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 371123783  22 ELTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQ 101
Cdd:cd04159    1 EITLVGLQNSGKTTLVNVIASGQFSEDTIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADR 80

                         90       100
                 ....*....|....*....|....*..
gi 371123783 102 EKIEASKNELHNLLDKPQLQGIPESVC 128
Cdd:cd04159   81 EKLEVAKNELHDLLEKPSLEGIPLLVL 107

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 371123783  22 ELTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQ 101
Cdd:cd04159    1 EITLVGLQNSGKTTLVNVIASGQFSEDTIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADR 80

                         90       100
                 ....*....|....*....|....*..
gi 371123783 102 EKIEASKNELHNLLDKPQLQGIPESVC 128
Cdd:cd04159   81 EKLEVAKNELHDLLEKPSLEGIPLLVL 107

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 371123783    12 FKALFWKEEMELTLVGLQYSGKTTFVNVIASGQFnEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSA 91
Cdd:smart00177   5 FSKLFGNKEMRILMVGLDAAGKTTILYKLKLGES-VTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQG 83

                           90       100       110
                   ....*....|....*....|....*....|
gi 371123783    92 IVYMVDAADQEKIEASKNELHNLLDKPQLQ 121
Cdd:smart00177  84 LIFVVDSNDRDRIDEAREELHRMLNEDELR 113

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 371123783  31 SGKTTFVNVIASGQFN-EDMIPTVGFNMRK----ITKGNVTIKLWDIGGQPRFRSMWERYCR---GVSAIVYMVDAADQE 102
Cdd:COG1100   14 VGKTSLVNRLVGDIFSlEKYLSTNGVTIDKkelkLDGLDVDLVIWDTPGQDEFRETRQFYARqltGASLYLFVVDGTREE 93

                         90
                 ....*....|....
gi 371123783 103 KIEASKNELHNLLD 116
Cdd:COG1100   94 TLQSLYELLESLRR 107

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 371123783  22 ELTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQ 101
Cdd:cd04159    1 EITLVGLQNSGKTTLVNVIASGQFSEDTIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADR 80

                         90       100
                 ....*....|....*....|....*..
gi 371123783 102 EKIEASKNELHNLLDKPQLQGIPESVC 128
Cdd:cd04159   81 EKLEVAKNELHDLLEKPSLEGIPLLVL 107

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 371123783   8 LLDWFKALF-----WKEEMELTLVGLQYSGKTTFVNVIASGQFNEdMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMW 82
Cdd:cd00879    2 IFDWFYNVLsslglYKKEAKIVFLGLDNAGKTTLLHMLKDDRLAQ-HVPTLHPTSEELTIGNVKFTTFDLGGHEQARRVW 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 371123783  83 ERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIP 124
Cdd:cd00879   81 KDYFPEVDGIVFLVDAADPERFQESKEELDSLLNDEELANVP 122

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 371123783    12 FKALFWKEEMELTLVGLQYSGKTTFVNVIASGQFnEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSA 91
Cdd:smart00177   5 FSKLFGNKEMRILMVGLDAAGKTTILYKLKLGES-VTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQG 83

                           90       100       110
                   ....*....|....*....|....*....|
gi 371123783    92 IVYMVDAADQEKIEASKNELHNLLDKPQLQ 121
Cdd:smart00177  84 LIFVVDSNDRDRIDEAREELHRMLNEDELR 113

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 371123783  22 ELTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQ 101
Cdd:cd04162    1 QILVLGLDGAGKTSLLHSLSSERSLESVVPTTGFNSVAIPTQDAIMELLEIGGSQNLRKYWKRYLSGSQGLIFVVDSADS 80

                         90
                 ....*....|....*..
gi 371123783 102 EKIEASKNELHNLLDKP 118
Cdd:cd04162   81 ERLPLARQELHQLLQHP 97

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 371123783  12 FKALFWKEEMELTLVGLQYSGKTTFVNVIASGQfNEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSA 91
Cdd:cd04149    1 LSKLFGNKEMRILMLGLDAAGKTTILYKLKLGQ-SVTTIPTVGFNVETVTYKNVKFNVWDVGGQDKIRPLWRHYYTGTQG 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 371123783  92 IVYMVDAADQEKIEASKNELHNLLDKPQLQG 122
Cdd:cd04149   80 LIFVVDSADRDRIDEARQELHRIINDREMRD 110

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 371123783  12 FKALFWKEEMELTLVGLQYSGKTTFVNVIASGQFnEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSA 91
Cdd:PTZ00133   9 FKSLFGKKEVRILMVGLDAAGKTTILYKLKLGEV-VTTIPTIGFNVETVEYKNLKFTMWDVGGQDKLRPLWRHYYQNTNG 87

                         90       100       110
                 ....*....|....*....|....*....|
gi 371123783  92 IVYMVDAADQEKIEASKNELHNLLDKPQLQ 121
Cdd:PTZ00133  88 LIFVVDSNDRERIGDAREELERMLSEDELR 117

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 371123783  26 VGLQYSGKTTFVNVIA-SGQFNEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKI 104
Cdd:cd04157    5 LGLDNSGKTTIINQLKpSNAQSQNIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDRLRM 84

                         90       100
                 ....*....|....*....|..
gi 371123783 105 EASKNELHNLLDKPQL--QGIP 124
Cdd:cd04157   85 VVAKDELELLLNHPDIkhRRIP 106

ADP ribosylation factor 1 (Arf1); Arl1 subfamily. Arl1 (Arf-like 1) localizes to the Golgi complex, where it is believed to recruit effector proteins to the trans-Golgi network. Like most members of the Arf family, Arl1 is myristoylated at its N-terminal helix and mutation of the myristoylation site disrupts Golgi targeting. In humans, the Golgi-localized proteins golgin-97 and golgin-245 have been identified as Arl1 effectors. Golgins are large coiled-coil proteins found in the Golgi, and these golgins contain a C-terminal GRIP domain, which is the site of Arl1 binding. Additional Arl1 effectors include the GARP (Golgi-associated retrograde protein)/VFT (Vps53) vesicle-tethering complex and Arfaptin 2. Arl1 is not required for exocytosis, but appears necessary for trafficking from the endosomes to the Golgi. In Drosophila zygotes, mutation of Arl1 is lethal, and in the host-bloodstream form of Trypanosoma brucei, Arl1 is essential for viability.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 371123783  25 LVGLQYSGKTTfvnVIASGQFNE--DMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQE 102
Cdd:cd04151    4 ILGLDGAGKTT---ILYRLQVGEvvTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAIIYVVDSTDRD 80

                         90       100
                 ....*....|....*....|..
gi 371123783 103 KIEASKNELHNLLDKPQLQGIP 124
Cdd:cd04151   81 RLGISKSELHAMLEEEELKDAV 102

Arf-like 2 (Arl2) GTPase; Arl2 (Arf-like 2) GTPases are members of the Arf family that bind GDP and GTP with very low affinity. Unlike most Arf family proteins, Arl2 is not myristoylated at its N-terminal helix. The protein PDE-delta, first identified in photoreceptor rod cells, binds specifically to Arl2 and is structurally very similar to RhoGDI. Despite the high structural similarity between Arl2 and Rho proteins and between PDE-delta and RhoGDI, the interactions between the GTPases and their effectors are very different. In its GTP bound form, Arl2 interacts with the protein Binder of Arl2 (BART), and the complex is believed to play a role in mitochondrial adenine nucleotide transport. In its GDP bound form, Arl2 interacts with tubulin- folding Cofactor D; this interaction is believed to play a role in regulation of microtubule dynamics that impact the cytoskeleton, cell division, and cytokinesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 371123783  18 KE-EMELTLVGLQYSGKTTFVNVIaSGQFNEDMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMV 96
Cdd:cd04154   11 KErEMRILMLGLDNAGKTTILKKF-NGEDISTISPTLGFNIKTLEYNGYKLNIWDVGGQKSLRSYWRNYFESTDALIWVV 89

                         90       100
                 ....*....|....*....|....*.
gi 371123783  97 DAADQEKIEASKNELHNLLDKPQLQG 122
Cdd:cd04154   90 DSSDRARLEDCKRELQKLLVEERLAG 115

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 371123783     9 LDWFKALF-----WKEEMELTLVGLQYSGKTTFVNVIASGQFNEdMIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWE 83
Cdd:smart00178   1 FDWFYDILaslglWNKHAKILFLGLDNAGKTTLLHMLKNDRLAQ-HQPTQHPTSEELAIGNIKFTTFDLGGHQQARRLWK 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 371123783    84 RYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIP 124
Cdd:smart00178  80 DYFPEVNGIVYLVDAYDKERFAESKRELDALLSDEELATVP 120

(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 371123783  26 VGLQYSGKTTFVNVIASGQFNEDmIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIE 105
Cdd:cd04158    5 LGLDGAGKTTILFKLKQDEFMQP-IPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRDRVS 83

                         90
                 ....*....|....*.
gi 371123783 106 ASKNELHNLLDKPQLQ 121
Cdd:cd04158   84 EAHSELAKLLTEKELR 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 371123783  25 LVGLQYSGKTTFVNVIASGQFNEDMIPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSA--IVY 94
Cdd:cd00154    5 LIGDSGVGKTSLLLRFVDNKFSENYKSTIGvdFKSKTIEVDGKKVKLqiWDTAGQERFRSITSSYYRGAHGaiLVY 80

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 371123783  25 LVGLQYSGKTTFVNVIASGQFNE---DMIPTVGFNMRKIT--KGNVTIKLWDIGGQPRFRSMWE-----RYCRGVSAIVY 94
Cdd:cd00882    2 VVGRGGVGKSSLLNALLGGEVGEvsdVPGTTRDPDVYVKEldKGKVKLVLVDTPGLDEFGGLGReelarLLLRGADLILL 81

                         90       100       110
                 ....*....|....*....|....*....|
gi 371123783  95 MVDAADQEKIEASKNELHNLLDKPqlqGIP 124
Cdd:cd00882   82 VVDSTDRESEEDAKLLILRRLRKE---GIP 108

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 371123783    32 GKTTFVNVIASGQFNEDMIPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEAS 107
Cdd:smart00175  12 GKSSLLSRFTDGKFSEQYKSTIGvdFKTKTIEVDGKRVKLqiWDTAGQERFRSITSSYYRGAVGALLVYDITNRESFENL 91

                   ....*....
gi 371123783   108 KNELHNLLD 116
Cdd:smart00175  92 ENWLKELRE 100

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 371123783  23 LTLVGLQYSGKTTFVNVIASGQFNEDMIPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDA 98
Cdd:cd01863    3 ILLIGDSGVGKSSLLLRFTDDTFDEDLSSTIGvdFKVKTVTVDGKKVKLaiWDTAGQERFRTLTSSYYRGAQGVILVYDV 82

                         90       100
                 ....*....|....*....|...
gi 371123783  99 ADQE---KIEASKNELHNLLDKP 118
Cdd:cd01863   83 TRRDtfdNLDTWLNELDTYSTNP 105

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 371123783  23 LTLVGLQYSGKTTFVNVIASGQFNEDMIPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDA 98
Cdd:cd01869    5 LLLIGDSGVGKSCLLLRFADDTYTESYISTIGvdFKIRTIELDGKTVKLqiWDTAGQERFRTITSSYYRGAHGIIIVYDV 84

                 ....
gi 371123783  99 ADQE 102
Cdd:cd01869   85 TDQE 88

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 371123783  25 LVGLQYSGKTTFVNVIASGQFNEDMIPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDAAD 100
Cdd:cd04113    5 IIGSAGTGKSCLLHQFIENKFKQDSNHTIGveFGSRVVNVGGKSVKLqiWDTAGQERFRSVTRSYYRGAAGALLVYDITS 84

                         90
                 ....*....|.
gi 371123783 101 QEKIEASKNEL 111
Cdd:cd04113   85 RESFNALTNWL 95

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 371123783  25 LVGLQYSGKTTFVNVIASGQFNE---DMIPTVGFNMRKITKGNVtIKLWDIGGQPRFRSM-WERYCRGVSAIVYMVD-AA 99
Cdd:cd04105    5 LLGPSDSGKTALFTKLTTGKVRStvtSIEPNVASFYSNSSKGKK-LTLVDVPGHEKLRDKlLEYLKASLKAIVFVVDsAT 83

                         90
                 ....*....|....*.
gi 371123783 100 DQEKIEASKNELHNLL 115
Cdd:cd04105   84 FQKNIRDVAEFLYDIL 99

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 371123783  32 GKTTFVNVIASGQFNEDMIPTVGFNMRK----ITKGNVTIKLWDIGGQPRFR-SMWERYCRGVSAIVYMVD 97
Cdd:cd04115   14 GKTCLTYRFCAGRFPERTEATIGVDFRErtveIDGERIKVQLWDTAGQERFRkSMVQHYYRNVHAVVFVYD 84

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 371123783  12 FKALFwkeemELTLVGLQYSGKTTFVNVIASGQFNEDMIPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCR 87
Cdd:cd04114    4 YDFLF-----KIVLIGNAGVGKTCLVRRFTQGLFPPGQGATIGvdFMIKTVEIKGEKIKLqiWDTAGQERFRSITQSYYR 78

                         90
                 ....*....|....*
gi 371123783  88 GVSAIVYMVDAADQE 102
Cdd:cd04114   79 SANALILTYDITCEE 93

Ras-related nuclear proteins (Ran)/TC4 family of small GTPases; Ran GTPase is involved in diverse biological functions, such as nuclear transport, spindle formation during mitosis, DNA replication, and cell division. Among the Ras superfamily, Ran is a unique small G protein. It does not have a lipid modification motif at the C-terminus to bind to the membrane, which is often observed within the Ras superfamily. Ran may therefore interact with a wide range of proteins in various intracellular locations. Like other GTPases, Ran exists in GTP- and GDP-bound conformations that interact differently with effectors. Conversion between these forms and the assembly or disassembly of effector complexes requires the interaction of regulator proteins. The intrinsic GTPase activity of Ran is very low, but it is greatly stimulated by a GTPase-activating protein (RanGAP1) located in the cytoplasm. By contrast, RCC1, a guanine nucleotide exchange factor that generates RanGTP, is bound to chromatin and confined to the nucleus. Ran itself is mobile and is actively imported into the nucleus by a mechanism involving NTF-2. Together with the compartmentalization of its regulators, this is thought to produce a relatively high concentration of RanGTP in the nucleus.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 371123783  23 LTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKI----TKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVD 97
Cdd:cd00877    3 LVLVGDGGTGKTTFVKRHLTGEFEKKYVATLGVEVHPLdfhtNRGKIRFNVWDTAGQEKFGGLRDGYYIQGQCAIIMFD 81

Rab GTPase families 34 (Rab34) and 36 (Rab36); Rab34/Rab36 subfamily. Rab34, found primarily in the Golgi, interacts with its effector, Rab-interacting lysosomal protein (RILP). This enables its participation in microtubular dynenin-dynactin-mediated repositioning of lysosomes from the cell periphery to the Golgi. A Rab34 (Rah) isoform that lacks the consensus GTP-binding region has been identified in mice. This isoform is associated with membrane ruffles and promotes macropinosome formation. Rab36 has been mapped to human chromosome 22q11.2, a region that is homozygously deleted in malignant rhabdoid tumors (MRTs). However, experimental assessments do not implicate Rab36 as a tumor suppressor that would enable tumor formation through a loss-of-function mechanism. 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 371123783  26 VGLQYSGKTTFVNVIASGQFNEDMIPTVG--FNMRKITKGNV--TIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQ 101
Cdd:cd04108    6 VGDLSVGKTCLINRFCKDVFDKNYKATIGvdFEMERFEVLGVpfSLQLWDTAGQERFKCIASTYYRGAQAIIIVFDLTDV 85

                         90
                 ....*....|....
gi 371123783 102 EKIEASKNELHNLL 115
Cdd:cd04108   86 ASLEHTRQWLEDAL 99

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. 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 371123783  25 LVGLQYSGKTTFVNVIASGQFNEDMIPTV--GFNMRKIT--KGNVTIKLWDIGGQPRFRSMWERYCRGVSA--IVYmvDA 98
Cdd:cd04123    5 LLGEGRVGKTSLVLRYVENKFNEKHESTTqaSFFQKTVNigGKRIDLAIWDTAGQERYHALGPIYYRDADGaiLVY--DI 82

                         90
                 ....*....|....*.
gi 371123783  99 ADQEKIEASKNELHNL 114
Cdd:cd04123   83 TDADSFQKVKKWIKEL 98

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. 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 371123783  31 SGKTTFVNVIASGQFNEDMIPTVG--FNMRKIT---KGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIE 105
Cdd:cd04107   11 VGKTSIIKRYVHGVFSQHYKATIGvdFALKVIEwdpNTVVRLQLWDIAGQERFGGMTRVYYKGAVGAIIVFDVTRPSTFE 90

                         90
                 ....*....|....*
gi 371123783 106 ASKNELHNLLDKPQL 120
Cdd:cd04107   91 AVLKWKADLDSKVTL 105

GTP-binding nuclear protein Ran; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 371123783  23 LTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKI----TKGNVTIKLWDIGGQPRFRSMWE-RYCRGVSAIVyMVD 97
Cdd:PLN03071  16 LVIVGDGGTGKTTFVKRHLTGEFEKKYEPTIGVEVHPLdfftNCGKIRFYCWDTAGQEKFGGLRDgYYIHGQCAII-MFD 94

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. 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 371123783  25 LVGLQYSGKTTFVNVIASGQFNEDMIPTVG--FNMRKIT---KGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAA 99
Cdd:cd04109    5 VLGDGASGKTSLIRRFAQEGFGKSYKQTIGldFFSRRITlpgSLNVTLQVWDIGGQQIGGKMLDKYIYGAQAVCLVYDIT 84

                 ....*.
gi 371123783 100 DQEKIE 105
Cdd:cd04109   85 NSQSFE 90

Rab GTPase family 20 (Rab20); Rab20 is one of several Rab proteins that appear to be restricted in expression to the apical domain of murine polarized epithelial cells. It is expressed on the apical side of polarized kidney tubule and intestinal epithelial cells, and in non-polarized cells. It also localizes to vesico-tubular structures below the apical brush border of renal proximal tubule cells and in the apical region of duodenal epithelial cells. Rab20 has also been shown to colocalize with vacuolar H+-ATPases (V-ATPases) in mouse kidney cells, suggesting a role in the regulation of V-ATPase traffic in specific portions of the nephron. It was also shown to be one of several proteins whose expression is upregulated in human myelodysplastic syndrome (MDS) patients. 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 371123783  32 GKTTFVNVIASGQFnEDMIPTVG--FNMRKITKGNVTIklWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKN 109
Cdd:cd04126   12 GKTSLLHRYMERRF-KDTVSTVGgaFYLKQWGPYNISI--WDTAGREQFHGLGSMYCRGAAAVILTYDVSNVQSLEELED 88

                 ....*..
gi 371123783 110 ELHNLLD 116
Cdd:cd04126   89 RFLGLTD 95

Rab GTPase family 12 (Rab12); Rab12 was first identified in canine cells, where it was localized to the Golgi complex. The specific function of Rab12 remains unknown, and inconsistent results about its cellular localization have been reported. More recent studies have identified Rab12 associated with post-Golgi vesicles, or with other small vesicle-like structures but not with the Golgi complex. 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. 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 371123783  21 MELTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKIT---KGN-VTIKLWDIGGQPRFRSMWERYCRGVSAIVYMV 96
Cdd:cd04120    1 LQVIIIGSRGVGKTSLMERFTDDTFCEACKSTVGVDFKIKTvelRGKkIRLQIWDTAGQERFNSITSAYYRSAKGIILVY 80

                 ....*....
gi 371123783  97 DAADQEKIE 105
Cdd:cd04120   81 DITKKETFD 89