Rag GTPase, subfamily of Ras-related GTPases, includes Ras-related GTP-binding proteins C and D; RagC and RagD are closely related Rag GTPases (ras-related GTP-binding protein C and D) that constitute a unique subgroup of the Ras superfamily, and are functional homologs of Saccharomyces cerevisiae Gtr2. These domains form heterodimers with RagA or RagB, and similarly, Gtr2 dimerizes with Gtr1 in order to function. They play an essential role in regulating amino acid-induced target of rapamycin complex 1 (TORC1) kinase signaling, exocytic cargo sorting at endosomes, and epigenetic control of gene expression. In response to amino acids, the Rag GTPases guide the TORC1 complex to activate the platform containing Rheb proto-oncogene by driving the relocalization of mTORC1 from discrete locations in the cytoplasm to a late endosomal and/or lysosomal compartment that is Rheb-enriched and contains Rab-7.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIQKVVFHKMSPSETLFLESTNRICREDVSNSSFVNFQIWDFPGQIDFFDPTFDYEMIFRGTGALIF 142
Cdd:cd11385    1 RILLMGLRRSGKSSIQKVVFHKMSPNETLFLESTNKITKDDISNSSFVNFQIWDFPGQLDPFDPTLDPEMIFSGCGALVF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910 143 VIDSQDDYMEALARLHLTVTRAYKVNTDINFEVFIHKVDGLSDDHKIETQRDIHQRANDDLADAGLEKIHLSFYLTSIYD 222
Cdd:cd11385   81 VIDAQDDYDEAIARLVETVTKAYKVNPNINFEVFIHKVDGLSEDHKIETQRDIQQRVTDELADAGLEDVQISFYLTSIYD 160

                        170
                 ....*....|....*
gi 120444910 223 HSIFEAFSKVVQKLI 237
Cdd:cd11385  161 HSIFEAFSKVVQKLI 175

Rag GTPase, subfamily of Ras-related GTPases, includes Ras-related GTP-binding proteins C and D; RagC and RagD are closely related Rag GTPases (ras-related GTP-binding protein C and D) that constitute a unique subgroup of the Ras superfamily, and are functional homologs of Saccharomyces cerevisiae Gtr2. These domains form heterodimers with RagA or RagB, and similarly, Gtr2 dimerizes with Gtr1 in order to function. They play an essential role in regulating amino acid-induced target of rapamycin complex 1 (TORC1) kinase signaling, exocytic cargo sorting at endosomes, and epigenetic control of gene expression. In response to amino acids, the Rag GTPases guide the TORC1 complex to activate the platform containing Rheb proto-oncogene by driving the relocalization of mTORC1 from discrete locations in the cytoplasm to a late endosomal and/or lysosomal compartment that is Rheb-enriched and contains Rab-7.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIQKVVFHKMSPSETLFLESTNRICREDVSNSSFVNFQIWDFPGQIDFFDPTFDYEMIFRGTGALIF 142
Cdd:cd11385    1 RILLMGLRRSGKSSIQKVVFHKMSPNETLFLESTNKITKDDISNSSFVNFQIWDFPGQLDPFDPTLDPEMIFSGCGALVF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910 143 VIDSQDDYMEALARLHLTVTRAYKVNTDINFEVFIHKVDGLSDDHKIETQRDIHQRANDDLADAGLEKIHLSFYLTSIYD 222
Cdd:cd11385   81 VIDAQDDYDEAIARLVETVTKAYKVNPNINFEVFIHKVDGLSEDHKIETQRDIQQRVTDELADAGLEDVQISFYLTSIYD 160

                        170
                 ....*....|....*
gi 120444910 223 HSIFEAFSKVVQKLI 237
Cdd:cd11385  161 HSIFEAFSKVVQKLI 175

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSS-IQKVVFHKMSPSETLfleSTNRIcreDVSNSSF------VNFQIWDFPGQIDFFDPTFDYEMIFR 135
Cdd:COG1100    5 KIVVVGTGGVGKTSlVNRLVGDIFSLEKYL---STNGV---TIDKKELkldgldVDLVIWDTPGQDEFRETRQFYARQLT 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910 136 GTGALIFVIDS-QDDYMEALARLHLTVTRAYKVNTDInfeVFIHKVDgLSDDHKIETQrdihqranDDLADAGLEKIHLS 214
Cdd:COG1100   79 GASLYLFVVDGtREETLQSLYELLESLRRLGKKSPII---LVLNKID-LYDEEEIEDE--------ERLKEALSEDNIVE 146

                        170       180
                 ....*....|....*....|...
gi 120444910 215 FYLTSIYD-HSIFEAFSKVVQKL 236
Cdd:COG1100  147 VVATSAKTgEGVEELFAALAEIL 169

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIqkvvFHKMSPSETLFLESTNRICREDVSNSSfVNFQIWDFPGQiDFFDPTFDYemIFRGTGALIF 142
Cdd:PLN00223  19 RILMVGLDAAGKTTI----LYKLKLGEIVTTIPTIGFNVETVEYKN-ISFTVWDVGGQ-DKIRPLWRH--YFQNTQGLIF 90

                         90
                 ....*....|....*...
gi 120444910 143 VIDSQDD--YMEALARLH 158
Cdd:PLN00223  91 VVDSNDRdrVVEARDELH 108

Rag GTPase, subfamily of Ras-related GTPases, includes Ras-related GTP-binding proteins C and D; RagC and RagD are closely related Rag GTPases (ras-related GTP-binding protein C and D) that constitute a unique subgroup of the Ras superfamily, and are functional homologs of Saccharomyces cerevisiae Gtr2. These domains form heterodimers with RagA or RagB, and similarly, Gtr2 dimerizes with Gtr1 in order to function. They play an essential role in regulating amino acid-induced target of rapamycin complex 1 (TORC1) kinase signaling, exocytic cargo sorting at endosomes, and epigenetic control of gene expression. In response to amino acids, the Rag GTPases guide the TORC1 complex to activate the platform containing Rheb proto-oncogene by driving the relocalization of mTORC1 from discrete locations in the cytoplasm to a late endosomal and/or lysosomal compartment that is Rheb-enriched and contains Rab-7.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIQKVVFHKMSPSETLFLESTNRICREDVSNSSFVNFQIWDFPGQIDFFDPTFDYEMIFRGTGALIF 142
Cdd:cd11385    1 RILLMGLRRSGKSSIQKVVFHKMSPNETLFLESTNKITKDDISNSSFVNFQIWDFPGQLDPFDPTLDPEMIFSGCGALVF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910 143 VIDSQDDYMEALARLHLTVTRAYKVNTDINFEVFIHKVDGLSDDHKIETQRDIHQRANDDLADAGLEKIHLSFYLTSIYD 222
Cdd:cd11385   81 VIDAQDDYDEAIARLVETVTKAYKVNPNINFEVFIHKVDGLSEDHKIETQRDIQQRVTDELADAGLEDVQISFYLTSIYD 160

                        170
                 ....*....|....*
gi 120444910 223 HSIFEAFSKVVQKLI 237
Cdd:cd11385  161 HSIFEAFSKVVQKLI 175

Rag GTPase subfamily of Ras-related GTPases; Rag GTPases (ras-related GTP-binding proteins) constitute a unique subgroup of the Ras superfamily, playing an essential role in regulating amino acid-induced target of rapamycin complex 1 (TORC1) kinase signaling, exocytic cargo sorting at endosomes, and epigenetic control of gene expression. This subfamily consists of RagA and RagB as well as RagC and RagD that are closely related. Saccharomyces cerevisiae encodes single orthologs of metazoan RagA/B and RagC/D, Gtr1 and Gtr2, respectively. Dimer formation is important for their cellular function; these domains form heterodimers, as RagA or RagB dimerizes with RagC or RagD, and similarly, Gtr1 dimerizes with Gtr2. In response to amino acids, the Rag GTPases guide the TORC1 complex to activate the platform containing Rheb proto-oncogene by driving the relocalization of mTORC1 from discrete locations in the cytoplasm to a late endosomal and/or lysosomal compartment that is Rheb-enriched and contains Rab-7.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIQKVVFHKMSPSETLFLESTNRICREDVSNSSFVNFQIWDFPGQIDFFDPTFDYEMIFRGTGALIF 142
Cdd:cd09915    1 KLLL*GRRRSGKSSIRKVVFHNYSPFDTLRLESTIDVEHSHLSFLGN*TLNLWDCPGQDVFFEPTKDKEHIFQ*VGALIY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910 143 VIDSQDDYMEALARLHLTVTRAYKVNTDINFEVFIHKVDGLSDDHKIETQRDIHQRANDDLADAGLEKIHLSFYLTSIYD 222
Cdd:cd09915   81 VIDVQDEYLKAITILAKALKQAYKVNPDANIEVLIHKVDGLSLDKKEELQRDI*QRLSETLSEFGLEFPNLSFYLTSIWD 160

                        170
                 ....*....|....*
gi 120444910 223 HSIFEAFSKVVQKLI 237
Cdd:cd09915  161 HSIYEAFSQIVQKLI 175

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  65 LLMGLRRSGKSSIQKVVFHKMSPSETLFLESTNRICREDVSNSS-FVNFQIWDFPGQIDFFDPTF--DYEMIFRGTGALI 141
Cdd:cd00882    1 VVVGRGGVGKSSLLNALLGGEVGEVSDVPGTTRDPDVYVKELDKgKVKLVLVDTPGLDEFGGLGReeLARLLLRGADLIL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910 142 FVIDSQDDYMEALARLHLtvtRAYKVNTDINFEVFIHKVDGLSDDHKIEtqrdihqranDDLADAGLEKIHLSFYLTSIY 221
Cdd:cd00882   81 LVVDSTDRESEEDAKLLI---LRRLRKEGIPIILVGNKIDLLEEREVEE----------LLRLEELAKILGVPVFEVSAK 147

                        170
                 ....*....|....
gi 120444910 222 DHS-IFEAFSKVVQ 234
Cdd:cd00882  148 TGEgVDELFEKLIE 161

ADP-ribosylation factor(Arf)/Arf-like (Arl) small GTPases; Arf (ADP-ribosylation factor)/Arl (Arf-like) small GTPases. Arf proteins are activators of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. Arfs are N-terminally myristoylated. Members of the Arf family are regulators of vesicle formation in intracellular traffic that interact reversibly with membranes of the secretory and endocytic compartments in a GTP-dependent manner. They depart from other small GTP-binding proteins by a unique structural device, interswitch toggle, that implements front-back communication from N-terminus to the nucleotide binding site. Arf-like (Arl) proteins are close relatives of the Arf, but only Arl1 has been shown to function in membrane traffic like the Arf proteins. Arl2 has an unrelated function in the folding of native tubulin, and Arl4 may function in the nucleus. Most other Arf family proteins are so far relatively poorly characterized. Thus, despite their significant sequence homologies, Arf family proteins may regulate unrelated functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIqkvvFHKMSPSETLFLESTNRICREDVSnSSFVNFQIWDFPGQIDFFDPTFDYemiFRGTGALIF 142
Cdd:cd00878    1 RILMLGLDGAGKTTI----LYKLKLGEVVTTIPTIGFNVETVE-YKNVKFTVWDVGGQDKIRPLWKHY---YENTDGLIF 72

                 ....*.
gi 120444910 143 VIDSQD 148
Cdd:cd00878   73 VVDSSD 78

ADP ribosylation factor 6 (Arf6); Arf6 subfamily. Arf6 (ADP ribosylation factor 6) proteins localize to the plasma membrane, where they perform a wide variety of functions. In its active, GTP-bound form, Arf6 is involved in cell spreading, Rac-induced formation of plasma membrane ruffles, cell migration, wound healing, and Fc-mediated phagocytosis. Arf6 appears to change the actin structure at the plasma membrane by activating Rac, a Rho family protein involved in membrane ruffling. Arf6 is required for and enhances Rac formation of ruffles. Arf6 can regulate dendritic branching in hippocampal neurons, and in yeast it localizes to the growing bud, where it plays a role in polarized growth and bud site selection. In leukocytes, Arf6 is required for chemokine-stimulated migration across endothelial cells. Arf6 also plays a role in down-regulation of beta2-adrenergic receptors and luteinizing hormone receptors by facilitating the release of sequestered arrestin to allow endocytosis. Arf6 is believed to function at multiple sites on the plasma membrane through interaction with a specific set of GEFs, GAPs, and effectors. Arf6 has been implicated in breast cancer and melanoma cell invasion, and in actin remodelling at the invasion site of Chlamydia infection.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIqkvvFHKMSPSETLFLESTNRICREDVSNSSfVNFQIWDFPGQiDFFDPTFDYemIFRGTGALIF 142
Cdd:cd04149   11 RILMLGLDAAGKTTI----LYKLKLGQSVTTIPTVGFNVETVTYKN-VKFNVWDVGGQ-DKIRPLWRH--YYTGTQGLIF 82

                         90
                 ....*....|....*...
gi 120444910 143 VIDSQD-DYM-EALARLH 158
Cdd:cd04149   83 VVDSADrDRIdEARQELH 100

Arf-like 3 (Arl3) GTPase; Arl3 (Arf-like 3) is an Arf family protein that differs from most Arf family members in the N-terminal extension. In is inactive, GDP-bound form, the N-terminal extension forms an elongated loop that is hydrophobically anchored into the membrane surface; however, it has been proposed that this region might form a helix in the GTP-bound form. The delta subunit of the rod-specific cyclic GMP phosphodiesterase type 6 (PDEdelta) is an Arl3 effector. Arl3 binds microtubules in a regulated manner to alter specific aspects of cytokinesis via interactions with retinitis pigmentosa 2 (RP2). It has been proposed that RP2 functions in concert with Arl3 to link the cell membrane and the cytoskeleton in photoreceptors as part of the cell signaling or vesicular transport machinery. In mice, the absence of Arl3 is associated with abnormal epithelial cell proliferation and cyst formation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  57 STEVKPRILLMGLRRSGKSSIQKvvfhkmspsetlflestnRICREDVS-------------NSSFVNFQIWDFPGQ--I 121
Cdd:cd04155   11 SSRQEVRILLLGLDNAGKTTILK------------------QLASEDIShitptqgfniknvQADGFKLNVWDIGGQrkI 72

                         90       100
                 ....*....|....*....|....*..
gi 120444910 122 DFFdptfdYEMIFRGTGALIFVIDSQD 148
Cdd:cd04155   73 RPY-----WRNYFENTDVLIYVIDSAD 94

ADP-ribosylation factor-1 (Arf1) and ADP-ribosylation factor-5 (Arf5); The Arf1-Arf5-like subfamily contains Arf1, Arf2, Arf3, Arf4, Arf5, and related proteins. Arfs1-5 are soluble proteins that are crucial for assembling coat proteins during vesicle formation. Each contains an N-terminal myristoylated amphipathic helix that is folded into the protein in the GDP-bound state. GDP/GTP exchange exposes the helix, which anchors to the membrane. Following GTP hydrolysis, the helix dissociates from the membrane and folds back into the protein. A general feature of Arf1-5 signaling may be the cooperation of two Arfs at the same site. Arfs1-5 are generally considered to be interchangeable in function and location, but some specific functions have been assigned. Arf1 localizes to the early/cis-Golgi, where it is activated by GBF1 and recruits the coat protein COPI. It also localizes to the trans-Golgi network (TGN), where it is activated by BIG1/BIG2 and recruits the AP1, AP3, AP4, and GGA proteins. Humans, but not rodents and other lower eukaryotes, lack Arf2. Human Arf3 shares 96% sequence identity with Arf1 and is believed to generally function interchangeably with Arf1. Human Arf4 in the activated (GTP-bound) state has been shown to interact with the cytoplasmic domain of epidermal growth factor receptor (EGFR) and mediate the EGF-dependent activation of phospholipase D2 (PLD2), leading to activation of the activator protein 1 (AP-1) transcription factor. Arf4 has also been shown to recognize the C-terminal sorting signal of rhodopsin and regulate its incorporation into specialized post-Golgi rhodopsin transport carriers (RTCs). There is some evidence that Arf5 functions at the early-Golgi and the trans-Golgi to affect Golgi-associated alpha-adaptin homology Arf-binding proteins (GGAs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  63 RILLMGLRRSGKSSIqkvvFHKMSPSETLFLESTNRICREDVSNSSfVNFQIWDFPGQiDFFDPTFDYemIFRGTGALIF 142
Cdd:cd04150    2 RILMVGLDAAGKTTI----LYKLKLGEIVTTIPTIGFNVETVEYKN-ISFTVWDVGGQ-DKIRPLWRH--YFQNTQGLIF 73

                 ....*.
gi 120444910 143 VIDSQD 148
Cdd:cd04150   74 VVDSND 79

ADP-ribosylation factor family; Pfam combines a number of different Prosite families together

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910   63 RILLMGLRRSGKSSIqkvvFHKMSPSETLFLESTNRICREDVSNSSfVNFQIWDFPGQIDFFDPTFDYemiFRGTGALIF 142
Cdd:pfam00025   2 RILILGLDNAGKTTI----LYKLKLGEIVTTIPTIGFNVETVTYKN-VKFTVWDVGGQESLRPLWRNY---FPNTDAVIF 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 120444910  143 VIDSQDD--YMEALARLHLTVTRayKVNTDINFEVFIHKVD 181
Cdd:pfam00025  74 VVDSADRdrIEEAKEELHALLNE--EELADAPLLILANKQD 112

Arf-like 6 (Arl6) GTPase; Arl6 (Arf-like 6) forms a subfamily of the Arf family of small GTPases. Arl6 expression is limited to the brain and kidney in adult mice, but it is expressed in the neural plate and somites during embryogenesis, suggesting a possible role for Arl6 in early development. Arl6 is also believed to have a role in cilia or flagella function. Several proteins have been identified that bind Arl6, including Arl6 interacting protein (Arl6ip), and SEC61beta, a subunit of the heterotrimeric conducting channel SEC61p. Based on Arl6 binding to these effectors, Arl6 is also proposed to play a role in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. At least three specific homozygous Arl6 mutations in humans have been found to cause Bardet-Biedl syndrome, a disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120444910  64 ILLMGLRRSGKSSIqkVVFHKMSPSETLFLESTNRICREDVSNSSfVNFQIWDFPGQIDFFDPtfdYEMIFRGTGALIFV 143
Cdd:cd04157    2 ILVLGLDNSGKTTI--INQLKPSNAQSQNIVPTVGFNVESFKKGN-LSFTAFDMSGQGKYRGL---WEHYYKNIQGIIFV 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 120444910 144 IDSQDDYMEALAR--LHLTVTRAYKVNTDINFEVFIHKVD 181
Cdd:cd04157   76 IDSSDRLRMVVAKdeLELLLNHPDIKHRRIPILFYANKMD 115