P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718       5 FGNLLKSLIGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQN 84
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718      85 TQGLIFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGD 164
Cdd:smart00177  81 TQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGD 160

                          170
                   ....*....|....*
gi 6680718     165 GLYEGLDWLANQLKN 179
Cdd:smart00177 161 GLYEGLTWLSNNLKN 175

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 6680718       5 FGNLLKSLIGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQN 84
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718      85 TQGLIFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGD 164
Cdd:smart00177  81 TQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGD 160

                          170
                   ....*....|....*
gi 6680718     165 GLYEGLDWLANQLKN 179
Cdd:smart00177 161 GLYEGLTWLSNNLKN 175

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 6680718   18 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 97
Cdd:cd04150   1 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6680718   98 ERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLANQ 176
Cdd:cd04150  81 ERIGEAREELQRMLNEDELRDAVLLVFANKQDLPNAMSAAEVTDKLGLHSLRNRNWYIQATCATSGDGLYEGLDWLSNN 159

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 6680718     17 EMRILMVGLDAAGKTTILYKLKLGE--IVTTIPTIGFNVET--VEYKNIS--FTVWDVGGQDKIRPLWRHYFQNTQGLIF 90
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGNKgsITEYYPGTTRNYVTtvIEEDGKTykFNLLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 6680718     91 VVDSNdrERVNEAREELM--RMLAEDELR-DAVLLVFANKQDLPNA 133
Cdd:TIGR00231  81 VFDIV--ILVLDVEEILEkqTKEIIHHADsGVPIILVGNKIDLKDA 124

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 6680718       5 FGNLLKSLIGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQN 84
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718      85 TQGLIFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGD 164
Cdd:smart00177  81 TQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGD 160

                          170
                   ....*....|....*
gi 6680718     165 GLYEGLDWLANQLKN 179
Cdd:smart00177 161 GLYEGLTWLSNNLKN 175

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718     1 MGNIFGNLLKSLIGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRH 80
Cdd:PTZ00133   1 MGLWLSSAFKSLFGKKEVRILMVGLDAAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNLKFTMWDVGGQDKLRPLWRH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718    81 YFQNTQGLIFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCA 160
Cdd:PTZ00133  81 YYQNTNGLIFVVDSNDRERIGDAREELERMLSEDELRDAVLLVFANKQDLPNAMSTTEVTEKLGLHSVRQRNWYIQGCCA 160

                        170       180
                 ....*....|....*....|.
gi 6680718   161 TSGDGLYEGLDWLANQLKNKK 181
Cdd:PTZ00133 161 TTAQGLYEGLDWLSANIKKSM 181

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 6680718   19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 98
Cdd:cd00878   1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRE 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6680718   99 RVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLANQ 176
Cdd:cd00878  81 RIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESIKGRRWHIQPCSAVTGDGLDEGLDWLIEQ 158

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 6680718    9 LKSLIGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGL 88
Cdd:cd04149   1 LSKLFGNKEMRILMLGLDAAGKTTILYKLKLGQSVTTIPTVGFNVETVTYKNVKFNVWDVGGQDKIRPLWRHYYTGTQGL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   89 IFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGDGLYE 168
Cdd:cd04149  81 IFVVDSADRDRIDEARQELHRIINDREMRDALLLVFANKQDLPDAMKPHEIQEKLGLTRIRDRNWYVQPSCATSGDGLYE 160

                ....*..
gi 6680718  169 GLDWLAN 175
Cdd:cd04149 161 GLTWLSS 167

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 6680718    3 NIFGNLLKSLIGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYF 82
Cdd:cd04153   1 LLFSSLWSLFFPRKEYKVIIVGLDNAGKTTILYQFLLGEVVHTSPTIGSNVEEIVYKNIRFLMWDIGGQESLRSSWNTYY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   83 QNTQGLIFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATS 162
Cdd:cd04153  81 TNTDAVILVIDSTDRERLPLTKEELYKMLAHEDLRKAVLLVLANKQDLKGAMTPAEISESLGLTSIRDHTWHIQGCCALT 160

                       170
                ....*....|....
gi 6680718  163 GDGLYEGLDWLANQ 176
Cdd:cd04153 161 GEGLPEGLDWIASR 174

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 6680718   16 KEMRILMVGLDAAGKTTILYKLkLGEIVTTI-PTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDS 94
Cdd:cd04154  13 REMRILMLGLDNAGKTTILKKF-NGEDISTIsPTLGFNIKTLEYNGYKLNIWDVGGQKSLRSYWRNYFESTDALIWVVDS 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   95 NDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLA 174
Cdd:cd04154  92 SDRARLEDCKRELQKLLVEERLAGATLLIFANKQDLPGALSPEEIREVLELDSIKSHHWRIFGCSAVTGENLLDGIDWLV 171

                .
gi 6680718  175 N 175
Cdd:cd04154 172 D 172

(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 6680718   19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 98
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   99 RVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSL-RHRNWYIQATCATSGDGLYEGLDWLANQL 177
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

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 6680718   20 ILMVGLDAAGKTTILYKLKLGEIVTTI--PTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 97
Cdd:cd04157   2 ILVLGLDNSGKTTIINQLKPSNAQSQNivPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDR 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   98 ERVNEAREELMRMLAEDEL--RDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLAN 175
Cdd:cd04157  82 LRMVVAKDELELLLNHPDIkhRRIPILFYANKMDLPDALTAVKITQLLCLENIKDKPWHIFASSALTGEGLDEGVDWLQA 161

                .
gi 6680718  176 Q 176
Cdd:cd04157 162 Q 162

Arf-related protein 1 (Arfrp1); Arfrp1 (Arf-related protein 1), formerly known as ARP, is a membrane-associated Arf family member that lacks the N-terminal myristoylation motif. Arfrp1 is mainly associated with the trans-Golgi compartment and the trans-Golgi network, where it regulates the targeting of Arl1 and the GRIP domain-containing proteins, golgin-97 and golgin-245, onto Golgi membranes. It is also involved in the anterograde transport of the vesicular stomatitis virus G protein from the Golgi to the plasma membrane, and in the retrograde transport of TGN38 and Shiga toxin from endosomes to the trans-Golgi network. Arfrp1 also inhibits Arf/Sec7-dependent activation of phospholipase D. Deletion of Arfrp1 in mice causes embryonic lethality at the gastrulation stage and apoptosis of mesodermal cells, indicating its importance in development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   20 ILMVGLDAAGKTTILYKLK-----------LGEIVttiPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGL 88
Cdd:cd04160   2 VLILGLDNAGKTTFLEQTKtkfsknykglnPSKIT---PTVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAESHGV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   89 IFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITD--KLGLHSLRHRNWYIQATCATSGDGL 166
Cdd:cd04160  79 IYVIDSTDRERFNESKSAFEKVINNEALEGVPLLVLANKQDLPDALSVAEIKEvfDDCIALIGRRDCLVQPVSALEGEGV 158

                ....*..
gi 6680718  167 YEGLDWL 173
Cdd:cd04160 159 EEGIEWL 165

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 6680718   20 ILMVGLDAAGKTTILYKLKLGE-IVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 98
Cdd:cd04159   2 ITLVGLQNSGKTTLVNVIASGQfSEDTIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADRE 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6680718   99 RVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWL 173
Cdd:cd04159  82 KLEVAKNELHDLLEKPSLEGIPLLVLGNKNDLPGALSVDELIEQMNLKSITDREVSCYSISAKEKTNIDIVLDWL 156

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 6680718       3 NIFGNLLKSL-IGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHY 81
Cdd:smart00178   2 DWFYDILASLgLWNKHAKILFLGLDNAGKTTLLHMLKNDRLAQHQPTQHPTSEELAIGNIKFTTFDLGGHQQARRLWKDY 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 6680718      82 FQNTQGLIFVVDSNDRERVNEAREELMRMLAEDELRDAVLLVFANKQDLPNAMNAAEITDKLGL 145
Cdd:smart00178  82 FPEVNGIVYLVDAYDKERFAESKRELDALLSDEELATVPFLILGNKIDAPYAASEDELRYALGL 145

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 6680718   23 VGLDAAGKTTILYKLKLGEIV----TTIPTIGFNVETVEY--KNISFTVWDVGGQDKIRPLW-----RHYFQNTQGLIFV 91
Cdd:cd00882   3 VGRGGVGKSSLLNALLGGEVGevsdVPGTTRDPDVYVKELdkGKVKLVLVDTPGLDEFGGLGreelaRLLLRGADLILLV 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   92 VDSNDRERVNEAREELMRMLAEDELRdavLLVFANKQDLPNAMNAAEItdKLGLHSLRHRNWYIQATCATSGDGLYEGLD 171
Cdd:cd00882  83 VDSTDRESEEDAKLLILRRLRKEGIP---IILVGNKIDLLEEREVEEL--LRLEELAKILGVPVFEVSAKTGEGVDELFE 157

                ....
gi 6680718  172 WLAN 175
Cdd:cd00882 158 KLIE 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 6680718   20 ILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETV---EYKNISFTVWDVGGQDKIRP-LWRHYFQNTQGLIFVVDSN 95
Cdd:cd04105   3 VLLLGPSDSGKTALFTKLTTGKVRSTVTSIEPNVASFysnSSKGKKLTLVDVPGHEKLRDkLLEYLKASLKAIVFVVDSA 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 6680718   96 DRER-VNEAREELMRMLAEDELRDAV--LLVFANKQDLPNAMNAAEITDKL 143
Cdd:cd04105  83 TFQKnIRDVAEFLYDILTDLEKIKNKipILIACNKQDLFTAKPAKKIKELL 133

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718    19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVE----TVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDS 94
Cdd:PLN03118  16 KILLIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKikqlTVGGKRLKLTIWDTAGQERFRTLTSSYYRNAQGIILVYDV 95

                 ....
gi 6680718    95 NDRE 98
Cdd:PLN03118  96 TRRE 99

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 6680718   19 RILMVGLDAAGKTTILYKLKLGEIVTTI-PTIG--FNVE--TVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVD 93
Cdd:cd01863   2 KILLIGDSGVGKSSLLLRFTDDTFDEDLsSTIGvdFKVKtvTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   94 SNDRERVnearEELMRMLAEDEL----RDAVLLVFANKQDLPNamnaAEITDKLGLHSLRHRNWYIQATCATSGDGLYEG 169
Cdd:cd01863  82 VTRRDTF----DNLDTWLNELDTystnPDAVKMLVGNKIDKEN----REVTREEGQKFARKHNMLFIETSAKTRIGVQQA 153

                ....*...
gi 6680718  170 LDWLANQL 177
Cdd:cd01863 154 FEELVEKI 161

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 6680718     19 RILMVGLDAAGKTTILYKLKLGEIVTT-IPTIG--FNVETVEY--KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVD 93
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEyIPTIGvdFYTKTIEVdgKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 6680718     94 SNDRERVNEAR---EELMRMLAEdelrDAVLLVFANKQDL 130
Cdd:pfam00071  81 ITSRDSFENVKkwvEEILRHADE----NVPIVLVGNKCDL 116

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 6680718   18 MRILMVGLDAAGKTTILYKLKLGEIVTT-IPTIG--FNVETVEY--KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 92
Cdd:cd01867   4 FKLLLIGDSGVGKSCLLLRFSEDSFNPSfISTIGidFKIRTIELdgKKIKLQIWDTAGQERFRTITTSYYRGAMGIILVY 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6680718   93 DSNDRERVNEAReELMRMLAEDELRDAVLLVFANKQDLPN 132
Cdd:cd01867  84 DITDEKSFENIK-NWMRNIDEHASEDVERMLVGNKCDMEE 122

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   19 RILMVGLDAAGKTTILYKLKLGEIVTT-IPTIG--FNVETVEY--KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVD 93
Cdd:cd01869   4 KLLLIGDSGVGKSCLLLRFADDTYTESyISTIGvdFKIRTIELdgKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYD 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718   94 SNDRERVNEARE---ELMRMLAEDELRdavLLVfANKQDLPNA-----MNAAEITDKLGL 145
Cdd:cd01869  84 VTDQESFNNVKQwlqEIDRYASENVNK---LLV-GNKCDLTDKkvvdyTEAKEFADELGI 139

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680718    19 RILMVGLDAAGKTTILYKLKLGEI-VTTIPTIGFNVET----VEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVD 93
Cdd:PLN03110  14 KIVLIGDSGVGKSNILSRFTRNEFcLESKSTIGVEFATrtlqVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGALLVYD 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 6680718    94 SNDRERVnearEELMRMLAedELRD-----AVLLVFANKQDLPNAMNAAE 138
Cdd:PLN03110  94 ITKRQTF----DNVQRWLR--ELRDhadsnIVIMMAGNKSDLNHLRSVAE 137

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. 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 6680718   18 MRILMVGLDAAGKTTILYKLKLG-----EIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 92
Cdd:cd04123   1 FKVVLLGEGRVGKTSLVLRYVENkfnekHESTTQASFFQKTVNIGGKRIDLAIWDTAGQERYHALGPIYYRDADGAILVY 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 6680718   93 DSNDR---ERVNEAREELMRMLAEdelrDAVLLVFANKQDLPN 132
Cdd:cd04123  81 DITDAdsfQKVKKWIKELKQMRGN----NISLVIVGNKIDLER 119

Signal recognition particle receptor subunit beta, a GTPase [Intracellular trafficking, secretion, and vesicular transport];