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 2024420929  20 YKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:cd01860     2 FKLVLLGDSSVGKSSIVLRFVKNEFSENqESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVVY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  99 DLTNKETLNRAKQWLMELEKEfLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVAH 178
Cdd:cd01860    82 DITSEESFEKAKSWVKELQEH-GPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEIAR 160

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 2024420929  20 YKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:cd01860     2 FKLVLLGDSSVGKSSIVLRFVKNEFSENqESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVVY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  99 DLTNKETLNRAKQWLMELEKEfLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVAH 178
Cdd:cd01860    82 DITSEESFEKAKSWVKELQEH-GPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEIAR 160

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929   20 YKMVLLGSTSVGKSSLAYRYVKNDFKE-SLPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEqYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024420929   99 DLTNKETLNRAKQWLMELEkEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVA 177
Cdd:smart00175  81 DITNRESFENLENWLKELR-EYASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEELA 158

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  21 KMVLLGSTSVGKSSLAYRYVKNDFKES--LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVcHLYY----RGAHAA 94
Cdd:COG1100     5 KIVVVGTGGVGKTSLVNRLVGDIFSLEkyLSTNGVTIDKKELKLDGLDVDLVIWDTPGQDEFRET-RQFYarqlTGASLY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  95 LLVYDLTNKETLNRAKQWLMELEKEFLPDEIViaLVGNKTDLADEREVAAEDG--EEFARSRSLLFMETSAKSNHQVNDV 172
Cdd:COG1100    84 LFVVDGTREETLQSLYELLESLRRLGKKSPII--LVLNKIDLYDEEEIEDEERlkEALSEDNIVEVVATSAKTGEGVEEL 161

                  ....*
gi 2024420929 173 FMAVA 177
Cdd:COG1100   162 FAALA 166

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 2024420929  20 YKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:cd01860     2 FKLVLLGDSSVGKSSIVLRFVKNEFSENqESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVVY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  99 DLTNKETLNRAKQWLMELEKEfLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVAH 178
Cdd:cd01860    82 DITSEESFEKAKSWVKELQEH-GPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEIAR 160

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 2024420929  21 KMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVYD 99
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEyIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929 100 LTNKETLNRAKQWLMELeKEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVAHL 179
Cdd:pfam00071  81 ITSRDSFENVKKWVEEI-LRHADENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEELARE 159

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 2024420929  18 YIYKMVLLGSTSVGKSSLAYRYVKNDF-KESLPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALL 96
Cdd:cd01868     2 YLFKIVLIGDSGVGKSNLLSRFTRNEFnLDSKSTIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGALL 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2024420929  97 VYDLTNKETLNRAKQWLMELeKEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFM 174
Cdd:cd01868    82 VYDITKKSTFENVERWLKEL-RDHADSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSALDGTNVEEAFK 158

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER 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 2024420929  20 YKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:cd01861     1 HKLVFLGDQSVGKTSIITRFMYDTFDNQyQATIGIDFLSKTMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVVY 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024420929  99 DLTNKETLNRAKQWLMELEKEFLpDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVA 177
Cdd:cd01861    81 DITNRQSFDNTDKWIDDVRDERG-NDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLFKKIA 158

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. 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 2024420929  18 YIYKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALL 96
Cdd:cd01867     2 YLFKLLLIGDSGVGKSCLLLRFSEDSFNPSfISTIGIDFKIRTIELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGIIL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  97 VYDLTNKETLNRAKQWLMELEkEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAV 176
Cdd:cd01867    82 VYDITDEKSFENIKNWMRNID-EHASEDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKANINVEEAFLTL 160

                  .
gi 2024420929 177 A 177
Cdd:cd01867   161 A 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  18 YIYKMVLLGSTSVGKSSLAYRYVKNDFKESLP-TVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALL 96
Cdd:cd01866     3 YLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDlTIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGALL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  97 VYDLTNKETLNRAKQWLMELeKEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAV 176
Cdd:cd01866    83 VYDITRRETFNHLTSWLEDA-RQHSNSNMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAFINT 161

                  .
gi 2024420929 177 A 177
Cdd:cd01866   162 A 162

Rab GTPase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  18 YIYKMVLLGSTSVGKSSLAYRYVKNDF-KESLPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALL 96
Cdd:PLN03110   11 YLFKIVLIGDSGVGKSNILSRFTRNEFcLESKSTIGVEFATRTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGALL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  97 VYDLTNKETLNRAKQWLMELeKEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAV 176
Cdd:PLN03110   91 VYDITKRQTFDNVQRWLREL-RDHADSNIVIMMAGNKSDLNHLRSVAEEDGQALAEKEGLSFLETSALEATNVEKAFQTI 169

                         170
                  ....*....|
gi 2024420929 177 A----HLSSK 182
Cdd:PLN03110  170 LleiyHIISK 179

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 2024420929  20 YKMVLLGSTSVGKSSLAYRYVKNDFKESLP-TVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:cd04113     1 FKFLIIGSAGTGKSCLLHQFIENKFKQDSNhTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVY 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024420929  99 DLTNKETLNRAKQWLMELEKEFLPDeIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVA 177
Cdd:cd04113    81 DITSRESFNALTNWLTDARTLASPD-IVIILVGNKKDLEDDREVTFLEASRFAQENGLLFLETSALTGENVEEAFLKCA 158

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  21 KMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGcSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVYD 99
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEyDPTIE-DSYRKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYS 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2024420929 100 LTNKETLNRAKQWLMEL----EKEFLPdeivIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVF 173
Cdd:cd00876    80 ITSRESFEEIKNIREQIlrvkDKEDVP----IVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNINIDELF 153

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 2024420929  20 YKMVLLGSTSVGKSSLAYRYVKNDFKES--LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLV 97
Cdd:cd04112     1 FKVMLVGDSGVGKTCLLVRFKDGAFLAGsfIATVGIQFTNKVVTVDGVKVKLQIWDTAGQERFRSVTHAYYRDAHALLLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  98 YDLTNKETLNRAKQWLMELeKEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVA 177
Cdd:cd04112    81 YDVTNKSSFDNIRAWLTEI-LEYAQSDVVIMLLGNKADMSGERVVKREDGERLAKEYGVPFMETSAKTGLNVELAFTAVA 159

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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 2024420929  19 IYKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLV 97
Cdd:cd01865     1 MFKLLIIGNSSVGKTSFLFRYADDSFTSAfVSTVGIDFKVKTVYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILM 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024420929  98 YDLTNKETLNRAKQWLMELeKEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVF 173
Cdd:cd01865    81 YDITNEESFNAVQDWSTQI-KTYSWDNAQVILVGNKCDMEDERVVSAERGRQLADQLGFEFFEASAKENINVKQVF 155

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 2024420929  18 YIYKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALL 96
Cdd:cd04110     5 HLFKLLIIGDSGVGKSSLLLRFADNTFSGSyITTIGVDFKIRTVEINGERVKLQIWDTAGQERFRTITSTYYRGTHGVIV 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  97 VYDLTNKETLNRAKQWLMELEKEFlpDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAV 176
Cdd:cd04110    85 VYDVTNGESFVNVKRWLQEIEQNC--DDVCKVLVGNKNDDPERKVVETEDAYKFAGQMGISLFETSAKENINVEEMFNCI 162

                  ...
gi 2024420929 177 AHL 179
Cdd:cd04110   163 TEL 165

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 2024420929  21 KMVLLGSTSVGKSSLAYRYVKNDFKESLP-TVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVYD 99
Cdd:cd04120     2 QVIIIGSRGVGKTSLMERFTDDTFCEACKsTVGVDFKIKTVELRGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILVYD 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024420929 100 LTNKETLNRAKQWLMELEKeFLPDEIVIALVGNKTDLADEREVAAEDGEEFA-RSRSLLFMETSAKSNHQVNDVFM 174
Cdd:cd04120    82 ITKKETFDDLPKWMKMIDK-YASEDAELLLVGNKLDCETDREITRQQGEKFAqQITGMRFCEASAKDNFNVDEIFL 156

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 2024420929   20 YKMVLLGSTSVGKSSLAYRYVKNDFKESL-PTVGCSFfTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:smart00010   3 YKLVVLGGGGVGKSALTIQFVQGHFVDEYdPTIEDSY-RKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVY 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024420929   99 DLTNKETLNRAKqwlmELEKEFL----PDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVF 173
Cdd:smart00010  82 SITDRQSFEEIA----KFREQILrvkdRDDVPIVLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKERINVDEAF 156

Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C-terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro. The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways. 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 2024420929  21 KMVLLGSTSVGKSSLAYRYVKNDF--KESLPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:cd04118     2 KVVMLGKESVGKTSLVERYVHHRFlvGPYQNTIGAAFVAKRMVVGERVVTLGIWDTAGSERYEAMSRIYYRGAKAAIVCY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  99 DLTNKETLNRAKQWLMELEKefLPDEIVIALVGNKTDLADE----REVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFM 174
Cdd:cd04118    82 DLTDSSSFERAKFWVKELQN--LEEHCKIYLCGTKSDLIEQdrslRQVDFHDVQDFADEIKAQHFETSSKTGQNVDELFQ 159

                  ...
gi 2024420929 175 AVA 177
Cdd:cd04118   160 KVA 162

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 2024420929  20 YKMVLLGSTSVGKSSLAYRYVKNDFKES-LPTVGCSFFTQTIQLETATIKLEIWDTAGQEKYHSVCHLYYRGAHAALLVY 98
Cdd:cd04117     1 FRLLLIGDSGVGKTCLLCRFTDNEFHSShISTIGVDFKMKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  99 DLTNKETLNRAKQWLMELEkEFLPDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVAH 178
Cdd:cd04117    81 DISSERSYQHIMKWVSDVD-EYAPEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETSACTNKNIKESFTRLTE 159

                  ....
gi 2024420929 179 LSSK 182
Cdd:cd04117   160 LVLQ 163

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 2024420929  21 KMVLLGSTSVGKSSLAYRYVKNDF-KESLPTVGCSFFTQTIQLETA--TIKLEIWDTAGQEKYHSVCHLYYRGAHAALLV 97
Cdd:cd04106     2 KVIVVGNGNVGKSSMIQRFVKGIFtKDYKKTIGVDFLEKQIFLRQSdeDVRLMLWDTAGQEEFDAITKAYYRGAQACILV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024420929  98 YDLTNKETLNRAKQWLMELEKEFlpDEIVIALVGNKTDLADEREVAAEDGEEFARSRSLLFMETSAKSNHQVNDVFMAVA 177
Cdd:cd04106    82 FSTTDRESFEAIESWKEKVEAEC--GDIPMVLVQTKIDLLDQAVITNEEAEALAKRLQLPLFRTSVKDDFNVTELFEYLA 159