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 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDIiacAKQNITTAEISAREGTGL 80
Cdd:cd00878    72 FVVDSSDRERIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESI---KGRRWHIQPCSAVTGDGL 148

                  ....*...
gi 1331940733  81 AGVLAWLQ 88
Cdd:cd00878   149 DEGLDWLI 156

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 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDIiacAKQNITTAEISAREGTGL 80
Cdd:cd00878    72 FVVDSSDRERIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESI---KGRRWHIQPCSAVTGDGL 148

                  ....*...
gi 1331940733  81 AGVLAWLQ 88
Cdd:cd00878   149 DEGLDWLI 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
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1331940733    1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRL 56
Cdd:smart00178  90 YLVDAYDKERFAESKRELDALLSDEELATVPFLILGNKIDAPYAASEDELRYALGL 145

50S ribosomal subunit-associated GTPase HflX [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331940733   2 VMDASDP---TQLSASCvQLLGLLSAEqlaEASVLILFNKIDLpcyMSTEEMKSL-IRLPDIIAcakqnittaeISAREG 77
Cdd:COG2262   285 VVDASDPdfeEQIETVN-EVLEELGAD---DKPIILVFNKIDL---LDDEELERLrAGYPDAVF----------ISAKTG 347

                  ....*...
gi 1331940733  78 TGLAGVLA 85
Cdd:COG2262   348 EGIDELLE 355

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 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDIiacAKQNITTAEISAREGTGL 80
Cdd:cd00878    72 FVVDSSDRERIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESI---KGRRWHIQPCSAVTGDGL 148

                  ....*...
gi 1331940733  81 AGVLAWLQ 88
Cdd:cd00878   149 DEGLDWLI 156

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDIiacAKQNITTAEISAREGTGL 80
Cdd:pfam00025  73 FVVDSADRDRIEEAKEELHALLNEEELADAPLLILANKQDLPGAMSEAEIRELLGLHEL---KDRPWEIQGCSAVTGEGL 149

                  ....*..
gi 1331940733  81 AGVLAWL 87
Cdd:pfam00025 150 DEGLDWL 156

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 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLpDIIACAKQNITTAEISAREGTGL 80
Cdd:cd04160    80 YVIDSTDRERFNESKSAFEKVINNEALEGVPLLVLANKQDLPDALSVAEIKEVFDD-CIALIGRRDCLVQPVSALEGEGV 158

                  ....*..
gi 1331940733  81 AGVLAWL 87
Cdd:cd04160   159 EEGIEWL 165

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDII-------ACakqnittaeiS 73
Cdd:cd04155    88 YVIDSADRKRFEEAGQELVELLEEEKLAGVPVLVFANKQDLLTAAPAEEVAEALNLHDIRdrswhiqAC----------S 157

                          90
                  ....*....|....
gi 1331940733  74 AREGTGLAGVLAWL 87
Cdd:cd04155   158 AKTGEGLQEGMNWV 171

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 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDIiacAKQNITTAEISAREGTGL 80
Cdd:cd04151    72 YVVDSTDRDRLGISKSELHAMLEEEELKDAVLLVFANKQDMPGALSEAEVAEKLGLSEL---KDRTWQIFKTSATKGEGL 148

                  ....*..
gi 1331940733  81 AGVLAWL 87
Cdd:cd04151   149 DEGMDWL 155

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 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDiiaCAKQNITTAEISAREGTGL 80
Cdd:cd04150    73 FVVDSNDRERIGEAREELQRMLNEDELRDAVLLVFANKQDLPNAMSAAEVTDKLGLHS---LRNRNWYIQATCATSGDGL 149

                          90
                  ....*....|
gi 1331940733  81 AGVLAWLQAT 90
Cdd:cd04150   150 YEGLDWLSNN 159

ADP-ribosylation factor; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILFNKIDLPCYMSTEEMKSLIRLPDIiacAKQNITTAEISAREGTGL 80
Cdd:PLN00223   90 FVVDSNDRDRVVEARDELHRMLNEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSL---RQRHWYIQSTCATSGEGL 166

                          90
                  ....*....|
gi 1331940733  81 AGVLAWLQAT 90
Cdd:PLN00223  167 YEGLDWLSNN 176

hydrogenase nickel incorporation protein HypB; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1331940733  30 ASVLILFNKIDLPCYMSTEEMKSlirlpdiIACAKQ---NITTAEISAREGTGLAGVLAWLQATHRA 93
Cdd:PRK10463  231 AASLMLLNKVDLLPYLNFDVEKC-------IACAREvnpEIEIILISATSGEGMDQWLNWLETQRCA 290

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 1331940733   1 FVMDASDPTQLSASCVQLLGLLSAEQLAEASVLILF--NKIDLPCYMSTEEMKSLIRLpDIIACAKQNITTAeiSAREGT 78
Cdd:cd04157    74 FVIDSSDRLRMVVAKDELELLLNHPDIKHRRIPILFyaNKMDLPDALTAVKITQLLCL-ENIKDKPWHIFAS--SALTGE 150

                          90
                  ....*....|..
gi 1331940733  79 GLAGVLAWLQAT 90
Cdd:cd04157   151 GLDEGVDWLQAQ 162

GTPase RsgA; Reviewed

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1331940733  27 LAEA---SVLILFNKIDLpcYMSTEEMKSLIRLpdiiacaKQNI--TTAEISAREGTGLAGVLAWLQ 88
Cdd:PRK00098  106 LAEAngiKPIIVLNKIDL--LDDLEEARELLAL-------YRAIgyDVLELSAKEGEGLDELKPLLA 163

HflX GTPase family; HflX subfamily. A distinct conserved domain with a glycine-rich segment N-terminal of the GTPase domain characterizes the HflX subfamily. The E. coli HflX has been implicated in the control of the lambda cII repressor proteolysis, but the actual biological functions of these GTPases remain unclear. HflX is widespread, but not universally represented in all three superkingdoms.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331940733   2 VMDASDPT---QLSAScVQLLGLLSAEqlaEASVLILFNKIDLpcyMSTEEMKSLIR--LPDIIAcakqnittaeISARE 76
Cdd:cd01878   127 VVDASDPDreeQIETV-EEVLKELGAD---DIPIILVLNKIDL---LDDEELEERLRagRPDAVF----------ISAKT 189

                          90
                  ....*....|.
gi 1331940733  77 GTGLAGVLAWL 87
Cdd:cd01878   190 GEGLDLLKEAI 200

trmE is a tRNA modification GTPase; TrmE (MnmE, ThdF, MSS1) is a 3-domain protein found in bacteria and eukaryotes. It controls modification of the uridine at the wobble position (U34) of tRNAs that read codons ending with A or G in the mixed codon family boxes. TrmE contains a GTPase domain that forms a canonical Ras-like fold. It functions a molecular switch GTPase, and apparently uses a conformational change associated with GTP hydrolysis to promote the tRNA modification reaction, in which the conserved cysteine in the C-terminal domain is thought to function as a catalytic residue. In bacteria that are able to survive in extremely low pH conditions, TrmE regulates glutamate-dependent acid resistance.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331940733   1 FVMDASDPTQLSAscvqllgLLSAEQLAEASVLILFNKIDLpcyMSTEEMKSLIRLPDIIAcakqnittaeISAREGTGL 80
Cdd:cd04164    88 LVVDASEGLDEED-------LEILELPAKKPVIVVLNKSDL---LSDAEGISELNGKPIIA----------ISAKTGEGI 147