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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574    14 AQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELeRNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVDSTD 93
Cdd:pfam00025   1 MRILILGLDNAGKTTILYKLKLGEIVTTIPTIGFNVETVTY-KNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSAD 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13376574    94 KQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLCsDRNWYVQPCCALTGEGLAQGFRKLT 172
Cdd:pfam00025  80 RDRIEEAKEELHALLNEEELADAPLLILANKQDLPGAMSEAEIRELLGLHELK-DRPWEIQGCSAVTGEGLDEGLDWLS 157

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574   10 QTKQAQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELeRNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVV 89
Cdd:PTZ00133  14 GKKEVRILMVGLDAAGKTTILYKLKLGEVVTTIPTIGFNVETVEY-KNLKFTMWDVGGQDKLRPLWRHYYQNTNGLIFVV 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574   90 DSTDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLcSDRNWYVQPCCALTGEGLAQGFR 169
Cdd:PTZ00133  93 DSNDRERIGDAREELERMLSEDELRDAVLLVFANKQDLPNAMSTTEVTEKLGLHSV-RQRNWYIQGCCATTAQGLYEGLD 171

                        170
                 ....*....|.
gi 13376574  170 KLTGFVKSHMK 180
Cdd:PTZ00133 172 WLSANIKKSMQ 182

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 13376574    16 VLLLGLDSAGKSTLLYKLKLAKDITT--IPTIGFNVEMIELERN---LSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVD 90
Cdd:TIGR00231   4 IVIVGHPNVGKSTLLNSLLGNKGSITeyYPGTTRNYVTTVIEEDgktYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVFD 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 13376574    91 ST----DKQRLEESQRQfehILKNEHIKNVPVVLLANKQDMPGA 130
Cdd:TIGR00231  84 IVilvlDVEEILEKQTK---EIIHHADSGVPIILVGNKIDLKDA 124

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 13376574  15 QVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELeRNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVDSTDK 94
Cdd:cd00878   1 RILMLGLDGAGKTTILYKLKLGEVVTTIPTIGFNVETVEY-KNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDR 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13376574  95 QRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKlCSDRNWYVQPCCALTGEGLAQGFRKL 171
Cdd:cd00878  80 ERIEEAKNELHKLLNEEELKGAPLLILANKQDLPGALTESELIELLGLES-IKGRRWHIQPCSAVTGDGLDEGLDWL 155

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574      1 MGSLGSKNPQTKQAQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELeRNLSLTVWDVGGQEKMRTVWGCYCE 80
Cdd:smart00177   1 MGKLFSKLFGNKEMRILMVGLDAAGKTTILYKLKLGESVTTIPTIGFNVETVTY-KNISFTVWDVGGQDKIRPLWRHYYT 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574     81 NTDGLVYVVDSTDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLcSDRNWYVQPCCALT 160
Cdd:smart00177  80 NTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFANKQDLPDAMKAAEITEKLGLHSI-RDRNWYIQPTCATS 158

                          170
                   ....*....|....*..
gi 13376574    161 GEGLAQGFRKLTGFVKS 177
Cdd:smart00177 159 GDGLYEGLTWLSNNLKN 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 13376574  15 QVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELeRNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVDSTDK 94
Cdd:cd04150   2 RILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEY-KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13376574  95 QRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLcSDRNWYVQPCCALTGEGLAQGFRKLT 172
Cdd:cd04150  81 ERIGEAREELQRMLNEDELRDAVLLVFANKQDLPNAMSAAEVTDKLGLHSL-RNRNWYIQATCATSGDGLYEGLDWLS 157

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 13376574  11 TKQAQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELeRNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVD 90
Cdd:cd04149   7 NKEMRILMLGLDAAGKTTILYKLKLGQSVTTIPTVGFNVETVTY-KNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIFVVD 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  91 STDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLcSDRNWYVQPCCALTGEGLAQGFRK 170
Cdd:cd04149  86 SADRDRIDEARQELHRIINDREMRDALLLVFANKQDLPDAMKPHEIQEKLGLTRI-RDRNWYVQPSCATSGDGLYEGLTW 164

                ..
gi 13376574 171 LT 172
Cdd:cd04149 165 LS 166

Arf-like 4 (Arl4) and 7 (Arl7) GTPases; Arl4 (Arf-like 4) is highly expressed in testicular germ cells, and is found in the nucleus and nucleolus. In mice, Arl4 is developmentally expressed during embryogenesis, and a role in somite formation and central nervous system differentiation has been proposed. Arl7 has been identified as the only Arf/Arl protein to be induced by agonists of liver X-receptor and retinoid X-receptor and by cholesterol loading in human macrophages. Arl7 is proposed to play a role in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. 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 13376574  16 VLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIEL----ERNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVDS 91
Cdd:cd04152   6 IVMLGLDSAGKTTVLYRLKFNEFVNTVPTKGFNTEKIKVslgnAKGVTFHFWDVGGQEKLRPLWKSYTRCTDGIVFVVDS 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  92 TDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLCSDRNWYVQPCCALTGEGLAQGFRKL 171
Cdd:cd04152  86 VDVERMEEAKTELHKITKFSENQGVPVLVLANKQDLPNALPVSEVEKLLALHELSSSTPWHVQPACAIIGEGLQEGLEKL 165

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 13376574  12 KQAQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELeRNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVDS 91
Cdd:cd04153  14 KEYKVIIVGLDNAGKTTILYQFLLGEVVHTSPTIGSNVEEIVY-KNIRFLMWDIGGQESLRSSWNTYYTNTDAVILVIDS 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 13376574  92 TDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLcSDRNWYVQPCCALTGEGLAQG 167
Cdd:cd04153  93 TDRERLPLTKEELYKMLAHEDLRKAVLLVLANKQDLKGAMTPAEISESLGLTSI-RDHTWHIQGCCALTGEGLPEG 167

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 13376574  16 VLLLGLDSAGKSTLLYKLK---------LAKD-ITtiPTIGFNVEMIELErNLSLTVWDVGGQEKMRTVWGCYCENTDGL 85
Cdd:cd04160   2 VLILGLDNAGKTTFLEQTKtkfsknykgLNPSkIT--PTVGLNIGTIEVG-KARLMFWDLGGQEELRSLWDKYYAESHGV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  86 VYVVDSTDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFK-VKKLCSDRNWYVQPCCALTGEGL 164
Cdd:cd04160  79 IYVIDSTDRERFNESKSAFEKVINNEALEGVPLLVLANKQDLPDALSVAEIKEVFDdCIALIGRRDCLVQPVSALEGEGV 158

                ...
gi 13376574 165 AQG 167
Cdd:cd04160 159 EEG 161

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 13376574   2 GSLGSKNpqtKQAQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELErNLSLTVWDVGGQEKMRTVWGCYCEN 81
Cdd:cd00879  11 SSLGLYK---KEAKIVFLGLDNAGKTTLLHMLKDDRLAQHVPTLHPTSEELTIG-NVKFTTFDLGGHEQARRVWKDYFPE 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  82 TDGLVYVVDSTDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAED----------ITRMFKVKKLCSD-RN 150
Cdd:cd00879  87 VDGIVFLVDAADPERFQESKEELDSLLNDEELANVPILILGNKIDKPGAVSEEElrealglygtTTGKGGVSLKVSNiRP 166

                       170       180
                ....*....|....*....|.
gi 13376574 151 WYVQPCCALTGEGLAQGFRKL 171
Cdd:cd00879 167 VEVFMCSVVKRQGYGEGFRWL 187

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  15 QVLLLGLDSAGKSTLLYKL--KLAKDiTTIPTIGFNVEMIeLERNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVDST 92
Cdd:cd04162   1 QILVLGLDGAGKTSLLHSLssERSLE-SVVPTTGFNSVAI-PTQDAIMELLEIGGSQNLRKYWKRYLSGSQGLIFVVDSA 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13376574  93 DKQRLEESQRQFEHILknEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLCSDRNWYVQPC 156
Cdd:cd04162  79 DSERLPLARQELHQLL--QHPPDLPLVVLANKQDLPAARSVQEIHKELELEPIARGRRWILQGT 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 13376574      1 MGSLGSKNpqtKQAQVLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMIELErNLSLTVWDVGGQEKMRTVWGCYCE 80
Cdd:smart00178   8 LASLGLWN---KHAKILFLGLDNAGKTTLLHMLKNDRLAQHQPTQHPTSEELAIG-NIKFTTFDLGGHQQARRLWKDYFP 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574     81 NTDGLVYVVDSTDKQRLEESQRQFEHILKNEHIKNVPVVLLANKQDMPGALTAED------ITRMFKVKKLCSDRNWYVQ 154
Cdd:smart00178  84 EVNGIVYLVDAYDKERFAESKRELDALLSDEELATVPFLILGNKIDAPYAASEDElryalgLTNTTTGKGKVGVRPVEVF 163

                          170       180
                   ....*....|....*....|.
gi 13376574    155 PCCALTGEGLAQGFRKLTGFV 175
Cdd:smart00178 164 MCSVVRRMGYGEGFKWLSQYI 184

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 13376574  17 LLLGLDSAGKSTLLYKL----KLAKDITTIPTIGFNVEMIELERNL-SLTVWDVGGQEKMRTVWGC-----YCENTDGLV 86
Cdd:cd00882   1 VVVGRGGVGKSSLLNALlggeVGEVSDVPGTTRDPDVYVKELDKGKvKLVLVDTPGLDEFGGLGREelarlLLRGADLIL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  87 YVVDSTDKQRLEESQrqfEHILKNEHIKNVPVVLLANKQDMPGALTAEDITRMFKVKKLcsdRNWYVQPCCALTGEGLAQ 166
Cdd:cd00882  81 LVVDSTDRESEEDAK---LLILRRLRKEGIPIILVGNKIDLLEEREVEELLRLEELAKI---LGVPVFEVSAKTGEGVDE 154

                ....*
gi 13376574 167 GFRKL 171
Cdd:cd00882 155 LFEKL 159

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 13376574  16 VLLLGlDSA-GKSTLLYKLKLAK-DITTIPTIG--FNVEMIELE-RNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVD 90
Cdd:cd00154   3 IVLIG-DSGvGKTSLLLRFVDNKfSENYKSTIGvdFKSKTIEVDgKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  91 STDkqrlEESqrqFEHI------LKNEHIKNVPVVLLANKQDmpgaLTAEDITRMFKVKKLCSDRNWYVQPCCALTGEGL 164
Cdd:cd00154  82 VTN----RES---FENLdkwlneLKEYAPPNIPIILVGNKSD----LEDERQVSTEEAQQFAKENGLLFFETSAKTGENV 150

                ....*...
gi 13376574 165 AQGFRKLT 172
Cdd:cd00154 151 DEAFESLA 158

Signal recognition particle receptor, beta subunit (SR-beta), together with SR-alpha, forms the heterodimeric signal recognition particle (SRP); Signal recognition particle receptor, beta subunit (SR-beta). SR-beta and SR-alpha form the heterodimeric signal recognition particle (SRP or SR) receptor that binds SRP to regulate protein translocation across the ER membrane. Nascent polypeptide chains are synthesized with an N-terminal hydrophobic signal sequence that binds SRP54, a component of the SRP. SRP directs targeting of the ribosome-nascent chain complex (RNC) to the ER membrane via interaction with the SR, which is localized to the ER membrane. The RNC is then transferred to the protein-conducting channel, or translocon, which facilitates polypeptide translation across the ER membrane or integration into the ER membrane. SR-beta is found only in eukaryotes; it is believed to control the release of the signal sequence from SRP54 upon binding of the ribosome to the translocon. High expression of SR-beta has been observed in human colon cancer, suggesting it may play a role in the development of this type of cancer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574  16 VLLLGLDSAGKSTLLYKLKLAKDITTIPTIGFNVEMI--ELERNLSLTVWDVGGQEKMRT-VWGCYCENTDGLVYVVDST 92
Cdd:cd04105   3 VLLLGPSDSGKTALFTKLTTGKVRSTVTSIEPNVASFysNSSKGKKLTLVDVPGHEKLRDkLLEYLKASLKAIVFVVDSA 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 13376574  93 DKQR--LEESQRQFEHILKNEHIKN-VPVVLLANKQDMPGALTAEDI 136
Cdd:cd04105  83 TFQKniRDVAEFLYDILTDLEKIKNkIPILIACNKQDLFTAKPAKKI 129

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 13376574  15 QVLLLGLDSAGKSTLLykLKLAKDI---TTIPTIG--FNVEMIELE-RNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYV 88
Cdd:cd01867   5 KLLLIGDSGVGKSCLL--LRFSEDSfnpSFISTIGidFKIRTIELDgKKIKLQIWDTAGQERFRTITTSYYRGAMGIILV 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 13376574  89 VDSTDKQRLEESQRQFEHIlkNEHI-KNVPVVLLANKQDMP 128
Cdd:cd01867  83 YDITDEKSFENIKNWMRNI--DEHAsEDVERMLVGNKCDME 121

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 13376574  15 QVLLLGLDSAGKSTLLykLKLAKDITT---IPTIG--FNVEMIELE-RNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYV 88
Cdd:cd01869   4 KLLLIGDSGVGKSCLL--LRFADDTYTesyISTIGvdFKIRTIELDgKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIV 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 13376574  89 VDSTDKQRLEESQRQFEHILK--NEhikNVPVVLLANKQDMP 128
Cdd:cd01869  82 YDVTDQESFNNVKQWLQEIDRyaSE---NVNKLLVGNKCDLT 120

Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376574     16 VLLLGlDSA-GKSTLLYKLKLAK-DITTIPTIG--FNVEMIELE-RNLSLTVWDVGGQEKMRTVWGCYCENTDGLVYVVD 90
Cdd:smart00175   3 IILIG-DSGvGKSSLLSRFTDGKfSEQYKSTIGvdFKTKTIEVDgKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVYD 81

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 13376574     91 STDKQRLEESQRQFEHIlkNEHIK-NVPVVLLANKQDM 127
Cdd:smart00175  82 ITNRESFENLENWLKEL--REYASpNVVIMLVGNKSDL 117

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. 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 13376574  15 QVLLLGLDSAGKSTLLykLKLAKD------ITTIpTIGFNVEMIELE-RNLSLTVWDVGGQEKMRTVWGCYCENTDGLVY 87
Cdd:cd04110   8 KLLIIGDSGVGKSSLL--LRFADNtfsgsyITTI-GVDFKIRTVEINgERVKLQIWDTAGQERFRTITSTYYRGTHGVIV 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 13376574  88 VVDSTDKQRLEESQRQFEHIlkNEHIKNVPVVLLANKQDMP 128
Cdd:cd04110  85 VYDVTNGESFVNVKRWLQEI--EQNCDDVCKVLVGNKNDDP 123

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 13376574  13 QAQVLLLGLDSAGKSTLLYKLKLAK--DITTiPTIG--FNVEMIELE--RNLSLTVWDVGGQEKMRTVWGCYCENTDGLV 86
Cdd:cd04111   2 QFRLIVIGDSTVGKSSLLKRFTEGRfaEVSD-PTVGvdFFSRLIEIEpgVRIKLQLWDTAGQERFRSITRSYYRNSVGVL 80

                        90       100
                ....*....|....*....|.
gi 13376574  87 YVVDSTDKqrleesqRQFEHI 107
Cdd:cd04111  81 LVFDITNR-------ESFEHV 94