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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039762225   1 MNEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRK 80
Cdd:pfam00025  22 LGEIVTTIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADRDRIEEAKEELHALLNEEELAD 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039762225  81 AAVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTSRI 139
Cdd:pfam00025 102 APLLILANKQDLPGAMSEAEIRELLGLHELKDRPWEIQGCSAVTGEGLDEGLDWLSNYI 160

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 1039762225    1 MNEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRK 80
Cdd:smart00177  35 LGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRD 114

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039762225   81 AAVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTSRI 139
Cdd:smart00177 115 AVILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNNL 173

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039762225   9 PTIGSNVEEIVVK----NTHFLMWDIGGQ---ESLRSSWNTYYSNTEFIILVVDSidreRLAITKEELYRMLAH-EDLRK 80
Cdd:COG1100    35 STNGVTIDKKELKldglDVDLVIWDTPGQdefRETRQFYARQLTGASLYLFVVDG----TREETLQSLYELLESlRRLGK 110

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039762225  81 AA-VLIFANKQDMkgcMTAAEISKYLTLSSI--KDHPWHIQSCCALTGEGL 128
Cdd:COG1100   111 KSpIILVLNKIDL---YDEEEIEDEERLKEAlsEDNIVEVVATSAKTGEGV 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 1039762225   2 NEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRKA 81
Cdd:cd00878    22 GEVVTTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDRERIEEAKNELHKLLNEEELKGA 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039762225  82 AVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTSR 138
Cdd:cd00878   102 PLLILANKQDLPGALTESELIELLGLESIKGRRWHIQPCSAVTGDGLDEGLDWLIEQ 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 1039762225   1 MNEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRK 80
Cdd:cd04151    21 VGEVVTTIPTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAIIYVVDSTDRDRLGISKSELHAMLEEEELKD 100

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039762225  81 AAVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTSR 138
Cdd:cd04151   101 AVLLVFANKQDMPGALSEAEVAEKLGLSELKDRTWQIFKTSATKGEGLDEGMDWLVNT 158

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 1039762225    1 MNEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRK 80
Cdd:smart00177  35 LGESVTTIPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRD 114

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039762225   81 AAVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTSRI 139
Cdd:smart00177 115 AVILVFANKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNNL 173

ADP-ribosylation factor; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039762225   1 MNEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRK 80
Cdd:PLN00223   39 LGEIVTTIPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRDRVVEARDELHRMLNEDELRD 118

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039762225  81 AAVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTSRIGVR 142
Cdd:PLN00223  119 AVLLVFANKQDLPNAMNAAEITDKLGLHSLRQRHWYIQSTCATSGEGLYEGLDWLSNNIANK 180

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 1039762225   1 MNEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRK 80
Cdd:cd04149    31 LGQSVTTIPTVGFNVETVTYKNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIFVVDSADRDRIDEARQELHRIINDREMRD 110

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039762225  81 AAVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTS 137
Cdd:cd04149   111 ALLLVFANKQDLPDAMKPHEIQEKLGLTRIRDRNWYVQPSCATSGDGLYEGLTWLSS 167

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 1039762225   6 HTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDL--RKAAV 83
Cdd:cd04157    28 NIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDRLRMVVAKDELELLLNHPDIkhRRIPI 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039762225  84 LIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTS 137
Cdd:cd04157   108 LFYANKMDLPDALTAVKITQLLCLENIKDKPWHIFASSALTGEGLDEGVDWLQA 161

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 1039762225   3 EVVHTSPTIGSNVEEI-VVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRKA 81
Cdd:cd04156    23 ELVTTIPTVGFNVEMLqLEKHLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVDSSDEARLDESQKELKHILKNEHIKGV 102

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039762225  82 AVLIFANKQDMKGCMTAAEISKYLTLSSI-KDHPWHIQSCCALTGEGLCQGLEWMTS 137
Cdd:cd04156   103 PVVLLANKQDLPGALTAEEITRRFKLKKYcSDRDWYVQPCSAVTGEGLAEAFRKLAS 159

(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 1039762225   2 NEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRKA 81
Cdd:cd04158    22 DEFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHRDRVSEAHSELAKLLTEKELRDA 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039762225  82 AVLIFANKQDMKGCMTAAEISKYLTLSSI-KDHPWHIQSCCALTGEGLCQGLEWMTSRI 139
Cdd:cd04158   102 LLLIFANKQDVAGALSVEEMTELLSLHKLcCGRSWYIQGCDARSGMGLYEGLDWLSRQL 160

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 1039762225   2 NEVVHTSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRKA 81
Cdd:cd00879    42 DRLAQHVPTLHPTSEELTIGNVKFTTFDLGGHEQARRVWKDYFPEVDGIVFLVDAADPERFQESKEELDSLLNDEELANV 121

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039762225  82 AVLIFANKQDMKGCMTAAEISKYLTLS---------SIKD---HPWHIQSCCALTGEGLCQGLEWM 135
Cdd:cd00879   122 PILILGNKIDKPGAVSEEELREALGLYgtttgkggvSLKVsniRPVEVFMCSVVKRQGYGEGFRWL 187

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 1039762225   7 TSPTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRKAAVLIF 86
Cdd:cd04161    27 VAPTVGFTPTKLRLDKYEVCIFDLGGGANFRGIWVNYYAEAHGLVFVVDSSDDDRVQEVKEILRELLQHPRVSGKPILVL 106

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039762225  87 ANKQDMKGCMTAAEISKYLTLSSIKDH---PWHIQSCCALTGEG------LCQGLEWM 135
Cdd:cd04161   107 ANKQDKKNALLGADVIEYLSLEKLVNEnksLCHIEPCSAIEGLGkkidpsIVEGLRWL 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 1039762225   6 HTSPTIGSNVE--EIVVKNTHFLMWDIGGQESLRSSWNT-----YYSNTEFIILVVDSIDRERLaitKEELYRMLAHEDL 78
Cdd:cd00882    28 VPGTTRDPDVYvkELDKGKVKLVLVDTPGLDEFGGLGREelarlLLRGADLILLVVDSTDRESE---EDAKLLILRRLRK 104

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039762225  79 RKAAVLIFANKQDMKGCMTAAEISKYLTLSSIKDHPwhIQSCCALTGEGLCQGLEWMTS 137
Cdd:cd00882   105 EGIPIILVGNKIDLLEEREVEELLRLEELAKILGVP--VFEVSAKTGEGVDELFEKLIE 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039762225   4 VVHTS-PTIGSNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVV------------DSIDR--ERLAITKEe 68
Cdd:pfam00503 147 ILRARvKTTGIIETKFEFKGLKFRLFDVGGQRSERKKWIHCFEDVTAIIFVVslseydqvlyedDSTNRmeESLKLFEE- 225

                          90       100
                  ....*....|....*....|....
gi 1039762225  69 lyrMLAHEDLRKAAVLIFANKQDM 92
Cdd:pfam00503 226 ---ICNSPWFKNTPIILFLNKKDL 246

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 1039762225   4 VVHTSPTIGSNVEEIVV----KNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDR-ERLAITKEELYRMLAHEDL 78
Cdd:TIGR00231  28 ITEYYPGTTRNYVTTVIeedgKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVFDIVILvLDVEEILEKQTKEIIHHAD 107

                          90
                  ....*....|....*.
gi 1039762225  79 RKAAVLIFANKQDMKG 94
Cdd:TIGR00231 108 SGVPIILVGNKIDLKD 123

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 1039762225   6 HTSPTIGSN--VEEIVVKNTHFLM--WDIGGQESLRSSWNTYYSNTEFIILVVDsidrerlaITKEELYRMLA--HEDLR 79
Cdd:cd00154    28 NYKSTIGVDfkSKTIEVDGKKVKLqiWDTAGQERFRSITSSYYRGAHGAILVYD--------VTNRESFENLDkwLNELK 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039762225  80 KAA-----VLIFANKQDMKG--CMTAAEISKYltlssIKDHPWHIQSCCALTGEG 127
Cdd:cd00154   100 EYAppnipIILVGNKSDLEDerQVSTEEAQQF-----AKENGLLFFETSAKTGEN 149

Rab family protein; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039762225  27 MWDIGGQESLRSSWNTYYSNTEFIILVVDsidrerlaITKEELYRMLAH--EDLRKAA-----VLIFANKQDM 92
Cdd:PLN03108   59 IWDTAGQESFRSITRSYYRGAAGALLVYD--------ITRRETFNHLASwlEDARQHAnanmtIMLIGNKCDL 123

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 1039762225   7 TSPTIG----SNVEEIVVKNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEEL--YRMLAHEDLrk 80
Cdd:cd04113    29 SNHTIGvefgSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVYDITSRESFNALTNWLtdARTLASPDI-- 106

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039762225  81 aAVLIFANKQDMK--GCMTAAEISKYltlssIKDHPWHIQSCCALTGEGL 128
Cdd:cd04113   107 -VIILVGNKKDLEddREVTFLEASRF-----AQENGLLFLETSALTGENV 150

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 1039762225  27 MWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRKAAVLIFANKQDMKGCMTAAEISK-YL 105
Cdd:cd04108    53 LWDTAGQERFKCIASTYYRGAQAIIIVFDLTDVASLEHTRQWLEDALKENDPSSVLLFLVGTKKDLSSPAQYALMEQdAI 132

                          90       100
                  ....*....|....*....|....
gi 1039762225 106 TLS-SIKDHPWhiqSCCALTGEGL 128
Cdd:cd04108   133 KLArEMKAEYW---AVSALTGENV 153

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 1039762225   9 PTIG--SNVEEIVVKNTHFLM--WDIGGQE---SLRSSwntYYSNTEFIILVVDsidrerlaITKEELYRMLA--HEDLR 79
Cdd:pfam00071  30 PTIGvdFYTKTIEVDGKTVKLqiWDTAGQErfrALRPL---YYRGADGFLLVYD--------ITSRDSFENVKkwVEEIL 98

                          90
                  ....*....|....*....
gi 1039762225  80 KAA-----VLIFANKQDMK 93
Cdd:pfam00071  99 RHAdenvpIVLVGNKCDLE 117

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039762225  27 MWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKE---ELYRmLAHEDLRKaavLIFANKQDMK 93
Cdd:cd01869    55 IWDTAGQERFRTITSSYYRGAHGIIIVYDVTDQESFNNVKQwlqEIDR-YASENVNK---LLVGNKCDLT 120

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039762225   7 TSPTIGSN--VEEIVV--KNTHFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRE 60
Cdd:cd01863    29 LSSTIGVDfkVKTVTVdgKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVYDVTRRD 86