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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660387  80 TNEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEA----------------------------LQD 131
Cdd:pfam00025  22 LGEIVTTIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAvifvvdsadrdrieeakeelhallneeeLAD 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958660387 132 ASVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 189
Cdd:pfam00025 102 APLLILANKQDLPGAMSEAEIRELLGLHELKDRPWEIQGCSAVTGEGLDEGLDWLSNY 159

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 1958660387   82 EVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEA----------------------------LQDAS 133
Cdd:smart00177  37 ESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGlifvvdsndrdrideareelhrmlnedeLRDAV 116

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958660387  134 VLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 189
Cdd:smart00177 117 ILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNN 172

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 1958660387  79 LTNEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEA----------------------------LQ 130
Cdd:cd00878    20 KLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGlifvvdssdrerieeaknelhkllneeeLK 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958660387 131 DASVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 189
Cdd:cd00878   100 GAPLLILANKQDLPGALTESELIELLGLESIKGRRWHIQPCSAVTGDGLDEGLDWLIEQ 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 1958660387  81 NEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEA----------------------------LQDA 132
Cdd:cd04151    22 GEVVTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAiiyvvdstdrdrlgiskselhamleeeeLKDA 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958660387 133 SVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWM 186
Cdd:cd04151   102 VLLVFANKQDMPGALSEAEVAEKLGLSELKDRTWQIFKTSATKGEGLDEGMDWL 155

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 1958660387   82 EVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEA----------------------------LQDAS 133
Cdd:smart00177  37 ESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGlifvvdsndrdrideareelhrmlnedeLRDAV 116

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958660387  134 VLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 189
Cdd:smart00177 117 ILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNN 172

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 1958660387  78 SLTNEVVHTCS-TIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEA------------LQD------------- 131
Cdd:cd04154    33 KFNGEDISTISpTLGFNIKTLEYNGYKLNIWDVGGQKSLRSYWRNYFESTDAliwvvdssdrarLEDckrelqkllveer 112

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958660387 132 ---ASVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWM 186
Cdd:cd04154   113 lagATLLIFANKQDLPGALSPEEIREVLELDSIKSHHWRIFGCSAVTGENLLDGIDWL 170

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 1958660387  79 LTNEVV-HTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEALQ---DAS--------------------- 133
Cdd:cd04155    35 LASEDIsHITPTQGFNIKNVQADGFKLNVWDIGGQRKIRPYWRNYFENTDVLIyviDSAdrkrfeeagqelvelleeekl 114

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958660387 134 ----VLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQW 185
Cdd:cd04155   115 agvpVLVFANKQDLLTAAPAEEVAEALNLHDIRDRSWHIQACSAKTGEGLQEGMNW 170

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 1958660387  75 KTPSLTNEvvHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEAL---QDAS------------------ 133
Cdd:cd04157    20 KPSNAQSQ--NIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIifvIDSSdrlrmvvakdelelllnh 97

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958660387 134 ---------VLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 189
Cdd:cd04157    98 pdikhrripILFYANKMDLPDALTAVKITQLLCLENIKDKPWHIFASSALTGEGLDEGVDWLQAQ 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 1958660387  89 TIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYS----------------------------NAEALQDASVLIFANK 140
Cdd:cd04160    38 TVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAeshgviyvidstdrerfnesksafekviNNEALEGVPLLVLANK 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958660387 141 QDVKDSMTTAEISQFLTLSAIKDHP--WHIQGCCALTGEGLLAGLQWM 186
Cdd:cd04160   118 QDLPDALSVAEIKEVFDDCIALIGRrdCLVQPVSALEGEGVEEGIEWL 165

(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 1958660387  81 NEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEA----------------------------LQDA 132
Cdd:cd04158    22 DEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAvvfvidsshrdrvseahselaklltekeLRDA 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958660387 133 SVLIFANKQDVKDSMTTAEISQFLTLSAIK-DHPWHIQGCCALTGEGLLAGLQWMHSQ 189
Cdd:cd04158   102 LLLIFANKQDVAGALSVEEMTELLSLHKLCcGRSWYIQGCDARSGMGLYEGLDWLSRQ 159

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 1958660387  71 LHLDKTpsltNEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNA------------------------ 126
Cdd:cd00879    36 LHMLKD----DRLAQHVPTLHPTSEELTIGNVKFTTFDLGGHEQARRVWKDYFPEVdgivflvdaadperfqeskeelds 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958660387 127 ----EALQDASVLIFANKQDVKDSMTTAEISQFLTLSA------------IKDHPWHIQGCCALTGEGLLAGLQWM 186
Cdd:cd00879   112 llndEELANVPILILGNKIDKPGAVSEEELREALGLYGtttgkggvslkvSNIRPVEVFMCSVVKRQGYGEGFRWL 187

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660387  88 STIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEAL--------------------------QDASVLIFANKQ 141
Cdd:cd04162    30 PTTGFNSVAIPTQDAIMELLEIGGSQNLRKYWKRYLSGSQGLifvvdsadserlplarqelhqllqhpPDLPLVVLANKQ 109

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1958660387 142 DVKDSMTTAEISQFLTLSAI-KDHPWHIQGC 171
Cdd:cd04162   110 DLPAARSVQEIHKELELEPIaRGRRWILQGT 140