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 15218575  14 FKVLLIGDSGVGKSSLLLSFTSNTFD-DLSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 92
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTDDTFDeDLSSTIGVDFKVKTVTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  93 DVTRRDTFTNLsDIWAKEIDLYSTNQDCIKMLVGNKVDKESeRAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEELV 172
Cdd:cd01863  81 DVTRRDTFDNL-DTWLNELDTYSTNPDAVKMLVGNKIDKEN-REVTREEGQKFARKHNMLFIETSAKTRIGVQQAFEELV 158

                ...
gi 15218575 173 LKI 175
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 15218575    15 KVLLIGDSGVGKSSLLLSFTSNTFDDLS-PTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVYD 93
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYiPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575    94 VTRRDTFTNLSDiWAKEIDLYsTNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEELVL 173
Cdd:pfam00071  81 ITSRDSFENVKK-WVEEILRH-ADENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEELAR 158

                  ....
gi 15218575   174 KILE 177
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 15218575    14 FKVLLIGDSGVGKSSLLLSFTSNTF--DDLSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMV 91
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLGNKGsiTEYYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575    92 YDVtrrdTFTNLSDIWAKEIDLYSTNQDCIK----MLVGNKVDKESERaVSKKEGIDFAREYGCLFLECSAKTRVNVEQC 167
Cdd:TIGR00231  82 FDI----VILVLDVEEILEKQTKEIIHHADSgvpiILVGNKIDLKDAD-LKTHVASEFAKLNGEPIIPLSAETGKNIDSA 156

                  ....*
gi 15218575   168 FEELV 172
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 15218575  14 FKVLLIGDSGVGKSSLLLSFTSNTFD-DLSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 92
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTDDTFDeDLSSTIGVDFKVKTVTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  93 DVTRRDTFTNLsDIWAKEIDLYSTNQDCIKMLVGNKVDKESeRAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEELV 172
Cdd:cd01863  81 DVTRRDTFDNL-DTWLNELDTYSTNPDAVKMLVGNKIDKEN-REVTREEGQKFARKHNMLFIETSAKTRIGVQQAFEELV 158

                ...
gi 15218575 173 LKI 175
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 15218575  14 FKVLLIGDSGVGKSSLLLSFTSNTFD-DLSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 92
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSeNYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  93 DVTRRDTFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEELV 172
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 15218575  11 DYLFKVLLIGDSGVGKSSLLLSFTSNTFDD-LSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGII 89
Cdd:cd01867   1 DYLFKLLLIGDSGVGKSCLLLRFSEDSFNPsFISTIGIDFKIRTIELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGII 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  90 MVYDVTRRDTFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFE 169
Cdd:cd01867  81 LVYDITDEKSFENIKN-WMRNIDEHA-SEDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKANINVEEAFL 158

                ....*...
gi 15218575 170 ELVLKILE 177
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 15218575  11 DYLFKVLLIGDSGVGKSSLLLSFTSNTFDDLS-PTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGII 89
Cdd:cd01868   1 DYLFKIVLIGDSGVGKSNLLSRFTRNEFNLDSkSTIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGAL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  90 MVYDVTRRDTFTNLsDIWAKEIDLYStNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFE 169
Cdd:cd01868  81 LVYDITKKSTFENV-ERWLKELRDHA-DSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSALDGTNVEEAFK 158

                ....*.
gi 15218575 170 ELVLKI 175
Cdd:cd01868 159 QLLTEI 164

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 15218575  10 FDYLFKVLLIGDSGVGKSSLLLSFTSNTFD---DLspTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQ 86
Cdd:cd01866   1 YAYLFKYIIIGDTGVGKSCLLLQFTDKRFQpvhDL--TIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAA 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  87 GIIMVYDVTRRDTFTNLSdIWAKEIDLYSTNQDCIkMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQ 166
Cdd:cd01866  79 GALLVYDITRRETFNHLT-SWLEDARQHSNSNMTI-MLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEE 156

                       170
                ....*....|.
gi 15218575 167 CFEELVLKILE 177
Cdd:cd01866 157 AFINTAKEIYD 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  12 YLFKVLLIGDSGVGKSSLLLSFTSNTF-DDLSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIM 90
Cdd:cd04122   1 YIFKYIIIGDMGVGKSCLLHQFTEKKFmADCPHTIGVEFGTRIIEVNGQKIKLQIWDTAGQERFRAVTRSYYRGAAGALM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  91 VYDVTRRDTFTNLSDIWAKEIDLysTNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEE 170
Cdd:cd04122  81 VYDITRRSTYNHLSSWLTDARNL--TNPNTVIFLIGNKADLEAQRDVTYEEAKQFADENGLLFLECSAKTGENVEDAFLE 158

                ....*..
gi 15218575 171 LVLKILE 177
Cdd:cd04122 159 TAKKIYQ 165

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 15218575   9 EFDYLFKVLLIGDSGVGKSSLLLSFTSNTFD-DLSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQG 87
Cdd:cd04114   3 DYDFLFKIVLIGNAGVGKTCLVRRFTQGLFPpGQGATIGVDFMIKTVEIKGEKIKLQIWDTAGQERFRSITQSYYRSANA 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  88 IIMVYDVTRRDTFTNLSDiWAKEIDLYSTNQdCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQC 167
Cdd:cd04114  83 LILTYDITCEESFRCLPE-WLREIEQYANNK-VITILVGNKIDLAERREVSQQRAEEFSDAQDMYYLETSAKESDNVEKL 160

                ....*....
gi 15218575 168 FEELVLKIL 176
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 15218575  12 YLFKVLLIGDSGVGKSSLLLSFTSNTFDDLS-PTIGVDFKVKYLTIGE-KKLKLAIWDTAGQERFRTLTSSYYRGAQGII 89
Cdd:cd04111   1 YQFRLIVIGDSTVGKSSLLKRFTEGRFAEVSdPTVGVDFFSRLIEIEPgVRIKLQLWDTAGQERFRSITRSYYRNSVGVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  90 MVYDVTRRDTFTNLSDiWAKEIDLYSTNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFE 169
Cdd:cd04111  81 LVFDITNRESFEHVHD-WLEEARSHIQPHRPVFILVGHKCDLESQRQVTREEAEKLAKDLGMKYIETSARTGDNVEEAFE 159

                ....*...
gi 15218575 170 ELVLKILE 177
Cdd:cd04111 160 LLTQEIYE 167

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575    9 EFDYLFKVLLIGDSGVGKSSLLLSFTSNTFD-DLSPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQG 87
Cdd:PLN03110   8 EYDYLFKIVLIGDSGVGKSNILSRFTRNEFClESKSTIGVEFATRTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575   88 IIMVYDVTRRDTFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQC 167
Cdd:PLN03110  88 ALLVYDITKRQTFDNVQR-WLRELRDHA-DSNIVIMMAGNKSDLNHLRSVAEEDGQALAEKEGLSFLETSALEATNVEKA 165

                 ....*...
gi 15218575  168 FEELVLKI 175
Cdd:PLN03110 166 FQTILLEI 173

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  14 FKVLLIGDSGVGKSSLLLSFTSNTFDDLSP-TIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 92
Cdd:cd04123   1 FKVVLLGEGRVGKTSLVLRYVENKFNEKHEsTTQASFFQKTVNIGGKRIDLAIWDTAGQERYHALGPIYYRDADGAILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  93 DVTRRDTFTNLSdIWAKEidLYSTNQDCIKM-LVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEEL 171
Cdd:cd04123  81 DITDADSFQKVK-KWIKE--LKQMRGNNISLvIVGNKIDLERQRVVSKSEAEEYAKSVGAKHFETSAKTGKGIEELFLSL 157

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 15218575  15 KVLLIGDSGVGKSSLLLSFTSNTFDDL-SPTIGvDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVYD 93
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEyDPTIE-DSYRKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYS 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  94 VTRRDTFTNLSDIWaKEIDLYSTNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEELVL 173
Cdd:cd00876  80 ITSRESFEEIKNIR-EQILRVKDKEDVPIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNTLVR 158

                ..
gi 15218575 174 KI 175
Cdd:cd00876 159 EI 160

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  14 FKVLLIGDSGVGKSSLLLSFTSNTFDDL-SPTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 92
Cdd:cd01862   1 LKVIILGDSGVGKTSLMNQYVNKKFSNQyKATIGADFLTKEVTVDDRLVTLQIWDTAGQERFQSLGVAFYRGADCCVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  93 DVTRRDTFTNLsDIWAKEIDLYSTNQDCIK---MLVGNKVDKESERAVSKKEGIDFAREYGCL-FLECSAKTRVNVEQCF 168
Cdd:cd01862  81 DVTNPKSFESL-DSWRDEFLIQASPRDPENfpfVVLGNKIDLEEKRQVSTKKAQQWCKSKGNIpYFETSAKEAINVDQAF 159

                ....*....
gi 15218575 169 EELVLKILE 177
Cdd:cd01862 160 ETIARLALE 168

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 15218575  14 FKVLLIGDSGVGKSSLLLSFTSNTFDDLS-PTIGVDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 92
Cdd:cd04117   1 FRLLLIGDSGVGKTCLLCRFTDNEFHSSHiSTIGVDFKMKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  93 DVTRRDTFTNLSDiWAKEIDLYStNQDCIKMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEELV 172
Cdd:cd04117  81 DISSERSYQHIMK-WVSDVDEYA-PEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETSACTNKNIKESFTRLT 158

                ....*
gi 15218575 173 LKILE 177
Cdd:cd04117 159 ELVLQ 163

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 15218575     14 FKVLLIGDSGVGKSSLLLSFTSNTF-DDLSPTIGvDFKVKYLTIGEKKLKLAIWDTAGQERFRTLTSSYYRGAQGIIMVY 92
Cdd:smart00010   3 YKLVVLGGGGVGKSALTIQFVQGHFvDEYDPTIE-DSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575     93 DVTRRDTFTNLSDIWAKEIDLYSTNQDCIkMLVGNKVDKESERAVSKKEGIDFAREYGCLFLECSAKTRVNVEQCFEELV 172
Cdd:smart00010  82 SITDRQSFEEIAKFREQILRVKDRDDVPI-VLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKERINVDEAFYDLV 160

                   ...
gi 15218575    173 LKI 175
Cdd:smart00010 161 REI 163

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 15218575  10 FDYLFKVLLIGDSGVGKSSLLLSFTSNTFD-DLSPTIGVDFKVKYL---------TIGEK-KLKLAIWDTAGQERFRTLT 78
Cdd:cd04127   1 YDYLIKLLALGDSGVGKTTFLYRYTDNKFNpKFITTVGIDFREKRVvynsqgpdgTSGKAfRVHLQLWDTAGQERFRSLT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218575  79 SSYYRGAQGIIMVYDVTRRDTFTNLSDiWAKEI--DLYSTNQDCIkmLVGNKVDKESERAVSKKEGIDFAREYGCLFLEC 156
Cdd:cd04127  81 TAFFRDAMGFLLMFDLTSEQSFLNVRN-WMSQLqaHAYCENPDIV--LIGNKADLPDQREVSERQARELADKYGIPYFET 157

                       170       180
                ....*....|....*....|.
gi 15218575 157 SAKTRVNVEQCFEELVLKILE 177
Cdd:cd04127 158 SAATGQNVEKAVETLLDLIMK 178