNSGVGKSCIIKRYCEGRFVSKYLPTIGIDYGVKKVSVRNKEVRVNFFDLSGHPEYLEVRNEFYKDTQGVLLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  90 DVTNAASFKSLDSWRDEFlIQ--ASPRDPDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGNIpYYEVSAKEALNVEAA 167
Cdd:cd04119  81 DVTDRQSFEALDSWLKEM-KQegGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLWAESKGFK-YFETSACTGEGVNEM 158

                       170
                ....*....|
gi 17536699 168 FLAIARDALA 177
Cdd:cd04119 159 FQTLFSSIVD 168

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. 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 17536699  11 KVIILGDSGVGKTSLMNQYVNRRF-SNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAF 89
Cdd:cd04112   2 KVMLVGDSGVGKTCLLVRFKDGAFlAGSFIATVGIQFTNKVVTVDGVKVKLQIWDTAGQERFRSVTHAYYRDAHALLLLY 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  90 DVTNAASFKSLDSWRDEFLIQASprdpDHFPFVLLGNKVDLESQRAVSSKRAQSWCQTKGnIPYYEVSAKEALNVEAAFL 169
Cdd:cd04112  82 DVTNKSSFDNIRAWLTEILEYAQ----SDVVIMLLGNKADMSGERVVKREDGERLAKEYG-VPFMETSAKTGLNVELAFT 156

                       170
                ....*....|....*.
gi 17536699 170 AIARDALARESQETND 185
Cdd:cd04112 157 AVAKELKHRSVEQPDE 172

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699     11 KVIILGDSGVGKTSLMNQYVNRRFSNQYKATIgADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCVLAFD 90
Cdd:smart00010   4 KLVVLGGGGVGKSALTIQFVQGHFVDEYDPTI-EDSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699     91 VTNAASFKSLDSWRDEFLiqaSPRDPDHFPFVLLGNKVDLESQRAVSS----KRAQSWcqtkgNIPYYEVSAKEALNVEA 166
Cdd:smart00010  83 ITDRQSFEEIAKFREQIL---RVKDRDDVPIVLVGNKCDLENERVVSTeegkELARQW-----GCPFLETSAKERINVDE 154

                   ....*....
gi 17536699    167 AFLAIARDA 175
Cdd:smart00010 155 AFYDLVREI 163

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 17536699   7 KALLKVIILGDSGVGKTSLMNQYVNRRFSNQYKATIGADFLTRDVNIDDRTVTLQIWDTAGQERFQSLGVAFYRGADCCV 86
Cdd:cd04114   5 DFLFKIVLIGNAGVGKTCLVRRFTQGLFPPGQGATIGVDFMIKTVEIKGEKIKLQIWDTAGQERFRSITQSYYRSANALI 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17536699  87 LAFDVTNAASFKSLDSWRDEFLIQASPRdpdhFPFVLLGNKVDLESQRAVSSKRAQSWCQTKgNIPYYEVSAKEALNVEA 166
Cdd:cd04114  85 LTYDITCEESFRCLPEWLREIEQYANNK----VITILVGNKIDLAERREVSQQRAEEFSDAQ-DMYYLETSAKESDNVEK 159

                ....*.
gi 17536699 167 AFLAIA 172
Cdd:cd04114 160 LFLDLA 165