EF hand associated; This region predominantly appears near EF-hands (pfam00036) in GTP-binding proteins. It is found in all three eukaryotic kingdoms.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570700820   92 TPLAPQALEDVKNVVRKHISDGVADSGLTLKGFLFLHTLFIQRGRHETTWTVLRRFGYDDDLDLTPEYLFPLLKIPPDCT 171
Cdd:pfam08356   1 KPLSPQELEDIKSVVQKNLPDGVSDNGLTLKGFLFLNKLFIEKGRHETTWTILRKFGYTDSLSLKDDYLHPKFDVPPDSS 80

                  ....*
gi 570700820  172 TELNH 176
Cdd:pfam08356  81 VELSP 85

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
                 ....*....|....*....|....*....|....*....|..
gi 570700820   1 METILPIMNQYTEIETCVECSAKNLKNISELFYYAQKAVLHP 42
Cdd:cd01893  127 EEEMLPIMNEFREIETCVECSAKTLINVSEVFYYAQKAVLHP 168

EF hand associated; This region predominantly appears near EF-hands (pfam00036) in GTP-binding proteins. It is found in all three eukaryotic kingdoms.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570700820   92 TPLAPQALEDVKNVVRKHISDGVADSGLTLKGFLFLHTLFIQRGRHETTWTVLRRFGYDDDLDLTPEYLFPLLKIPPDCT 171
Cdd:pfam08356   1 KPLSPQELEDIKSVVQKNLPDGVSDNGLTLKGFLFLNKLFIEKGRHETTWTILRKFGYTDSLSLKDDYLHPKFDVPPDSS 80

                  ....*
gi 570700820  172 TELNH 176
Cdd:pfam08356  81 VELSP 85

Mitochondrial Rho family 1 (Miro1), N-terminal; Miro1 subfamily. Miro (mitochondrial Rho) proteins have tandem GTP-binding domains separated by a linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins were found in several eukaryotic organisms. This CD represents the N-terminal GTPase domain of Miro proteins. These atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. Most Rho proteins contain a lipid modification site at the C-terminus; however, Miro is one of few Rho subfamilies that lack this feature.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 570700820   1 METILPIMNQYTEIETCVECSAKNLKNISELFYYAQKAVLHP 42
Cdd:cd01893  127 EEEMLPIMNEFREIETCVECSAKTLINVSEVFYYAQKAVLHP 168

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 570700820   367 LVYDVSNPKSFEYCARIFK--QHFMDSRIPCLIVAAKSDL---HEVKQEysiSPTDFCRKHKMP 425
Cdd:smart00175  78 LVYDITNRESFENLENWLKelREYASPNVVIMLVGNKSDLeeqRQVSRE---EAEAFAEEHGLP 138

EF hand associated; This region predominantly appears near EF-hands (pfam00036) in GTP-binding proteins. It is found in all three eukaryotic kingdoms.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570700820   92 TPLAPQALEDVKNVVRKHISDGVADSGLTLKGFLFLHTLFIQRGRHETTWTVLRRFGYDDDLDLTPEYLFPLLKIPPDCT 171
Cdd:pfam08356   1 KPLSPQELEDIKSVVQKNLPDGVSDNGLTLKGFLFLNKLFIEKGRHETTWTILRKFGYTDSLSLKDDYLHPKFDVPPDSS 80

                  ....*
gi 570700820  172 TELNH 176
Cdd:pfam08356  81 VELSP 85

Mitochondrial Rho family 1 (Miro1), N-terminal; Miro1 subfamily. Miro (mitochondrial Rho) proteins have tandem GTP-binding domains separated by a linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins were found in several eukaryotic organisms. This CD represents the N-terminal GTPase domain of Miro proteins. These atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. Most Rho proteins contain a lipid modification site at the C-terminus; however, Miro is one of few Rho subfamilies that lack this feature.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 570700820   1 METILPIMNQYTEIETCVECSAKNLKNISELFYYAQKAVLHP 42
Cdd:cd01893  127 EEEMLPIMNEFREIETCVECSAKTLINVSEVFYYAQKAVLHP 168

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570700820 293 RCNVIGVKNCGKSGVLQALLGRNLMRQKKIREDHKSYYAINTVYVYGQEKY--LLLHDISESEfltEAEIICD------- 363
Cdd:cd04101    2 QCAVVGDPAVGKSALVQMFHSDGATFQKNYTMTTGCDLVVKTVPVPDTSDSveLFIFDSAGQE---LFSDMVEnvweqpa 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 570700820 364 VVCLVYDVSNPKSFEYCARIFKQ---HFMDSRIPCLIVAAKSDLHEVKQEYSISPTDFCRKHKM 424
Cdd:cd04101   79 VVCVVYDVTNEVSFNNCSRWINRvrtHSHGLHTPGVLVGNKCDLTDRREVDAAQAQALAQANTL 142

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 570700820 362 CDVVCLVYDVSNPKSFEYCARIFKQ---HFMDSRIPCLIVAAKSDLHEVKQEYSISPTDFCRKHKMP 425
Cdd:cd04139   72 GEGFLLVFSITDMESFTALAEFREQilrVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVN 138

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 570700820   367 LVYDVSNPKSFEYCARIFK--QHFMDSRIPCLIVAAKSDL---HEVKQEysiSPTDFCRKHKMP 425
Cdd:smart00175  78 LVYDITNRESFENLENWLKelREYASPNVVIMLVGNKSDLeeqRQVSRE---EAEAFAEEHGLP 138

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 570700820 339 GQEKYLLLHDISESEflteaeiiCDVVCLVYDVSNPKSFEYCARIFKQ-HFM--DSRIPCLIVAAKSDLH---EVKQE 410
Cdd:cd00876   56 GQEEFSAMRDQYIRN--------GDGFILVYSITSRESFEEIKNIREQiLRVkdKEDVPIVLVGNKCDLEnerQVSTE 125

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 570700820 367 LVYDVSNPKSFEYCARIFKQ--HFMDSRIPCLIVAAKSDLHEVKQEYSISPTDFCRKHKM 424
Cdd:cd01868   81 LVYDITKKSTFENVERWLKElrDHADSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGL 140

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 570700820 363 DVVCLVYDVSNPKSFEYCA---RIFKQHFMDSRIPCLI--VAAKSDLHEVKQEYSISPTDFCRKHKMPP 426
Cdd:cd04109   75 QAVCLVYDITNSQSFENLEdwlSVVKKVNEESETKPKMvlVGNKTDLEHNRQVTAEKHARFAQENDMES 143