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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635     24 KTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:smart00175   2 KIILIGDSGVGKSSLLSRFTDGKFSE-QYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635    104 DITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAKE 183
Cdd:smart00175  81 DITNRESFENLENWLKELREYASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEELARE 160

                   ..
gi 28376635    184 LK 185
Cdd:smart00175 161 IL 162

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635   22 LHKTILVGDSGVGKTSLLVQFDQGKFIPGSFSaTVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLL 101
Cdd:PLN03110  12 LFKIVLIGDSGVGKSNILSRFTRNEFCLESKS-TIGVEFATRTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGALL 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635  102 LYDITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIA 181
Cdd:PLN03110  91 VYDITKRQTFDNVQRWLRELRDHADSNIVIMMAGNKSDLNHLRSVAEEDGQALAEKEGLSFLETSALEATNVEKAFQTIL 170

                 ...
gi 28376635  182 KEL 184
Cdd:PLN03110 171 LEI 173

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 28376635    24 KTILVGDSGVGKTSLLVQFDQGKFIPGSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:TIGR00231   3 KIVIVGHPNVGKSTLLNSLLGNKGSITEYYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVF 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 28376635   104 DITN-KSSFDNI-RAWLTEIHEYAQRDVVIMLLGNKADMSSERViRSEDGETLAREYGVPFLETSAKTGMNVELAF 177
Cdd:TIGR00231  83 DIVIlVLDVEEIlEKQTKEIIHHADSGVPIILVGNKIDLKDADL-KTHVASEFAKLNGEPIIPLSAETGKNIDSAF 157

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635     24 KTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:smart00175   2 KIILIGDSGVGKSSLLSRFTDGKFSE-QYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635    104 DITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAKE 183
Cdd:smart00175  81 DITNRESFENLENWLKELREYASPNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEELARE 160

                   ..
gi 28376635    184 LK 185
Cdd:smart00175 161 IL 162

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 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:cd00154   2 KIVLIGDSGVGKTSLLLRFVDNKFSE-NYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 28376635 104 DITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAK 182
Cdd:cd00154  81 DVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDLEDERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESLAR 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 28376635  22 LHKTILVGDSGVGKTSLLVQFDQGKFIPGSFSaTVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLL 101
Cdd:cd01868   3 LFKIVLIGDSGVGKSNLLSRFTRNEFNLDSKS-TIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGALL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 102 LYDITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIA 181
Cdd:cd01868  82 VYDITKKSTFENVERWLKELRDHADSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSALDGTNVEEAFKQLL 161

                ...
gi 28376635 182 KEL 184
Cdd:cd01868 162 TEI 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 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:cd01860   3 KLVLLGDSSVGKSSIVLRFVKNEFSE-NQESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVVY 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 104 DITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAKE 183
Cdd:cd01860  82 DITSEESFEKAKSWVKELQEHGPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEIARK 161

                .
gi 28376635 184 L 184
Cdd:cd01860 162 L 162

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 28376635  23 HKTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLL 102
Cdd:cd01861   1 HKLVFLGDQSVGKTSIITRFMYDTFDN-QYQATIGIDFLSKTMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 103 YDITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAK 182
Cdd:cd01861  80 YDITNRQSFDNTDKWIDDVRDERGNDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLFKKIAQ 159

                ..
gi 28376635 183 EL 184
Cdd:cd01861 160 AL 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 28376635  20 HVLHKTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQAL 99
Cdd:cd01866   2 AYLFKYIIIGDTGVGKSCLLLQFTDKRFQP-VHDLTIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 100 LLLYDITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLA 179
Cdd:cd01866  81 LLVYDITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAFIN 160

                ....*
gi 28376635 180 IAKEL 184
Cdd:cd01866 161 TAKEI 165

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 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFIPGSfSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:cd04113   2 KFLIIGSAGTGKSCLLHQFIENKFKQDS-NHTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 104 DITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAKE 183
Cdd:cd04113  81 DITSRESFNALTNWLTDARTLASPDIVIILVGNKKDLEDDREVTFLEASRFAQENGLLFLETSALTGENVEEAFLKCARS 160

                .
gi 28376635 184 L 184
Cdd:cd04113 161 I 161

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635   22 LHKTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLL 101
Cdd:PLN03108   6 LFKYIIIGDTGVGKSCLLLQFTDKRFQP-VHDLTIGVEFGARMITIDNKPIKLQIWDTAGQESFRSITRSYYRGAAGALL 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635  102 LYDITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIA 181
Cdd:PLN03108  85 VYDITRRETFNHLASWLEDARQHANANMTIMLIGNKCDLAHRRAVSTEEGEQFAKEHGLIFMEASAKTAQNVEEAFIKTA 164

                 ...
gi 28376635  182 KEL 184
Cdd:PLN03108 165 AKI 167

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFIPGSfSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:cd04122   4 KYIIIGDMGVGKSCLLHQFTEKKFMADC-PHTIGVEFGTRIIEVNGQKIKLQIWDTAGQERFRAVTRSYYRGAAGALMVY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 104 DITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAKE 183
Cdd:cd04122  83 DITRRSTYNHLSSWLTDARNLTNPNTVIFLIGNKADLEAQRDVTYEEAKQFADENGLLFLECSAKTGENVEDAFLETAKK 162

                .
gi 28376635 184 L 184
Cdd:cd04122 163 I 163

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 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFIPGSFSaTVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:cd04117   2 RLLLIGDSGVGKTCLLCRFTDNEFHSSHIS-TIGVDFKMKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 104 DITNKSSFDNIRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAkE 183
Cdd:cd04117  81 DISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETSACTNKNIKESFTRLT-E 159

                ....*
gi 28376635 184 LKYRA 188
Cdd:cd04117 160 LVLQA 164

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 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFiPGSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:cd01862   2 KVIILGDSGVGKTSLMNQYVNKKF-SNQYKATIGADFLTKEVTVDDRLVTLQIWDTAGQERFQSLGVAFYRGADCCVLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 104 DITNKSSFDNIRAWLTEI------HEYAQRDVVImlLGNKADMSSERVIRSEDGETLAREYG-VPFLETSAKTGMNVELA 176
Cdd:cd01862  81 DVTNPKSFESLDSWRDEFliqaspRDPENFPFVV--LGNKIDLEEKRQVSTKKAQQWCKSKGnIPYFETSAKEAINVDQA 158

                ....*.
gi 28376635 177 FLAIAK 182
Cdd:cd01862 159 FETIAR 164

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635  19 DHvLHKTILVGDSGVGKTSLLVQFDQGKFiPGSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQA 98
Cdd:cd04110   4 DH-LFKLLIIGDSGVGKSSLLLRFADNTF-SGSYITTIGVDFKIRTVEINGERVKLQIWDTAGQERFRTITSTYYRGTHG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635  99 LLLLYDITNKSSFDNIRAWLTEIHEYAQrDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFL 178
Cdd:cd04110  82 VIVVYDVTNGESFVNVKRWLQEIEQNCD-DVCKVLVGNKNDDPERKVVETEDAYKFAGQMGISLFETSAKENINVEEMFN 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 28376635 179 AIAkELKYRAgHQADEPSFQIRDYVESQK-----KRSSCC 213
Cdd:cd04110 161 CIT-ELVLRA-KKDNLAKQQQQQQNDVVKlpknsKRKKRC 198

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 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFtNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLY 103
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVE-EYDPTIEDSY-RKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVY 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 104 DITNKSSFDNIRAWLTEIHEYAQRDVV-IMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAK 182
Cdd:cd00876  79 SITSRESFEEIKNIREQILRVKDKEDVpIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNTLVR 158

                ..
gi 28376635 183 EL 184
Cdd:cd00876 159 EI 160

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635  24 KTILVGDSGVGKTSLLVQFDQGKFiPGSFSATVGIGFTNKVVTVDGVRVKLQIWDTAGQERFR-SVTHAYYRDAQALLLL 102
Cdd:cd04115   4 KIIVIGDSNVGKTCLTYRFCAGRF-PERTEATIGVDFRERTVEIDGERIKVQLWDTAGQERFRkSMVQHYYRNVHAVVFV 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635 103 YDITNKSSFDNIRAWLTEIHEYA-QRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAK---TGMNVELAFL 178
Cdd:cd04115  83 YDVTNMASFHSLPSWIEECEQHSlPNEVPRILVGNKCDLREQIQVPTDLAQRFADAHSMPLFETSAKdpsENDHVEAIFM 162

                ....*..
gi 28376635 179 AIAKELK 185
Cdd:cd04115 163 TLAHKLK 169

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 28376635     23 HKTILVGDSGVGKTSLLVQFDQGKFIPgSFSATVGIGFTnKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLL 102
Cdd:smart00010   3 YKLVVLGGGGVGKSALTIQFVQGHFVD-EYDPTIEDSYR-KQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28376635    103 YDITNKSSFDNIRawltEIHEYAQR-----DVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAF 177
Cdd:smart00010  81 YSITDRQSFEEIA----KFREQILRvkdrdDVPIVLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKERINVDEAF 156

                   ....*...
gi 28376635    178 LAIAKELK 185
Cdd:smart00010 157 YDLVREIR 164

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. 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.