P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  19 CILILGLDNAGKTTFLEQSKTRFNKNYKGMSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIY 98
Cdd:cd04160    1 CVLILGLDNAGKTTFLEQTKTKFSKNYKGLNPSKITPTVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAESHGVIY 80

                         90       100
                 ....*....|....*....|..
gi 388890214  99 VIDSTDEERLAESKQAFDVPLN 120
Cdd:cd04160   81 VIDSTDRERFNESKSAFEKVIN 102

Arf-related protein 1 (Arfrp1); Arfrp1 (Arf-related protein 1), formerly known as ARP, is a membrane-associated Arf family member that lacks the N-terminal myristoylation motif. Arfrp1 is mainly associated with the trans-Golgi compartment and the trans-Golgi network, where it regulates the targeting of Arl1 and the GRIP domain-containing proteins, golgin-97 and golgin-245, onto Golgi membranes. It is also involved in the anterograde transport of the vesicular stomatitis virus G protein from the Golgi to the plasma membrane, and in the retrograde transport of TGN38 and Shiga toxin from endosomes to the trans-Golgi network. Arfrp1 also inhibits Arf/Sec7-dependent activation of phospholipase D. Deletion of Arfrp1 in mice causes embryonic lethality at the gastrulation stage and apoptosis of mesodermal cells, indicating its importance in development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  19 CILILGLDNAGKTTFLEQSKTRFNKNYKGMSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIY 98
Cdd:cd04160    1 CVLILGLDNAGKTTFLEQTKTKFSKNYKGLNPSKITPTVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAESHGVIY 80

                         90       100
                 ....*....|....*....|..
gi 388890214  99 VIDSTDEERLAESKQAFDVPLN 120
Cdd:cd04160   81 VIDSTDRERFNESKSAFEKVIN 102

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214   1 MYTLLSGLYKYMFQKDEYCILILGLDNAGKTTFLeqsktrfnknYKgMSLSKITTT---VGLNIGTVDVGKARLMFWDLG 77
Cdd:PTZ00133   1 MGLWLSSAFKSLFGKKEVRILMVGLDAAGKTTIL----------YK-LKLGEVVTTiptIGFNVETVEYKNLKFTMWDVG 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 388890214  78 GQEELQSLWDKYYAECHGVIYVIDSTDEERLAESKQAFDVPLN 120
Cdd:PTZ00133  70 GQDKLRPLWRHYYQNTNGLIFVVDSNDRERIGDAREELERMLS 112

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 388890214   20 ILILGLDNAGKTTFLEqsKTRFNKNYKGMSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIYV 99
Cdd:TIGR00231   4 IVIVGHPNVGKSTLLN--SLLGNKGSITEYYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRV 81

                  ....
gi 388890214  100 IDST 103
Cdd:TIGR00231  82 FDIV 85

Arf-related protein 1 (Arfrp1); Arfrp1 (Arf-related protein 1), formerly known as ARP, is a membrane-associated Arf family member that lacks the N-terminal myristoylation motif. Arfrp1 is mainly associated with the trans-Golgi compartment and the trans-Golgi network, where it regulates the targeting of Arl1 and the GRIP domain-containing proteins, golgin-97 and golgin-245, onto Golgi membranes. It is also involved in the anterograde transport of the vesicular stomatitis virus G protein from the Golgi to the plasma membrane, and in the retrograde transport of TGN38 and Shiga toxin from endosomes to the trans-Golgi network. Arfrp1 also inhibits Arf/Sec7-dependent activation of phospholipase D. Deletion of Arfrp1 in mice causes embryonic lethality at the gastrulation stage and apoptosis of mesodermal cells, indicating its importance in development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  19 CILILGLDNAGKTTFLEQSKTRFNKNYKGMSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIY 98
Cdd:cd04160    1 CVLILGLDNAGKTTFLEQTKTKFSKNYKGLNPSKITPTVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAESHGVIY 80

                         90       100
                 ....*....|....*....|..
gi 388890214  99 VIDSTDEERLAESKQAFDVPLN 120
Cdd:cd04160   81 VIDSTDRERFNESKSAFEKVIN 102

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214   20 ILILGLDNAGKTTFLeqsktrfnKNYKGMSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIYV 99
Cdd:pfam00025   3 ILILGLDNAGKTTIL--------YKLKLGEIVTTIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFV 74

                          90       100
                  ....*....|....*....|.
gi 388890214  100 IDSTDEERLAESKQAFDVPLN 120
Cdd:pfam00025  75 VDSADRDRIEEAKEELHALLN 95

Arf-like 3 (Arl3) GTPase; Arl3 (Arf-like 3) is an Arf family protein that differs from most Arf family members in the N-terminal extension. In is inactive, GDP-bound form, the N-terminal extension forms an elongated loop that is hydrophobically anchored into the membrane surface; however, it has been proposed that this region might form a helix in the GTP-bound form. The delta subunit of the rod-specific cyclic GMP phosphodiesterase type 6 (PDEdelta) is an Arl3 effector. Arl3 binds microtubules in a regulated manner to alter specific aspects of cytokinesis via interactions with retinitis pigmentosa 2 (RP2). It has been proposed that RP2 functions in concert with Arl3 to link the cell membrane and the cytoskeleton in photoreceptors as part of the cell signaling or vesicular transport machinery. In mice, the absence of Arl3 is associated with abnormal epithelial cell proliferation and cyst formation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214   4 LLSGLYKYM-FQKDEYCILILGLDNAGKTTFLEQSKTRfnknykgmSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEEL 82
Cdd:cd04155    1 LLSILRKLKpSSRQEVRILLLGLDNAGKTTILKQLASE--------DISHITPTQGFNIKNVQADGFKLNVWDIGGQRKI 72

                         90       100       110
                 ....*....|....*....|....*....|....
gi 388890214  83 QSLWDKYYAECHGVIYVIDSTDEERLAESKQAFD 116
Cdd:cd04155   73 RPYWRNYFENTDVLIYVIDSADRKRFEEAGQELV 106

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214   1 MYTLLSGLYKYMFQKDEYCILILGLDNAGKTTFLeqsktrfnknYKgMSLSKITTT---VGLNIGTVDVGKARLMFWDLG 77
Cdd:PTZ00133   1 MGLWLSSAFKSLFGKKEVRILMVGLDAAGKTTIL----------YK-LKLGEVVTTiptIGFNVETVEYKNLKFTMWDVG 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 388890214  78 GQEELQSLWDKYYAECHGVIYVIDSTDEERLAESKQAFDVPLN 120
Cdd:PTZ00133  70 GQDKLRPLWRHYYQNTNGLIFVVDSNDRERIGDAREELERMLS 112

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 388890214  20 ILILGLDNAGKTTFLeqsktrfnknYKGMSLSKITT--TVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVI 97
Cdd:cd04151    2 ILILGLDGAGKTTIL----------YRLQVGEVVTTipTIGFNVETVTYKNLKFQVWDLGGQTSIRPYWRCYYSNTDAII 71

                         90
                 ....*....|....*...
gi 388890214  98 YVIDSTDEERLAESKQAF 115
Cdd:cd04151   72 YVVDSTDRDRLGISKSEL 89

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 388890214  20 ILILGLDNAGKTTFLEQSKTRFNKNykgmslSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIYV 99
Cdd:cd04157    2 ILVLGLDNSGKTTIINQLKPSNAQS------QNIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFV 75

                         90       100
                 ....*....|....*....|.
gi 388890214 100 IDSTDEERLAESKQAFDVPLN 120
Cdd:cd04157   76 IDSSDRLRMVVAKDELELLLN 96

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 388890214  20 ILILGLDNAGKTTFLeqsktrfnknYKGMSLSKITT--TVGLNIGTVDV-GKARLMFWDLGGQEELQSLWDKYYAECHGV 96
Cdd:cd04156    2 VLLLGLDSAGKSTLL----------YKLKHAELVTTipTVGFNVEMLQLeKHLSLTVWDVGGQEKMRTVWKCYLENTDGL 71

                         90       100
                 ....*....|....*....|....
gi 388890214  97 IYVIDSTDEERLAESKQAFDVPLN 120
Cdd:cd04156   72 VYVVDSSDEARLDESQKELKHILK 95

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 388890214  20 ILILGLDNAGKTTFLeqsktrfnKNYKGMSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIYV 99
Cdd:cd04161    2 LLTVGLDNAGKTTLV--------SALQGEIPKKVAPTVGFTPTKLRLDKYEVCIFDLGGGANFRGIWVNYYAEAHGLVFV 73

                         90
                 ....*....|....*
gi 388890214 100 IDSTDEERLAESKQA 114
Cdd:cd04161   74 VDSSDDDRVQEVKEI 88

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 388890214    20 ILILGLDNAGKTTFLEQSKtrfNKNYKGMSLSKITTTVGLNIGTVdvgkaRLMFWDLGGQEELQSLWDKYYAECHGVIYV 99
Cdd:smart00178  20 ILFLGLDNAGKTTLLHMLK---NDRLAQHQPTQHPTSEELAIGNI-----KFTTFDLGGHQQARRLWKDYFPEVNGIVYL 91

                           90       100
                   ....*....|....*....|.
gi 388890214   100 IDSTDEERLAESKQAFDVPLN 120
Cdd:smart00178  92 VDAYDKERFAESKRELDALLS 112

Arf-like 4 (Arl4) and 7 (Arl7) GTPases; Arl4 (Arf-like 4) is highly expressed in testicular germ cells, and is found in the nucleus and nucleolus. In mice, Arl4 is developmentally expressed during embryogenesis, and a role in somite formation and central nervous system differentiation has been proposed. Arl7 has been identified as the only Arf/Arl protein to be induced by agonists of liver X-receptor and retinoid X-receptor and by cholesterol loading in human macrophages. Arl7 is proposed to play a role in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  20 ILILGLDNAGKTTFLeqSKTRFNKnykgmsLSKITTTVGLNIGTVDV--GKAR---LMFWDLGGQEELQSLWDKYYAECH 94
Cdd:cd04152    6 IVMLGLDSAGKTTVL--YRLKFNE------FVNTVPTKGFNTEKIKVslGNAKgvtFHFWDVGGQEKLRPLWKSYTRCTD 77

                         90
                 ....*....|....*...
gi 388890214  95 GVIYVIDSTDEERLAESK 112
Cdd:cd04152   78 GIVFVVDSVDVERMEEAK 95

(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 388890214  20 ILILGLDNAGKTTFLEQSKTRfnknykgmSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIYV 99
Cdd:cd04158    2 VVTLGLDGAGKTTILFKLKQD--------EFMQPIPTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFV 73

                         90
                 ....*....|..
gi 388890214 100 IDSTDEERLAES 111
Cdd:cd04158   74 IDSSHRDRVSEA 85

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 388890214  21 LILGLDNAGKTTFLEQsktrFNKNYKGMSLSKITTTVGLNIG--TVDVGKARLMFWDLGGQEELQSLWD-----KYYAEC 93
Cdd:cd00882    1 VVVGRGGVGKSSLLNA----LLGGEVGEVSDVPGTTRDPDVYvkELDKGKVKLVLVDTPGLDEFGGLGReelarLLLRGA 76

                         90
                 ....*....|....*..
gi 388890214  94 HGVIYVIDSTDEERLAE 110
Cdd:cd00882   77 DLILLVVDSTDRESEED 93

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 388890214  20 ILILGLDNAGKTTFLEQ-SKTRFNKNYKgmslskitTTVGLNIGT----VDVGKARLMFWDLGGQEELQSLWDKYYAECH 94
Cdd:cd00154    3 IVLIGDSGVGKTSLLLRfVDNKFSENYK--------STIGVDFKSktieVDGKKVKLQIWDTAGQERFRSITSSYYRGAH 74

                         90
                 ....*....|..
gi 388890214  95 GVIYVIDSTDEE 106
Cdd:cd00154   75 GAILVYDVTNRE 86

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  20 ILILGLDNAGKTTFLEqsktRFNKNYkgMSLSKITTTVGLNIG----TVDVGKARLMFWDLGGQEELQS---LWDKYYAE 92
Cdd:COG1100    6 IVVVGTGGVGKTSLVN----RLVGDI--FSLEKYLSTNGVTIDkkelKLDGLDVDLVIWDTPGQDEFREtrqFYARQLTG 79

                         90       100
                 ....*....|....*....|..
gi 388890214  93 CHGVIYVIDSTDEERLAESKQA 114
Cdd:COG1100   80 ASLYLFVVDGTREETLQSLYEL 101

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214   6 SGLYKYMFQkdeycILILGLDNAGKTTFLeqsktrfnKNYKGMSLSKITTTVGLNIG----TVDVGKARLMFWDLGGQEE 81
Cdd:PLN03118   8 SSGYDLSFK-----ILLIGDSGVGKSSLL--------VSFISSSVEDLAPTIGVDFKikqlTVGGKRLKLTIWDTAGQER 74

                         90       100
                 ....*....|....*....|....*
gi 388890214  82 LQSLWDKYYAECHGVIYVIDSTDEE 106
Cdd:PLN03118  75 FRTLTSSYYRNAQGIILVYDVTRRE 99

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 388890214   20 ILILGLDNAGKTTFLEQ-SKTRFNKNYKgmslskitTTVGLNIGT----VDVGKARLMFWDLGGQEELQSLWDKYYAECH 94
Cdd:pfam00071   2 LVLVGDGGVGKSSLLIRfTQNKFPEEYI--------PTIGVDFYTktieVDGKTVKLQIWDTAGQERFRALRPLYYRGAD 73

                          90
                  ....*....|..
gi 388890214   95 GVIYVIDSTDEE 106
Cdd:pfam00071  74 GFLLVYDITSRD 85

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 388890214  20 ILILGLDNAGKTTFLeqskTRFNKNykgMSLSKITTTVGLN--IGTVDVG--KARLMFWDLGGQEELQSLWDKYYAECHG 95
Cdd:cd01863    3 ILLIGDSGVGKSSLL----LRFTDD---TFDEDLSSTIGVDfkVKTVTVDgkKVKLAIWDTAGQERFRTLTSSYYRGAQG 75

                         90
                 ....*....|.
gi 388890214  96 VIYVIDSTDEE 106
Cdd:cd01863   76 VILVYDVTRRD 86

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 388890214  20 ILILGLDNAGKTTFLEqsktRFNKNyKGMSLSKITTTVGLNIGTVDV--GKARLMFWDLGGQEELQSLWDKYYAECHGVI 97
Cdd:cd04120    3 VIIIGSRGVGKTSLME----RFTDD-TFCEACKSTVGVDFKIKTVELrgKKIRLQIWDTAGQERFNSITSAYYRSAKGII 77

                 ....*....
gi 388890214  98 YVIDSTDEE 106
Cdd:cd04120   78 LVYDITKKE 86

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214    20 ILILGLDNAGKTTFLEQ-SKTRFNKNYKgmslskitTTVGLNIGT----VDVGKARLMFWDLGGQEELQSLWDKYYAECH 94
Cdd:smart00175   3 IILIGDSGVGKSSLLSRfTDGKFSEQYK--------STIGVDFKTktieVDGKRVKLQIWDTAGQERFRSITSSYYRGAV 74

                           90
                   ....*....|..
gi 388890214    95 GVIYVIDSTDEE 106
Cdd:smart00175  75 GALLVYDITNRE 86

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214   9 YKYMFQkdeycILILGLDNAGKTTFLEQ-SKTRFNknykgmslSKITTTVGLNI-------------GTVDVG-KARLMF 73
Cdd:cd04127    1 YDYLIK-----LLALGDSGVGKTTFLYRyTDNKFN--------PKFITTVGIDFrekrvvynsqgpdGTSGKAfRVHLQL 67

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 388890214  74 WDLGGQEELQSLWDKYYAECHGVIYVIDSTDEERLAE 110
Cdd:cd04127   68 WDTAGQERFRSLTTAFFRDAMGFLLMFDLTSEQSFLN 104

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  29 GKTTFLEQSKT-RFNKNYKgmslskitTTVGLNIGTVD----VGKARLMFWDLGGQEELQSLWDKYYAECHGVIYVIDST 103
Cdd:cd00877   12 GKTTFVKRHLTgEFEKKYV--------ATLGVEVHPLDfhtnRGKIRFNVWDTAGQEKFGGLRDGYYIQGQCAIIMFDVT 83

                 .
gi 388890214 104 D 104
Cdd:cd00877   84 S 84

GTP-binding nuclear protein Ran; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  12 MFQKDEYCILILGLDNAGKTTFLEQSKT-RFNKNYkgmslskiTTTVGLNIGT----VDVGKARLMFWDLGGQEELQSLW 86
Cdd:PTZ00132   4 MDEVPEFKLILVGDGGVGKTTFVKRHLTgEFEKKY--------IPTLGVEVHPlkfyTNCGPICFNVWDTAGQEKFGGLR 75

                         90
                 ....*....|....*..
gi 388890214  87 DKYYAECHGVIYVIDST 103
Cdd:PTZ00132  76 DGYYIKGQCAIIMFDVT 92

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214   9 YKYMFQkdeycILILGLDNAGKTTFLEQSKtrfNKNYKGMSLSKITTTVGLNIGTVDVGKARLMFWDLGGQEELQSLWDK 88
Cdd:PLN03108   3 YAYLFK-----YIIIGDTGVGKSCLLLQFT---DKRFQPVHDLTIGVEFGARMITIDNKPIKLQIWDTAGQESFRSITRS 74

                         90
                 ....*....|....*...
gi 388890214  89 YYAECHGVIYVIDSTDEE 106
Cdd:PLN03108  75 YYRGAAGALLVYDITRRE 92

Rab GTPase family 19 (Rab19); Rab19 subfamily. Rab19 proteins are associated with Golgi stacks. Similarity analysis indicated that Rab41 is closely related to Rab19. However, the function of these Rabs is not yet characterized. 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 388890214  20 ILILGLDNAGKTTFLEQSKTrfnknykGMSLSKITTTVGLN--IGTVDVG--KARLMFWDLGGQEELQSLWDKYYAECHG 95
Cdd:cd01864    6 IILIGDSNVGKTCVVQRFKS-------GTFSERQGNTIGVDftMKTLEIQgkRVKLQIWDTAGQERFRTITQSYYRSANG 78

                 ....*...
gi 388890214  96 VIYVIDST 103
Cdd:cd01864   79 AIIAYDIT 86

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388890214  20 ILILGLDNAGKTTFLEQSKTrfnKNYKGMSLSKITTTVGLN-IGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIY 98
Cdd:cd04112    3 VMLVGDSGVGKTCLLVRFKD---GAFLAGSFIATVGIQFTNkVVTVDGVKVKLQIWDTAGQERFRSVTHAYYRDAHALLL 79

                 ....*..
gi 388890214  99 VIDSTDE 105
Cdd:cd04112   80 LYDVTNK 86

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. 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 388890214  20 ILILGLDNAGKTTFLEQSKT-RFNKNYKGmslskittTVGLNIGTVDV---GKARLM-FWDLGGQEELQSLWDKYY--AE 92
Cdd:cd01862    3 VIILGDSGVGKTSLMNQYVNkKFSNQYKA--------TIGADFLTKEVtvdDRLVTLqIWDTAGQERFQSLGVAFYrgAD 74

                         90
                 ....*....|....
gi 388890214  93 CHGVIYviDSTDEE 106
Cdd:cd01862   75 CCVLVY--DVTNPK 86