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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        3 SIKLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVV 82
Cdd:cd01860   1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       83 YDVTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLG 162
Cdd:cd01860  81 YDITSEESFEKAKSWVKELQEHGPPNIVIALAGNKADLES---KRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTE 157

                ....*.
1EK0_A      163 IGEKIP 168
Cdd:cd01860 158 IARKLP 163

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        3 SIKLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVV 82
Cdd:cd01860   1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       83 YDVTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLG 162
Cdd:cd01860  81 YDITSEESFEKAKSWVKELQEHGPPNIVIALAGNKADLES---KRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTE 157

                ....*.
1EK0_A      163 IGEKIP 168
Cdd:cd01860 158 IARKLP 163

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A           4 IKLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVY 83
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A          84 DVTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQEggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGI 163
Cdd:smart00175  81 DITNRESFENLENWLKELREYASPNVVIMLVGNKSD-LEE--QRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEEL 157

                   ....
1EK0_A         164 GEKI 167
Cdd:smart00175 158 AREI 161

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        3 SIKLVLLGEAAVGKSSIVLRFVSNDF-AENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRN---AQA 78
Cdd:COG1100   3 EKKIVVVGTGGVGKTSLVNRLVGDIFsLEKYLSTNGVTIDKKELKLDGLDVDLVIWDTPGQDEFRETRQFYARQltgASL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       79 ALVVYDVTKPQSFIKARHWVKELhEQASKDIIIALVGNKID*LQEgGERKVAREEGEKLAEEKGLLFFETSAKTGENVND 158
Cdd:COG1100  83 YLFVVDGTREETLQSLYELLESL-RRLGKKSPIILVLNKIDLYDE-EEIEDEERLKEALSEDNIVEVVATSAKTGEGVEE 160

                ....*....
1EK0_A      159 VFLGIGEKI 167
Cdd:COG1100 161 LFAALAEIL 169

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        3 SIKLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVV 82
Cdd:cd01860   1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       83 YDVTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLG 162
Cdd:cd01860  81 YDITSEESFEKAKSWVKELQEHGPPNIVIALAGNKADLES---KRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTE 157

                ....*.
1EK0_A      163 IGEKIP 168
Cdd:cd01860 158 IARKLP 163

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        4 IKLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVY 83
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       84 DVTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGI 163
Cdd:cd00154  81 DVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDLED---ERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESL 157

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        4 IKLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVY 83
Cdd:cd04123   1 FKVVLLGEGRVGKTSLVLRYVENKFNEKHESTTQASFFQKTVNIGGKRIDLAIWDTAGQERYHALGPIYYRDADGAILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       84 DVTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGI 163
Cdd:cd04123  81 DITDADSFQKVKKWIKELKQMRGNNISLVIVGNKIDLER---QRVVSKSEAEEYAKSVGAKHFETSAKTGKGIEELFLSL 157

                ....
1EK0_A      164 GEKI 167
Cdd:cd04123 158 AKRM 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:cd01868   5 KIVLIGDSGVGKSNLLSRFTRNEFNLDSKSTIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGALLVYD 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       85 VTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGIG 164
Cdd:cd01868  85 ITKKSTFENVERWLKELRDHADSNIVIMLVGNKSDLRH---LRAVPTEEAKAFAEKNGLSFIETSALDGTNVEEAFKQLL 161

                ...
1EK0_A      165 EKI 167
Cdd:cd01868 162 TEI 164

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQrVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDSYRKQ-IVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYS 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       85 VTKPQSFIKarhwVKELHEQ-----ASKDIIIALVGNKID*lqEGGERKVAREEGEKLAEEKGLLFFETSAKTGENVNDV 159
Cdd:cd00876  80 ITSRESFEE----IKNIREQilrvkDKEDVPIVLVGNKCD---LENERQVSTEEGEALAEEWGCPFLETSAKTNINIDEL 152

                .
1EK0_A      160 F 160
Cdd:cd00876 153 F 153

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:cd04113   2 KFLIIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       85 VTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQEggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGIG 164
Cdd:cd04113  82 ITSRESFNALTNWLTDARTLASPDIVIILVGNKKD-LED--DREVTFLEASRFAQENGLLFLETSALTGENVEEAFLKCA 158

                ...
1EK0_A      165 EKI 167
Cdd:cd04113 159 RSI 161

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:cd01866   6 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGALLVYD 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       85 VTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*lqeGGERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGIG 164
Cdd:cd01866  86 ITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDL---ESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAFINTA 162

                ...
1EK0_A      165 EKI 167
Cdd:cd01866 163 KEI 165

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHT-VKFEIWDTAGQERFASLAP*YYRNAQAALVVY 83
Cdd:cd04111   4 RLIVIGDSTVGKSSLLKRFTEGRFAEVSDPTVGVDFFSRLIEIEPGVrIKLQLWDTAGQERFRSITRSYYRNSVGVLLVF 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       84 DVTKPQSFIKARHWVKE--LHEQASKdIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFL 161
Cdd:cd04111  84 DITNRESFEHVHDWLEEarSHIQPHR-PVFILVGHKCDLES---QRQVTREEAEKLAKDLGMKYIETSARTGDNVEEAFE 159

                ....*.
1EK0_A      162 GIGEKI 167
Cdd:cd04111 160 LLTQEI 165

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDF-AENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVY 83
Cdd:cd04112   2 KVMLVGDSGVGKTCLLVRFKDGAFlAGSFIATVGIQFTNKVVTVDGVKVKLQIWDTAGQERFRSVTHAYYRDAHALLLLY 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       84 DVTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*lqEGGERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGI 163
Cdd:cd04112  82 DVTNKSSFDNIRAWLTEILEYAQSDVVIMLLGNKAD---MSGERVVKREDGERLAKEYGVPFMETSAKTGLNVELAFTAV 158

                ....
1EK0_A      164 GEKI 167
Cdd:cd04112 159 AKEL 162

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:cd01862   2 KVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVTVDDRLVTLQIWDTAGQERFQSLGVAFYRGADCCVLVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       85 VTKPQSFIKARHWVKELHEQAS----KDIIIALVGNKID*lqEGGERKVAREEGEKLAEEKGLL-FFETSAKTGENVNDV 159
Cdd:cd01862  82 VTNPKSFESLDSWRDEFLIQASprdpENFPFVVLGNKID---LEEKRQVSTKKAQQWCKSKGNIpYFETSAKEAINVDQA 158

                ....
1EK0_A      160 FLGI 163
Cdd:cd01862 159 FETI 162

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A         5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:PLN03108   8 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDNKPIKLQIWDTAGQESFRSITRSYYRGAAGALLVYD 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        85 VTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGIG 164
Cdd:PLN03108  88 ITRRETFNHLASWLEDARQHANANMTIMLIGNKCDLAH---RRAVSTEEGEQFAKEHGLIFMEASAKTAQNVEEAFIKTA 164

                 ...
1EK0_A       165 EKI 167
Cdd:PLN03108 165 AKI 167

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:cd04122   4 KYIIIGDMGVGKSCLLHQFTEKKFMADCPHTIGVEFGTRIIEVNGQKIKLQIWDTAGQERFRAVTRSYYRGAAGALMVYD 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       85 VTKPQSFIKARHWVKELHEQASKDIIIALVGNKID*lqeGGERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGIG 164
Cdd:cd04122  84 ITRRSTYNHLSSWLTDARNLTNPNTVIFLIGNKADL---EAQRDVTYEEAKQFADENGLLFLECSAKTGENVEDAFLETA 160

                ...
1EK0_A      165 EKI 167
Cdd:cd04122 161 KKI 163

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:cd04110   8 KLLIIGDSGVGKSSLLLRFADNTFSGSYITTIGVDFKIRTVEINGERVKLQIWDTAGQERFRTITSTYYRGTHGVIVVYD 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       85 VTKPQSFIKARHWVKELhEQASKDIIIALVGNKID*lqEGGERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGIG 164
Cdd:cd04110  88 VTNGESFVNVKRWLQEI-EQNCDDVCKVLVGNKND---DPERKVVETEDAYKFAGQMGISLFETSAKENINVEEMFNCIT 163

                ...
1EK0_A      165 EKI 167
Cdd:cd04110 164 ELV 166

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A           5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFlTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYD 84
Cdd:smart00010   4 KLVVLGGGGVGKSALTIQFVQGHFVDEYDPTIEDSY-RKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A          85 VTKPQSFikarHWVKELHEQ-----ASKDIIIALVGNKID*LQEggeRKVAREEGEKLAEEKGLLFFETSAKTGENVNDV 159
Cdd:smart00010  83 ITDRQSF----EEIAKFREQilrvkDRDDVPIVLVGNKCDLENE---RVVSTEEGKELARQWGCPFLETSAKERINVDEA 155

                   .
1EK0_A         160 F 160
Cdd:smart00010 156 F 156

rab6; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        26 NDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERFASLAP*YYRNAQAALVVYDVTKPQSFIKARHWVKELHEQA 105
Cdd:PTZ00099   3 DTFDNNYQSTIGIDFLSKTLYLDEGPVRLQLWDTAGQERFRSLIPSYIRDSAAAIVVYDITNRQSFENTTKWIQDILNER 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
1EK0_A       106 SKDIIIALVGNKID*lqeGGERKVAREEGEKLAEEKGLLFFETSAKTGENVNDVFLGIGEKIP 168
Cdd:PTZ00099  83 GKDVIIALVGNKTDL---GDLRKVTYEEGMQKAQEYNTMFHETSAKAGHNIKVLFKKIAAKLP 142

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        5 KLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINEHTVKFEIWDTAGQERF-ASLAP*YYRNAQAALVVY 83
Cdd:cd04115   4 KIIVIGDSNVGKTCLTYRFCAGRFPERTEATIGVDFRERTVEIDGERIKVQLWDTAGQERFrKSMVQHYYRNVHAVVFVY 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       84 DVTKPQSFIKARHWVKELHEQA-SKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAK---TGENVNDV 159
Cdd:cd04115  84 DVTNMASFHSLPSWIEECEQHSlPNEVPRILVGNKCDLRE---QIQVPTDLAQRFADAHSMPLFETSAKdpsENDHVEAI 160

                ..
1EK0_A      160 FL 161
Cdd:cd04115 161 FM 162

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A        4 IKLVLLGEAAVGKSSIVLRFVSNDFAENKEPTIGAAFLTQRVTINE----------HTVKFEIWDTAGQERFASLAP*YY 73
Cdd:cd04127   5 IKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYNSqgpdgtsgkaFRVHLQLWDTAGQERFRSLTTAFF 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1EK0_A       74 RNAQAALVVYDVTKPQSFIKARHWVKELHEQA-SKDIIIALVGNKID*LQeggERKVAREEGEKLAEEKGLLFFETSAKT 152
Cdd:cd04127  85 RDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAyCENPDIVLIGNKADLPD---QREVSERQARELADKYGIPYFETSAAT 161