Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic transport and is expressed most highly in polarized epithelial cells. However, trypanosomal Rab, TbRAB18, is upregulated in the BSF (Blood Stream Form) stage and localized predominantly to elements of the Golgi complex. In human and mouse cells, Rab18 has been identified in lipid droplets, organelles that store neutral lipids. 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 351725909  18 FKLLLIGDSGVGKSTLLLSFTSDTFE-DLSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:cd01863    1 LKILLIGDSGVGKSSLLLRFTDDTFDeDLSSTIGVDFKVKTVTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  97 DVTRRETFTNLsDIWAKEIDLYSTNQDCIKMLVGNKVDKESeRVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELV 176
Cdd:cd01863   81 DVTRRDTFDNL-DTWLNELDTYSTNPDAVKMLVGNKIDKEN-REVTREEGQKFARKHNMLFIETSAKTRIGVQQAFEELV 158

                 ...
gi 351725909 177 MKI 179
Cdd:cd01863  159 EKI 161

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 351725909   19 KLLLIGDSGVGKSTLLLSFTSDTF-EDLSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVYD 97
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFpEEYIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909   98 VTRRETFTNLSDiWAKEIDLYsTNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELVM 177
Cdd:pfam00071  81 ITSRDSFENVKK-WVEEILRH-ADENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEELAR 158

                  ....
gi 351725909  178 KILE 181
Cdd:pfam00071 159 EILK 162

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909   18 FKLLLIGDSGVGKSTLLLSFTSDT-FEDLS-PTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMV 95
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLGNKgSITEYyPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909   96 YDVtrreTFTNLSDIWAKEIDLYSTNQDCIK----MLVGNKVDKESERvVSKKEGIDFAREYGCLYTECSAKTRVNVAQC 171
Cdd:TIGR00231  82 FDI----VILVLDVEEILEKQTKEIIHHADSgvpiILVGNKIDLKDAD-LKTHVASEFAKLNGEPIIPLSAETGKNIDSA 156

                  ....*
gi 351725909  172 FDELV 176
Cdd:TIGR00231 157 FKIVE 161

Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic transport and is expressed most highly in polarized epithelial cells. However, trypanosomal Rab, TbRAB18, is upregulated in the BSF (Blood Stream Form) stage and localized predominantly to elements of the Golgi complex. In human and mouse cells, Rab18 has been identified in lipid droplets, organelles that store neutral lipids. 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 351725909  18 FKLLLIGDSGVGKSTLLLSFTSDTFE-DLSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:cd01863    1 LKILLIGDSGVGKSSLLLRFTDDTFDeDLSSTIGVDFKVKTVTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  97 DVTRRETFTNLsDIWAKEIDLYSTNQDCIKMLVGNKVDKESeRVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELV 176
Cdd:cd01863   81 DVTRRDTFDNL-DTWLNELDTYSTNPDAVKMLVGNKIDKEN-REVTREEGQKFARKHNMLFIETSAKTRIGVQQAFEELV 158

                 ...
gi 351725909 177 MKI 179
Cdd:cd01863  159 EKI 161

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 351725909  18 FKLLLIGDSGVGKSTLLLSFTSDTF-EDLSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:cd00154    1 FKIVLIGDSGVGKTSLLLRFVDNKFsENYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  97 DVTRRETFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELV 176
Cdd:cd00154   81 DVTNRESFENLDK-WLNELKEYA-PPNIPIILVGNKSDLEDERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESLA 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 351725909  15 DYLFKLLLIGDSGVGKSTLLLSFTSDTFED-LSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGII 93
Cdd:cd01867    1 DYLFKLLLIGDSGVGKSCLLLRFSEDSFNPsFISTIGIDFKIRTIELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGII 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  94 MVYDVTRRETFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFD 173
Cdd:cd01867   81 LVYDITDEKSFENIKN-WMRNIDEHA-SEDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKANINVEEAFL 158

                 ....*...
gi 351725909 174 ELVMKILE 181
Cdd:cd01867  159 TLAKDILK 166

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 351725909  15 DYLFKLLLIGDSGVGKSTLLLSFTSDTFEDLS-PTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGII 93
Cdd:cd01868    1 DYLFKIVLIGDSGVGKSNLLSRFTRNEFNLDSkSTIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGAL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  94 MVYDVTRRETFTNLsDIWAKEIDLYStNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFD 173
Cdd:cd01868   81 LVYDITKKSTFENV-ERWLKELRDHA-DSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSALDGTNVEEAFK 158

                 ....*.
gi 351725909 174 ELVMKI 179
Cdd:cd01868  159 QLLTEI 164

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 351725909  18 FKLLLIGDSGVGKSTLLLSFTSDTF-EDLSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:cd01860    2 FKLVLLGDSSVGKSSIVLRFVKNEFsENQESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVVY 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  97 DVTRRETFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELV 176
Cdd:cd01860   82 DITSEESFEKAKS-WVKELQEHG-PPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEIA 159

                 ....
gi 351725909 177 MKIL 180
Cdd:cd01860  160 RKLP 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  13 EFDYLFKLLLIGDSGVGKSTLLLSFTSDTF-EDLSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQG 91
Cdd:cd04110    2 DYDHLFKLLIIGDSGVGKSSLLLRFADNTFsGSYITTIGVDFKIRTVEINGERVKLQIWDTAGQERFRTITSTYYRGTHG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  92 IIMVYDVTRRETFTNLSDiWAKEIDlysTNQDCI-KMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQ 170
Cdd:cd04110   82 VIVVYDVTNGESFVNVKR-WLQEIE---QNCDDVcKVLVGNKNDDPERKVVETEDAYKFAGQMGISLFETSAKENINVEE 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 351725909 171 CFDELVMKILETPslLAEGSSGVKKNIFKQKPPQSDASSSGCC 213
Cdd:cd04110  158 MFNCITELVLRAK--KDNLAKQQQQQQNDVVKLPKNSKRKKRC 198

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 351725909  13 EFDYLFKLLLIGDSGVGKSTLLLSFTSDTFE-DLSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQG 91
Cdd:cd04114    3 DYDFLFKIVLIGNAGVGKTCLVRRFTQGLFPpGQGATIGVDFMIKTVEIKGEKIKLQIWDTAGQERFRSITQSYYRSANA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  92 IIMVYDVTRRETFTNLSDiWAKEIDLYSTNQdCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQC 171
Cdd:cd04114   83 LILTYDITCEESFRCLPE-WLREIEQYANNK-VITILVGNKIDLAERREVSQQRAEEFSDAQDMYYLETSAKESDNVEKL 160

                 ....*....
gi 351725909 172 FDELVMKIL 180
Cdd:cd04114  161 FLDLACRLI 169

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  16 YLFKLLLIGDSGVGKSTLLLSFTSDTFEDLS-PTIGVDFKVKYVTMG-GKKSKLAIWDTAGQERFRTLTSSYYRGAQGII 93
Cdd:cd04111    1 YQFRLIVIGDSTVGKSSLLKRFTEGRFAEVSdPTVGVDFFSRLIEIEpGVRIKLQLWDTAGQERFRSITRSYYRNSVGVL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  94 MVYDVTRRETFTNLSDiWAKEIDLYSTNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFD 173
Cdd:cd04111   81 LVFDITNRESFEHVHD-WLEEARSHIQPHRPVFILVGHKCDLESQRQVTREEAEKLAKDLGMKYIETSARTGDNVEEAFE 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 351725909 174 ELVMKI---LETPSLLAE-GSSGVKKNI-------FKQKPPQSDASSSGCC 213
Cdd:cd04111  160 LLTQEIyerIKRGELCALdGWDGVKSGFpagrafsLEERSPTFASPEKSCC 210

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 351725909  18 FKLLLIGDSGVGKSTLLLSFTSDTFEDLS-PTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:cd01861    1 HKLVFLGDQSVGKTSIITRFMYDTFDNQYqATIGIDFLSKTMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVVY 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 351725909  97 DVTRRETFTNLSDiWAKEIDLySTNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDEL 175
Cdd:cd01861   81 DITNRQSFDNTDK-WIDDVRD-ERGNDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLFKKI 157

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 351725909  17 LFKLLLIGDSGVGKSTLLLSFTSDTFED-LSPTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMV 95
Cdd:cd01865    1 MFKLLIIGNSSVGKTSFLFRYADDSFTSaFVSTVGIDFKVKTVYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  96 YDVTRRETFTNLSDiWAKEIDLYSTNQDCIkMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDEL 175
Cdd:cd01865   81 YDITNEESFNAVQD-WSTQIKTYSWDNAQV-ILVGNKCDMEDERVVSAERGRQLADQLGFEFFEASAKENINVKQVFERL 158

                 ....*.
gi 351725909 176 VMKILE 181
Cdd:cd01865  159 VDIICD 164

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 351725909  18 FKLLLIGDSGVGKSTLLLSFTSDTFEDLSP-TIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:cd04113    1 FKFLIIGSAGTGKSCLLHQFIENKFKQDSNhTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  97 DVTRRETFTNLSDiWAKEIDLYSTnQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELV 176
Cdd:cd04113   81 DITSRESFNALTN-WLTDARTLAS-PDIVIILVGNKKDLEDDREVTFLEASRFAQENGLLFLETSALTGENVEEAFLKCA 158

                 ...
gi 351725909 177 MKI 179
Cdd:cd04113  159 RSI 161

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 351725909  19 KLLLIGDSGVGKSTLLLSFTSDTF-EDLSPTIGvDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVYD 97
Cdd:cd00876    1 KLVVLGAGGVGKSALTIRFVSGEFvEEYDPTIE-DSYRKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  98 VTRRETFTNLSDIWaKEIDLYSTNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELVM 177
Cdd:cd00876   80 ITSRESFEEIKNIR-EQILRVKDKEDVPIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNTLVR 158

                 ..
gi 351725909 178 KI 179
Cdd:cd00876  159 EI 160

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 351725909  18 FKLLLIGDSGVGKSTLLLSFTSDTFEDLS-PTIGVDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:cd04117    1 FRLLLIGDSGVGKTCLLCRFTDNEFHSSHiSTIGVDFKMKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  97 DVTRRETFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELV 176
Cdd:cd04117   81 DISSERSYQHIMK-WVSDVDEYA-PEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETSACTNKNIKESFTRLT 158

                 ....*
gi 351725909 177 MKILE 181
Cdd:cd04117  159 ELVLQ 163

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909    18 FKLLLIGDSGVGKSTLLLSFTSDTF-EDLSPTIGvDFKVKYVTMGGKKSKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 96
Cdd:smart00173   1 YKLVVLGSGGVGKSALTIQFIQGHFvDDYDPTIE-DSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVY 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909    97 DVTRRETFTNLSDIWAKEIDLYSTNQDCIkMLVGNKVDKESERVVSKKEGIDFAREYGCLYTECSAKTRVNVAQCFDELV 176
Cdd:smart00173  80 SITDRQSFEEIKKFREQILRVKDRDDVPI-VLVGNKCDLESERVVSTEEGKELARQWGCPFLETSAKERVNVDEAFYDLV 158

                   ...
gi 351725909   177 MKI 179
Cdd:smart00173 159 REI 161

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 351725909  14 FDYLFKLLLIGDSGVGKSTLLLSFTSDTFE-DLSPTIGVDFKVKYVT--------MGGKKSK--LAIWDTAGQERFRTLT 82
Cdd:cd04127    1 YDYLIKLLALGDSGVGKTTFLYRYTDNKFNpKFITTVGIDFREKRVVynsqgpdgTSGKAFRvhLQLWDTAGQERFRSLT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351725909  83 SSYYRGAQGIIMVYDVTRRETFTNLSDiWAKEI--DLYSTNQDCIkmLVGNKVDKESERVVSKKEGIDFAREYGCLYTEC 160
Cdd:cd04127   81 TAFFRDAMGFLLMFDLTSEQSFLNVRN-WMSQLqaHAYCENPDIV--LIGNKADLPDQREVSERQARELADKYGIPYFET 157

                        170       180
                 ....*....|....*....|.
gi 351725909 161 SAKTRVNVAQCFDELVMKILE 181
Cdd:cd04127  158 SAATGQNVEKAVETLLDLIMK 178