(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 4502197  406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGRSWYIQGCDARSGMGLYEGLDWLSRQL 565
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLCCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

                ....*....
gi 4502197  566 VAAGVLDVA 574
Cdd:cd04158 161 VAAGVLDVA 169

Modified RING finger, HC subclass (C3HC3D-type), found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a modified C3HC3D-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4502197   28 VLECGVCEDVFSLQGDKVPRLLLCGHTVCHDCLTRLPLHGRAIRCPFDRQ 77
Cdd:cd16645   1 VLECGVCEDVFSLQGDKVPRLLLCGHTVCHDCLTRLPLHGRAVRCPFDRQ 50

second B-box-type 2 zinc finger found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, two Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4502197  174 EKTMCSQHQVHAIEFVCLEEGCQTSPLMCCVCKEYGKHQGHKHSVLEPEA 223
Cdd:cd19774   1 EKPKCPIHPDHLIEFVCLEEDCQESPLMCIICKEYGKHQGHKHELLEEEA 50

(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 4502197  406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGRSWYIQGCDARSGMGLYEGLDWLSRQL 565
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLCCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

                ....*....
gi 4502197  566 VAAGVLDVA 574
Cdd:cd04158 161 VAAGVLDVA 169

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197   402 KMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDS 481
Cdd:PTZ00133  15 KKEVRILMVGLDAAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNLKFTMWDVGGQDKLRPLWRHYYQNTNGLIFVVDS 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197   482 SHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWL 561
Cdd:PTZ00133  95 NDRERIGDAREELERMLSEDELRDAVLLVFANKQDLPNAMSTTEVTEKLGLHSV-RQRNWYIQGCCATTAQGLYEGLDWL 173

                 ....
gi 4502197   562 SRQL 565
Cdd:PTZ00133 174 SANI 177

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197     226 IRASILDMAHCIRTFTEEISDYSRKLVGIVQHIEGgeqivedgigmahtehvpgTAENARSCIRAYFYDLHETLCRQEEM 305
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEE-------------------NAADVEAQIKAAFDELRNALNKRKKQ 61

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4502197     306 ALSVVDAHVREKLIWLRQQQEDMTILLSEVSAACLHCEKTLQQDDC-RVVLAKQEITRLLETLQKQ 370
Cdd:smart00502  62 LLEDLEEQKENKLKVLEQQLESLTQKQEKLSHAINFTEEALNSGDPtELLLSKKLIIERLQNLLKQ 127

first B-box-type 2 zinc finger found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, two Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4502197  123 SIIRCDEDEAHLASVYCTVCATHLCSECSQVTHSTKTLAKHRRVPLADKP 172
Cdd:cd19773   1 PSIPCDENEDHEATLYCTVCSTNLCEECFTSTHSTKTLSKHRRVPLSEKP 50

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  404 EIRVVTLGLDGAGKTTILFKLKQDEFMQP--IPTIGFNVETVEYK----NLKFTIWDVGG---KHKLRPLWKHYYLNTQA 474
Cdd:COG1100   3 EKKIVVVGTGGVGKTSLVNRLVGDIFSLEkyLSTNGVTIDKKELKldglDVDLVIWDTPGqdeFRETRQFYARQLTGASL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  475 VVFVVDSSHRD-RISEAhsELAKLLTEKELRDALLLIFaNKQDVAGALSVEEITELLSLHKLCCGRSWYIqgCDARSGMG 553
Cdd:COG1100  83 YLFVVDGTREEtLQSLY--ELLESLRRLGKKSPIILVL-NKIDLYDEEEIEDEERLKEALSEDNIVEVVA--TSAKTGEG 157

                .
gi 4502197  554 L 554
Cdd:COG1100 158 V 158

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 4502197     173 HEKTMCSQHQVHAIEFVCLEegCQTspLMCCVCKEYgKHQGHKHSVL 219
Cdd:smart00336   1 QRAPKCDSHGDEPAEFFCEE--CGA--LLCRTCDEA-EHRGHTVVLL 42

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4502197     29 LECGVCEDVFslqgdKVPRLLLCGHTVCHDCLTR-LPLHGRAIRCPFDRQVTDlgdsgvwgLKKNFALLELLERLQN 104
Cdd:TIGR00599  27 LRCHICKDFF-----DVPVLTSCSHTFCSLCIRRcLSNQPKCPLCRAEDQESK--------LRSNWLVSEIVESFKN 90

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 4502197    125 IRCDEDEAHLASVYCTVCATHLCSECSQVTHStktlaKHRRVPL 168
Cdd:pfam00643   4 RLCPEHEEEPLTLYCNDCQELLCEECSVGEHR-----GHTVVPL 42

(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 4502197  406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGRSWYIQGCDARSGMGLYEGLDWLSRQL 565
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLCCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

                ....*....
gi 4502197  566 VAAGVLDVA 574
Cdd:cd04158 161 VAAGVLDVA 169

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 4502197  406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd00878   1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRE 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4502197  486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKlCCGRSWYIQGCDARSGMGLYEGLDWLSRQ 564
Cdd:cd00878  81 RIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLES-IKGRRWHIQPCSAVTGDGLDEGLDWLIEQ 158

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 4502197  405 IRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHR 484
Cdd:cd04150   1 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  485 DRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQ 564
Cdd:cd04150  81 ERIGEAREELQRMLNEDELRDAVLLVFANKQDLPNAMSAAEVTDKLGLHSL-RNRNWYIQATCATSGDGLYEGLDWLSNN 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 4502197     402 KMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDS 481
Cdd:smart00177  11 NKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDS 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197     482 SHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWL 561
Cdd:smart00177  91 NDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSI-RDRNWYIQPTCATSGDGLYEGLTWL 169

                   ....
gi 4502197     562 SRQL 565
Cdd:smart00177 170 SNNL 173

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 4502197  406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04151   1 RILILGLDGAGKTTILYRLQVGEVVTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAIIYVVDSTDRD 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4502197  486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQ 564
Cdd:cd04151  81 RLGISKSELHAMLEEEELKDAVLLVFANKQDMPGALSEAEVAEKLGLSEL-KDRTWQIFKTSATKGEGLDEGMDWLVNT 158

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 4502197  401 PKMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVD 480
Cdd:cd04155  12 SRQEVRILLLGLDNAGKTTILKQLASEDISHITPTQGFNIKNVQADGFKLNVWDIGGQRKIRPYWRNYFENTDVLIYVID 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  481 SSHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDW 560
Cdd:cd04155  92 SADRKRFEEAGQELVELLEEEKLAGVPVLVFANKQDLLTAAPAEEVAEALNLHDI-RDRSWHIQACSAKTGEGLQEGMNW 170

                ....
gi 4502197  561 LSRQ 564
Cdd:cd04155 171 VCKN 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 4502197  404 EIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSH 483
Cdd:cd04154  14 EMRILMLGLDNAGKTTILKKFNGEDISTISPTLGFNIKTLEYNGYKLNIWDVGGQKSLRSYWRNYFESTDALIWVVDSSD 93

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4502197  484 RDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWL 561
Cdd:cd04154  94 RARLEDCKRELQKLLVEERLAGATLLIFANKQDLPGALSPEEIREVLELDSI-KSHHWRIFGCSAVTGENLLDGIDWL 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 4502197  407 VVTLGLDGAGKTTILFKLKQDEFM--QPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHR 484
Cdd:cd04157   2 ILVLGLDNSGKTTIINQLKPSNAQsqNIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDR 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  485 DRISEAHSELAKLLTEKEL--RDALLLIFANKQDVAGALSVEEITELLSLhKLCCGRSWYIQGCDARSGMGLYEGLDWLS 562
Cdd:cd04157  82 LRMVVAKDELELLLNHPDIkhRRIPILFYANKMDLPDALTAVKITQLLCL-ENIKDKPWHIFASSALTGEGLDEGVDWLQ 160

                ..
gi 4502197  563 RQ 564
Cdd:cd04157 161 AQ 162

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 4502197  402 KMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDS 481
Cdd:cd00879  17 KKEAKIVFLGLDNAGKTTLLHMLKDDRLAQHVPTLHPTSEELTIGNVKFTTFDLGGHEQARRVWKDYFPEVDGIVFLVDA 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  482 SHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLC---------CGRSWYIQG--CDARS 550
Cdd:cd00879  97 ADPERFQESKEELDSLLNDEELANVPILILGNKIDKPGAVSEEELREALGLYGTTtgkggvslkVSNIRPVEVfmCSVVK 176

                       170
                ....*....|....*
gi 4502197  551 GMGLYEGLDWLSRQL 565
Cdd:cd00879 177 RQGYGEGFRWLSQYL 191

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 4502197  404 EIRVVtlGLDGAGKTTILFKLKQDEFMQP-IPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSS 482
Cdd:cd04159   1 EITLV--GLQNSGKTTLVNVIASGQFSEDtIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAA 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  483 HRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLS 562
Cdd:cd04159  79 DREKLEVAKNELHDLLEKPSLEGIPLLVLGNKNDLPGALSVDELIEQMNLKSI-TDREVSCYSISAKEKTNIDIVLDWLI 157

                .
gi 4502197  563 R 563
Cdd:cd04159 158 K 158

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 4502197  407 VVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRDR 486
Cdd:cd04161   2 LLTVGLDNAGKTTLVSALQGEIPKKVAPTVGFTPTKLRLDKYEVCIFDLGGGANFRGIWVNYYAEAHGLVFVVDSSDDDR 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  487 ISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCC-GRSWY-IQGCDARSGMG------LYEGL 558
Cdd:cd04161  82 VQEVKEILRELLQHPRVSGKPILVLANKQDKKNALLGADVIEYLSLEKLVNeNKSLChIEPCSAIEGLGkkidpsIVEGL 161

                ...
gi 4502197  559 DWL 561
Cdd:cd04161 162 RWL 164

Modified RING finger, HC subclass (C3HC3D-type), found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a modified C3HC3D-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4502197   28 VLECGVCEDVFSLQGDKVPRLLLCGHTVCHDCLTRLPLHGRAIRCPFDRQ 77
Cdd:cd16645   1 VLECGVCEDVFSLQGDKVPRLLLCGHTVCHDCLTRLPLHGRAVRCPFDRQ 50

second B-box-type 2 zinc finger found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, two Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4502197  174 EKTMCSQHQVHAIEFVCLEEGCQTSPLMCCVCKEYGKHQGHKHSVLEPEA 223
Cdd:cd19774   1 EKPKCPIHPDHLIEFVCLEEDCQESPLMCIICKEYGKHQGHKHELLEEEA 50

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 4502197  408 VTLGLDGAGKTTILFKLKQDEFMQ----PIPTIGFNVE--TVEYKNLKFTIWDVGGKHKLRPLW-----KHYYLNTQAVV 476
Cdd:cd00882   1 VVVGRGGVGKSSLLNALLGGEVGEvsdvPGTTRDPDVYvkELDKGKVKLVLVDTPGLDEFGGLGreelaRLLLRGADLIL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502197  477 FVVDSSHRDRISEAHSELAKLLtekELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGRSWYiqgCDARSGMGLYE 556
Cdd:cd00882  81 LVVDSTDRESEEDAKLLILRRL---RKEGIPIILVGNKIDLLEEREVEELLRLEELAKILGVPVFE---VSAKTGEGVDE 154

                ....*
gi 4502197  557 GLDWL 561
Cdd:cd00882 155 LFEKL 159

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 4502197  405 IRVVTLGLDGAGKTTILFKLKQDEFMQPI-PTIG--FNVE--TVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVV 479
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTDDTFDEDLsSTIGvdFKVKtvTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVY 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 4502197  480 DSSHRDRISEAHSELAKLLTEKELRDALLLIFANKQD 516
Cdd:cd01863  81 DVTRRDTFDNLDTWLNELDTYSTNPDAVKMLVGNKID 117

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 4502197    404 EIRVVTLGLDGAGKTTILFKLKQDEFM--QPIPTIGFNVET--VEYKNL--KFTIWDVGGKHKLRPLWKHYYLNTQAVVF 477
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGNKGSitEYYPGTTRNYVTtvIEEDGKtyKFNLLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 4502197    478 VVD-SSHRDRISEahselAKLLTEKELRDAL-----LLIFANKQD 516
Cdd:TIGR00231  81 VFDiVILVLDVEE-----ILEKQTKEIIHHAdsgvpIILVGNKID 120