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 194382070     5 FANLFKGLFGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQN 84
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070    85 TQGLIFVVDSNDRERVNEAREELMRML-------------------------AEITDKLGLHSLRHRNWYIQATCATSGD 139
Cdd:smart00177  81 TQGLIFVVDSNDRDRIDEAREELHRMLnedelrdavilvfankqdlpdamkaAEITEKLGLHSIRDRNWYIQPTCATSGD 160

                          170
                   ....*....|....*
gi 194382070   140 GLYEGLDWLSNQLRN 154
Cdd:smart00177 161 GLYEGLTWLSNNLKN 175

ARF-like small GTPases; ARF, ADP-ribosylation factor; Ras homologues involved in vesicular transport. Activator of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. ARFs are N-terminally myristoylated. Contains ATP/GTP-binding motif (P-loop).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070     5 FANLFKGLFGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQN 84
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070    85 TQGLIFVVDSNDRERVNEAREELMRML-------------------------AEITDKLGLHSLRHRNWYIQATCATSGD 139
Cdd:smart00177  81 TQGLIFVVDSNDRDRIDEAREELHRMLnedelrdavilvfankqdlpdamkaAEITEKLGLHSIRDRNWYIQPTCATSGD 160

                          170
                   ....*....|....*
gi 194382070   140 GLYEGLDWLSNQLRN 154
Cdd:smart00177 161 GLYEGLTWLSNNLKN 175

ADP-ribosylation factor-1 (Arf1) and ADP-ribosylation factor-5 (Arf5); The Arf1-Arf5-like subfamily contains Arf1, Arf2, Arf3, Arf4, Arf5, and related proteins. Arfs1-5 are soluble proteins that are crucial for assembling coat proteins during vesicle formation. Each contains an N-terminal myristoylated amphipathic helix that is folded into the protein in the GDP-bound state. GDP/GTP exchange exposes the helix, which anchors to the membrane. Following GTP hydrolysis, the helix dissociates from the membrane and folds back into the protein. A general feature of Arf1-5 signaling may be the cooperation of two Arfs at the same site. Arfs1-5 are generally considered to be interchangeable in function and location, but some specific functions have been assigned. Arf1 localizes to the early/cis-Golgi, where it is activated by GBF1 and recruits the coat protein COPI. It also localizes to the trans-Golgi network (TGN), where it is activated by BIG1/BIG2 and recruits the AP1, AP3, AP4, and GGA proteins. Humans, but not rodents and other lower eukaryotes, lack Arf2. Human Arf3 shares 96% sequence identity with Arf1 and is believed to generally function interchangeably with Arf1. Human Arf4 in the activated (GTP-bound) state has been shown to interact with the cytoplasmic domain of epidermal growth factor receptor (EGFR) and mediate the EGF-dependent activation of phospholipase D2 (PLD2), leading to activation of the activator protein 1 (AP-1) transcription factor. Arf4 has also been shown to recognize the C-terminal sorting signal of rhodopsin and regulate its incorporation into specialized post-Golgi rhodopsin transport carriers (RTCs). There is some evidence that Arf5 functions at the early-Golgi and the trans-Golgi to affect Golgi-associated alpha-adaptin homology Arf-binding proteins (GGAs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  18 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 97
Cdd:cd04150    1 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 194382070  98 ERVNEAREELMRML-------------------------AEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLSNQ 151
Cdd:cd04150   81 ERIGEAREELQRMLnedelrdavllvfankqdlpnamsaAEVTDKLGLHSLRNRNWYIQATCATSGDGLYEGLDWLSNN 159

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   17 EMRILMVGLDAAGKTTILYKLKLGE--IVTTIPTIGFNVET--VEYKNIS--FTVWDVGGQDKIRPLWRHYFQNTQGLIF 90
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGNKgsITEYYPGTTRNYVTtvIEEDGKTykFNLLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100
                  ....*....|....*....|....*.
gi 194382070   91 VVDSNdrERVNEAREELMRMLAEITD 116
Cdd:TIGR00231  81 VFDIV--ILVLDVEEILEKQTKEIIH 104

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 194382070     5 FANLFKGLFGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQN 84
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070    85 TQGLIFVVDSNDRERVNEAREELMRML-------------------------AEITDKLGLHSLRHRNWYIQATCATSGD 139
Cdd:smart00177  81 TQGLIFVVDSNDRDRIDEAREELHRMLnedelrdavilvfankqdlpdamkaAEITEKLGLHSIRDRNWYIQPTCATSGD 160

                          170
                   ....*....|....*
gi 194382070   140 GLYEGLDWLSNQLRN 154
Cdd:smart00177 161 GLYEGLTWLSNNLKN 175

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   1 MGNIFANLFKGLFGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRH 80
Cdd:PTZ00133   1 MGLWLSSAFKSLFGKKEVRILMVGLDAAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNLKFTMWDVGGQDKLRPLWRH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  81 YFQNTQGLIFVVDSNDRERVNEAREELMRMLAE-------------------------ITDKLGLHSLRHRNWYIQATCA 135
Cdd:PTZ00133  81 YYQNTNGLIFVVDSNDRERIGDAREELERMLSEdelrdavllvfankqdlpnamstteVTEKLGLHSVRQRNWYIQGCCA 160

                        170       180
                 ....*....|....*....|.
gi 194382070 136 TSGDGLYEGLDWLSNQLRNQK 156
Cdd:PTZ00133 161 TTAQGLYEGLDWLSANIKKSM 181

ADP-ribosylation factor(Arf)/Arf-like (Arl) small GTPases; Arf (ADP-ribosylation factor)/Arl (Arf-like) small GTPases. Arf proteins are activators of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. Arfs are N-terminally myristoylated. Members of the Arf family are regulators of vesicle formation in intracellular traffic that interact reversibly with membranes of the secretory and endocytic compartments in a GTP-dependent manner. They depart from other small GTP-binding proteins by a unique structural device, interswitch toggle, that implements front-back communication from N-terminus to the nucleotide binding site. Arf-like (Arl) proteins are close relatives of the Arf, but only Arl1 has been shown to function in membrane traffic like the Arf proteins. Arl2 has an unrelated function in the folding of native tubulin, and Arl4 may function in the nucleus. Most other Arf family proteins are so far relatively poorly characterized. Thus, despite their significant sequence homologies, Arf family proteins may regulate unrelated functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 98
Cdd:cd00878    1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRE 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 194382070  99 RVNEAREELMRML-------------------------AEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLSNQ 151
Cdd:cd00878   81 RIEEAKNELHKLLneeelkgapllilankqdlpgalteSELIELLGLESIKGRRWHIQPCSAVTGDGLDEGLDWLIEQ 158

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   18 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 97
Cdd:pfam00025   1 MRILILGLDNAGKTTILYKLKLGEIVTTIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   98 ERVNEAREELMRML-------------------------AEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLSNQL 152
Cdd:pfam00025  81 DRIEEAKEELHALLneeeladapllilankqdlpgamseAEIRELLGLHELKDRPWEIQGCSAVTGEGLDEGLDWLSNYI 160

Arf-like 5 (Arl5) and 8 (Arl8) GTPases; Arl5/Arl8 subfamily. Arl5 (Arf-like 5) and Arl8, like Arl4 and Arl7, are localized to the nucleus and nucleolus. Arl5 is developmentally regulated during embryogenesis in mice. Human Arl5 interacts with the heterochromatin protein 1-alpha (HP1alpha), a nonhistone chromosomal protein that is associated with heterochromatin and telomeres, and prevents telomere fusion. Arl5 may also play a role in embryonic nuclear dynamics and/or signaling cascades. Arl8 was identified from a fetal cartilage cDNA library. It is found in brain, heart, lung, cartilage, and kidney. No function has been assigned for Arl8 to date.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   3 NIFANLFKGLFGKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYF 82
Cdd:cd04153    1 LLFSSLWSLFFPRKEYKVIIVGLDNAGKTTILYQFLLGEVVHTSPTIGSNVEEIVYKNIRFLMWDIGGQESLRSSWNTYY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  83 QNTQGLIFVVDSNDRERVNEAREELMRML-------------------------AEITDKLGLHSLRHRNWYIQATCATS 137
Cdd:cd04153   81 TNTDAVILVIDSTDRERLPLTKEELYKMLahedlrkavllvlankqdlkgamtpAEISESLGLTSIRDHTWHIQGCCALT 160

                        170
                 ....*....|....
gi 194382070 138 GDGLYEGLDWLSNQ 151
Cdd:cd04153  161 GEGLPEGLDWIASR 174

Arf-like tumor suppressor gene 1 (ARLTS1 or Arl11); ARLTS1 (Arf-like tumor suppressor gene 1), also known as Arl11, is a member of the Arf family of small GTPases that is believed to play a major role in apoptotic signaling. ARLTS1 is widely expressed and functions as a tumor suppressor gene in several human cancers. ARLTS1 is a low-penetrance suppressor that accounts for a small percentage of familial melanoma or familial chronic lymphocytic leukemia (CLL). ARLTS1 inactivation seems to occur most frequently through biallelic down-regulation by hypermethylation of the promoter. In breast cancer, ARLTS1 alterations were typically a combination of a hypomorphic polymorphism plus loss of heterozygosity. In a case of thyroid adenoma, ARLTS1 alterations were polymorphism plus promoter hypermethylation. The nonsense polymorphism Trp149Stop occurs with significantly greater frequency in familial cancer cases than in sporadic cancer cases, and the Cys148Arg polymorphism is associated with an increase in high-risk familial breast cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEY-KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 97
Cdd:cd04156    1 QVLLLGLDSAGKSTLLYKLKHAELVTTIPTVGFNVEMLQLeKHLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVDSSDE 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 194382070  98 ERVNEAREELMRML-------------------------AEITDKLGLHSL-RHRNWYIQATCATSGDGLYEGL 145
Cdd:cd04156   81 ARLDESQKELKHILknehikgvpvvllankqdlpgaltaEEITRRFKLKKYcSDRDWYVQPCSAVTGEGLAEAF 154

(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 194382070  19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 98
Cdd:cd04158    1 RVVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  99 RVNEAREELMRMLA-------------------------EITDKLGLHSL-RHRNWYIQATCATSGDGLYEGLDWLSNQL 152
Cdd:cd04158   81 RVSEAHSELAKLLTekelrdalllifankqdvagalsveEMTELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

Arf-like 6 (Arl6) GTPase; Arl6 (Arf-like 6) forms a subfamily of the Arf family of small GTPases. Arl6 expression is limited to the brain and kidney in adult mice, but it is expressed in the neural plate and somites during embryogenesis, suggesting a possible role for Arl6 in early development. Arl6 is also believed to have a role in cilia or flagella function. Several proteins have been identified that bind Arl6, including Arl6 interacting protein (Arl6ip), and SEC61beta, a subunit of the heterotrimeric conducting channel SEC61p. Based on Arl6 binding to these effectors, Arl6 is also proposed to play a role in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. At least three specific homozygous Arl6 mutations in humans have been found to cause Bardet-Biedl syndrome, a disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  20 ILMVGLDAAGKTTILYKLKLGEIVTTI--PTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 97
Cdd:cd04157    2 ILVLGLDNSGKTTIINQLKPSNAQSQNivPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  98 ERVNEAREELMRML---------------------------AEITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWLSN 150
Cdd:cd04157   82 LRMVVAKDELELLLnhpdikhrripilfyankmdlpdaltaVKITQLLCLENIKDKPWHIFASSALTGEGLDEGVDWLQA 161

                 .
gi 194382070 151 Q 151
Cdd:cd04157  162 Q 162

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  20 ILMVGLDAAGKTTILYKLK-----------LGEIVttiPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGL 88
Cdd:cd04160    2 VLILGLDNAGKTTFLEQTKtkfsknykglnPSKIT---PTVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAESHGV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  89 IFVVDSNDRERVNEAREELMRMLA----------------EITDKLGL-----------HSLRHRNWYIQATCATSGDGL 141
Cdd:cd04160   79 IYVIDSTDRERFNESKSAFEKVINnealegvpllvlankqDLPDALSVaeikevfddciALIGRRDCLVQPVSALEGEGV 158

                 ....*...
gi 194382070 142 YEGLDWLS 149
Cdd:cd04160  159 EEGIEWLV 166

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 194382070  20 ILMVGLDAAGKTTILYKLKLGE-IVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE 98
Cdd:cd04159    2 ITLVGLQNSGKTTLVNVIASGQfSEDTIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADRE 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 194382070  99 RVNEAREELMRMLA-------------------------EITDKLGLHSLRHRNWYIQATCATSGDGLYEGLDWL 148
Cdd:cd04159   82 KLEVAKNELHDLLEkpslegipllvlgnkndlpgalsvdELIEQMNLKSITDREVSCYSISAKEKTNIDIVLDWL 156

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 194382070  20 ILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRER 99
Cdd:cd04161    2 LLTVGLDNAGKTTLVSALQGEIPKKVAPTVGFTPTKLRLDKYEVCIFDLGGGANFRGIWVNYYAEAHGLVFVVDSSDDDR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070 100 VNEAREELMRML-------------------------AEITDKLGLHSL--RHRNWYIQATCATSGDG-------LYEGL 145
Cdd:cd04161   82 VQEVKEILRELLqhprvsgkpilvlankqdkknallgADVIEYLSLEKLvnENKSLCHIEPCSAIEGLgkkidpsIVEGL 161

                 ...
gi 194382070 146 DWL 148
Cdd:cd04161  162 RWL 164

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVE----TVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDS 94
Cdd:PLN03118  16 KILLIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKikqlTVGGKRLKLTIWDTAGQERFRTLTSSYYRNAQGIILVYDV 95

                 ....
gi 194382070  95 NDRE 98
Cdd:PLN03118  96 TRRE 99

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. 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 mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. 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. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  18 MRILMVGlDAA-GKTTILYKLKLGE-IVTTIPTIG--FNVETVEY--KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFV 91
Cdd:cd00154    1 FKIVLIG-DSGvGKTSLLLRFVDNKfSENYKSTIGvdFKSKTIEVdgKKVKLQIWDTAGQERFRSITSSYYRGAHGAILV 79

                 ....*..
gi 194382070  92 VDSNDRE 98
Cdd:cd00154   80 YDVTNRE 86

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   19 RILMVGLDAAGKTTILYKLKLGE-IVTTIPTIGFNVETVEY-------KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIF 90
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTfDPKYKSTIGVDFKTKTVlenddngKKIKLNIWDTAGQERFRSLHPFYYRGAAAALL 80

                          90
                  ....*....|..
gi 194382070   91 VVDSNDRERVNE 102
Cdd:pfam08477  81 VYDSRTFSNLKY 92

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   19 RILMVGLDAAGKTTILYKLKLGEIVTT-IPTIG--FNVETVEY--KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVD 93
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEyIPTIGvdFYTKTIEVdgKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100
                  ....*....|....*....|
gi 194382070   94 SNDRERVNEAR---EELMRM 110
Cdd:pfam00071  81 ITSRDSFENVKkwvEEILRH 100

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  18 MRILMVGLDAAGKTTILYKLKLGEIVTT-IPTIG--FNVETVEY--KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 92
Cdd:cd01867    4 FKLLLIGDSGVGKSCLLLRFSEDSFNPSfISTIGidFKIRTIELdgKKIKLQIWDTAGQERFRTITTSYYRGAMGIILVY 83

                         90
                 ....*....|..
gi 194382070  93 DSNDRERVNEAR 104
Cdd:cd01867   84 DITDEKSFENIK 95

G-protein alpha subunit; G proteins couple receptors of extracellular signals to intracellular signaling pathways. The G protein alpha subunit binds guanyl nucleotide and is a weak GTPase. A set of residues that are unique to G-alpha as compared to its ancestor the Arf-like family form a ring of residues centered on the nucleotide binding site. A Ggamma is found fused to an inactive Galpha in the Dictyostelium protein gbqA.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 194382070   46 IPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 92
Cdd:pfam00503 152 VKTTGIIETKFEFKGLKFRLFDVGGQRSERKKWIHCFEDVTAIIFVV 198

Signal recognition particle receptor beta subunit; The beta subunit of the signal recognition particle receptor (SRP) is a transmembrane GTPase which anchors the alpha subunit to the endoplasmic reticulum membrane.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   19 RILMVGLDAAGKTTILYKLKLGEIVTTIPTI--GFNVETVEYKNISFTVWDVGGQDKIRP--LWRHYFQ-NTQGLIFVVD 93
Cdd:pfam09439   5 AVIIAGLCDSGKTSLFTLLTTDSVRPTVTSQepSAAYRYMLNKGNSFTLIDFPGHVKLRYklLETLKDSsSLKGIVFVVD 84

                          90       100
                  ....*....|....*....|.
gi 194382070   94 SN-DRERVNEAREELMRMLAE 113
Cdd:pfam09439  85 STiFPKEVTDTAEFLYDILSI 105

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. 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 194382070  19 RILMVGLDAAGKTTILYKLKLGEIV-TTIPTIG--FNVETVEY--KNISFTVWDVGGQDKIR-PLWRHYFQNTQGLIFVV 92
Cdd:cd04115    4 KIIVIGDSNVGKTCLTYRFCAGRFPeRTEATIGvdFRERTVEIdgERIKVQLWDTAGQERFRkSMVQHYYRNVHAVVFVY 83

                 .
gi 194382070  93 D 93
Cdd:cd04115   84 D 84

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  19 RILMVGLDAAGKTTILYKLKLGEIV-TTIPTIGFN-----VETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 92
Cdd:cd04111    4 RLIVIGDSTVGKSSLLKRFTEGRFAeVSDPTVGVDffsrlIEIEPGVRIKLQLWDTAGQERFRSITRSYYRNSVGVLLVF 83

                 ....*.
gi 194382070  93 DSNDRE 98
Cdd:cd04111   84 DITNRE 89

Ras homology family 2 (Rho2) of small guanosine triphosphatases (GTPases); Rho2 is a fungal GTPase that plays a role in cell morphogenesis, control of cell wall integrity, control of growth polarity, and maintenance of growth direction. Rho2 activates the protein kinase C homolog Pck2, and Pck2 controls Mok1, the major (1-3) alpha-D-glucan synthase. Together with Rho1 (RhoA), Rho2 regulates the construction of the cell wall. Unlike Rho1, Rho2 is not an essential protein, but its overexpression is lethal. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for proper intracellular localization via membrane attachment. As with other Rho family GTPases, the GDP/GTP cycling is regulated by GEFs (guanine nucleotide exchange factors), GAPs (GTPase-activating proteins) and GDIs (guanine nucleotide dissociation inhibitors).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070  19 RILMVGLDAAGKTTILYKLKLGEIVTT-IPTIGFNVET---VEYKNISFTVWDVGGQ---DKIRPLwrHYFQNTQGLI-F 90
Cdd:cd04129    3 KLVIVGDGACGKTSLLYVFTLGEFPEEyHPTVFENYVTdcrVDGKPVQLALWDTAGQeeyERLRPL--SYSKAHVILIgF 80

                 ....*.
gi 194382070  91 VVDSND 96
Cdd:cd04129   81 AIDTPD 86

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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 194382070  19 RILMVGLDAAGKTTILYKLK----LGEIVTTIpTIGFNVETV--EYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 92
Cdd:cd01865    3 KLLIIGNSSVGKTSFLFRYAddsfTSAFVSTV-GIDFKVKTVyrNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILMY 81

                         90
                 ....*....|...
gi 194382070  93 DSNDRERVNEARE 105
Cdd:cd01865   82 DITNEESFNAVQD 94

Rab GTPase family 30 (Rab30); Rab30 subfamily. Rab30 appears to be associated with the Golgi stack. It is expressed in a wide variety of tissue types and in humans maps to chromosome 11. 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 194382070  19 RILMVGLDAAGKTTILYKLKLGeivtTIP-----TIG--FNVETVEYKN--ISFTVWDVGGQDKIRPLWRHYFQNTQGLI 89
Cdd:cd04114    9 KIVLIGNAGVGKTCLVRRFTQG----LFPpgqgaTIGvdFMIKTVEIKGekIKLQIWDTAGQERFRSITQSYYRSANALI 84

                 ....
gi 194382070  90 FVVD 93
Cdd:cd04114   85 LTYD 88

G protein alpha subunit; Subunit of G proteins that contains the guanine nucleotide binding site

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 194382070    46 IPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV-----DSNDRERVNEAR-EELMRMLAEI 114
Cdd:smart00275 169 VPTTGIQETAFIVKKLFFRMFDVGGQRSERKKWIHCFDNVTAIIFCValseyDQVLEEDESTNRmQESLNLFESI 243

Gtr1/RagA G protein conserved region; GTR1 was first identified in S. cerevisiae as a suppressor of a mutation in RCC1. Biochemical analysis revealed that Gtr1 is in fact a G protein of the Ras family. The RagA/B proteins are the human homologs of Gtr1. Included in this family is the human Rag C, a novel protein that has been shown to interact with RagA/B.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 194382070   19 RILMVGLDAAGKTT----ILYKLKLGEIVTTIPTIGFNVETVE-YKNISFTVWDVGGQDKIRPLWRHY-----FQNTQGL 88
Cdd:pfam04670   1 KVLLMGLSGSGKSSmrsvIFSNYSPRDTLRLGATIDVEHSHVRfLGNLVLNLWDCGGQDDFFDNYLTFqkehiFSNVGVL 80

                          90
                  ....*....|
gi 194382070   89 IFVVDSNDRE 98
Cdd:pfam04670  81 IYVFDVQSRE 90