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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144    18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:pfam00025   2 RILILGLDNAGKTTILYKLKLGEIVTTIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADRD 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33695144    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 33695144      1 MGILFTRiwrLFNHQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTY 80
Cdd:smart00177   1 MGKLFSK---LFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144     81 YTNTEFVIVVVDSTDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCAL 160
Cdd:smart00177  78 YTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCAT 157

                          170
                   ....*....|....*..
gi 33695144    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 33695144  16 EHKVIIVGLDNAGKTTILYQFSMNEV--VHTSPTIGSNVEEIVV----NNTRFLMWDIGGQ---ESLRPSWNTYYTNTEF 86
Cdd:COG1100   3 EKKIVVVGTGGVGKTSLVNRLVGDIFslEKYLSTNGVTIDKKELkldgLDVDLVIWDTPGQdefRETRQFYARQLTGASL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  87 VIVVVDSTdrerISVTREELYKMLahEDLRKAG----LLIFANKQDvkeCMTVAEISQFLKLTSI--KDHQWHIQACCAL 160
Cdd:COG1100  83 YLFVVDGT----REETLQSLYELL--ESLRRLGkkspIILVLNKID---LYDEEEIEDEERLKEAlsEDNIVEVVATSAK 153

                ....*
gi 33695144 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 33695144  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd00878   1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRE 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33695144  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 33695144  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd04151   1 RILILGLDGAGKTTILYRLQVGEVVTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAIIYVVDSTDRD 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33695144  98 RISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGLEWM 172
Cdd:cd04151  81 RLGISKSELHAMLEEEELKDAVLLVFANKQDMPGALSEAEVAEKLGLSELKDRTWQIFKTSATKGEGLDEGMDWL 155

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144    1 MGILFTRIW-RLFNHQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNT 79
Cdd:PLN00223   1 MGLSFTKLFsRLFAKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144   80 YYTNTEFVIVVVDSTDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCA 159
Cdd:PLN00223  81 YFQNTQGLIFVVDSNDRDRVVEARDELHRMLNEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRQRHWYIQSTCA 160

                        170       180
                 ....*....|....*....|
gi 33695144  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 33695144  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd04150   2 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33695144  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 33695144  10 RLFNHQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIV 89
Cdd:cd04149   3 KLFGNKEMRILMLGLDAAGKTTILYKLKLGQSVTTIPTVGFNVETVTYKNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIF 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  90 VVDSTDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGL 169
Cdd:cd04149  83 VVDSADRDRIDEARQELHRIINDREMRDALLLVFANKQDLPDAMKPHEIQEKLGLTRIRDRNWYVQPSCATSGDGLYEGL 162

                ...
gi 33695144 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 33695144  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVN-NTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDR 96
Cdd:cd04156   1 QVLLLGLDSAGKSTLLYKLKHAELVTTIPTVGFNVEMLQLEkHLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVDSSDE 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33695144  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 33695144  19 VIIVGLDNAGKTTILYQF--SMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDR 96
Cdd:cd04157   2 ILVLGLDNSGKTTIINQLkpSNAQSQNIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDR 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33695144  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 33695144  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDRE 97
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  98 RISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLTSI-KDHQWHIQACCALTGEGLCQGLEWMMSRL 176
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

Sar1 is an essential component of COPII vesicle coats; Sar1 is an essential component of COPII vesicle coats involved in export of cargo from the ER. The GTPase activity of Sar1 functions as a molecular switch to control protein-protein and protein-lipid interactions that direct vesicle budding from the ER. Activation of the GDP to the GTP-bound form of Sar1 involves the membrane-associated guanine nucleotide exchange factor (GEF) Sec12. Sar1 is unlike all Ras superfamily GTPases that use either myristoyl or prenyl groups to direct membrane association and function, in that Sar1 lacks such modification. Instead, Sar1 contains a unique nine-amino-acid N-terminal extension. This extension contains an evolutionarily conserved cluster of bulky hydrophobic amino acids, referred to as the Sar1-N-terminal activation recruitment (STAR) motif. The STAR motif mediates the recruitment of Sar1 to ER membranes and facilitates its interaction with mammalian Sec12 GEF leading to activation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  14 HQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDS 93
Cdd:cd00879  17 KKEAKIVFLGLDNAGKTTLLHMLKDDRLAQHVPTLHPTSEELTIGNVKFTTFDLGGHEQARRVWKDYFPEVDGIVFLVDA 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  94 TDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFLKLT---------SIKDHQWHIQA---CCALT 161
Cdd:cd00879  97 ADPERFQESKEELDSLLNDEELANVPILILGNKIDKPGAVSEEELREALGLYgtttgkggvSLKVSNIRPVEvfmCSVVK 176

                       170
                ....*....|.
gi 33695144 162 GEGLCQGLEWM 172
Cdd:cd00879 177 RQGYGEGFRWL 187

Arl2-like protein 1 (Arl2l1) and Arl13; Arl2l1 (Arl2-like protein 1) and Arl13 form a subfamily of the Arf family of small GTPases. Arl2l1 was identified in human cells during a search for the gene(s) responsible for Bardet-Biedl syndrome (BBS). Like Arl6, the identified BBS gene, Arl2l1 is proposed to have cilia-specific functions. Arl13 is found on the X chromosome, but its expression has not been confirmed; it may be a pseudogene.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  19 VIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVDSTDRER 98
Cdd:cd04161   2 LLTVGLDNAGKTTLVSALQGEIPKKVAPTVGFTPTKLRLDKYEVCIFDLGGGANFRGIWVNYYAEAHGLVFVVDSSDDDR 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  99 ISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQFL---KLTSIKDHQWHIQACCALTGEG------LCQGL 169
Cdd:cd04161  82 VQEVKEILRELLQHPRVSGKPILVLANKQDKKNALLGADVIEYLsleKLVNENKSLCHIEPCSAIEGLGkkidpsIVEGL 161

                ....*
gi 33695144 170 EWMMS 174
Cdd:cd04161 162 RWLLA 166

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 33695144  21 IVGLDNAGKTTILYQFSMNEVVHTS----PTIGSNVE--EIVVNNTRFLMWDIGGQESLRPSWNT-----YYTNTEFVIV 89
Cdd:cd00882   2 VVGRGGVGKSSLLNALLGGEVGEVSdvpgTTRDPDVYvkELDKGKVKLVLVDTPGLDEFGGLGREelarlLLRGADLILL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  90 VVDSTDRERISVTREELYKMLAHEDLRkagLLIFANKQDVKECMTVAEISQFLKLTSIKDHqwHIQACCALTGEGLCQGL 169
Cdd:cd00882  82 VVDSTDRESEEDAKLLILRRLRKEGIP---IILVGNKIDLLEEREVEELLRLEELAKILGV--PVFEVSAKTGEGVDELF 156

                ....*
gi 33695144 170 EWMMS 174
Cdd:cd00882 157 EKLIE 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 33695144  19 VIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVVNNTRFLMW---DIGGQESLRPSWNTYYTNTEFVIV-VVDST 94
Cdd:cd04105   3 VLLLGPSDSGKTALFTKLTTGKVRSTVTSIEPNVASFYSNSSKGKKLtlvDVPGHEKLRDKLLEYLKASLKAIVfVVDSA 82

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 33695144  95 DRER-ISVTREELYKMLAHEDLRKAG--LLIFANKQDV 129
Cdd:cd04105  83 TFQKnIRDVAEFLYDILTDLEKIKNKipILIACNKQDL 120

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  16 EHKVIIVGLDNAGKTTILYQFSMNEV--VHTSPTIGSNVEEIVV----NNTRFLMWDIGGQ---ESLRPSWNTYYTNTEF 86
Cdd:COG1100   3 EKKIVVVGTGGVGKTSLVNRLVGDIFslEKYLSTNGVTIDKKELkldgLDVDLVIWDTPGQdefRETRQFYARQLTGASL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  87 VIVVVDSTdrerISVTREELYKMLahEDLRKAG----LLIFANKQDvkeCMTVAEISQFLKLTSI--KDHQWHIQACCAL 160
Cdd:COG1100  83 YLFVVDGT----REETLQSLYELL--ESLRRLGkkspIILVLNKID---LYDEEEIEDEERLKEAlsEDNIVEVVATSAK 153

                ....*
gi 33695144 161 TGEGL 165
Cdd:COG1100 154 TGEGV 158

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 33695144    18 KVIIVGLDNAGKTTILYQFSMNEVVHTS-PTIG--SNVEEIVVNNTRFLM--WDIGGQE---SLRPSwntYYTNTEFVIV 89
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYiPTIGvdFYTKTIEVDGKTVKLqiWDTAGQErfrALRPL---YYRGADGFLL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144    90 VVDSTDR---ERISVTREELykmlahedLRKAG----LLIFANKQDVKE--CMTVAEISQFLKltsikdhQWHIQ--ACC 158
Cdd:pfam00071  78 VYDITSRdsfENVKKWVEEI--------LRHADenvpIVLVGNKCDLEDqrVVSTEEGEALAK-------ELGLPfmETS 142

                  ....*.
gi 33695144   159 ALTGEG 164
Cdd:pfam00071 143 AKTNEN 148

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  17 HKVIIVGLDNAGKTTILYQFSMNEVVHT-SPTIG-SNVEEIVVNNTRFLM--WDIGGQESLRPSWNTYYTNTEFVIVVVD 92
Cdd:cd04139   1 HKVIMVGSGGVGKSALTLQFMYDEFVEDyEPTKAdSYRKKVVLDGEEVQLniLDTAGQEDYAAIRDNYFRSGEGFLLVFS 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33695144  93 STDRERISVTREELYKMLAHEDLRKAGLLIFANKQDV--KECMTVAEISQFLkltsikdHQWHIQ 155
Cdd:cd04139  81 ITDMESFTALAEFREQILRVKEDDNVPLLLVGNKCDLedKRQVSVEEAANLA-------EQWGVN 138

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 33695144  18 KVIIVGLDNAGKTTILYQFSMNEVVHTSP-TIGSNVEEIVVN----NTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVVD 92
Cdd:cd04113   2 KFLIIGSAGTGKSCLLHQFIENKFKQDSNhTIGVEFGSRVVNvggkSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVYD 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33695144  93 STDRERISVTREEL--YKMLAHEDLRkagLLIFANKQDVKEC--MTVAEISQFlkltsIKDHQWHIQACCALTGEGL 165
Cdd:cd04113  82 ITSRESFNALTNWLtdARTLASPDIV---IILVGNKKDLEDDreVTFLEASRF-----AQENGLLFLETSALTGENV 150

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33695144  10 RLFNHQeHKVIIVGLDNAGKTTILYQFSMNEVVHTS-PTIGSN--VEEIVVNNTR--FLMWDIGGQESLRPSWNTYYTNT 84
Cdd:cd04110   1 RDYDHL-FKLLIIGDSGVGKSSLLLRFADNTFSGSYiTTIGVDfkIRTVEINGERvkLQIWDTAGQERFRTITSTYYRGT 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 33695144  85 EFVIVVVDSTDRERISVTREELYKMLAHEDLRKAGLLifANKQD 128
Cdd:cd04110  80 HGVIVVYDVTNGESFVNVKRWLQEIEQNCDDVCKVLV--GNKND 121

Rab GTPase families 34 (Rab34) and 36 (Rab36); Rab34/Rab36 subfamily. Rab34, found primarily in the Golgi, interacts with its effector, Rab-interacting lysosomal protein (RILP). This enables its participation in microtubular dynenin-dynactin-mediated repositioning of lysosomes from the cell periphery to the Golgi. A Rab34 (Rah) isoform that lacks the consensus GTP-binding region has been identified in mice. This isoform is associated with membrane ruffles and promotes macropinosome formation. Rab36 has been mapped to human chromosome 22q11.2, a region that is homozygously deleted in malignant rhabdoid tumors (MRTs). However, experimental assessments do not implicate Rab36 as a tumor suppressor that would enable tumor formation through a loss-of-function mechanism. 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 33695144  17 HKVIIVGLDNAGKTTILYQFSMNEV-VHTSPTIGSNVE----EIVVNNTRFLMWDIGGQESLRPSWNTYYTNTEFVIVVV 91
Cdd:cd04108   1 SKVIVVGDLSVGKTCLINRFCKDVFdKNYKATIGVDFEmerfEVLGVPFSLQLWDTAGQERFKCIASTYYRGAQAIIIVF 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33695144  92 DSTDRERISVTREELYKMLAHEDLRKAGLLIFANKQDVKECMTVAEISQ-FLKLT-SIKDHQWhiqACCALTGEGL 165
Cdd:cd04108  81 DLTDVASLEHTRQWLEDALKENDPSSVLLFLVGTKKDLSSPAQYALMEQdAIKLArEMKAEYW---AVSALTGENV 153