Mitochondrial Rho family 2 (Miro2), C-terminal; Miro2 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 putative GTPase domain in the C terminus 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 341 QRNVFRCNVIGVKGCGKTGVLQSLLGRNLMrQKKIRDDHKSYYAINTVYVYGQEKYLLLHDISESEFLTEAETI----CD 416
Cdd:cd01892     1 QRNVFLCFVLGAKGSGKSALLQAFLGRSFS-QNAYSPTIKPRYAVNTVEVPGQEKYLILREVGEDEEAILLNDAelaaCD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 417 VVCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNTADaPSKDIF 496
Cdd:cd01892    80 VACLVYDSSDPNSFSYCAEVYKKYFMLGEIPCLFVAAKADLDEQQQRAEVQPDEFCRKLGLPPPLHFSSRLGD-SSNELF 158

                         170
                  ....*....|
gi 1385123334 497 VKLTTMAMYP 506
Cdd:cd01892   159 TKLATAAQYP 168

EF hand associated; This region typically appears on the C-terminus of EF hands in GTP-binding proteins such as Arht/Rhot (may be involved in mitochondrial homeostasis and apoptosis). The EF hand associated region is found in yeast, vertebrates and plants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1385123334 267 W-GPDVNNTVCTNERGWITYQGFLSQWTLTTYLDVQRCLEYLGYLGYSILTEQESQaSAITVTRDKKIDLQ 336
Cdd:pfam08355   1 WlEPDFPDTVVTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQ-SAIKVTRPRKLDRK 70

Mitochondrial Rho family 2 (Miro2), C-terminal; Miro2 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 putative GTPase domain in the C terminus 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 341 QRNVFRCNVIGVKGCGKTGVLQSLLGRNLMrQKKIRDDHKSYYAINTVYVYGQEKYLLLHDISESEFLTEAETI----CD 416
Cdd:cd01892     1 QRNVFLCFVLGAKGSGKSALLQAFLGRSFS-QNAYSPTIKPRYAVNTVEVPGQEKYLILREVGEDEEAILLNDAelaaCD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 417 VVCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNTADaPSKDIF 496
Cdd:cd01892    80 VACLVYDSSDPNSFSYCAEVYKKYFMLGEIPCLFVAAKADLDEQQQRAEVQPDEFCRKLGLPPPLHFSSRLGD-SSNELF 158

                         170
                  ....*....|
gi 1385123334 497 VKLTTMAMYP 506
Cdd:cd01892   159 TKLATAAQYP 168

EF hand associated; This region typically appears on the C-terminus of EF hands in GTP-binding proteins such as Arht/Rhot (may be involved in mitochondrial homeostasis and apoptosis). The EF hand associated region is found in yeast, vertebrates and plants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1385123334 267 W-GPDVNNTVCTNERGWITYQGFLSQWTLTTYLDVQRCLEYLGYLGYSILTEQESQaSAITVTRDKKIDLQ 336
Cdd:pfam08355   1 WlEPDFPDTVVTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQ-SAIKVTRPRKLDRK 70

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 392 GQEKYlllHDISESEFLTeaetiCDVVCLVYDVTNPKSFEYCARIFKQ--HFMDSRIPCLIVAAKSDLHEVKQehsISPT 469
Cdd:pfam00071  57 GQERF---RALRPLYYRG-----ADGFLLVYDITSRDSFENVKKWVEEilRHADENVPIVLVGNKCDLEDQRV---VSTE 125

                          90
                  ....*....|..
gi 1385123334 470 D---FCRKHKMP 478
Cdd:pfam00071 126 EgeaLAKELGLP 137

Rho (Ras homology) subfamily of Ras-like small GTPases; Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1385123334   38 PLILVGNKSDLVEYSSMETILPIMNQ--YTEIETC-----------VECSAKNLKNISELFYYAQKAVLHP 95
Cdd:smart00174 104 PIILVGTKLDLRNDKSTLEELSKKKQepVTYEQGQalakrigavkyLECSALTQEGVREVFEEAIRAALNK 174

GTPase Era, involved in 16S rRNA processing [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1385123334  34 LKEL--PLILVGNKSDLVeysSMETILPIMNQYTEI---ETCVECSAKNLKNISELFyyaqKAVLH--PTGPLYCPEE 104
Cdd:COG1159   107 LKKLktPVILVINKIDLV---KKEELLPLLAEYSELldfAEIVPISALKGDNVDELL----DEIAKllPEGPPYYPED 177

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1385123334  25 LPQRAECWDLKE--LPLILVGNKSDLVEYSSME---TILPIMNQYTEIETcvecSAKNLKNISELFYY 87
Cdd:TIGR00231  96 EKQTKEIIHHADsgVPIILVGNKIDLKDADLKThvaSEFAKLNGEPIIPL----SAETGKNIDSAFKI 159

Mitochondrial Rho family 2 (Miro2), C-terminal; Miro2 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 putative GTPase domain in the C terminus 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 341 QRNVFRCNVIGVKGCGKTGVLQSLLGRNLMrQKKIRDDHKSYYAINTVYVYGQEKYLLLHDISESEFLTEAETI----CD 416
Cdd:cd01892     1 QRNVFLCFVLGAKGSGKSALLQAFLGRSFS-QNAYSPTIKPRYAVNTVEVPGQEKYLILREVGEDEEAILLNDAelaaCD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 417 VVCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNTADaPSKDIF 496
Cdd:cd01892    80 VACLVYDSSDPNSFSYCAEVYKKYFMLGEIPCLFVAAKADLDEQQQRAEVQPDEFCRKLGLPPPLHFSSRLGD-SSNELF 158

                         170
                  ....*....|
gi 1385123334 497 VKLTTMAMYP 506
Cdd:cd01892   159 TKLATAAQYP 168

EF hand associated; This region typically appears on the C-terminus of EF hands in GTP-binding proteins such as Arht/Rhot (may be involved in mitochondrial homeostasis and apoptosis). The EF hand associated region is found in yeast, vertebrates and plants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1385123334 267 W-GPDVNNTVCTNERGWITYQGFLSQWTLTTYLDVQRCLEYLGYLGYSILTEQESQaSAITVTRDKKIDLQ 336
Cdd:pfam08355   1 WlEPDFPDTVVTNEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQ-SAIKVTRPRKLDRK 70

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 349 VIGVKGCGKTGVLQSLLGRNLMRQKKIRD--DHKSYYAINTVYVYGQekyLLLHD---ISESEFLTEAETI------CDV 417
Cdd:cd00882     2 VVGRGGVGKSSLLNALLGGEVGEVSDVPGttRDPDVYVKELDKGKVK---LVLVDtpgLDEFGGLGREELArlllrgADL 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 418 VCLVYDVTNPKSFEYCARIFKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPPQAFTCNT 487
Cdd:cd00882    79 ILLVVDSTDRESEEDAKLLILRRLRKEGIPIILVGNKIDLLEEREVEELLRLEELAKILGVPVFEVSAKT 148

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 1385123334 346 RCNVIGVKGCGKTGVLQSLLGRNLMRQKKIRDDHKSYYAINTVYVYGQEKY--LLLHDISESEfltEAETICD------- 416
Cdd:cd04101     2 QCAVVGDPAVGKSALVQMFHSDGATFQKNYTMTTGCDLVVKTVPVPDTSDSveLFIFDSAGQE---LFSDMVEnvweqpa 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1385123334 417 VVCLVYDVTNPKSFEYCARIFKQ---HFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKM 477
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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 349 VIGVKGCGKtgvlqSLLGRNLM---------------RQKKIRDDHKSYyAINTVYVYGQEKYLLLHDisesefltEAET 413
Cdd:cd04139     5 MVGSGGVGK-----SALTLQFMydefvedyeptkadsYRKKVVLDGEEV-QLNILDTAGQEDYAAIRD--------NYFR 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1385123334 414 ICDVVCLVYDVTNPKSFEYCARIFKQ---HFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMP 478
Cdd:cd04139    71 SGEGFLLVFSITDMESFTALAEFREQilrVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVN 138

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 356 GKTGVLQSLLGRNLMRQKKIRDDHKS----YYAiNTVYVYGQEKYLLLHDISESEFLTEAE----TICDVVCLVYDVTNP 427
Cdd:cd04148     7 GDSGVGKSSLANIFTAGVYEDSAYEAsgddTYE-RTVSVDGEEATLVVYDHWEQEDGMWLEdscmQVGDAYVIVYSVTDR 85

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1385123334 428 KSFEYCARI---FKQHFMDSRIPCLIVAAKSDL 457
Cdd:cd04148    86 SSFEKASELriqLRRARQAEDIPIILVGNKSDL 118

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 1385123334 392 GQEKYLLLHDISESEflteaetiCDVVCLVYDVTNPKSFEYCARIFKQ-HFM--DSRIPCLIVAAKSDLH---EVKQE 463
Cdd:cd00876    56 GQEEFSAMRDQYIRN--------GDGFILVYSITSRESFEEIKNIREQiLRVkdKEDVPIVLVGNKCDLEnerQVSTE 125

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. 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 1385123334 418 VCLVYDVTNPKSF-------EYCarifKQHFMDSRIPCLIVAAKSDLHEVKQEHSISPTDFCRKHKMPPpqaFTCNTADA 490
Cdd:cd04115    79 VVFVYDVTNMASFhslpswiEEC----EQHSLPNEVPRILVGNKCDLREQIQVPTDLAQRFADAHSMPL---FETSAKDP 151

                          90
                  ....*....|...
gi 1385123334 491 PSKD----IFVKL 499
Cdd:cd04115   152 SENDhveaIFMTL 164

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334   1 MKEQTKTAGSHYVFLAGL-------ELTKLHlPQRAECWDLKELPLILVGNKSDLV--------EYSSMETILPIMnqYt 65
Cdd:cd04145    66 MREQYMRTGEGFLLVFSVtdrgsfeEVDKFH-TQILRVKDRDEFPMILVGNKADLEhqrqvsreEGQELARQLKIP--Y- 141

                          90       100
                  ....*....|....*....|.
gi 1385123334  66 eietcVECSAKNLKNISELFY 86
Cdd:cd04145   142 -----IETSAKDRVNVDKAFH 157

Rho (Ras homology) subfamily of Ras-like small GTPases; Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1385123334   38 PLILVGNKSDLVEYSSMETILPIMNQ--YTEIETC-----------VECSAKNLKNISELFYYAQKAVLHP 95
Cdd:smart00174 104 PIILVGTKLDLRNDKSTLEELSKKKQepVTYEQGQalakrigavkyLECSALTQEGVREVFEEAIRAALNK 174

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 1385123334 416 DVVCLVYDVTNPKSFEYCA---RIFKQHFMDSRIPCLI--VAAKSDLHEVKQEHSISPTDFCRKHKMPP 479
Cdd:cd04109    75 QAVCLVYDITNSQSFENLEdwlSVVKKVNEESETKPKMvlVGNKTDLEHNRQVTAEKHARFAQENDMES 143

GTPase Era; Reviewed

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1385123334  38 PLILVGNKSDLVeySSMETILPIMNQYTE----IETcVECSAKNLKNISELFYYAQKAVlhPTGPLYCPEE 104
Cdd:PRK00089  115 PVILVLNKIDLV--KDKEELLPLLEELSElmdfAEI-VPISALKGDNVDELLDVIAKYL--PEGPPYYPED 180

Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like families; RERG (Ras-related and Estrogen- Regulated Growth inhibitor) and Ras-like 11 are members of a novel subfamily of Ras that were identified based on their behavior in breast and prostate tumors, respectively. RERG expression was decreased or lost in a significant fraction of primary human breast tumors that lack estrogen receptor and are correlated with poor clinical prognosis. Elevated RERG expression correlated with favorable patient outcome in a breast tumor subtype that is positive for estrogen receptor expression. In contrast to most Ras proteins, RERG overexpression inhibited the growth of breast tumor cells in vitro and in vivo. RasL11 was found to be ubiquitously expressed in human tissue, but down-regulated in prostate tumors. Both RERG and RasL11 lack the C-terminal CaaX prenylation motif, where a = an aliphatic amino acid and X = any amino acid, and are localized primarily in the cytoplasm. Both are believed to have tumor suppressor activity.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1385123334 416 DVVCLVYDVTNPKSFEYCARIFKQ----HFMDSRIPCLIVAAKSDLHEVKQ 462
Cdd:cd04146    74 DGFVLVYSITDRSSFDVVSQLLQLireiKKRDGEIPVILVGNKADLLHSRQ 124

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1385123334 401 DISESE----FLTEAETICDVVCLVYDVTNPKSFEycaRI-------FKQHFMdsRIPCLIVAAKSDL----HEVKQEHS 465
Cdd:cd01893    55 DTSSRPqdraNLAAEIRKANVICLVYSVDRPSTLE---RIrtkwlplIRRLGV--KVPIILVGNKSDLrdgsSQAGLEEE 129

                  ...
gi 1385123334 466 ISP 468
Cdd:cd01893   130 MLP 132

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
                   ....*....|....*....|....*....|....*....|....*..
gi 1385123334  419 CLVYDVTNPKSFEYCARIFKQHFM---DSRIPCLIVAAKSDLHEVKQ 462
Cdd:smart00010  78 LLVYSITDRQSFEEIAKFREQILRvkdRDDVPIVLVGNKCDLENERV 124

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1385123334  35 KELPLILVGNKSDLVEYSSMETILPIMNQYTE--IETCVECSAKNLKNISELF 85
Cdd:COG1100   110 KKSPIILVLNKIDLYDEEEIEDEERLKEALSEdnIVEVVATSAKTGEGVEELF 162

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. 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 1385123334 421 VYDVTNPKSFEyCARIFKQHfMDSR--------IPCLIVAAKSDLhevKQEHSISPTD----FCRKHKMP 478
Cdd:cd04107    80 VFDVTRPSTFE-AVLKWKAD-LDSKvtlpngepIPALLLANKCDL---KKERLAKDPEqmdqFCKENGFI 144

E. coli Ras-like protein (Era) is a multifunctional GTPase; Era (E. coli Ras-like protein) is a multifunctional GTPase found in all bacteria except some eubacteria. It binds to the 16S ribosomal RNA (rRNA) of the 30S subunit and appears to play a role in the assembly of the 30S subunit, possibly by chaperoning the 16S rRNA. It also contacts several assembly elements of the 30S subunit. Era couples cell growth with cytokinesis and plays a role in cell division and energy metabolism. Homologs have also been found in eukaryotes. Era contains two domains: the N-terminal GTPase domain and a C-terminal domain KH domain that is critical for RNA binding. Both domains are important for Era function. Era is functionally able to compensate for deletion of RbfA, a cold-shock adaptation protein that is required for efficient processing of the 16S rRNA.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1385123334  35 KELPLILVGNKSDLVeySSMETILPIMNQYTE---IETCVECSAKNLKNISELF 85
Cdd:cd04163   110 SKTPVILVLNKIDLV--KDKEDLLPLLEKLKElhpFAEIFPISALKGENVDELL 161

ADP-ribosylation factor(Arf)/Arf-like (Arl) small GTPases; Arf (ADP-ribosylation factor)/Arl (Arf-like) small GTPases. Arf proteins are activators of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. Arfs are N-terminally myristoylated. Members of the Arf family are regulators of vesicle formation in intracellular traffic that interact reversibly with membranes of the secretory and endocytic compartments in a GTP-dependent manner. They depart from other small GTP-binding proteins by a unique structural device, interswitch toggle, that implements front-back communication from N-terminus to the nucleotide binding site. Arf-like (Arl) proteins are close relatives of the Arf, but only Arl1 has been shown to function in membrane traffic like the Arf proteins. Arl2 has an unrelated function in the folding of native tubulin, and Arl4 may function in the nucleus. Most other Arf family proteins are so far relatively poorly characterized. Thus, despite their significant sequence homologies, Arf family proteins may regulate unrelated functions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1385123334  33 DLKELPLILVGNKSDLVEYSSMETILPIMNQYTEIE---TCVECSAKNLKNISELF 85
Cdd:cd00878    97 ELKGAPLLILANKQDLPGALTESELIELLGLESIKGrrwHIQPCSAVTGDGLDEGL 152