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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347   18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:pfam00025   2 RILILGLDNAGKTTILYKLKLGEIVTTIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADRD 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 402888347   98 RISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGLEWM 172
Cdd:pfam00025  82 RIEEAKEELHALLNEEELADAPLLILANKQDLPGAMSEAEIRELLGLHELKDRPWEIQGCSAVTGEGLDEGLDWL 156

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 402888347     1 MGILFTRiwrLFNHQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTY 80
Cdd:smart00177   1 MGKLFSK---LFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347    81 YTNTEFVIVVVDSTDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCAL 160
Cdd:smart00177  78 YTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCAT 157

                          170
                   ....*....|....*..
gi 402888347   161 TGEGLCQGLEWMMSRLK 177
Cdd:smart00177 158 SGDGLYEGLTWLSNNLK 174

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  16 EHKVIIVGLDNAGKTTILYQFSMNEV--VHTSPTIGSNVEEIVI----NNTRFLMWDIGGQ---ESLRSSWNTYYTNTEF 86
Cdd:COG1100    3 EKKIVVVGTGGVGKTSLVNRLVGDIFslEKYLSTNGVTIDKKELkldgLDVDLVIWDTPGQdefRETRQFYARQLTGASL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  87 VIVVVDSTdrerISVTREELYKMLahEDLRKAG----LLIFANKQDvkeCMTVAEISQFLKLTSI--KDHQWHIQACCAL 160
Cdd:COG1100   83 YLFVVDGT----REETLQSLYELL--ESLRRLGkkspIILVLNKID---LYDEEEIEDEERLKEAlsEDNIVEVVATSAK 153

                 ....*
gi 402888347 161 TGEGL 165
Cdd:COG1100  154 TGEGV 158

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 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd00878    1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRE 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 402888347  98 RISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGLEWMMSR 175
Cdd:cd00878   81 RIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESIKGRRWHIQPCSAVTGDGLDEGLDWLIEQ 158

ADP ribosylation factor 1 (Arf1); Arl1 subfamily. Arl1 (Arf-like 1) localizes to the Golgi complex, where it is believed to recruit effector proteins to the trans-Golgi network. Like most members of the Arf family, Arl1 is myristoylated at its N-terminal helix and mutation of the myristoylation site disrupts Golgi targeting. In humans, the Golgi-localized proteins golgin-97 and golgin-245 have been identified as Arl1 effectors. Golgins are large coiled-coil proteins found in the Golgi, and these golgins contain a C-terminal GRIP domain, which is the site of Arl1 binding. Additional Arl1 effectors include the GARP (Golgi-associated retrograde protein)/VFT (Vps53) vesicle-tethering complex and Arfaptin 2. Arl1 is not required for exocytosis, but appears necessary for trafficking from the endosomes to the Golgi. In Drosophila zygotes, mutation of Arl1 is lethal, and in the host-bloodstream form of Trypanosoma brucei, Arl1 is essential for viability.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd04151    1 RILILGLDGAGKTTILYRLQVGEVVTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAIIYVVDSTDRD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 402888347  98 RISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGLEWM 172
Cdd:cd04151   81 RLGISKSELHAMLEEEELKDAVLLVFANKQDMPGALSEAEVAEKLGLSELKDRTWQIFKTSATKGEGLDEGMDWL 155

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347   1 MGILFTRIW-RLFNHQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNT 79
Cdd:PLN00223   1 MGLSFTKLFsRLFAKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  80 YYTNTEFVIVVVDSTDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCA 159
Cdd:PLN00223  81 YFQNTQGLIFVVDSNDRDRVVEARDELHRMLNEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRQRHWYIQSTCA 160

                        170       180
                 ....*....|....*....|
gi 402888347 160 LTGEGLCQGLEWMMSRLKIR 179
Cdd:PLN00223 161 TSGEGLYEGLDWLSNNIANK 180

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 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd04150    2 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 402888347  98 RISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGLEWM 172
Cdd:cd04150   82 RIGEAREELQRMLNEDELRDAVLLVFANKQDLPNAMSAAEVTDKLGLHSLRNRNWYIQATCATSGDGLYEGLDWL 156

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 402888347  10 RLFNHQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIV 89
Cdd:cd04149    3 KLFGNKEMRILMLGLDAAGKTTILYKLKLGQSVTTIPTVGFNVETVTYKNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIF 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  90 VVDSTDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGL 169
Cdd:cd04149   83 VVDSADRDRIDEARQELHRIINDREMRDALLLVFANKQDLPDAMKPHEIQEKLGLTRIRDRNWYVQPSCATSGDGLYEGL 162

                 ...
gi 402888347 170 EWM 172
Cdd:cd04149  163 TWL 165

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 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVIN-NTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDR 96
Cdd:cd04156    1 QVLLLGLDSAGKSTLLYKLKHAELVTTIPTVGFNVEMLQLEkHLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVDSSDE 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 402888347  97 ERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSI-KDHQWHIQACCALTGEGLCQGL 169
Cdd:cd04156   81 ARLDESQKELKHILKNEHIKGVPVVLLANKQDLPGALTAEEITRRFKLKKYcSDRDWYVQPCSAVTGEGLAEAF 154

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 402888347  19 VIIVGLDNAGKTTILYQF--SMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDR 96
Cdd:cd04157    2 ILVLGLDNSGKTTIINQLkpSNAQSQNIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDR 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 402888347  97 ERISVTREELYKMLAHEDL--RKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGLEWM 172
Cdd:cd04157   82 LRMVVAKDELELLLNHPDIkhRRIPILFYANKMDLPDALTAVKITQLLCLENIKDKPWHIFASSALTGEGLDEGVDWL 159

(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 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd04158    1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  98 RISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSI-KDHQWHIQACCALTGEGLCQGLEWMMSRL 176
Cdd:cd04158   81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

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 402888347  21 IVGLDNAGKTTILYQFSMNEVVH-TSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDRERI 99
Cdd:cd04159    4 LVGLQNSGKTTLVNVIASGQFSEdTIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADREKL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347 100 SVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWhiqaCC----ALTGEGLCQGLEWMMSR 175
Cdd:cd04159   84 EVAKNELHDLLEKPSLEGIPLLVLGNKNDLPGALSVDELIEQMNLKSITDREV----SCysisAKEKTNIDIVLDWLIKH 159

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 402888347    14 HQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDS 93
Cdd:smart00178  15 NKHAKILFLGLDNAGKTTLLHMLKNDRLAQHQPTQHPTSEELAIGNIKFTTFDLGGHQQARRLWKDYFPEVNGIVYLVDA 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347    94 TDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQA-------CCALTGEGLC 166
Cdd:smart00178  95 YDKERFAESKRELDALLSDEELATVPFLILGNKIDAPYAASEDELRYALGLTNTTTGKGKVGVrpvevfmCSVVRRMGYG 174

                   ....*.
gi 402888347   167 QGLEWM 172
Cdd:smart00178 175 EGFKWL 180

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 402888347  21 IVGLDNAGKTTILYQFSMNEVVHTS----PTIGSNVE--EIVINNTRFLMWDIGGQESLRSSWNT-----YYTNTEFVIV 89
Cdd:cd00882    2 VVGRGGVGKSSLLNALLGGEVGEVSdvpgTTRDPDVYvkELDKGKVKLVLVDTPGLDEFGGLGREelarlLLRGADLILL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  90 VVDSTDRERISVTREELYKMLAHEDLRkagLLIFANKQDVKECMTVAEISQFLKLTSIKDHqwHIQACCALTGEGLCQGL 169
Cdd:cd00882   82 VVDSTDRESEEDAKLLILRRLRKEGIP---IILVGNKIDLLEEREVEELLRLEELAKILGV--PVFEVSAKTGEGVDELF 156

                 ....*
gi 402888347 170 EWMMS 174
Cdd:cd00882  157 EKLIE 161

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  18 KVIIVGLDNAGKTTILYQFSMNE-VVHTSPTIGSN--VEEIVINNTRFLM--WDIGGQESLRSSWNTYYTNTEFVIVVVD 92
Cdd:cd00154    2 KIVLIGDSGVGKTSLLLRFVDNKfSENYKSTIGVDfkSKTIEVDGKKVKLqiWDTAGQERFRSITSSYYRGAHGAILVYD 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 402888347  93 STDRErisvTREELYKMLahEDLRKAG-----LLIFANKQDVKECMTV--AEISQFlkltsIKDHQWHIQACCALTGEG 164
Cdd:cd00154   82 VTNRE----SFENLDKWL--NELKEYAppnipIILVGNKSDLEDERQVstEEAQQF-----AKENGLLFFETSAKTGEN 149

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  16 EHKVIIVGLDNAGKTTILYQFSMNEV--VHTSPTIGSNVEEIVI----NNTRFLMWDIGGQ---ESLRSSWNTYYTNTEF 86
Cdd:COG1100    3 EKKIVVVGTGGVGKTSLVNRLVGDIFslEKYLSTNGVTIDKKELkldgLDVDLVIWDTPGQdefRETRQFYARQLTGASL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  87 VIVVVDSTdrerISVTREELYKMLahEDLRKAG----LLIFANKQDvkeCMTVAEISQFLKLTSI--KDHQWHIQACCAL 160
Cdd:COG1100   83 YLFVVDGT----REETLQSLYELL--ESLRRLGkkspIILVLNKID---LYDEEEIEDEERLKEAlsEDNIVEVVATSAK 153

                 ....*
gi 402888347 161 TGEGL 165
Cdd:COG1100  154 TGEGV 158

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSN--VEEIVINNTRF--LMWDIGGQESLRSSWNTYYTNTEFVIVVVDS 93
Cdd:PLN03118  16 KILLIGDSGVGKSSLLVSFISSSVEDLAPTIGVDfkIKQLTVGGKRLklTIWDTAGQERFRTLTSSYYRNAQGIILVYDV 95

                 ....
gi 402888347  94 TDRE 97
Cdd:PLN03118  96 TRRE 99

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 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSP-TIGSNVEEIVIN----NTRFLMWDIGGQESLRSSWNTYYTNTEFVIVVVD 92
Cdd:cd04113    2 KFLIIGSAGTGKSCLLHQFIENKFKQDSNhTIGVEFGSRVVNvggkSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVYD 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 402888347  93 STDRERISVTREEL--YKMLAHEDLRkagLLIFANKQDVKEC--MTVAEISQFlkltsIKDHQWHIQACCALTGEGL 165
Cdd:cd04113   82 ITSRESFNALTNWLtdARTLASPDIV---IILVGNKKDLEDDreVTFLEASRF-----AQENGLLFLETSALTGENV 150

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  18 KVIIVGLDNAGKTTILYQFSMNEVV-HTSPTIGSNVEEIVIN----NTRFLMWDIGGQESLRSSW-NTYYTNTEFVIVVV 91
Cdd:cd04115    4 KIIVIGDSNVGKTCLTYRFCAGRFPeRTEATIGVDFRERTVEidgeRIKVQLWDTAGQERFRKSMvQHYYRNVHAVVFVY 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 402888347  92 DSTDRERISVTR---EELYK-MLAHEDLRkaglLIFANKQDVKECMTV 135
Cdd:cd04115   84 DVTNMASFHSLPswiEECEQhSLPNEVPR----ILVGNKCDLREQIQV 127

Signal recognition particle receptor beta subunit; The beta subunit of the signal recognition particle receptor (SRP) is a transmembrane GTPase which anchors the alpha subunit to the endoplasmic reticulum membrane.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347   19 VIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINN--TRFLMWDIGGQESLRSSWNTYY---TNTEFVIVVVDS 93
Cdd:pfam09439   6 VIIAGLCDSGKTSLFTLLTTDSVRPTVTSQEPSAAYRYMLNkgNSFTLIDFPGHVKLRYKLLETLkdsSSLKGIVFVVDS 85

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 402888347   94 T-DRERISVTREELYKMLAHEDLRKAG--LLIFANKQD 128
Cdd:pfam09439  86 TiFPKEVTDTAEFLYDILSITELLKNGidILIACNKQE 123

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 402888347  17 HKVIIVGLDNAGKTTILYQFSMNEVV-HTSPTIGS-------NVEEIVInntRFLMWDIGGQESLRSSWNTYYTNTEFVI 88
Cdd:cd01861    1 HKLVFLGDQSVGKTSIITRFMYDTFDnQYQATIGIdflsktmYVDDKTV---RLQLWDTAGQERFRSLIPSYIRDSSVAV 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 402888347  89 VVVDSTDRERISVTReELYKMLAHEDLRKAGLLIFANKQDVKECMTV 135
Cdd:cd01861   78 VVYDITNRQSFDNTD-KWIDDVRDERGNDVIIVLVGNKTDLSDKRQV 123