Arf-like 4 (Arl4) and 7 (Arl7) GTPases; Arl4 (Arf-like 4) is highly expressed in testicular germ cells, and is found in the nucleus and nucleolus. In mice, Arl4 is developmentally expressed during embryogenesis, and a role in somite formation and central nervous system differentiation has been proposed. Arl7 has been identified as the only Arf/Arl protein to be induced by agonists of liver X-receptor and retinoid X-receptor and by cholesterol loading in human macrophages. Arl7 is proposed to play a role in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. 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 540344578  11 FQSLHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNGTAKGISCHFWDVGGQEKLRPLWKSYSRCTDGII 90
Cdd:cd04152    1 FQSLHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTKGFNTEKIKVSLGNAKGVTFHFWDVGGQEKLRPLWKSYTRCTDGIV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  91 YVVDSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELIPATTYHVQPACAIIGEGLTE 170
Cdd:cd04152   81 FVVDSVDVERMEEAKTELHKITKFSENQGVPVLVLANKQDLPNALPVSEVEKLLALHELSSSTPWHVQPACAIIGEGLQE 160

                        170       180
                 ....*....|....*....|..
gi 540344578 171 GMDKLYEMILKRRKSLKQKKKR 192
Cdd:cd04152  161 GLEKLYEMILKRRKMLRQQKKK 182

Arf-like 4 (Arl4) and 7 (Arl7) GTPases; Arl4 (Arf-like 4) is highly expressed in testicular germ cells, and is found in the nucleus and nucleolus. In mice, Arl4 is developmentally expressed during embryogenesis, and a role in somite formation and central nervous system differentiation has been proposed. Arl7 has been identified as the only Arf/Arl protein to be induced by agonists of liver X-receptor and retinoid X-receptor and by cholesterol loading in human macrophages. Arl7 is proposed to play a role in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. 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 540344578  11 FQSLHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNGTAKGISCHFWDVGGQEKLRPLWKSYSRCTDGII 90
Cdd:cd04152    1 FQSLHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTKGFNTEKIKVSLGNAKGVTFHFWDVGGQEKLRPLWKSYTRCTDGIV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  91 YVVDSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELIPATTYHVQPACAIIGEGLTE 170
Cdd:cd04152   81 FVVDSVDVERMEEAKTELHKITKFSENQGVPVLVLANKQDLPNALPVSEVEKLLALHELSSSTPWHVQPACAIIGEGLQE 160

                        170       180
                 ....*....|....*....|..
gi 540344578 171 GMDKLYEMILKRRKSLKQKKKR 192
Cdd:cd04152  161 GLEKLYEMILKRRKMLRQQKKK 182

ARF-like small GTPases; ARF, ADP-ribosylation factor; Ras homologues involved in vesicular transport. Activator 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. Contains ATP/GTP-binding motif (P-loop).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578     1 MGNISSNISAFQSLHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIklsngTAKGISCHFWDVGGQEKLRPLWK 80
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETV-----TYKNISFTVWDVGGQDKIRPLWR 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578    81 SYSRCTDGIIYVVDSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHElIPATTYHVQPA 160
Cdd:smart00177  76 HYYTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHS-IRDRNWYIQPT 154

                          170
                   ....*....|....*
gi 540344578   161 CAIIGEGLTEGMDKL 175
Cdd:smart00177 155 CATSGDGLYEGLTWL 169

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  16 IVMLGLDSAGKTTVLYRLKFNEF--VNTVPTIGFNTEK--IKLSNGTAKGIschFWDVGGQEKLRPLWKSYSRC---TDG 88
Cdd:COG1100    6 IVVVGTGGVGKTSLVNRLVGDIFslEKYLSTNGVTIDKkeLKLDGLDVDLV---IWDTPGQDEFRETRQFYARQltgASL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  89 IIYVVDSVDVDRLEEAKTELHKVTKFAENqgTPLLVIANKQDLpksLPVAEIEKQLALHELIPA-TTYHVQPACAIIGEG 167
Cdd:COG1100   83 YLFVVDGTREETLQSLYELLESLRRLGKK--SPIILVLNKIDL---YDEEEIEDEERLKEALSEdNIVEVVATSAKTGEG 157

                        170
                 ....*....|....*....
gi 540344578 168 LTEGMDKLYEMILKRRKSL 186
Cdd:COG1100  158 VEELFAALAEILRGEGDSL 176

Arf-like 4 (Arl4) and 7 (Arl7) GTPases; Arl4 (Arf-like 4) is highly expressed in testicular germ cells, and is found in the nucleus and nucleolus. In mice, Arl4 is developmentally expressed during embryogenesis, and a role in somite formation and central nervous system differentiation has been proposed. Arl7 has been identified as the only Arf/Arl protein to be induced by agonists of liver X-receptor and retinoid X-receptor and by cholesterol loading in human macrophages. Arl7 is proposed to play a role in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. 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 540344578  11 FQSLHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNGTAKGISCHFWDVGGQEKLRPLWKSYSRCTDGII 90
Cdd:cd04152    1 FQSLHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTKGFNTEKIKVSLGNAKGVTFHFWDVGGQEKLRPLWKSYTRCTDGIV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  91 YVVDSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELIPATTYHVQPACAIIGEGLTE 170
Cdd:cd04152   81 FVVDSVDVERMEEAKTELHKITKFSENQGVPVLVLANKQDLPNALPVSEVEKLLALHELSSSTPWHVQPACAIIGEGLQE 160

                        170       180
                 ....*....|....*....|..
gi 540344578 171 GMDKLYEMILKRRKSLKQKKKR 192
Cdd:cd04152  161 GLEKLYEMILKRRKMLRQQKKK 182

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 540344578  15 HIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKlsngtAKGISCHFWDVGGQEKLRPLWKSYSRCTDGIIYVVD 94
Cdd:cd00878    1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVE-----YKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVD 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  95 SVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELIPaTTYHVQPACAIIGEGLTEGMDK 174
Cdd:cd00878   76 SSDRERIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESIKG-RRWHIQPCSAVTGDGLDEGLDW 154

                 ....
gi 540344578 175 LYEM 178
Cdd:cd00878  155 LIEQ 158

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 540344578  14 LHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNgtakgISCHFWDVGGQEKLRPLWKSYSRCTDGIIYVV 93
Cdd:cd04150    1 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKN-----ISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  94 DSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELiPATTYHVQPACAIIGEGLTEGMD 173
Cdd:cd04150   76 DSNDRERIGEAREELQRMLNEDELRDAVLLVFANKQDLPNAMSAAEVTDKLGLHSL-RNRNWYIQATCATSGDGLYEGLD 154

                 ..
gi 540344578 174 KL 175
Cdd:cd04150  155 WL 156

Arf-like tumor suppressor gene 1 (ARLTS1 or Arl11); ARLTS1 (Arf-like tumor suppressor gene 1), also known as Arl11, is a member of the Arf family of small GTPases that is believed to play a major role in apoptotic signaling. ARLTS1 is widely expressed and functions as a tumor suppressor gene in several human cancers. ARLTS1 is a low-penetrance suppressor that accounts for a small percentage of familial melanoma or familial chronic lymphocytic leukemia (CLL). ARLTS1 inactivation seems to occur most frequently through biallelic down-regulation by hypermethylation of the promoter. In breast cancer, ARLTS1 alterations were typically a combination of a hypomorphic polymorphism plus loss of heterozygosity. In a case of thyroid adenoma, ARLTS1 alterations were polymorphism plus promoter hypermethylation. The nonsense polymorphism Trp149Stop occurs with significantly greater frequency in familial cancer cases than in sporadic cancer cases, and the Cys148Arg polymorphism is associated with an increase in high-risk familial breast cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  15 HIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSngtaKGISCHFWDVGGQEKLRPLWKSYSRCTDGIIYVVD 94
Cdd:cd04156    1 QVLLLGLDSAGKSTLLYKLKHAELVTTIPTVGFNVEMLQLE----KHLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVD 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  95 SVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELIPATTYHVQPACAIIGEGLTEGMDK 174
Cdd:cd04156   77 SSDEARLDESQKELKHILKNEHIKGVPVVLLANKQDLPGALTAEEITRRFKLKKYCSDRDWYVQPCSAVTGEGLAEAFRK 156

                 ....
gi 540344578 175 LYEM 178
Cdd:cd04156  157 LASF 160

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 540344578  14 LHIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNgtakgISCHFWDVGGQEKLRPLWKSYSRCTDGIIYVV 93
Cdd:cd04149   10 MRILMLGLDAAGKTTILYKLKLGQSVTTIPTVGFNVETVTYKN-----VKFNVWDVGGQDKIRPLWRHYYTGTQGLIFVV 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 540344578  94 DSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHeLIPATTYHVQPACAIIGEGLTEGM 172
Cdd:cd04149   85 DSADRDRIDEARQELHRIINDREMRDALLLVFANKQDLPDAMKPHEIQEKLGLT-RIRDRNWYVQPSCATSGDGLYEGL 162

Arf-like 5 (Arl5) and 8 (Arl8) GTPases; Arl5/Arl8 subfamily. Arl5 (Arf-like 5) and Arl8, like Arl4 and Arl7, are localized to the nucleus and nucleolus. Arl5 is developmentally regulated during embryogenesis in mice. Human Arl5 interacts with the heterochromatin protein 1-alpha (HP1alpha), a nonhistone chromosomal protein that is associated with heterochromatin and telomeres, and prevents telomere fusion. Arl5 may also play a role in embryonic nuclear dynamics and/or signaling cascades. Arl8 was identified from a fetal cartilage cDNA library. It is found in brain, heart, lung, cartilage, and kidney. No function has been assigned for Arl8 to date.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  16 IVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNgtakgisCHF--WDVGGQEKLRPLWKSYSRCTDGIIYVV 93
Cdd:cd04153   18 VIIVGLDNAGKTTILYQFLLGEVVHTSPTIGSNVEEIVYKN-------IRFlmWDIGGQESLRSSWNTYYTNTDAVILVI 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  94 DSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHElIPATTYHVQPACAIIGEGLTEGMD 173
Cdd:cd04153   91 DSTDRERLPLTKEELYKMLAHEDLRKAVLLVLANKQDLKGAMTPAEISESLGLTS-IRDHTWHIQGCCALTGEGLPEGLD 169

Arf-like 2 (Arl2) GTPase; Arl2 (Arf-like 2) GTPases are members of the Arf family that bind GDP and GTP with very low affinity. Unlike most Arf family proteins, Arl2 is not myristoylated at its N-terminal helix. The protein PDE-delta, first identified in photoreceptor rod cells, binds specifically to Arl2 and is structurally very similar to RhoGDI. Despite the high structural similarity between Arl2 and Rho proteins and between PDE-delta and RhoGDI, the interactions between the GTPases and their effectors are very different. In its GTP bound form, Arl2 interacts with the protein Binder of Arl2 (BART), and the complex is believed to play a role in mitochondrial adenine nucleotide transport. In its GDP bound form, Arl2 interacts with tubulin- folding Cofactor D; this interaction is believed to play a role in regulation of microtubule dynamics that impact the cytoskeleton, cell division, and cytokinesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  14 LHIVMLGLDSAGKTTVLYRLKfNEFVNTV-PTIGFNTEKIKLsngtaKGISCHFWDVGGQEKLRPLWKSYSRCTDGIIYV 92
Cdd:cd04154   15 MRILMLGLDNAGKTTILKKFN-GEDISTIsPTLGFNIKTLEY-----NGYKLNIWDVGGQKSLRSYWRNYFESTDALIWV 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  93 VDSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELipaTTYH--VQPACAIIGEGLTE 170
Cdd:cd04154   89 VDSSDRARLEDCKRELQKLLVEERLAGATLLIFANKQDLPGALSPEEIREVLELDSI---KSHHwrIFGCSAVTGENLLD 165

                 ....*
gi 540344578 171 GMDKL 175
Cdd:cd04154  166 GIDWL 170

(ADP-ribosylation factor domain protein 1 (ARD1); ARD1 (ADP-ribosylation factor domain protein 1) is an unusual member of the Arf family. In addition to the C-terminal Arf domain, ARD1 has an additional 46-kDa N-terminal domain that contains a RING finger domain, two predicted B-Boxes, and a coiled-coil protein interaction motif. This domain belongs to the TRIM (tripartite motif) or RBCC (RING, B-Box, coiled-coil) family. Like most Arfs, the ARD1 Arf domain lacks detectable GTPase activity. However, unlike most Arfs, the full-length ARD1 protein has significant GTPase activity due to the GAP (GTPase-activating protein) activity exhibited by the 46-kDa N-terminal domain. The GAP domain of ARD1 is specific for its own Arf domain and does not bind other Arfs. The rate of GDP dissociation from the ARD1 Arf domain is slowed by the adjacent 15 amino acids, which act as a GDI (GDP-dissociation inhibitor) domain. ARD1 is ubiquitously expressed in cells and localizes to the Golgi and to the lysosomal membrane. Two Tyr-based motifs in the Arf domain are responsible for Golgi localization, while the GAP domain controls lysosomal localization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  16 IVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNgtakgISCHFWDVGGQEKLRPLWKSYSRCTDGIIYVVDS 95
Cdd:cd04158    2 VVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKN-----LKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDS 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  96 VDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELIPATTYHVQPACAIIGEGLTEGMDKL 175
Cdd:cd04158   77 SHRDRVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLCCGRSWYIQGCDARSGMGLYEGLDWL 156

Arf-like 9 (Arl9) and 10 (Arl10) GTPases; Arl10-like subfamily. Arl9/Arl10 was identified from a human cancer-derived EST dataset. No functional information about the subfamily is available at the current time, but crystal structures of human Arl10b and Arl10c have been solved.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  16 IVMLGLDSAGKTTVLYRLKFNEFV-NTVPTIGFNTEKIKLSNGTAKgischFWDVGGQEKLRPLWKSYSRCTDGIIYVVD 94
Cdd:cd04159    2 ITLVGLQNSGKTTLVNVIASGQFSeDTIPTVGFNMRKVTKGNVTIK-----VWDLGGQPRFRSMWERYCRGVNAIVYVVD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 540344578  95 SVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHEL 149
Cdd:cd04159   77 AADREKLEVAKNELHDLLEKPSLEGIPLLVLGNKNDLPGALSVDELIEQMNLKSI 131

Arf-like 9 (Arl9)/Arfrp2-like GTPase; Arl9/Arfrp2-like subfamily. Arl9 (Arf-like 9) was first identified as part of the Human Cancer Genome Project. It maps to chromosome 4q12 and is sometimes referred to as Arfrp2 (Arf-related protein 2). This is a novel subfamily identified in human cancers that is uncharacterized to date.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  16 IVMLGLDSAGKTTVLYRLKFNEFV-NTVPTIGFNTEKIklsngTAKGISCHFWDVGGQEKLRPLWKSYSRCTDGIIYVVD 94
Cdd:cd04162    2 ILVLGLDGAGKTSLLHSLSSERSLeSVVPTTGFNSVAI-----PTQDAIMELLEIGGSQNLRKYWKRYLSGSQGLIFVVD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 540344578  95 SVDVDRLEEAKTELHKVtkFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHEL 149
Cdd:cd04162   77 SADSERLPLARQELHQL--LQHPPDLPLVVLANKQDLPAARSVQEIHKELELEPI 129

Sar1p-like members of the Ras-family of small GTPases; Yeast SAR1 is an essential gene required for transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578    16 IVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNgtakgISCHFWDVGGQEKLRPLWKSYSRCTDGIIYVVDS 95
Cdd:smart00178  20 ILFLGLDNAGKTTLLHMLKNDRLAQHQPTQHPTSEELAIGN-----IKFTTFDLGGHQQARRLWKDYFPEVNGIVYLVDA 94

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 540344578    96 VDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLAL 146
Cdd:smart00178  95 YDKERFAESKRELDALLSDEELATVPFLILGNKIDAPYAASEDELRYALGL 145

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 540344578   16 IVMLGLDSAGKTTVLYRLKFNEFVNT--VPTIGFNTEKIKLsngTAKGISCHF--WDVGGQEKLRPLWKSYSRCTDGIIY 91
Cdd:TIGR00231   4 IVIVGHPNVGKSTLLNSLLGNKGSITeyYPGTTRNYVTTVI---EEDGKTYKFnlLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 540344578   92 VVDSVD-VDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLP 132
Cdd:TIGR00231  81 VFDIVIlVLDVEEILEKQTKEIIHHADSGVPIILVGNKIDLK 122

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 540344578  17 VMLGLDSAGKTTVLYRLkFNEFVNTV-----PTIGFNTEKIKLSNgtaKGISCHFWDVGGQEKLRPLW-----KSYSRCT 86
Cdd:cd00882    1 VVVGRGGVGKSSLLNAL-LGGEVGEVsdvpgTTRDPDVYVKELDK---GKVKLVLVDTPGLDEFGGLGreelaRLLLRGA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  87 DGIIYVVDSVDVDRLEEAKTELHKvtkFAENQGTPLLVIANKQDLPKSLPVAEIEKQLALHELIPattYHVQPACAIIGE 166
Cdd:cd00882   77 DLILLVVDSTDRESEEDAKLLILR---RLRKEGIPIILVGNKIDLLEEREVEELLRLEELAKILG---VPVFEVSAKTGE 150

                        170
                 ....*....|.
gi 540344578 167 GLTEGMDKLYE 177
Cdd:cd00882  151 GVDELFEKLIE 161

Signal recognition particle receptor, beta subunit (SR-beta), together with SR-alpha, forms the heterodimeric signal recognition particle (SRP); Signal recognition particle receptor, beta subunit (SR-beta). SR-beta and SR-alpha form the heterodimeric signal recognition particle (SRP or SR) receptor that binds SRP to regulate protein translocation across the ER membrane. Nascent polypeptide chains are synthesized with an N-terminal hydrophobic signal sequence that binds SRP54, a component of the SRP. SRP directs targeting of the ribosome-nascent chain complex (RNC) to the ER membrane via interaction with the SR, which is localized to the ER membrane. The RNC is then transferred to the protein-conducting channel, or translocon, which facilitates polypeptide translation across the ER membrane or integration into the ER membrane. SR-beta is found only in eukaryotes; it is believed to control the release of the signal sequence from SRP54 upon binding of the ribosome to the translocon. High expression of SR-beta has been observed in human colon cancer, suggesting it may play a role in the development of this type of cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578  15 HIVMLGLDSAGKTTVLYRLKFNEFVNTVPTIGFNTEKIKLSNGTAKGIscHFWDVGGQEKLRP-LWKSYSRCTDGIIYVV 93
Cdd:cd04105    2 TVLLLGPSDSGKTALFTKLTTGKVRSTVTSIEPNVASFYSNSSKGKKL--TLVDVPGHEKLRDkLLEYLKASLKAIVFVV 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 540344578  94 DSVDVDR-LEEAKTELHKV--TKFAENQGTPLLVIANKQDLPKSLPVAEIEKQL 144
Cdd:cd04105   80 DSATFQKnIRDVAEFLYDIltDLEKIKNKIPILIACNKQDLFTAKPAKKIKELL 133

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 540344578  16 IVMLGLDSAGKTTVLYRLKFNEFV-NTVPTIG--FNTEKIKLSNGTAKgischF--WDVGGQEKLRPLWKSYSRCTDGII 90
Cdd:cd01860    4 LVLLGDSSVGKSSIVLRFVKNEFSeNQESTIGaaFLTQTVNLDDTTVK-----FeiWDTAGQERYRSLAPMYYRGAAAAI 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 540344578  91 YVVDSVDVDRLEEAKT---ELHKvtkfaenQGTPLLVIA---NKQDL 131
Cdd:cd01860   79 VVYDITSEESFEKAKSwvkELQE-------HGPPNIVIAlagNKADL 118

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 540344578  14 LHIVMLGLDSAGKTTVLYRLKFNEFV-NTVPTIG--FNTEKIKLSNGTAKgisCHFWDVGGQEKLRPLWKSYSRCTDGII 90
Cdd:cd01863    1 LKILLIGDSGVGKSSLLLRFTDDTFDeDLSSTIGvdFKVKTVTVDGKKVK---LAIWDTAGQERFRTLTSSYYRGAQGVI 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 540344578  91 YVVDSVDVDRLEEAKTELHKVTKFAENQGTPLLVIANKQDLPKSLPVAEIEKQLA 145
Cdd:cd01863   78 LVYDVTRRDTFDNLDTWLNELDTYSTNPDAVKMLVGNKIDKENREVTREEGQKFA 132

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 540344578  16 IVMLGLDSAGKTTVLYRLKFNEFVNT-VPTIG--FNTEKIKLSNgtaKGISCHFWDVGGQEKLRPLWKSYSRCTDGIIYV 92
Cdd:cd01867    6 LLLIGDSGVGKSCLLLRFSEDSFNPSfISTIGidFKIRTIELDG---KKIKLQIWDTAGQERFRTITTSYYRGAMGIILV 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 540344578  93 VDSVDVDRLEEAKTELHKVTKFAeNQGTPLLVIANKQDLPKSLPVAEIE-KQLA 145
Cdd:cd01867   83 YDITDEKSFENIKNWMRNIDEHA-SEDVERMLVGNKCDMEEKRVVSKEEgEALA 135

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344578    16 IVMLGlDSA-GKTTVLYRLKFNEFVN-TVPTIG--FNTEKIKLSNGTAKgisCHFWDVGGQEKLRPLWKSYSRCTDGIIY 91
Cdd:smart00175   3 IILIG-DSGvGKSSLLSRFTDGKFSEqYKSTIGvdFKTKTIEVDGKRVK---LQIWDTAGQERFRSITSSYYRGAVGALL 78