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 15208643 406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15208643 486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGRS 540
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLCCGRS 135

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 15208643  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 15208643 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 15208643 406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15208643 486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGRS 540
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLCCGRS 135

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15208643  402 KMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDS 481
Cdd:PTZ00133  15 KKEVRILMVGLDAAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNLKFTMWDVGGQDKLRPLWRHYYQNTNGLIFVVDS 94

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15208643  482 SHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKL---------CCGRS 540
Cdd:PTZ00133  95 NDRERIGDAREELERMLSEDELRDAVLLVFANKQDLPNAMSTTEVTEKLGLHSVrqrnwyiqgCCATT 162

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15208643    226 IRASILDMAHCIRTFTEEISDYSRKLVGIVQHIEGgeqivedgigmahtehvpgTAENARSCIRAYFYDLHETLCRQEEM 305
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEE-------------------NAADVEAQIKAAFDELRNALNKRKKQ 61

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15208643    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 15208643 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 15208643 404 EIRVVTLGLDGAGKTTILFKLKQDEFMQP--IPTIGFNVETVEYK----NLKFTIWDVGG---KHKLRPLWKHYYLNTQA 474
Cdd:COG1100   3 EKKIVVVGTGGVGKTSLVNRLVGDIFSLEkyLSTNGVTIDKKELKldglDVDLVIWDTPGqdeFRETRQFYARQLTGASL 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15208643 475 VVFVVDSSHRD-RISEAhsELAKLLTEKELRDALLLIFaNKQDVAGALSVEEITELLSL 532
Cdd:COG1100  83 YLFVVDGTREEtLQSLY--ELLESLRRLGKKSPIILVL-NKIDLYDEEEIEDEERLKEA 138

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 15208643    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 15208643    29 LECGVCEDVFslqgdKVPRLLLCGHTVCHDCLTR-LPLHGRAIRCPFDRQVTDlgdsgvwgLKKNFALLELLERLQN 104
Cdd:TIGR00599  27 LRCHICKDFF-----DVPVLTSCSHTFCSLCIRRcLSNQPKCPLCRAEDQESK--------LRSNWLVSEIVESFKN 90

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 15208643   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 15208643 406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04158   1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15208643 486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGRS 540
Cdd:cd04158  81 RVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKLCCGRS 135

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 15208643 406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd00878   1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRE 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15208643 486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKL---------CCGRS 540
Cdd:cd00878  81 RIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESIkgrrwhiqpCSAVT 144

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15208643  402 KMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDS 481
Cdd:PTZ00133  15 KKEVRILMVGLDAAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNLKFTMWDVGGQDKLRPLWRHYYQNTNGLIFVVDS 94

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15208643  482 SHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKL---------CCGRS 540
Cdd:PTZ00133  95 NDRERIGDAREELERMLSEDELRDAVLLVFANKQDLPNAMSTTEVTEKLGLHSVrqrnwyiqgCCATT 162

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 15208643    402 KMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDS 481
Cdd:smart00177  11 NKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDS 90

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 15208643    482 SHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKL 535
Cdd:smart00177  91 NDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSI 144

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 15208643 406 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHRD 485
Cdd:cd04151   1 RILILGLDGAGKTTILYRLQVGEVVTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAIIYVVDSTDRD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 15208643 486 RISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKL 535
Cdd:cd04151  81 RLGISKSELHAMLEEEELKDAVLLVFANKQDMPGALSEAEVAEKLGLSEL 130

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 15208643 401 PKMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVD 480
Cdd:cd04155  12 SRQEVRILLLGLDNAGKTTILKQLASEDISHITPTQGFNIKNVQADGFKLNVWDIGGQRKIRPYWRNYFENTDVLIYVID 91

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15208643 481 SSHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKL 535
Cdd:cd04155  92 SADRKRFEEAGQELVELLEEEKLAGVPVLVFANKQDLLTAAPAEEVAEALNLHDI 146

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 15208643 404 EIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSH 483
Cdd:cd04154  14 EMRILMLGLDNAGKTTILKKFNGEDISTISPTLGFNIKTLEYNGYKLNIWDVGGQKSLRSYWRNYFESTDALIWVVDSSD 93

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 15208643 484 RDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKL 535
Cdd:cd04154  94 RARLEDCKRELQKLLVEERLAGATLLIFANKQDLPGALSPEEIREVLELDSI 145

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 15208643 402 KMEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDS 481
Cdd:cd00879  17 KKEAKIVFLGLDNAGKTTLLHMLKDDRLAQHVPTLHPTSEELTIGNVKFTTFDLGGHEQARRVWKDYFPEVDGIVFLVDA 96

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15208643 482 SHRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCG 538
Cdd:cd00879  97 ADPERFQESKEELDSLLNDEELANVPILILGNKIDKPGAVSEEELREALGLYGTTTG 153

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 15208643 407 VVTLGLDGAGKTTILFKLKQDEFM--QPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSHR 484
Cdd:cd04157   2 ILVLGLDNSGKTTIINQLKPSNAQsqNIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDR 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 15208643 485 DRISEAHSELAKLLTEKEL--RDALLLIFANKQDVAGALSVEEITELLSLHKL 535
Cdd:cd04157  82 LRMVVAKDELELLLNHPDIkhRRIPILFYANKMDLPDALTAVKITQLLCLENI 134

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 15208643 404 EIRVVtlGLDGAGKTTILFKLKQDEFMQP-IPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSS 482
Cdd:cd04159   1 EITLV--GLQNSGKTTLVNVIASGQFSEDtIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAA 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15208643 483 HRDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLcCGR--SCFS 543
Cdd:cd04159  79 DREKLEVAKNELHDLLEKPSLEGIPLLVLGNKNDLPGALSVDELIEQMNLKSI-TDRevSCYS 140

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 15208643    404 EIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVVDSSH 483
Cdd:smart00178  17 HAKILFLGLDNAGKTTLLHMLKNDRLAQHQPTQHPTSEELAIGNIKFTTFDLGGHQQARRLWKDYFPEVNGIVYLVDAYD 96

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 15208643    484 RDRISEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEITELLSLHKLCCGR 539
Cdd:smart00178  97 KERFAESKRELDALLSDEELATVPFLILGNKIDAPYAASEDELRYALGLTNTTTGK 152

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 15208643  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 15208643 174 EKTMCSQHQVHAIEFVCLEEGCQTSPLMCCVCKEYGKHQGHKHSVLEPEA 223
Cdd:cd19774   1 EKPKCPIHPDHLIEFVCLEEDCQESPLMCIICKEYGKHQGHKHELLEEEA 50

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15208643 404 EIRVVTLGLDGAGKTTILFKLKQDEFMQP--IPTIGFNVETVEYK----NLKFTIWDVGG---KHKLRPLWKHYYLNTQA 474
Cdd:COG1100   3 EKKIVVVGTGGVGKTSLVNRLVGDIFSLEkyLSTNGVTIDKKELKldglDVDLVIWDTPGqdeFRETRQFYARQLTGASL 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15208643 475 VVFVVDSSHRD-RISEAhsELAKLLTEKELRDALLLIFaNKQDVAGALSVEEITELLSL 532
Cdd:COG1100  83 YLFVVDGTREEtLQSLY--ELLESLRRLGKKSPIILVL-NKIDLYDEEEIEDEERLKEA 138

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. 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 15208643 404 EIRVVTLGLDGAGKTTILFKLKQDEFMQPI-PTIG--FNVETVEY--KNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFV 478
Cdd:cd01860   1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQeSTIGaaFLTQTVNLddTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVV 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15208643 479 VDSSHRDRISEAHSELakllteKELR-----DALLLIFANKQDVAG--ALSVEEITELLSLHKL 535
Cdd:cd01860  81 YDITSEESFEKAKSWV------KELQehgppNIVIALAGNKADLESkrQVSTEEAQEYADENGL 138

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 15208643 408 VTLGLDGAGKTTILFKLKQDEFMQ----PIPTIGFNVETVEY--KNLKFTIWDVGGKHKLRPLW-----KHYYLNTQAVV 476
Cdd:cd00882   1 VVVGRGGVGKSSLLNALLGGEVGEvsdvPGTTRDPDVYVKELdkGKVKLVLVDTPGLDEFGGLGreelaRLLLRGADLIL 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15208643 477 FVVDSSHRDRISEAHSELAKLLtekELRDALLLIFANKQDVAGALSVEEITELLSLHKL 535
Cdd:cd00882  81 LVVDSTDRESEEDAKLLILRRL---RKEGIPIILVGNKIDLLEEREVEELLRLEELAKI 136

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15208643  403 MEIRVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVE----TVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFV 478
Cdd:PLN03118  13 LSFKILLIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKikqlTVGGKRLKLTIWDTAGQERFRTLTSSYYRNAQGIILV 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 15208643  479 VDSSHRDRISEAHSELAKlltEKEL----RDALLLIFANKQD 516
Cdd:PLN03118  93 YDVTRRETFTNLSDVWGK---EVELystnQDCVKMLVGNKVD 131

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 15208643  29 LECGVCEDVFSlQGDKVPRLLLCGHTVCHDCLTRLP--LHGRAIRCPFDRQV 78
Cdd:cd16587   1 LECPICLESFD-EGQLRPKLLHCGHTICEQCLEKLLasLSINGVRCPFCRKV 51

Modified RING finger, HC subclass (C3HC3D-type), found in Caenorhabditis elegans putative GTP-binding protein trim-23 homolog (arc-1) and similar proteins; arc-1, also called RING-type E3 ubiquitin transferase arc-1, is an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. arc-1 contains a modified C3HC3D-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 15208643  29 LECGVCEDVFSLQGD-KVPRLLL-CGHTVCHDCL-TRLPLHGRAIRCPFDRQVT 79
Cdd:cd23124   2 LECGICQQEYSADDPlLIPRILTeCGHTICTNCAgTILGQSSGSIFCPFDRIVT 55

RING finger, HC subclass, found in malin and similar proteins; Malin ("mal" for seizure in French), also known as NHL repeat-containing protein 1 (NHLRC1), or EPM2B, is a nuclear E3 ubiquitin-protein ligase that ubiquitinates and promotes the degradation of laforin (EPM2A encoding protein phosphatase). Malin and laforin operate as a functional complex that play key roles in regulating cellular functions such as glycogen metabolism, unfolded cellular stress response, and proteolytic processes. They act as pro-survival factors that negatively regulate the Hipk2-p53 cell death pathway. They also negatively regulate cellular glucose uptake by preventing plasma membrane targeting of glucose transporters. Moreover, they degrade polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase. Furthermore, they, together with Hsp70, form a new functional complex that suppress the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system. Defects in either malin or laforin may cause Lafora disease (LD), a fatal form of teenage-onset autosomal recessive progressive myoclonus epilepsy. In addition, malin may have function, independent of laforin, in lysosomal biogenesis and/or lysosomal glycogen disposal. Malin contains six NHL-repeat protein-protein interaction domains and a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 15208643  29 LECGVCEDVFSLQGDKVPRLLLCGHTVCHDCLTRL--PLHgRAIRCPFDRQVT 79
Cdd:cd16516   1 LECKVCFEKYSHQQEHRPRNLPCGHVLCRECVTALahPRR-SKLECPFCRKAC 52