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 2088136592   3 YAYLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGA 82
Cdd:cd01866     1 YAYLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  83 LLVYDITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFIN 162
Cdd:cd01866    81 LLVYDITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAFIN 160

                  ....*...
gi 2088136592 163 TAKVIYEK 170
Cdd:cd01866   161 TAKEIYDK 168

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 2088136592   8 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVYD 87
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  88 ITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAKVI 167
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHADENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEELAREI 160

                  ..
gi 2088136592 168 YE 169
Cdd:pfam00071 161 LK 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 2088136592   7 FKYIIIGDTGVGKSCLLLQFT-DKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLV 85
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLgNKGSITEYYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRV 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2088136592  86 YDIT-RRETF-NHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEaFAREHGLVFMETSAKTAINVEDAF 160
Cdd:TIGR00231  82 FDIViLVLDVeEILEKQTKEIIHHADSGVPIILVGNKIDLKDADLKTHVASE-FAKLNGEPIIPLSAETGKNIDSAF 157

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 2088136592   3 YAYLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGA 82
Cdd:cd01866     1 YAYLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  83 LLVYDITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFIN 162
Cdd:cd01866    81 LLVYDITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAFIN 160

                  ....*...
gi 2088136592 163 TAKVIYEK 170
Cdd:cd01866   161 TAKEIYDK 168

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 2088136592   7 FKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVY 86
Cdd:cd00154     1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2088136592  87 DITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAK 165
Cdd:cd00154    81 DVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDLEDERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESLAR 159

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 2088136592   8 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVYD 87
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  88 ITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAKVI 167
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHADENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEELAREI 160

                  ..
gi 2088136592 168 YE 169
Cdd:pfam00071 161 LK 162

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 2088136592   7 FKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVY 86
Cdd:cd04113     1 FKFLIIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  87 DITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAKV 166
Cdd:cd04113    81 DITSRESFNALTNWLTDARTLASPDIVIILVGNKKDLEDDREVTFLEASRFAQENGLLFLETSALTGENVEEAFLKCARS 160

                  .
gi 2088136592 167 I 167
Cdd:cd04113   161 I 161

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. 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 2088136592   5 YLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALL 84
Cdd:cd01869     1 YLFKLLLIGDSGVGKSCLLLRFADDTYTESYISTIGVDFKIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIII 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  85 VYDITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTA 164
Cdd:cd01869    81 VYDVTDQESFNNVKQWLQEIDRYASENVNKLLVGNKCDLTDKKVVDYTEAKEFADELGIPFLETSAKNATNVEEAFMTMA 160

                  ....*.
gi 2088136592 165 KVIYEK 170
Cdd:cd01869   161 REIKKR 166

Rab GTPase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592   3 YAYLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGA 82
Cdd:PLN03110    9 YDYLFKIVLIGDSGVGKSNILSRFTRNEFCLESKSTIGVEFATRTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGA 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  83 LLVYDITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFIN 162
Cdd:PLN03110   89 LLVYDITKRQTFDNVQRWLRELRDHADSNIVIMMAGNKSDLNHLRSVAEEDGQALAEKEGLSFLETSALEATNVEKAFQT 168

                         170       180
                  ....*....|....*....|....*...
gi 2088136592 163 TAKVIYEKIQEGVFDINNEANGIKIGPQ 190
Cdd:PLN03110  169 ILLEIYHIISKKALAAQEAAANSGLPGQ 196

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 2088136592   7 FKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVY 86
Cdd:cd01860     2 FKLVLLGDSSVGKSSIVLRFVKNEFSENQESTIGAAFLTQTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVVY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  87 DITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAKV 166
Cdd:cd01860    82 DITSEESFEKAKSWVKELQEHGPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEIARK 161

                  ..
gi 2088136592 167 IY 168
Cdd:cd01860   162 LP 163

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 2088136592   3 YAYLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGA 82
Cdd:cd04114     4 YDFLFKIVLIGNAGVGKTCLVRRFTQGLFPPGQGATIGVDFMIKTVEIKGEKIKLQIWDTAGQERFRSITQSYYRSANAL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  83 LLVYDITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFIN 162
Cdd:cd04114    84 ILTYDITCEESFRCLPEWLREIEQYANNKVITILVGNKIDLAERREVSQQRAEEFSDAQDMYYLETSAKESDNVEKLFLD 163

                  ..
gi 2088136592 163 TA 164
Cdd:cd04114   164 LA 165

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592   7 FKYIIIGDTGVGKSCLLLQFTDKRFQP-VHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLV 85
Cdd:cd04112     1 FKVMLVGDSGVGKTCLLVRFKDGAFLAgSFIATVGIQFTNKVVTVDGVKVKLQIWDTAGQERFRSVTHAYYRDAHALLLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  86 YDITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAK 165
Cdd:cd04112    81 YDVTNKSSFDNIRAWLTEILEYAQSDVVIMLLGNKADMSGERVVKREDGERLAKEYGVPFMETSAKTGLNVELAFTAVAK 160

                         170       180
                  ....*....|....*....|..
gi 2088136592 166 VI----YEKIQEGVFDINNEAN 183
Cdd:cd04112   161 ELkhrsVEQPDEPKFKIQDYVE 182

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 2088136592   7 FKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVY 86
Cdd:cd01862     1 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVTVDDRLVTLQIWDTAGQERFQSLGVAFYRGADCCVLVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  87 DITRRETFNHLTTWLED----ARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHG-LVFMETSAKTAINVEDAFI 161
Cdd:cd01862    81 DVTNPKSFESLDSWRDEfliqASPRDPENFPFVVLGNKIDLEEKRQVSTKKAQQWCKSKGnIPYFETSAKEAINVDQAFE 160

                         170
                  ....*....|..
gi 2088136592 162 NTAKVIYEKIQE 173
Cdd:cd01862   161 TIARLALEQEKE 172

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 2088136592   7 FKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVY 86
Cdd:cd04117     1 FRLLLIGDSGVGKTCLLCRFTDNEFHSSHISTIGVDFKMKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  87 DITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAKV 166
Cdd:cd04117    81 DISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQKRQVGDEQGNKLAKEYGMDFFETSACTNKNIKESFTRLTEL 160

                  .
gi 2088136592 167 I 167
Cdd:cd04117   161 V 161

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592   7 FKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITID-GKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLV 85
Cdd:cd04107     1 FKVLVIGDLGVGKTSIIKRYVHGVFSQHYKATIGVDFALKVIEWDpNTVVRLQLWDIAGQERFGGMTRVYYKGAVGAIIV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  86 YDITRRETFNHLTTWLED--ARQHSNSNMVI--MLIGNKSDLDNRREVRREEG-EAFAREHGLV-FMETSAKTAINVEDA 159
Cdd:cd04107    81 FDVTRPSTFEAVLKWKADldSKVTLPNGEPIpaLLLANKCDLKKERLAKDPEQmDQFCKENGFIgWFETSAKENINIEEA 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 2088136592 160 FINTAKVIYEKIQEGVFDINNEANGIK-IGPQHSPTSPSG 198
Cdd:cd04107   161 MRFLVKNILKNDKGLQSPEPDEDNVIDlKQETTTSKSKSC 200

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592   8 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITI---DGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALL 84
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKSTIGVDFKTKTVLEnddNGKKIKLNIWDTAGQERFRSLHPFYYRGAAAALL 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2088136592  85 VYDITrreTFNHLTTWLEDARQHSNsNMVIMLIGNKSD 122
Cdd:pfam08477  81 VYDSR---TFSNLKYWLRELKKYAG-NSPVILVGNKID 114

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 2088136592   6 LFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLV 85
Cdd:cd01865     1 MFKLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  86 YDITRRETFNHLTTWLEDARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAK 165
Cdd:cd01865    81 YDITNEESFNAVQDWSTQIKTYSWDNAQVILVGNKCDMEDERVVSAERGRQLADQLGFEFFEASAKENINVKQVFERLVD 160

                  ....*
gi 2088136592 166 VIYEK 170
Cdd:cd01865   161 IICDK 165

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 2088136592   8 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARmITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVYD 87
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDSYRKQ-IVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088136592  88 ITRRETFNHLTTWLEDARQHSNSNMV-IMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAFINTAKV 166
Cdd:cd00876    80 ITSRESFEEIKNIREQILRVKDKEDVpIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNTLVRE 159

                  .
gi 2088136592 167 I 167
Cdd:cd00876   160 I 160

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 2088136592    7 FKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGvEFGARMITIDGKPIKLQIWDTAGQEAFRSITRSYYRGAAGALLVY 86
Cdd:smart00010   3 YKLVVLGGGGVGKSALTIQFVQGHFVDEYDPTIE-DSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVY 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2088136592   87 DITRRETFNHLTTWLED-ARQHSNSNMVIMLIGNKSDLDNRREVRREEGEAFAREHGLVFMETSAKTAINVEDAF 160
Cdd:smart00010  82 SITDRQSFEEIAKFREQiLRVKDRDDVPIVLVGNKCDLENERVVSTEEGKELARQWGCPFLETSAKERINVDEAF 156

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. 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.