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 1428715351  11 AQVGKTSLILSLVGEEFPEEVPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIEK 90
Cdd:cd01893    11 EGVGKSSLIMSLVSEEFPENVPRVLPEITIPADVTPERVPTTIVDTSSRPQDRANLAAEIRKANVICLVYSVDRPSTLER 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  91 IRTKWIPLVNGRtatGPRLPIILVGNKSDLRPGST----MEAVLPIMSQFPEIETCVECSAKHLRNISELFYYAQKAVLH 166
Cdd:cd01893    91 IRTKWLPLIRRL---GVKVPIILVGNKSDLRDGSSqaglEEEMLPIMNEFREIETCVECSAKTLINVSEVFYYAQKAVLH 167

                  .
gi 1428715351 167 P 167
Cdd:cd01893   168 P 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 1428715351 339 W-GPELLHTVPT-QAGCLPLHGYLCQWTLMTYLDVQQCLAHLGYLGYPTLCEQDSQAqAITVTREKKLDQE 407
Cdd:pfam08355   1 WlEPDFPDTVVTnEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQS-AIKVTRPRKLDRK 70

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 1428715351  11 AQVGKTSLILSLVGEEFPEEVPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIEK 90
Cdd:cd01893    11 EGVGKSSLIMSLVSEEFPENVPRVLPEITIPADVTPERVPTTIVDTSSRPQDRANLAAEIRKANVICLVYSVDRPSTLER 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  91 IRTKWIPLVNGRtatGPRLPIILVGNKSDLRPGST----MEAVLPIMSQFPEIETCVECSAKHLRNISELFYYAQKAVLH 166
Cdd:cd01893    91 IRTKWLPLIRRL---GVKVPIILVGNKSDLRDGSSqaglEEEMLPIMNEFREIETCVECSAKTLINVSEVFYYAQKAVLH 167

                  .
gi 1428715351 167 P 167
Cdd:cd01893   168 P 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 1428715351 339 W-GPELLHTVPT-QAGCLPLHGYLCQWTLMTYLDVQQCLAHLGYLGYPTLCEQDSQAqAITVTREKKLDQE 407
Cdd:pfam08355   1 WlEPDFPDTVVTnEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQS-AIKVTRPRKLDRK 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 1428715351  13 VGKTSLILSLVGEEFPEE-VParaeeiTIPADVTPEKVPTH-------IVD------YSEAEQTEeelqeeIHKANVVCV 78
Cdd:pfam00071  10 VGKSSLLIRFTQNKFPEEyIP------TIGVDFYTKTIEVDgktvklqIWDtagqerFRALRPLY------YRGADGFLL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  79 VYDVSEETTIEKIRtKWIPLVNgRTAtGPRLPIILVGNKSDL---RPGSTMEAvlpimSQFPEIETC--VECSAKHLRNI 153
Cdd:pfam00071  78 VYDITSRDSFENVK-KWVEEIL-RHA-DENVPIVLVGNKCDLedqRVVSTEEG-----EALAKELGLpfMETSAKTNENV 149

                         170
                  ....*....|..
gi 1428715351 154 SELFYYAQKAVL 165
Cdd:pfam00071 150 EEAFEELAREIL 161

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  13 VGKTSLILSLVG-EEFPEEVPARAEEITIPADVT--PEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYD-VSEETTI 88
Cdd:TIGR00231  12 VGKSTLLNSLLGnKGSITEYYPGTTRNYVTTVIEedGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVFDiVILVLDV 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1428715351  89 EKIRTKWIPLVNGRTATGprLPIILVGNKSDLRPGSTMEAV---LPIMSQFPEIETcvecSAKHLRNISELFYY 159
Cdd:TIGR00231  92 EEILEKQTKEIIHHADSG--VPIILVGNKIDLKDADLKTHVaseFAKLNGEPIIPL----SAETGKNIDSAFKI 159

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        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  420 VLGARGVGKSAFLQAFLGNSLGEARDPpekfplhTIntvrvngQEKYLILCEVNA-DSLLDTsLDT-------------- 484
Cdd:smart00010   7 VLGGGGVGKSALTIQFVQGHFVDEYDP-------TI-------EDSYRKQIEIDGeVCLLDI-LDTagqeefsamrdqym 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1428715351  485 -TCDVACLMFDSSDPKTFVHCATIY---KRYYMDGQTPCLFIASKADL 528
Cdd:smart00010  72 rTGEGFLLVYSITDRQSFEEIAKFReqiLRVKDRDDVPIVLVGNKCDL 119

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

                          10        20        30
                  ....*....|....*....|....*....|
gi 1428715351 305 QFVQRMFEKHDQDHDGVLSPTELQNLFSVF 334
Cdd:COG5126    69 PFARAAFDLLDTDGDGKISADEFRRLLTAL 98

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 1428715351  11 AQVGKTSLILSLVGEEFPEEVPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIEK 90
Cdd:cd01893    11 EGVGKSSLIMSLVSEEFPENVPRVLPEITIPADVTPERVPTTIVDTSSRPQDRANLAAEIRKANVICLVYSVDRPSTLER 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  91 IRTKWIPLVNGRtatGPRLPIILVGNKSDLRPGST----MEAVLPIMSQFPEIETCVECSAKHLRNISELFYYAQKAVLH 166
Cdd:cd01893    91 IRTKWLPLIRRL---GVKVPIILVGNKSDLRDGSSqaglEEEMLPIMNEFREIETCVECSAKTLINVSEVFYYAQKAVLH 167

                  .
gi 1428715351 167 P 167
Cdd:cd01893   168 P 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 1428715351 339 W-GPELLHTVPT-QAGCLPLHGYLCQWTLMTYLDVQQCLAHLGYLGYPTLCEQDSQAqAITVTREKKLDQE 407
Cdd:pfam08355   1 WlEPDFPDTVVTnEKGWLTLQGFLAQWSLTTLLDPKRTLEYLAYLGYPGDLGSQSQS-AIKVTRPRKLDRK 70

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351   11 AQVGKTSLILSLVGEEFPEE-VPARAEEITIPADVTPEKVPTHIVD--------------YSeaeqteeelqeeihKANV 75
Cdd:smart00174   7 GAVGKTCLLIVYTTNAFPEDyVPTVFENYSADVEVDGKPVELGLWDtagqedydrlrplsYP--------------DTDV 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351   76 VCVVYDVSEETTIEKIRTKWIPLVNgrtATGPRLPIILVGNKSDLRPGSTMEAVLPIMSQFP-----------EIETC-- 142
Cdd:smart00174  73 FLICFSVDSPASFENVKEKWYPEVK---HFCPNVPIILVGTKLDLRNDKSTLEELSKKKQEPvtyeqgqalakRIGAVky 149

                          170       180
                   ....*....|....*....|....*
gi 1428715351  143 VECSAKHLRNISELFYYAQKAVLHP 167
Cdd:smart00174 150 LECSALTQEGVREVFEEAIRAALNK 174

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  13 VGKTSLILSLVGEEFPEEVPAraeeiTIPADVTPEKVPT-------HIVD-------------YseaeqteeelqeeIHK 72
Cdd:cd00154    11 VGKTSLLLRFVDNKFSENYKS-----TIGVDFKSKTIEVdgkkvklQIWDtagqerfrsitssY-------------YRG 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  73 ANVVCVVYDVSEETTIEKIRtKWIPLVngRTATGPRLPIILVGNKSDL---RPGSTMEAVLpiMSQFPEIEtCVECSAKH 149
Cdd:cd00154    73 AHGAILVYDVTNRESFENLD-KWLNEL--KEYAPPNIPIILVGNKSDLedeRQVSTEEAQQ--FAKENGLL-FFETSAKT 146

                         170
                  ....*....|.
gi 1428715351 150 LRNISELFYYA 160
Cdd:cd00154   147 GENVDEAFESL 157

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  13 VGKTSLILSLVGEEFPEE-VPARAE----EITIPadvTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETT 87
Cdd:cd04132    14 CGKTCLLMVYAQGSFPEEyVPTVFEnyvtTLQVP---NGKIIELALWDTAGQEDYDRLRPLSYPDVDVILICYSVDNPTS 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  88 IEKIRTKWIPLVNGRTatgPRLPIILVGNKSDLRPGSTMEAVLPIMSQFP-----EIETC--------VECSAKHLRNIS 154
Cdd:cd04132    91 LDNVEDKWYPEVNHFC---PGTPIVLVGLKTDLRKDKNSVSKLRAQGLEPvtpeqGESVAksigavayIECSAKLMENVD 167

                         170
                  ....*....|.
gi 1428715351 155 ELFYYAQKAVL 165
Cdd:cd04132   168 EVFDAAINVAL 178

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  13 VGKTSLILSLVGEEFPEE-VPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIEKI 91
Cdd:cd01875    14 VGKTCLLICYTTNAFPKEyIPTVFDNYSAQTAVDGRTVSLNLWDTAGQEEYDRLRTLSYPQTNVFIICFSIASPSSYENV 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  92 RTKWIPLVNGRTatgPRLPIILVGNKSDLRPGSTMEAVLPIMSQFP-----------EIETC--VECSAKHLRNISELFY 158
Cdd:cd01875    94 RHKWHPEVCHHC---PNVPILLVGTKKDLRNDADTLKKLKEQGQAPitpqqggalakQIHAVkyLECSALNQDGVKEVFA 170

                         170
                  ....*....|.
gi 1428715351 159 YAQKAVLHPTA 169
Cdd:cd01875   171 EAVRAVLNPTP 181

Rho family GTPase subfamily Rnd includes Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8; The Rnd subfamily contains Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8. These novel Rho family proteins have substantial structural differences compared to other Rho members, including N- and C-terminal extensions relative to other Rhos. Rnd3/RhoE is farnesylated at the C-terminal prenylation site, unlike most other Rho proteins that are geranylgeranylated. In addition, Rnd members are unable to hydrolyze GTP and are resistant to GAP activity. They are believed to exist only in the GTP-bound conformation, and are antagonists of RhoA activity. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  11 AQVGKTSLILSLVGEEFPEE-VPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIE 89
Cdd:cd04131    10 SQCGKTALLQVFAKDSFPENyVPTVFENYTASFEVDKQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICFDISRPETLD 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  90 KIRTKWIPLVNgrtATGPRLPIILVGNKSDLRPGSTMEAVLPIMSQFP-----------EI--ETCVECSAKHLRN-ISE 155
Cdd:cd04131    90 SVLKKWKGEVR---EFCPNTPVLLVGCKSDLRTDLSTLTELSNKRQIPvsheqgrnlakQIgaAAYVECSAKTSENsVRD 166

                         170
                  ....*....|
gi 1428715351 156 LFYYAQKAVL 165
Cdd:cd04131   167 VFEMATLACL 176

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 1428715351  13 VGKTSLILSLVGEEFPEEV-PARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEE---TTI 88
Cdd:cd04139    11 VGKSALTLQFMYDEFVEDYePTKADSYRKKVVLDGEEVQLNILDTAGQEDYAAIRDNYFRSGEGFLLVFSITDMesfTAL 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1428715351  89 EKIRTKWIPLVNGrtatgPRLPIILVGNKSDL----RPGSTMEAVLPIMSQFPEIETcvecSAKHLRNISELFY 158
Cdd:cd04139    91 AEFREQILRVKED-----DNVPLLLVGNKCDLedkrQVSVEEAANLAEQWGVNYVET----SAKTRANVDKVFF 155

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  11 AQVGKTSLILSLVGEEFPEEVPAraeeiTIPAD-----VTPEK-------------------VPTHIVDyseaeqteeel 66
Cdd:cd01861     9 QSVGKTSIITRFMYDTFDNQYQA-----TIGIDflsktMYVDDktvrlqlwdtagqerfrslIPSYIRD----------- 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  67 qeeihkANVVCVVYDVSEETTIEKIRtKWIPLVNGRTATGPRlpIILVGNKSDL---RPGSTMEAvlpimSQFPEIETC- 142
Cdd:cd01861    73 ------SSVAVVVYDITNRQSFDNTD-KWIDDVRDERGNDVI--IVLVGNKTDLsdkRQVSTEEG-----EKKAKENNAm 138

                         170
                  ....*....|....*.
gi 1428715351 143 -VECSAKHLRNISELF 157
Cdd:cd01861   139 fIETSAKAGHNVKQLF 154

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 1428715351   3 ASCCWARVAQVGKTSL--ILSLVGEEFPEE----VPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVV 76
Cdd:cd04101     1 AQCAVVGDPAVGKSALvqMFHSDGATFQKNytmtTGCDLVVKTVPVPDTSDSVELFIFDSAGQELFSDMVENVWEQPAVV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  77 CVVYDVSEETTIEKIrTKWIPLVngRTAT-GPRLPIILVGNKSDLRPGSTM-EAVLPIMSQFPEIEtCVECSAKHLRNIS 154
Cdd:cd04101    81 CVVYDVTNEVSFNNC-SRWINRV--RTHShGLHTPGVLVGNKCDLTDRREVdAAQAQALAQANTLK-FYETSAKEGVGYE 156

                  ...
gi 1428715351 155 ELF 157
Cdd:cd04101   157 APF 159

Rnd3/RhoE/Rho8 GTPases; Rnd3/RhoE/Rho8 subfamily. Rnd3/RhoE/Rho8 is a member of the novel Rho subfamily Rnd, together with Rnd1/Rho6 and Rnd2/Rho7. Rnd3/RhoE is known to bind the serine-threonine kinase ROCK I. Unphosphorylated Rnd3/RhoE associates primarily with membranes, but ROCK I-phosphorylated Rnd3/RhoE localizes in the cytosol. Phosphorylation of Rnd3/RhoE correlates with its activity in disrupting RhoA-induced stress fibers and inhibiting Ras-induced fibroblast transformation. In cells that lack stress fibers, such as macrophages and monocytes, Rnd3/RhoE induces a redistribution of actin, causing morphological changes in the cell. In addition, Rnd3/RhoE has been shown to inhibit cell cycle progression in G1 phase at a point upstream of the pRb family pocket protein checkpoint. Rnd3/RhoE has also been shown to inhibit Ras- and Raf-induced fibroblast transformation. In mammary epithelial tumor cells, Rnd3/RhoE regulates the assembly of the apical junction complex and tight junction formation. Rnd3/RhoE is underexpressed in prostate cancer cells both in vitro and in vivo; re-expression of Rnd3/RhoE suppresses cell cycle progression and increases apoptosis, suggesting it may play a role in tumor suppression. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  11 AQVGKTSLILSLVGEEFPEE-VPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIE 89
Cdd:cd04172    14 SQCGKTALLHVFAKDCFPENyVPTVFENYTASFEIDTQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICFDISRPETLD 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  90 KIRTKWiplvNGRTAT-GPRLPIILVGNKSDLRPGSTMEAVL------PI-------MSQFPEIETCVECSAKHLRN-IS 154
Cdd:cd04172    94 SVLKKW----KGEIQEfCPNTKMLLVGCKSDLRTDVSTLVELsnhrqtPVsydqganMAKQIGAATYIECSALQSENsVR 169

                  ....*....
gi 1428715351 155 ELFYYAQKA 163
Cdd:cd04172   170 DIFHVATLA 178

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  13 VGKTSLILSLVGEEFPEEVPAR--AEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIEK 90
Cdd:cd04122    13 VGKSCLLHQFTEKKFMADCPHTigVEFGTRIIEVNGQKIKLQIWDTAGQERFRAVTRSYYRGAAGALMVYDITRRSTYNH 92

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1428715351  91 IRTkWipLVNGRTATGPRLPIILVGNKSDLRpgSTMEAVLPIMSQFPEIE--TCVECSAKHLRNISELFYYAQKAV 164
Cdd:cd04122    93 LSS-W--LTDARNLTNPNTVIFLIGNKADLE--AQRDVTYEEAKQFADENglLFLECSAKTGENVEDAFLETAKKI 163

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  14 GKTSLILSLVGEEFPEE-VPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIEKIR 92
Cdd:cd04129    13 GKTSLLYVFTLGEFPEEyHPTVFENYVTDCRVDGKPVQLALWDTAGQEEYERLRPLSYSKAHVILIGFAIDTPDSLENVR 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  93 TKWIPLVNgrtATGPRLPIILVGNKSDLRPGSTMEAVlPIMSQFPEIETC------------VECSAKHLRNISELFYYA 160
Cdd:cd04129    93 TKWIEEVR---RYCPNVPVILVGLKKDLRQEAVAKGN-YATDEFVPIQQAklvaraigakkyMECSALTGEGVDDVFEAA 168

                  ....*
gi 1428715351 161 QKAVL 165
Cdd:cd04129   169 TRAAL 173

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  73 ANVVCVVYDVSEETTIEKIRTkWIPLVngRTATGPRLPIILVGNKSDL---RPGSTMEAvlpimSQFPEIETC--VECSA 147
Cdd:cd01860    74 AAAAIVVYDITSEESFEKAKS-WVKEL--QEHGPPNIVIALAGNKADLeskRQVSTEEA-----QEYADENGLlfMETSA 145

                          90
                  ....*....|....*.
gi 1428715351 148 KHLRNISELFYY-AQK 162
Cdd:cd01860   146 KTGENVNELFTEiARK 161

Rho GTPase TC10 (Tc10); TC10 is a Rho family protein that has been shown to induce microspike formation and neurite outgrowth in vitro. Its expression changes dramatically after peripheral nerve injury, suggesting an important role in promoting axonal outgrowth and regeneration. TC10 regulates translocation of insulin-stimulated GLUT4 in adipocytes and has also been shown to bind directly to Golgi COPI coat proteins. GTP-bound TC10 in vitro can bind numerous potential effectors. Depending on its subcellular localization and distinct functional domains, TC10 can differentially regulate two types of filamentous actin in adipocytes. TC10 mRNAs are highly expressed in three types of mouse muscle tissues: leg skeletal muscle, cardiac muscle, and uterus; they were also present in brain, with higher levels in adults than in newborns. TC10 has also been shown to play a role in regulating the expression of cystic fibrosis transmembrane conductance regulator (CFTR) through interactions with CFTR-associated ligand (CAL). The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated DFTR degradation in the lysosome. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  13 VGKTSLILSLVGEEFPEE-VPARAEEITIPADVTPEKVPTHIVDYSEAEQTEEELQEEIHKANVVCVVYDVSEETTIEKI 91
Cdd:cd04135    11 VGKTCLLMSYANDAFPEEyVPTVFDHYAVSVTVGGKQYLLGLYDTAGQEDYDRLRPLSYPMTDVFLICFSVVNPASFQNV 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351  92 RTKWIPLVNgrtATGPRLPIILVGNKSDLRPGSTMEAVLPIMSQFP-----------EIETC--VECSAKHLRNISELFY 158
Cdd:cd04135    91 KEEWVPELK---EYAPNVPYLLIGTQIDLRDDPKTLARLNDMKEKPitveqgqklakEIGACcyVECSALTQKGLKTVFD 167

                  ....*..
gi 1428715351 159 YAQKAVL 165
Cdd:cd04135   168 EAIIAIL 174

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1428715351 420 VLGARGVGKSAFLQAFLGNslgeardppeKFPLHTINTVRVN---------------------GQEKYlilcevnaDSLL 478
Cdd:cd00154     5 LIGDSGVGKTSLLLRFVDN----------KFSENYKSTIGVDfksktievdgkkvklqiwdtaGQERF--------RSIT 66

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1428715351 479 DTSLdTTCDVACLMFDSSDPKTFVHCATIYK--RYYMDGQTPCLFIASKADLPE 530
Cdd:cd00154    67 SSYY-RGAHGAILVYDVTNRESFENLDKWLNelKEYAPPNIPIILVGNKSDLED 119