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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660385  80 TNEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQD 159
Cdd:pfam00025  22 LGEIVTTIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADRDRIEEAKEELHALLNEEELAD 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958660385 160 ASVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 217
Cdd:pfam00025 102 APLLILANKQDLPGAMSEAEIRELLGLHELKDRPWEIQGCSAVTGEGLDEGLDWLSNY 159

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 1958660385   82 EVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDAS 161
Cdd:smart00177  37 ESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAV 116

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958660385  162 VLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 217
Cdd:smart00177 117 ILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNN 172

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660385  88 STIGSNVEEIVFQ----RTHFLMWDLGGQEALRSTWETY---YSNAEFVILVIDSTDRNRLSTSrEELYKILAHEALQDA 160
Cdd:COG1100    35 STNGVTIDKKELKldglDVDLVIWDTPGQDEFRETRQFYarqLTGASLYLFVVDGTREETLQSL-YELLESLRRLGKKSP 113

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958660385 161 SVLIFaNKQDV---KDSMTTAEISQFLTlsaiKDHPWHIQGCCALTGEGL 207
Cdd:COG1100   114 IILVL-NKIDLydeEEIEDEERLKEALS----EDNIVEVVATSAKTGEGV 158

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 1958660385  79 LTNEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQ 158
Cdd:cd00878    20 KLGEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRERIEEAKNELHKLLNEEELK 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958660385 159 DASVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 217
Cdd:cd00878   100 GAPLLILANKQDLPGALTESELIELLGLESIKGRRWHIQPCSAVTGDGLDEGLDWLIEQ 158

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 1958660385  81 NEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDA 160
Cdd:cd04151    22 GEVVTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAIIYVVDSTDRDRLGISKSELHAMLEEEELKDA 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958660385 161 SVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWM 214
Cdd:cd04151   102 VLLVFANKQDMPGALSEAEVAEKLGLSELKDRTWQIFKTSATKGEGLDEGMDWL 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 1958660385   82 EVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDAS 161
Cdd:smart00177  37 ESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAV 116

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958660385  162 VLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 217
Cdd:smart00177 117 ILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNN 172

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 1958660385  81 NEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDA 160
Cdd:cd04149    32 GQSVTTIPTVGFNVETVTYKNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIFVVDSADRDRIDEARQELHRIINDREMRDA 111

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958660385 161 SVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWM 214
Cdd:cd04149   112 LLLVFANKQDLPDAMKPHEIQEKLGLTRIRDRNWYVQPSCATSGDGLYEGLTWL 165

ADP-ribosylation factor; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660385  82 EVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDAS 161
Cdd:PLN00223   41 EIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRDRVVEARDELHRMLNEDELRDAV 120

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958660385 162 VLIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHS 216
Cdd:PLN00223  121 LLVFANKQDLPNAMNAAEITDKLGLHSLRQRHWYIQSTCATSGEGLYEGLDWLSN 175

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 1958660385  75 KTPSLTNEvvHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAH 154
Cdd:cd04157    20 KPSNAQSQ--NIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDRLRMVVAKDELELLLNH 97

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958660385 155 EALQDASV--LIFANKQDVKDSMTTAEISQFLTLSAIKDHPWHIQGCCALTGEGLLAGLQWMHSQ 217
Cdd:cd04157    98 PDIKHRRIpiLFYANKMDLPDALTAVKITQLLCLENIKDKPWHIFASSALTGEGLDEGVDWLQAQ 162

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 1958660385  82 EVVHTCSTIGSNVEEIVFQR-THFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDA 160
Cdd:cd04156    23 ELVTTIPTVGFNVEMLQLEKhLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVDSSDEARLDESQKELKHILKNEHIKGV 102

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958660385 161 SVLIFANKQDVKDSMTTAEISQFLTLSAI-KDHPWHIQGCCALTGEGLLAGLQ 212
Cdd:cd04156   103 PVVLLANKQDLPGALTAEEITRRFKLKKYcSDRDWYVQPCSAVTGEGLAEAFR 155

(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 1958660385  81 NEVVHTCSTIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDA 160
Cdd:cd04158    22 DEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRDRVSEAHSELAKLLTEKELRDA 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958660385 161 SVLIFANKQDVKDSMTTAEISQFLTLSAI-KDHPWHIQGCCALTGEGLLAGLQWMHSQ 217
Cdd:cd04158   102 LLLIFANKQDVAGALSVEEMTELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQ 159

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 1958660385  88 STIGSNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEAlqDASVLIFAN 167
Cdd:cd04162    30 PTTGFNSVAIPTQDAIMELLEIGGSQNLRKYWKRYLSGSQGLIFVVDSADSERLPLARQELHQLLQHPP--DLPLVVLAN 107

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958660385 168 KQDVKDSMTTAEISQFLTLSAI-KDHPWHIQGC 199
Cdd:cd04162   108 KQDLPAARSVQEIHKELELEPIaRGRRWILQGT 140

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 1958660385  85 HTCSTIGSNVEEIV-----FQRTHFL-------MWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKIL 152
Cdd:cd04161    14 TLVSALQGEIPKKVaptvgFTPTKLRldkyevcIFDLGGGANFRGIWVNYYAEAHGLVFVVDSSDDDRVQEVKEILRELL 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958660385 153 AHEALQDASVLIFANKQDVKDSMTTAEISQFLTLS-AIKDH--PWHIQGCCALTGEG------LLAGLQWM 214
Cdd:cd04161    94 QHPRVSGKPILVLANKQDKKNALLGADVIEYLSLEkLVNENksLCHIEPCSAIEGLGkkidpsIVEGLRWL 164

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 1958660385  73 LDKTPSLTNEVVHTcsTIGSNVE--EIVFQRTHFLMWDLGGQE---ALRSTWET--YYSNAEFVILVIDSTDRNrlsTSR 145
Cdd:cd00882    18 LGGEVGEVSDVPGT--TRDPDVYvkELDKGKVKLVLVDTPGLDefgGLGREELArlLLRGADLILLVVDSTDRE---SEE 92

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958660385 146 EELYKILAHEALQDASVLIFANKQDVKDSMTTAEISQFLTLSAIKDHPwhIQGCCALTGEGLLAGLQWM 214
Cdd:cd00882    93 DAKLLILRRLRKEGIPIILVGNKIDLLEEREVEELLRLEELAKILGVP--VFEVSAKTGEGVDELFEKL 159

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660385  88 STIGSNVEEIVFQR----THFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDR-NRLSTSREELYKILAHEALQDASV 162
Cdd:TIGR00231  33 PGTTRNYVTTVIEEdgktYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVFDIVILvLDVEEILEKQTKEIIHHADSGVPI 112

                          90       100
                  ....*....|....*....|....*...
gi 1958660385 163 LIFANKQDVKD-SMTTAEISQFLTLSAI 189
Cdd:TIGR00231 113 ILVGNKIDLKDaDLKTHVASEFAKLNGE 140

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. 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 1958660385 100 QRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDASVLIFANKQDVKD 173
Cdd:cd04127    61 FRVHLQLWDTAGQERFRSLTTAFFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAYCENPDIVLIGNKADLPD 134

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 1958660385 106 MWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKIlAHEALQDASVLIFANKQDVKDS--MTTAEISQF 183
Cdd:cd01869    55 IWDTAGQERFRTITSSYYRGAHGIIIVYDVTDQESFNNVKQWLQEI-DRYASENVNKLLVGNKCDLTDKkvVDYTEAKEF 133

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 1958660385 106 MWDLGGQEALRSTWETYYSNAEFVILVIDSTDR-------NRLSTSReelykilaHEALQDASVLIFANKQDVKDS--MT 176
Cdd:cd04113    53 IWDTAGQERFRSVTRSYYRGAAGALLVYDITSResfnaltNWLTDAR--------TLASPDIVIILVGNKKDLEDDreVT 124

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1958660385 177 TAEISQFltlsaIKDHPWHIQGCCALTGEGL 207
Cdd:cd04113   125 FLEASRF-----AQENGLLFLETSALTGENV 150

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 1958660385  96 EIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLStSREELYKILAHEALQDASVLIFANKQDVKdsm 175
Cdd:cd04120    43 ELRGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILVYDITKKETFD-DLPKWMKMIDKYASEDAELLLVGNKLDCE--- 118

                  ....*..
gi 1958660385 176 TTAEISQ 182
Cdd:cd04120   119 TDREITR 125

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958660385 107 WDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSR---EELYKILAhealQDASVLIFANKQDVKDSMT 176
Cdd:cd04123    54 WDTAGQERYHALGPIYYRDADGAILVYDITDADSFQKVKkwiKELKQMRG----NNISLVIVGNKIDLERQRV 122

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660385 106 MWDLGGQEALRSTWETYYSNAEFVILVIDSTDR---NRLSTSREELYKilahEALQDASVLIFANKQDV--KDSMTTAEI 180
Cdd:PLN03108   59 IWDTAGQESFRSITRSYYRGAAGALLVYDITRRetfNHLASWLEDARQ----HANANMTIMLIGNKCDLahRRAVSTEEG 134

                  ...
gi 1958660385 181 SQF 183
Cdd:PLN03108  135 EQF 137

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660385 101 RTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHeALQDASVLIFANKQD 170
Cdd:cd04112    49 KVKLQIWDTAGQERFRSVTHAYYRDAHALLLLYDVTNKSSFDNIRAWLTEILEY-AQSDVVIMLLGNKAD 117

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 1958660385  88 STIGSNVE----EIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHeALQDASVL 163
Cdd:cd01867    34 STIGIDFKirtiELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGIILVYDITDEKSFENIKNWMRNIDEH-ASEDVERM 112

                          90
                  ....*....|
gi 1958660385 164 IFANKQDVKD 173
Cdd:cd01867   113 LVGNKCDMEE 122

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 1958660385  88 STIG----SNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDRNRLSTSREELYKILAHEALQDASVL 163
Cdd:cd01863    31 STIGvdfkVKTVTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVYDVTRRDTFDNLDTWLNELDTYSTNPDAVKM 110

                  ....*..
gi 1958660385 164 IFANKQD 170
Cdd:cd01863   111 LVGNKID 117

Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases; Ran is involved in the active transport of proteins through nuclear pores.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660385   88 STIGSNVEEIVFQ----RTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDR---NRLSTSREELYKIlaheaLQDA 160
Cdd:smart00176  26 ATLGVEVHPLVFHtnrgPIRFNVWDTAGQEKFGGLRDGYYIQGQCAIIMFDVTARvtyKNVPNWHRDLVRV-----CENI 100

                           90       100
                   ....*....|....*....|...
gi 1958660385  161 SVLIFANKQDVKDSMTTAEISQF 183
Cdd:smart00176 101 PIVLCGNKVDVKDRKVKAKSITF 123

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 1958660385  88 STIG----SNVEEIVFQRTHFLMWDLGGQEALRSTWETYYSNAEFVILVIDSTDR---NRLSTSREElykiLAHEALQDA 160
Cdd:pfam00071  30 PTIGvdfyTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYDITSRdsfENVKKWVEE----ILRHADENV 105