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 1867988618   8 YQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRAGPRVKLQLWDTAGHERFSTLSAE---- 83
Cdd:cd04111     1 YQFRLIVIGDSTVGKSSLLKRFTEGRFAEVSDP-----TVGVDFFSRLIEIEPGVRIKLQLWDTAGQERFRSITRSyyrn 75

                  ....
gi 1867988618  84 -VGG 86
Cdd:cd04111    76 sVGV 79

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867988618   8 YQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRAGPRVKLQLWDTAGHERFSTLSAE---- 83
Cdd:cd04111     1 YQFRLIVIGDSTVGKSSLLKRFTEGRFAEVSDP-----TVGVDFFSRLIEIEPGVRIKLQLWDTAGQERFRSITRSyyrn 75

                  ....
gi 1867988618  84 -VGG 86
Cdd:cd04111    76 sVGV 79

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867988618  11 RVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTL 80
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIP-----TIGVDFYTKTIEVD-GKTVKLQIWDTAGQERFRAL 64

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1867988618   7 RYQFRVALLGDAAVGKTSLLRSYVagapGAPEPEPEPEPTVGAECYRRALQLRAGPrVKLQLWDTAGHERF 77
Cdd:COG1100     1 MGEKKIVVVGTGGVGKTSLVNRLV----GDIFSLEKYLSTNGVTIDKKELKLDGLD-VDLVIWDTPGQDEF 66

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867988618   8 YQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRAGPRVKLQLWDTAGHERFSTLSAE---- 83
Cdd:cd04111     1 YQFRLIVIGDSTVGKSSLLKRFTEGRFAEVSDP-----TVGVDFFSRLIEIEPGVRIKLQLWDTAGQERFRSITRSyyrn 75

                  ....
gi 1867988618  84 -VGG 86
Cdd:cd04111    76 sVGV 79

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1867988618  10 FRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd00154     1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKS-----TIGVDFKSKTIEVD-GKKVKLQIWDTAGQERFRSIT 66

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1867988618  11 RVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLR--AGPRVKLQLWDTAGHERFSTL 80
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKS-----TIGVDFKTKTVLENddNGKKIKLNIWDTAGQERFRSL 67

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1867988618  10 FRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTLSA 82
Cdd:cd01862     1 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKA-----TIGADFLTKEVTVD-DRLVTLQIWDTAGQERFQSLGV 67

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 1867988618  10 FRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd04123     1 FKVVLLGEGRVGKTSLVLRYVENKFNEKHES-----TTQASFFQKTVNIG-GKRIDLAIWDTAGQERYHALG 66

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1867988618   8 YQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTLSA 82
Cdd:cd01867     2 YLFKLLLIGDSGVGKSCLLLRFSEDSFNPSFIS-----TIGIDFKIRTIELD-GKKIKLQIWDTAGQERFRTITT 70

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 1867988618   8 YQFRVALLGDAAVGKTSLL---------RSYVAgapgapepepepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFS 78
Cdd:cd01869     1 YLFKLLLIGDSGVGKSCLLlrfaddtytESYIS--------------TIGVDFKIRTIELD-GKTVKLQIWDTAGQERFR 65

                  ...
gi 1867988618  79 TLS 81
Cdd:cd01869    66 TIT 68

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1867988618   8 YQFRVALLGDAAVGKTSLLRSYvagapGAPEPEPEPEPTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd01864     2 FLFKIILIGDSNVGKTCVVQRF-----KSGTFSERQGNTIGVDFTMKTLEIQ-GKRVKLQIWDTAGQERFRTIT 69

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867988618  10 FRVALLGDAAVGKTSLL---------RSYVAgapgapepepepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTL 80
Cdd:cd04110     7 FKLLIIGDSGVGKSSLLlrfadntfsGSYIT--------------TIGVDFKIRTVEIN-GERVKLQIWDTAGQERFRTI 71

                  ..
gi 1867988618  81 SA 82
Cdd:cd04110    72 TS 73

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. 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 1867988618  11 RVALLGDAAVGKTSLLRSYVagapgAPEPEPEPEPTVGAECYRRALQLR-AGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd04106     2 KVIVVGNGNVGKSSMIQRFV-----KGIFTKDYKKTIGVDFLEKQIFLRqSDEDVRLMLWDTAGQEEFDAIT 68

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1867988618   7 RYQFRVALLGDAAVGKTSLLRSYVagapGAPEPEPEPEPTVGAECYRRALQLRAGPrVKLQLWDTAGHERF 77
Cdd:COG1100     1 MGEKKIVVVGTGGVGKTSLVNRLV----GDIFSLEKYLSTNGVTIDKKELKLDGLD-VDLVIWDTPGQDEF 66

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. 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 1867988618   9 QFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTL 80
Cdd:cd01860     1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQES-----TIGAAFLTQTVNLD-DTTVKFEIWDTAGQERYRSL 66

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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 1867988618  10 FRVALLGDAAVGKTSLLRSYvagapGAPEPEPEPEPTVGAEcYRRALQLRAGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd01865     2 FKLLIIGNSSVGKTSFLFRY-----ADDSFTSAFVSTVGID-FKVKTVYRNDKRIKLQIWDTAGQERYRTIT 67

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1867988618  10 FRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLrAGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd04113     1 FKFLIIGSAGTGKSCLLHQFIENKFKQDSNH-----TIGVEFGSRVVNV-GGKSVKLQIWDTAGQERFRSVT 66

Ras homology family 4 (Rho4) of small guanosine triphosphatases (GTPases)-like; Rho4 is a GTPase that controls septum degradation by regulating secretion of Eng1 or Agn1 during cytokinesis. Rho4 also plays a role in cell morphogenesis. Rho4 regulates septation and cell morphology by controlling the actin cytoskeleton and cytoplasmic microtubules. The localization of Rho4 is modulated by Rdi1, which may function as a GDI, and by Rga9, which is believed to function as a GAP. In S. pombe, both Rho4 deletion and Rho4 overexpression result in a defective cell wall, suggesting a role for Rho4 in maintaining cell wall integrity. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1867988618   7 RYQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVgAECYRRALQLRAGPRVKLQLWDTAGHERFSTL 80
Cdd:cd04132     1 DLKVKIVVVGDGGCGKTCLLMVYAQGSFPEEYVP-----TV-FENYVTTLQVPNGKIIELALWDTAGQEDYDRL 68

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of 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 1867988618   8 YQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLrAGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd04122     1 YIFKYIIIGDMGVGKSCLLHQFTEKKFMADCPH-----TIGVEFGTRIIEV-NGQKIKLQIWDTAGQERFRAVT 68

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1867988618  10 FRVALLGDAAVGKTSLLRSYvagapGAPEPEPEPEPTVGAECYRRALQLRAGPRVKLQLWDTAG 73
Cdd:cd04109     1 IKIVVLGDGASGKTSLIRRF-----AQEGFGKSYKQTIGLDFFSRRITLPGSLNVTLQVWDIGG 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1867988618  10 FRVALLGDAAVGKTSLLRSYVAGAPGAPEPEPEPEPTVGAECYRRAlqlraGPRVKLQLWDTAGHERFSTLS 81
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLGNKGSITEYYPGTTRNYVTTVIEED-----GKTYKFNLLDTAGQEDYDAIR 68

Rab GTPase family 2 (Rab2); Rab2 is localized on cis-Golgi membranes and interacts with Golgi matrix proteins. Rab2 is also implicated in the maturation of vesicular tubular clusters (VTCs), which are microtubule-associated intermediates in transport between the ER and Golgi apparatus. In plants, Rab2 regulates vesicle trafficking between the ER and the Golgi bodies and is important to pollen tube growth. 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 1867988618   8 YQFRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRaGPRVKLQLWDTAGHERFSTLS 81
Cdd:cd01866     3 YLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDL-----TIGVEFGARMITID-GKQIKLQIWDTAGQESFRSIT 70

GTP-binding nuclear protein Ran; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1867988618   1 MEAEGCRYQFRVALLGDAAVGKTSLL---------RSYVagapgapepepepePTVGAECYRRALQLRAGPrVKLQLWDT 71
Cdd:PTZ00132    1 MQQMDEVPEFKLILVGDGGVGKTTFVkrhltgefeKKYI--------------PTLGVEVHPLKFYTNCGP-ICFNVWDT 65

                  ....*....
gi 1867988618  72 AGHERFSTL 80
Cdd:PTZ00132   66 AGQEKFGGL 74

Rab GTPase family 40 (Rab40) contains Rab40a, Rab40b and Rab40c; The Rab40 subfamily contains Rab40a, Rab40b, and Rab40c, which are all highly homologous. In rat, Rab40c is localized to the perinuclear recycling compartment (PRC), and is distributed in a tissue-specific manor, with high expression in brain, heart, kidney, and testis, low expression in lung and liver, and no expression in spleen and skeletal muscle. Rab40c is highly expressed in differentiated oligodendrocytes but minimally expressed in oligodendrocyte progenitors, suggesting a role in the vesicular transport of myelin components. Unlike most other Ras-superfamily proteins, Rab40c was shown to have a much lower affinity for GTP, and an affinity for GDP that is lower than for GTP. 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 1867988618   8 YQFRVALLGDAAVGKTSLLRSYvagapGAPEPEPEPEPTVGAEcYRRALQLRAGPRVKLQLWDTAGHERFSTL 80
Cdd:cd04121     5 YLLKFLLVGDSDVGKGEILASL-----QDGSTESPYGYNMGID-YKTTTILLDGRRVKLQLWDTSGQGRFCTI 71

Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 responsive Cdc42 homolog) is a Rho family GTPase that shares significant sequence and functional similarity with Cdc42. Wrch-1 was first identified in mouse mammary epithelial cells, where its transcription is upregulated in Wnt-1 transformation. Wrch-1 contains N- and C-terminal extensions relative to cdc42, suggesting potential differences in cellular localization and function. The Wrch-1 N-terminal extension contains putative SH3 domain-binding motifs and has been shown to bind the SH3 domain-containing protein Grb2, which increases the level of active Wrch-1 in cells. Unlike Cdc42, which localizes to the cytosol and perinuclear membranes, Wrch-1 localizes extensively with the plasma membrane and endosomes. The membrane association, localization, and biological activity of Wrch-1 indicate an atypical model of regulation distinct from other Rho family GTPases. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1867988618  14 LLGDAAVGKTSLLRSYVAGAPGAPEPEPEPeptvgaECYRRALQLRAGPrVKLQLWDTAGHERFSTL 80
Cdd:cd04130     5 LVGDGAVGKTSLIVSYTTNGYPTEYVPTAF------DNFSVVVLVDGKP-VRLQLCDTAGQDEFDKL 64

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1867988618  13 ALLGDAAVGKTSLLRSYVagAPGAPEPEPEPEPTVGAECYRRALQlraGPRVKLQLWDTAGHERFSTLSAE 83
Cdd:cd00882     1 VVVGRGGVGKSSLLNALL--GGEVGEVSDVPGTTRDPDVYVKELD---KGKVKLVLVDTPGLDEFGGLGRE 66

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 1867988618  10 FRVALLGDAAVGKTSLLR---------SYVAgapgapepepepepTVGAECYRRALQLRAGPrVKLQLWDTAGHERFSTL 80
Cdd:cd00877     1 FKLVLVGDGGTGKTTFVKrhltgefekKYVA--------------TLGVEVHPLDFHTNRGK-IRFNVWDTAGQEKFGGL 65

                  .
gi 1867988618  81 S 81
Cdd:cd00877    66 R 66

GTP-binding nuclear protein Ran; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1867988618  10 FRVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVGAECYRRALQLRAGPrVKLQLWDTAGHERFSTL 80
Cdd:PLN03071   14 FKLVIVGDGGTGKTTFVKRHLTGEFEKKYEP-----TIGVEVHPLDFFTNCGK-IRFYCWDTAGQEKFGGL 78

Ras homolog family, member G (RhoG) of small guanosine triphosphatases (GTPases); RhoG is a GTPase with high sequence similarity to members of the Rac subfamily, including the regions involved in effector recognition and binding. However, RhoG does not bind to known Rac1 and Cdc42 effectors, including proteins containing a Cdc42/Rac interacting binding (CRIB) motif. Instead, RhoG interacts directly with Elmo, an upstream regulator of Rac1, in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1. The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor. Thus RhoG activates Rac1 through Elmo and Dock180 to control cell morphology. RhoG has also been shown to play a role in caveolar trafficking and has a novel role in signaling the neutrophil respiratory burst stimulated by G protein-coupled receptor (GPCR) agonists. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1867988618  11 RVALLGDAAVGKTSLLRSYVAGAPGAPEPEPEPEPTVGAECYRralqlraGPRVKLQLWDTAGHE---RFSTLS 81
Cdd:cd01875     5 KCVVVGDGAVGKTCLLICYTTNAFPKEYIPTVFDNYSAQTAVD-------GRTVSLNLWDTAGQEeydRLRTLS 71

Rho family GTPase subfamily Rnd includes Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8; The Rnd subfamily contains Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8. These novel Rho family proteins have substantial structural differences compared to other Rho members, including N- and C-terminal extensions relative to other Rhos. Rnd3/RhoE is farnesylated at the C-terminal prenylation site, unlike most other Rho proteins that are geranylgeranylated. In addition, Rnd members are unable to hydrolyze GTP and are resistant to GAP activity. They are believed to exist only in the GTP-bound conformation, and are antagonists of RhoA activity. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1867988618  11 RVALLGDAAVGKTSLLRSYVAGAPGAPEPEpepepTVgAECYRRALQLRaGPRVKLQLWDTAGHERF 77
Cdd:cd04131     3 KIVLVGDSQCGKTALLQVFAKDSFPENYVP-----TV-FENYTASFEVD-KQRIELSLWDTSGSPYY 62