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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   1 MVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIR 54
Cdd:cd04138   109 MVLVGNKCDLAARTVSTRQGQDLAKSYGIPYIETSAKTRQGVEEAFYTLVREIR 162

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras 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 Ras 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 2186152419   1 MVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIR 54
Cdd:cd04138   109 MVLVGNKCDLAARTVSTRQGQDLAKSYGIPYIETSAKTRQGVEEAFYTLVREIR 162

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRK 55
Cdd:pfam00071 107 IVLVGNKCDLEDqRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEELAREILK 162

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2186152419   1 MVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVR 51
Cdd:TIGR00231 112 IILVGNKIDLKDADLKTHVASEFAKLNGEPIIPLSAETGKNIDSAFKIVEA 162

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras 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 Ras 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 2186152419   1 MVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIR 54
Cdd:cd04138   109 MVLVGNKCDLAARTVSTRQGQDLAKSYGIPYIETSAKTRQGVEEAFYTLVREIR 162

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2186152419    1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKH 56
Cdd:smart00010 110 IVLVGNKCDLENeRVVSTEEGKELARQWGCPFLETSAKERINVDEAFYDLVREIRKS 166

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras 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 Ras 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 2186152419   1 MVLVGNKCDL-PSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd00876   107 IVLVGNKCDLeNERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNTLVREI 160

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2186152419    2 VLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:smart00175 109 MLVGNKSDLEEqRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEELAREI 161

Ras-like protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRK 55
Cdd:PTZ00369  113 MILVGNKCDLDSeRQVSTGEGQELAKSFGIPFLETSAKQRVNVDEAFYELVREIRK 168

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   3 LVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRK 55
Cdd:cd01869   112 LVGNKCDLTDkKVVDYTEAKEFADELGIPFLETSAKNATNVEEAFMTMAREIKK 165

R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, and related members of the Ras family. M-Ras is expressed in lympho-hematopoetic cells. It interacts with some of the known Ras effectors, but appears to also have its own effectors. Expression of mutated M-Ras leads to transformation of several types of cell lines, including hematopoietic cells, mammary epithelial cells, and fibroblasts. Overexpression of M-Ras is observed in carcinomas from breast, uterus, thyroid, stomach, colon, kidney, lung, and rectum. In addition, expression of a constitutively active M-Ras mutant in murine bone marrow induces a malignant mast cell leukemia that is distinct from the monocytic leukemia induced by H-Ras. TC21, along with H-Ras, has been shown to regulate the branching morphogenesis of ureteric bud cell branching in mice. Most Ras 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 Ras 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 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIR 54
Cdd:cd04145   110 MILVGNKADLEHqRQVSREEGQELARQLKIPYIETSAKDRVNVDKAFHDLVRVIR 164

Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap subfamily of the Ras family. It can be further divided into the Rap1a and Rap1b isoforms. In humans, Rap1a and Rap1b share 95% sequence homology, but are products of two different genes located on chromosomes 1 and 12, respectively. Rap1a is sometimes called smg p21 or Krev1 in the older literature. Rap1 proteins are believed to perform different cellular functions, depending on the isoform, its subcellular localization, and the effector proteins it binds. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and the microsomal membrane of pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. High expression of Rap1 has been observed in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines; interestingly, in the SCCs, the active GTP-bound form localized to the nucleus, while the inactive GDP-bound form localized to the cytoplasm. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap1a, which is stimulated by T-cell receptor (TCR) activation, is a positive regulator of T cells by directing integrin activation and augmenting lymphocyte responses. In murine hippocampal neurons, Rap1b determines which neurite will become the axon and directs the recruitment of Cdc42, which is required for formation of dendrites and axons. In murine platelets, Rap1b is required for normal homeostasis in vivo and is involved in integrin activation. Most Ras 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 Ras 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 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRK 55
Cdd:cd04175   109 MILVGNKCDLEDeRVVGKEQGQNLARQWGCAFLETSAKAKINVNEIFYDLVRQINR 164

Rab GTPase family 11 (Rab11)-like includes Rab11a, Rab11b, and Rab25; Rab11a, Rab11b, and Rab25 are closely related, evolutionary conserved Rab proteins that are differentially expressed. Rab11a is ubiquitously synthesized, Rab11b is enriched in brain and heart and Rab25 is only found in epithelia. Rab11/25 proteins seem to regulate recycling pathways from endosomes to the plasma membrane and to the trans-Golgi network. Furthermore, Rab11a is thought to function in the histamine-induced fusion of tubulovesicles containing H+, K+ ATPase with the plasma membrane in gastric parietal cells and in insulin-stimulated insertion of GLUT4 in the plasma membrane of cardiomyocytes. Overexpression of Rab25 has recently been observed in ovarian cancer and breast cancer, and has been correlated with worsened outcomes in both diseases. In addition, Rab25 overexpression has also been observed in prostate cancer, transitional cell carcinoma of the bladder, and invasive breast tumor cells. 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 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd01868   111 IMLVGNKSDLRHlRAVPTEEAKAFAEKNGLSFIETSALDGTNVEEAFKQLLTEI 164

Ras-like protein in all tissues (Rit), Ras-like protein in neurons (Rin) and Ras-related protein which interacts with calmodulin (Ric); Rit (Ras-like protein in all tissues), Rin (Ras-like protein in neurons) and Ric (Ras-related protein which interacts with calmodulin) form a subfamily with several unique structural and functional characteristics. These proteins all lack a the C-terminal CaaX lipid-binding motif typical of Ras family proteins, and Rin and Ric contain calmodulin-binding domains. Rin, which is expressed only in neurons, induces neurite outgrowth in rat pheochromocytoma cells through its association with calmodulin and its activation of endogenous Rac/cdc42. Rit, which is ubiquitously expressed in mammals, inhibits growth-factor withdrawl-mediated apoptosis and induces neurite extension in pheochromocytoma cells. Rit and Rin are both able to form a ternary complex with PAR6, a cell polarity-regulating protein, and Rac/cdc42. This ternary complex is proposed to have physiological function in processes such as tumorigenesis. Activated Ric is likely to signal in parallel with the Ras pathway or stimulate the Ras pathway at some upstream point, and binding of calmodulin to Ric may negatively regulate Ric activity.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRK 55
Cdd:cd04141   110 LVLVGNKVDLEQqRQVTTEEGRNLAREFNCPFFETSAALRFYIDDAFHGLVREIRR 165

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd04123   108 LVIVGNKIDLERqRVVSKSEAEEYAKSVGAKHFETSAKTGKGIEELFLSLAKRM 161

Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, and RSR1. Rap subfamily proteins perform different cellular functions, depending on the isoform and its subcellular localization. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and microsomal membrane of the pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. Rap1 localizes in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap2 is involved in multiple functions, including activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton and activation of the Wnt/beta-catenin signaling pathway in embryonic Xenopus. A number of effector proteins for Rap2 have been identified, including isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK), and the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. RSR1 is the fungal homolog of Rap1 and Rap2. In budding yeasts, it is involved in selecting a site for bud growth, which directs the establishment of cell polarization. The Rho family GTPase Cdc42 and its GEF, Cdc24, then establish an axis of polarized growth. It is believed that Cdc42 interacts directly with RSR1 in vivo. In filamentous fungi such as Ashbya gossypii, RSR1 is a key regulator of polar growth in the hypha. Most Ras 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 Ras 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 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYG-IPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd04136   109 MILVGNKCDLEDeRVVSKEEGQNLARQWGnCPFLETSAKSKINVDEIFYDLVRQI 163

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2186152419   2 VLVGNKCDL-PSRTVDTKQAQDLARSYG-IPFIETSAKTRQGVDDAFYTLVR 51
Cdd:cd01862   113 VVLGNKIDLeEKRQVSTKKAQQWCKSKGnIPYFETSAKEAINVDQAFETIAR 164

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRK 55
Cdd:cd01866   112 IMLIGNKCDLESrREVSYEEGEAFAREHGLIFMETSAKTASNVEEAFINTAKEIYD 167

Rab family protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2186152419   1 MVLVGNKCDLP-SRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRK 55
Cdd:PLN03108  114 IMLIGNKCDLAhRRAVSTEEGEQFAKEHGLIFMEASAKTAQNVEEAFIKTAAKIYK 169

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. 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
                  ....*....|....*....|....*....|....*....|....*.
gi 2186152419   2 VLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAF 46
Cdd:cd01861   109 VLVGNKTDLSDkRQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLF 154

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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2186152419   2 VLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd04111   113 ILVGHKCDLESqRQVTREEAEKLAKDLGMKYIETSARTGDNVEEAFELLTQEI 165

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIrKHK 57
Cdd:cd04112   109 IMLLGNKADMSGeRVVKREDGERLAKEYGVPFMETSAKTGLNVELAFTAVAKEL-KHR 165

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2186152419   2 VLVGNKCDLPSR-TVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHK 57
Cdd:cd04110   114 VLVGNKNDDPERkVVETEDAYKFAGQMGISLFETSAKENINVEEMFNCITELVLRAK 170

Rab GTPase-like family 4 (Rab-like4); RabL4 (Rab-like4) subfamily. RabL4s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL4 lacks a prenylation site at the C-terminus. The specific function of RabL4 remains unknown.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2186152419   2 VLVGNKCDLPSRT-VDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVR 51
Cdd:cd04101   114 VLVGNKCDLTDRReVDAAQAQALAQANTLKFYETSAKEGVGYEAPFLSLAR 164

Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. 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 2186152419   2 VLVGNKCDLPSRTVDTKQAQDLARSYGI-PFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd04116   118 VILGNKIDIPERQVSTEEAQAWCRDNGDyPYFETSAKDATNVAAAFEEAVRRV 170

Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, Gem/Kir) subfamily of Ras GTPases are expressed in a tissue-specific manner and are dynamically regulated by transcriptional and posttranscriptional mechanisms in response to environmental cues. RGK proteins bind to the beta subunit of L-type calcium channels, causing functional down-regulation of these voltage-dependent calcium channels, and either termination of calcium-dependent secretion or modulation of electrical conduction and contractile function. Inhibition of L-type calcium channels by Rem2 may provide a mechanism for modulating calcium-triggered exocytosis in hormone-secreting cells, and has been proposed to influence the secretion of insulin in pancreatic beta cells. RGK proteins also interact with and inhibit the Rho/Rho kinase pathway to modulate remodeling of the cytoskeleton. Two characteristics of RGK proteins cited in the literature are N-terminal and C-terminal extensions beyond the GTPase domain typical of Ras superfamily members. The N-terminal extension is not conserved among family members; the C-terminal extension is reported to be conserved among the family and lack the CaaX prenylation motif typical of membrane-associated Ras proteins. However, a putative CaaX motif has been identified in the alignment of the C-terminal residues of this CD.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   2 VLVGNKCDLP-SRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIR 54
Cdd:cd04148   110 ILVGNKSDLVrSREVSVQEGRACAVVFDCKFIETSAALQHNVDELFEGIVRQVR 163

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   1 MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd04113   108 IILVGNKKDLEDdREVTFLEASRFAQENGLLFLETSALTGENVEEAFLKCARSI 161

Rab family protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2186152419   2 VLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:PLN03118  124 MLVGNKVDRESeRDVSREEGMALAKEHGCLFLECSAKTRENVEQCFEELALKI 176

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   1 MVLVGNKCDLP-SRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd04122   110 IFLIGNKADLEaQRDVTYEEAKQFADENGLLFLECSAKTGENVEDAFLETAKKI 163

GTPase CgtA; Reviewed

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2186152419   2 VLVGNKCD-LPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKE 58
Cdd:PRK12299  275 ILVLNKIDlLDEEEEREKRAALELAALGGPVFLISAVTGEGLDELLRALWELLEEARR 332

GTP-binding nuclear protein Ran; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2186152419   1 MVLVGNKCDLPSRTVDTKQAQdLARSYGIPFIETSAKTRQGVDDAFYTLVREI 53
Cdd:PTZ00132  116 IVLVGNKVDVKDRQVKARQIT-FHRKKNLQYYDISAKSNYNFEKPFLWLARRL 167

Obg GTPase; The Obg nucleotide binding protein subfamily has been implicated in stress response, chromosome partitioning, replication initiation, mycelium development, and sporulation. Obg proteins are among a large group of GTP binding proteins conserved from bacteria to humans. The E. coli homolog, ObgE is believed to function in ribosomal biogenesis. Members of the subfamily contain two equally and highly conserved domains, a C-terminal GTP binding domain and an N-terminal glycine-rich domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2186152419   1 MVLVGNKCDLP-SRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDafytLVREIRK 55
Cdd:cd01898   117 RIVVLNKIDLLdAEERFEKLKELLKELKGKKVFPISALTGEGLDE----LLKKLAK 168

GTPase RsgA; Reviewed

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2186152419   2 VLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDD 44
Cdd:PRK00098  115 IIVLNKIDLLDDLEEARELLALYRAIGYDVLELSAKEGEGLDE 157

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2186152419   1 MVLVGNKCDLPSRTVDTKQAQDLaRSYGIPFIETSAKTRQGVDDAFYTLVR 51
Cdd:cd00877   107 IVLCGNKVDIKDRKVKPKQITFH-RKKNLQYYEISAKSNYNFEKPFLWLAR 156

tRNA uridine-5-carboxymethylaminomethyl(34) synthesis GTPase MnmE;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2186152419   2 VLVGNKCDLPsrtvdtkQAQDLARSYGIPFIETSAKTRQGVDDafytLVREIRKH 56
Cdd:PRK05291  325 IVVLNKADLT-------GEIDLEEENGKPVIRISAKTGEGIDE----LREAIKEL 368

LepA also known as Elongation Factor 4 (EF4); LepA (also known as elongation factor 4, EF4) belongs to the GTPase family and exhibits significant homology to the translation factors EF-G and EF-Tu, indicating its possible involvement in translation and association with the ribosome. LepA is ubiquitous in bacteria and eukaryota (e.g. yeast GUF1p), but is missing from archaea. This pattern of phyletic distribution suggests that LepA evolved through a duplication of the EF-G gene in bacteria, followed by early transfer into the eukaryotic lineage, most likely from the promitochondrial endosymbiont. Yeast GUF1p is not essential and mutant cells did not reveal any marked phenotype.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2186152419   4 VGNKCDLPSRTVDtKQAQDLARSYGIP---FIETSAKTRQGVDDAFYTLVREI 53
Cdd:cd01890   125 VINKIDLPAADPD-RVKQEIEDVLGLDaseAILVSAKTGLGVEDLLEAIVERI 176

trmE is a tRNA modification GTPase; TrmE (MnmE, ThdF, MSS1) is a 3-domain protein found in bacteria and eukaryotes. It controls modification of the uridine at the wobble position (U34) of tRNAs that read codons ending with A or G in the mixed codon family boxes. TrmE contains a GTPase domain that forms a canonical Ras-like fold. It functions a molecular switch GTPase, and apparently uses a conformational change associated with GTP hydrolysis to promote the tRNA modification reaction, in which the conserved cysteine in the C-terminal domain is thought to function as a catalytic residue. In bacteria that are able to survive in extremely low pH conditions, TrmE regulates glutamate-dependent acid resistance.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2186152419   1 MVLVGNKCDLPSRTVDTKQAqdlarsYGIPFIETSAKTRQGVDDafytLVREIRK 55
Cdd:cd04164   112 VIVVLNKSDLLSDAEGISEL------NGKPIIAISAKTGEGIDE----LKEALLE 156

MnmE helical domain; The tRNA modification GTPase MnmE consists of three domains. An N-terminal domain, a helical domain and a GTPase domain which is nested within the helical domain. This family represents the helical domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   2 VLVGNKCDLPSRTVDTKQAQDlarsygIPFIETSAKTRQGVDDafytLVREIRK 55
Cdd:pfam12631 205 IVVLNKSDLLGEIDELEELKG------KPVLAISAKTGEGLDE----LEEAIKE 248

Ras homology family 2 (Rho2) of small guanosine triphosphatases (GTPases); Rho2 is a fungal GTPase that plays a role in cell morphogenesis, control of cell wall integrity, control of growth polarity, and maintenance of growth direction. Rho2 activates the protein kinase C homolog Pck2, and Pck2 controls Mok1, the major (1-3) alpha-D-glucan synthase. Together with Rho1 (RhoA), Rho2 regulates the construction of the cell wall. Unlike Rho1, Rho2 is not an essential protein, but its overexpression is lethal. 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 proper intracellular localization via membrane attachment. As with other Rho family GTPases, the GDP/GTP cycling is regulated by GEFs (guanine nucleotide exchange factors), GAPs (GTPase-activating proteins) and GDIs (guanine nucleotide dissociation inhibitors).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2186152419   2 VLVGNKCDL-----------PSRTVDTKQAQDLARSYGI-PFIETSAKTRQGVDDAFYT------LVREIRKHK 57
Cdd:cd04129   109 ILVGLKKDLrqeavakgnyaTDEFVPIQQAKLVARAIGAkKYMECSALTGEGVDDVFEAatraalLVRKSGKEE 182

Translation initiation factor IF-2, a GTPase [Translation, ribosomal structure and biogenesis]; Translation initiation factor IF-2, a GTPase is part of the Pathway/BioSystem: Translation factors

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2186152419   6 NKCDLPSRTVDtKQAQDLArSYGI---------PFIETSAKTRQGVDD 44
Cdd:COG0532   111 NKIDKPGANPD-RVKQELA-EHGLvpeewggdtIFVPVSAKTGEGIDE 156

Nucleolar GTP-binding protein (NOG); NOG1 is a nucleolar GTP-binding protein present in eukaryotes ranging from trypanosomes to humans. NOG1 is functionally linked to ribosome biogenesis and found in association with the nuclear pore complexes and identified in many preribosomal complexes. Thus, defects in NOG1 can lead to defects in 60S biogenesis. The S. cerevisiae NOG1 gene is essential for cell viability, and mutations in the predicted G motifs abrogate function. It is a member of the ODN family of GTP-binding proteins that also includes the bacterial Obg and DRG proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2186152419   1 MVLVGNKCDLpSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDA 45
Cdd:cd01897   115 VIVVLNKIDL-LTEEDLSEIEKELEKEGEEVIKISTLTEEGVDEL 158