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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22759382    25 LHVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQctlgkAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVI 104
Cdd:pfam00025   1 MRILILGLDNAGKTTILYKLKLGEIVTTIPTIGFNVETVT-----YKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVV 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 22759382   105 DSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNEL 160
Cdd:pfam00025  76 DSADRDRIEEAKEELHALLNEEELADAPLLILANKQDLPGAMSEAEIRELLGLHEL 131

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22759382   25 LHVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQctlgkAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVI 104
Cdd:PTZ00133  18 VRILMVGLDAAGKTTILYKLKLGEVVTTIPTIGFNVETVE-----YKNLKFTMWDVGGQDKLRPLWRHYYQNTNGLIFVV 92

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 22759382  105 DSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNELYN 162
Cdd:PTZ00133  93 DSNDRERIGDAREELERMLSEDELRDAVLLVFANKQDLPNAMSTTEVTEKLGLHSVRQ 150

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22759382  27 VVMLGLDSAGKTT---ALYRLKFDQYlNTVPTIGFNCEKVQCTLgKAKGVHFLVWDVGGQEKLRPLWRSYTRC---TDGI 100
Cdd:COG1100   6 IVVVGTGGVGKTSlvnRLVGDIFSLE-KYLSTNGVTIDKKELKL-DGLDVDLVIWDTPGQDEFRETRQFYARQltgASLY 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22759382 101 LFVIDSVDTERMEEAKMELMRTAKCpdNQGVPVLILANKQDLPNACGAMELEKLLGLNELYNPVPNI 167
Cdd:COG1100  84 LFVVDGTREETLQSLYELLESLRRL--GKKSPIILVLNKIDLYDEEEIEDEERLKEALSEDNIVEVV 148

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 22759382  26 HVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVqctlgKAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVID 105
Cdd:cd00878   1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETV-----EYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVD 75

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 22759382 106 SVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNELYN 162
Cdd:cd00878  76 SSDRERIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLESIKG 132

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 22759382  25 LHVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQctlgkAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVI 104
Cdd:cd04150   1 MRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVE-----YKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVV 75

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 22759382 105 DSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNELYN 162
Cdd:cd04150  76 DSNDRERIGEAREELQRMLNEDELRDAVLLVFANKQDLPNAMSAAEVTDKLGLHSLRN 133

ADP ribosylation factor 6 (Arf6); Arf6 subfamily. Arf6 (ADP ribosylation factor 6) proteins localize to the plasma membrane, where they perform a wide variety of functions. In its active, GTP-bound form, Arf6 is involved in cell spreading, Rac-induced formation of plasma membrane ruffles, cell migration, wound healing, and Fc-mediated phagocytosis. Arf6 appears to change the actin structure at the plasma membrane by activating Rac, a Rho family protein involved in membrane ruffling. Arf6 is required for and enhances Rac formation of ruffles. Arf6 can regulate dendritic branching in hippocampal neurons, and in yeast it localizes to the growing bud, where it plays a role in polarized growth and bud site selection. In leukocytes, Arf6 is required for chemokine-stimulated migration across endothelial cells. Arf6 also plays a role in down-regulation of beta2-adrenergic receptors and luteinizing hormone receptors by facilitating the release of sequestered arrestin to allow endocytosis. Arf6 is believed to function at multiple sites on the plasma membrane through interaction with a specific set of GEFs, GAPs, and effectors. Arf6 has been implicated in breast cancer and melanoma cell invasion, and in actin remodelling at the invasion site of Chlamydia infection.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22759382  25 LHVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVqctlgKAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVI 104
Cdd:cd04149  10 MRILMLGLDAAGKTTILYKLKLGQSVTTIPTVGFNVETV-----TYKNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIFVV 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 22759382 105 DSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNELYN 162
Cdd:cd04149  85 DSADRDRIDEARQELHRIINDREMRDALLLVFANKQDLPDAMKPHEIQEKLGLTRIRD 142

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 22759382  26 HVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQCTlgkaKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVID 105
Cdd:cd04156   1 QVLLLGLDSAGKSTLLYKLKHAELVTTIPTVGFNVEMLQLE----KHLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVD 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22759382 106 SVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNEL 160
Cdd:cd04156  77 SSDEARLDESQKELKHILKNEHIKGVPVVLLANKQDLPGALTAEEITRRFKLKKY 131

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22759382    1 MGATMVKplvkngnILDALPSQATLHVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQctlgkAKGVHFLVWDV 80
Cdd:PLN00223   1 MGLSFTK-------LFSRLFAKKEMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVE-----YKNISFTVWDV 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22759382   81 GGQEKLRPLWRSYTRCTDGILFVIDSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNEL 160
Cdd:PLN00223  69 GGQDKIRPLWRHYFQNTQGLIFVVDSNDRDRVVEARDELHRMLNEDELRDAVLLVFANKQDLPNAMNAAEITDKLGLHSL 148

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 22759382  15 ILDAL-----PSQATLHVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQctlgkAKGVHFLVWDVGGQEKLRPL 89
Cdd:cd04155   1 LLSILrklkpSSRQEVRILLLGLDNAGKTTILKQLASEDISHITPTQGFNIKNVQ-----ADGFKLNVWDIGGQRKIRPY 75

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 22759382  90 WRSYTRCTDGILFVIDSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNELYN 162
Cdd:cd04155  76 WRNYFENTDVLIYVIDSADRKRFEEAGQELVELLEEEKLAGVPVLVFANKQDLLTAAPAEEVAEALNLHDIRD 148

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 22759382  26 HVVMLGLDSAGKTTALYRLK--FDQYLNTVPTIGFNCEKVqctlgKAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFV 103
Cdd:cd04157   1 NILVLGLDNSGKTTIINQLKpsNAQSQNIVPTVGFNVESF-----KKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFV 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22759382 104 IDSVDTERMEEAKMELMRTAKCPD--NQGVPVLILANKQDLPNACGAMELEKLLGLNELYNPVPNI 167
Cdd:cd04157  76 IDSSDRLRMVVAKDELELLLNHPDikHRRIPILFYANKMDLPDALTAVKITQLLCLENIKDKPWHI 141

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 22759382  27 VVMLGLDSAGKTTALYRLKFDQYLNT--------VPTIGFNCEKVQctLGKAKgVHFlvWDVGGQEKLRPLWRSYTRCTD 98
Cdd:cd04160   2 VLILGLDNAGKTTFLEQTKTKFSKNYkglnpskiTPTVGLNIGTIE--VGKAR-LMF--WDLGGQEELRSLWDKYYAESH 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 22759382  99 GILFVIDSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLL 155
Cdd:cd04160  77 GVIYVIDSTDRERFNESKSAFEKVINNEALEGVPLLVLANKQDLPDALSVAEIKEVF 133

(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 22759382  27 VVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQctlgkAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVIDS 106
Cdd:cd04158   2 VVTLGLDGAGKTTILFKLKQDEFMQPIPTIGFNVETVE-----YKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDS 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 22759382 107 VDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNEL 160
Cdd:cd04158  77 SHRDRVSEAHSELAKLLTEKELRDALLLIFANKQDVAGALSVEEMTELLSLHKL 130

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 22759382  27 VVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFncEKVQCTLGKakgVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVIDS 106
Cdd:cd04161   2 LLTVGLDNAGKTTLVSALQGEIPKKVAPTVGF--TPTKLRLDK---YEVCIFDLGGGANFRGIWVNYYAEAHGLVFVVDS 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 22759382 107 VDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNACGAMELEKLLGLNELYNP 163
Cdd:cd04161  77 SDDDRVQEVKEILRELLQHPRVSGKPILVLANKQDKKNALLGADVIEYLSLEKLVNE 133

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 22759382    27 VVMLGLDSAGKTTALYRLKFDQYLNT--VPTIGFNCEKVQCTLgKAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVI 104
Cdd:TIGR00231   4 IVIVGHPNVGKSTLLNSLLGNKGSITeyYPGTTRNYVTTVIEE-DGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 22759382   105 DSVD-TERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPNA 145
Cdd:TIGR00231  83 DIVIlVLDVEEILEKQTKEIIHHADSGVPIILVGNKIDLKDA 124

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 22759382    27 VVMLGlDSA-GKTTALYRL---KF-DQYlntVPTIGFNCEKVQCTLGkAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGIL 101
Cdd:pfam00071   2 LVLVG-DGGvGKSSLLIRFtqnKFpEEY---IPTIGVDFYTKTIEVD-GKTVKLQIWDTAGQERFRALRPLYYRGADGFL 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 22759382   102 FVIDSVDTERMEEAKM---ELMRTakCPDNqgVPVLILANKQDL 142
Cdd:pfam00071  77 LVYDITSRDSFENVKKwveEILRH--ADEN--VPIVLVGNKCDL 116

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 22759382  27 VVMLGlDSA-GKTTALYRLKFDQY-LNTVPTIGFNCEKVQCTLGKaKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFVI 104
Cdd:cd00154   3 IVLIG-DSGvGKTSLLLRFVDNKFsENYKSTIGVDFKSKTIEVDG-KKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 22759382 105 D--SVDT-ER----MEEAKMelmrtaKCPDNqgVPVLILANKQDLPN 144
Cdd:cd00154  81 DvtNRESfENldkwLNELKE------YAPPN--IPIILVGNKSDLED 119

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 22759382  28 VMLGLDSAGKTTALYRLkFDQYLNTV-----PTIGFNcEKVQCTLGKAKGVHFlvWDVGGQEKLRPLWRSYT-----RCT 97
Cdd:cd00882   1 VVVGRGGVGKSSLLNAL-LGGEVGEVsdvpgTTRDPD-VYVKELDKGKVKLVL--VDTPGLDEFGGLGREELarlllRGA 76

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22759382  98 DGILFVIDSVDTERMEEAKMELMRTAKCPdnqGVPVLILANKQDLPNACGAMELEKLLGLNELYNP 163
Cdd:cd00882  77 DLILLVVDSTDRESEEDAKLLILRRLRKE---GIPIILVGNKIDLLEEREVEELLRLEELAKILGV 139

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. 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 22759382  27 VVMLGLDSAGKTTALYRLKFDQYLNT-VPTIG--FNCEKVQCtlgKAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFV 103
Cdd:cd01869   5 LLLIGDSGVGKSCLLLRFADDTYTESyISTIGvdFKIRTIEL---DGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIV 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 22759382 104 IDSVDTERMEEAKM---ELMRTAkcpdNQGVPVLILANKQDLPNA 145
Cdd:cd01869  82 YDVTDQESFNNVKQwlqEIDRYA----SENVNKLLVGNKCDLTDK 122

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22759382   24 TLHVVMLGLDSAGKTTALYRLKFDQYLNTVPTIGFNCEKVQCTLGkAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILFV 103
Cdd:PLN03118  14 SFKILLIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKIKQLTVG-GKRLKLTIWDTAGQERFRTLTSSYYRNAQGIILV 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 22759382  104 IDSVDTERMEE------AKMELMRTakcpdNQGVPVLILANKQD 141
Cdd:PLN03118  93 YDVTRRETFTNlsdvwgKEVELYST-----NQDCVKMLVGNKVD 131

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 22759382  25 LHVVMLGLDSAGKTTALYRL---KFDQylNTVPTIGFNCEKVQCTLGKAKgVHFLVWDVGGQEKLRPLWRSYTRCTDGIL 101
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFtddTFDE--DLSSTIGVDFKVKTVTVDGKK-VKLAIWDTAGQERFRTLTSSYYRGAQGVI 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 22759382 102 FVIDSVDTERMEEAKMELMRTAKCPDNQGVPVLILANKQDLPN 144
Cdd:cd01863  78 LVYDVTRRDTFDNLDTWLNELDTYSTNPDAVKMLVGNKIDKEN 120

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 22759382  27 VVMLGLDSAGKTTALYRL---KF-DQYlntVPTIgFNCEKVQCTLgKAKGVHFLVWDVGGQ---EKLRPLwrSYTRcTDG 99
Cdd:cd04129   4 LVIVGDGACGKTSLLYVFtlgEFpEEY---HPTV-FENYVTDCRV-DGKPVQLALWDTAGQeeyERLRPL--SYSK-AHV 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 22759382 100 IL--FVIDSVDTerMEEAKMELMRTAK--CPDnqgVPVLILANKQDL 142
Cdd:cd04129  76 ILigFAIDTPDS--LENVRTKWIEEVRryCPN---VPVILVGLKKDL 117

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. 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 22759382  28 VMLGLDSAGKTTALYRL---KFDQylNTVPTIG--FNCEKVQCtlgKAKGVHFLVWDVGGQEKLRPLWRSYTRCTDGILF 102
Cdd:cd04113   4 LIIGSAGTGKSCLLHQFienKFKQ--DSNHTIGveFGSRVVNV---GGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALL 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 22759382 103 VIDSVDTERMEEAKMEL--MRTAKCPDnqgVPVLILANKQDL 142
Cdd:cd04113  79 VYDITSRESFNALTNWLtdARTLASPD---IVIILVGNKKDL 117

Ras homology family A (RhoA)-like includes RhoA, RhoB and RhoC; The RhoA subfamily consists of RhoA, RhoB, and RhoC. RhoA promotes the formation of stress fibers and focal adhesions, regulating cell shape, attachment, and motility. RhoA can bind to multiple effector proteins, thereby triggering different downstream responses. In many cell types, RhoA mediates local assembly of the contractile ring, which is necessary for cytokinesis. RhoA is vital for muscle contraction; in vascular smooth muscle cells, RhoA plays a key role in cell contraction, differentiation, migration, and proliferation. RhoA activities appear to be elaborately regulated in a time- and space-dependent manner to control cytoskeletal changes. 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 membrane attachment, a key feature of most Rho proteins. RhoA and RhoC are observed only in geranylgeranylated forms; however, RhoB can be present in palmitoylated, farnesylated, and geranylgeranylated forms. RhoA and RhoC are highly relevant for tumor progression and invasiveness; however, RhoB has recently been suggested to be a tumor suppressor. 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 22759382  27 VVMLGLDSAGKTTALYRLKFDQYLNT-VPTIGFNceKVQCTLGKAKGVHFLVWDVGGQE---KLRPLwrSYTRcTDGIL- 101
Cdd:cd01870   4 LVIVGDGACGKTCLLIVFSKDQFPEVyVPTVFEN--YVADIEVDGKQVELALWDTAGQEdydRLRPL--SYPD-TDVILm 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 22759382 102 -FVIDSVDT-ERMEEAKMELMRTAkCPDnqgVPVLILANKQDLPN 144
Cdd:cd01870  79 cFSIDSPDSlENIPEKWTPEVKHF-CPN---VPIILVGNKKDLRN 119