Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  17 VKVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVY 96
Cdd:cd04119   1 IKVISMGNSGVGKSCIIKRYCEGRFVSKYLPTIGIDYGVKKVSVRNKEVRVNFFDLSGHPEYLEVRNEFYKDTQGVLLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  97 DVGLRESFDALDSWLTEMKQEMGSQANMENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQ 176
Cdd:cd04119  81 DVTDRQSFEALDSWLKEMKQEGGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLWAESKGFKYFETSACTGEGVNEMFQ 160

                ....*...
gi 55742336 177 SFFSSITD 184
Cdd:cd04119 161 TLFSSIVD 168

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  17 VKVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVY 96
Cdd:cd04119   1 IKVISMGNSGVGKSCIIKRYCEGRFVSKYLPTIGIDYGVKKVSVRNKEVRVNFFDLSGHPEYLEVRNEFYKDTQGVLLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  97 DVGLRESFDALDSWLTEMKQEMGSQANMENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQ 176
Cdd:cd04119  81 DVTDRQSFEALDSWLKEMKQEGGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLWAESKGFKYFETSACTGEGVNEMFQ 160

                ....*...
gi 55742336 177 SFFSSITD 184
Cdd:cd04119 161 TLFSSIVD 168

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 55742336    18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336    98 VGLRESFDALDSWLTEMKQEMGsqanmENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQS 177
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHAD-----ENVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTNENVEEAFEE 155

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 55742336    16 RVKVISLGNAEVGKSCIIKRYCE-KRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVIL 94
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGnKGSITEYYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336    95 VYD-VGLRESF-DALDSWLTEMKQEMGSqanmeNIIFVVCANKVDLtKRRVVDESEGRLWAESRGFHYFETSAQSGEGIN 172
Cdd:TIGR00231  81 VFDiVILVLDVeEILEKQTKEIIHHADS-----GVPIILVGNKIDL-KDADLKTHVASEFAKLNGEPIIPLSAETGKNID 154

                  ....
gi 55742336   173 EMFQ 176
Cdd:TIGR00231 155 SAFK 158

DnaJ domain; DnaJ domains (J-domains) are associated with hsp70 heat-shock system and it is thought that this domain mediates the interaction. DnaJ-domain is therefore part of a chaperone (protein folding) system. The T-antigens, although not in Prosite are confirmed as DnaJ containing domains from literature.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 55742336   220 DMLGVKPGATREEVNKAYRKLAVLLHPDKCV-APGSEDAFKAVVNA 264
Cdd:pfam00226   4 EILGVSPDASDEEIKKAYRKLALKYHPDKNPgDPEAEEKFKEINEA 49

DnaJ molecular chaperone homology domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 55742336    216 KDSWDMLGVKPGATREEVNKAYRKLAVLLHPDKCV--APGSEDAFKAVVNA 264
Cdd:smart00271   1 TDYYEILGVPRDASLDEIKKAYRKLALKYHPDKNPgdKEEAEEKFKEINEA 51

chaperone protein DnaJ; This model represents bacterial forms of DnaJ, part of the DnaK-DnaJ-GrpE chaperone system. The three components typically are encoded by consecutive genes. DnaJ homologs occur in many genomes, typically not near DnaK and GrpE-like genes; most such genes are not included by this family. Eukaryotic (mitochondrial and chloroplast) forms are not included in the scope of this family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 55742336   217 DSWDMLGVKPGATREEVNKAYRKLAVLLHPDKCVAPGSEDAFKAVVNA 264
Cdd:TIGR02349   1 DYYEILGVSKDASEEEIKKAYRKLAKKYHPDRNKDKEAEEKFKEINEA 48

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  17 VKVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVY 96
Cdd:cd04119   1 IKVISMGNSGVGKSCIIKRYCEGRFVSKYLPTIGIDYGVKKVSVRNKEVRVNFFDLSGHPEYLEVRNEFYKDTQGVLLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  97 DVGLRESFDALDSWLTEMKQEMGSQANMENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQ 176
Cdd:cd04119  81 DVTDRQSFEALDSWLKEMKQEGGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLWAESKGFKYFETSACTGEGVNEMFQ 160

                ....*...
gi 55742336 177 SFFSSITD 184
Cdd:cd04119 161 TLFSSIVD 168

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336     17 VKVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVY 96
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336     97 DVGLRESFDALDSWLTEMKQemgsQANmENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQ 176
Cdd:smart00175  81 DITNRESFENLENWLKELRE----YAS-PNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFE 155

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  17 VKVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVY 96
Cdd:cd04123   1 FKVVLLGEGRVGKTSLVLRYVENKFNEKHESTTQASFFQKTVNIGGKRIDLAIWDTAGQERYHALGPIYYRDADGAILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  97 DVGLRESFDALDSWLTEMKQEMGsqanmENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQ 176
Cdd:cd04123  81 DITDADSFQKVKKWIKELKQMRG-----NNISLVIVGNKIDLERQRVVSKSEAEEYAKSVGAKHFETSAKTGKGIEELFL 155

                .
gi 55742336 177 S 177
Cdd:cd04123 156 S 156

Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic transport and is expressed most highly in polarized epithelial cells. However, trypanosomal Rab, TbRAB18, is upregulated in the BSF (Blood Stream Form) stage and localized predominantly to elements of the Golgi complex. In human and mouse cells, Rab18 has been identified in lipid droplets, organelles that store neutral lipids. 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 55742336  17 VKVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVY 96
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTDDTFDEDLSSTIGVDFKVKTVTVDGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  97 DVGLRESFDALDSWLTEMKqemgSQANMENIIFVVCANKVDLTKrRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQ 176
Cdd:cd01863  81 DVTRRDTFDNLDTWLNELD----TYSTNPDAVKMLVGNKIDKEN-REVTREEGQKFARKHNMLFIETSAKTRIGVQQAFE 155

                ....*.
gi 55742336 177 SFFSSI 182
Cdd:cd01863 156 ELVEKI 161

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:cd01867   5 KLLLIGDSGVGKSCLLLRFSEDSFNPSFISTIGIDFKIRTIELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGIILVYD 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  98 VGLRESFDALDSWLTEMKQemgsQANmENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQS 177
Cdd:cd01867  85 ITDEKSFENIKNWMRNIDE----HAS-EDVERMLVGNKCDMEEKRVVSKEEGEALAREYGIKFLETSAKANINVEEAFLT 159

                ....*
gi 55742336 178 FFSSI 182
Cdd:cd01867 160 LAKDI 164

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336   18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:PLN03108   8 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDNKPIKLQIWDTAGQESFRSITRSYYRGAAGALLVYD 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336   98 VGLRESFDALDSWLTEMKQemgsQANmENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQS 177
Cdd:PLN03108  88 ITRRETFNHLASWLEDARQ----HAN-ANMTIMLIGNKCDLAHRRAVSTEEGEQFAKEHGLIFMEASAKTAQNVEEAFIK 162

                        170
                 ....*....|..
gi 55742336  178 FFSSITDMCENG 189
Cdd:PLN03108 163 TAAKIYKKIQDG 174

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:cd01869   4 KLLLIGDSGVGKSCLLLRFADDTYTESYISTIGVDFKIRTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYD 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  98 VGLRESFDALDSWLtemkQEMGSQANmENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQS 177
Cdd:cd01869  84 VTDQESFNNVKQWL----QEIDRYAS-ENVNKLLVGNKCDLTDKKVVDYTEAKEFADELGIPFLETSAKNATNVEEAFMT 158

                ....*
gi 55742336 178 FFSSI 182
Cdd:cd01869 159 MAREI 163

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYgVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDSY-RKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYS 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  98 VGLRESFDALDswltEMKQEMGSQANMENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQS 177
Cdd:cd00876  80 ITSRESFEEIK----NIREQILRVKDKEDVPIVLVGNKCDLENERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNT 155

                ....*
gi 55742336 178 FFSSI 182
Cdd:cd00876 156 LVREI 160

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336    18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRD---REIKVNIFDMAGHPFFYEVRNEFYKDSQGVIL 94
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKSTIGVDFKTKTVLENDdngKKIKLNIWDTAGQERFRSLHPFYYRGAAAALL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 55742336    95 VYDvglRESFDALDSWLTEMKQEMGsqanmeNIIFVVCANKVD 137
Cdd:pfam08477  81 VYD---SRTFSNLKYWLRELKKYAG------NSPVILVGNKID 114

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:cd01865   3 KLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILMYD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  98 VGLRESFDALDSWLTEMKQEMGSQANMeniifVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQS 177
Cdd:cd01865  83 ITNEESFNAVQDWSTQIKTYSWDNAQV-----ILVGNKCDMEDERVVSAERGRQLADQLGFEFFEASAKENINVKQVFER 157

                ....*..
gi 55742336 178 FFSSITD 184
Cdd:cd01865 158 LVDIICD 164

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRD-REIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVY 96
Cdd:cd04111   4 RLIVIGDSTVGKSSLLKRFTEGRFAEVSDPTVGVDFFSRLIEIEPgVRIKLQLWDTAGQERFRSITRSYYRNSVGVLLVF 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 55742336  97 DVGLRESFDALDSWLTEMKQEMGSQAnmenIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMF 175
Cdd:cd04111  84 DITNRESFEHVHDWLEEARSHIQPHR----PVFILVGHKCDLESQRQVTREEAEKLAKDLGMKYIETSARTGDNVEEAF 158

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:cd01868   5 KIVLIGDSGVGKSNLLSRFTRNEFNLDSKSTIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGALLVYD 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  98 VGLRESFDALDSWLTEMKqEMGSQanmeNIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEMFQS 177
Cdd:cd01868  85 ITKKSTFENVERWLKELR-DHADS----NIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSALDGTNVEEAFKQ 159

                ....*
gi 55742336 178 FFSSI 182
Cdd:cd01868 160 LLTEI 164

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 55742336  18 KVISLGNAEVGKSCIIKRYCEK--RFVPKYLATIGIDYGVTKVQVRDREIKVN--IFDMAGHPFFYEVRNEFYKDSQGVI 93
Cdd:cd04101   2 QCAVVGDPAVGKSALVQMFHSDgaTFQKNYTMTTGCDLVVKTVPVPDTSDSVElfIFDSAGQELFSDMVENVWEQPAVVC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  94 LVYDVGLRESFDALDSWLTEMKqemgSQANMENIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINE 173
Cdd:cd04101  82 VVYDVTNEVSFNNCSRWINRVR----THSHGLHTPGVLVGNKCDLTDRREVDAAQAQALAQANTLKFYETSAKEGVGYEA 157

                ....
gi 55742336 174 MFQS 177
Cdd:cd04101 158 PFLS 161

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  17 VKVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIF--DMAGHPFFYEVRNEFYKDSQGVIL 94
Cdd:cd04106   1 IKVIVVGNGNVGKSSMIQRFVKGIFTKDYKKTIGVDFLEKQIFLRQSDEDVRLMlwDTAGQEEFDAITKAYYRGAQACIL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  95 VYDVGLRESFDALDSWLTEMKQEMGsqanmeNIIFVVCANKVDLTKRRVVDESEGRLWAESRGFHYFETSAQSGEGINEM 174
Cdd:cd04106  81 VFSTTDRESFEAIESWKEKVEAECG------DIPMVLVQTKIDLLDQAVITNEEAEALAKRLQLPLFRTSVKDDFNVTEL 154

                ..
gi 55742336 175 FQ 176
Cdd:cd04106 155 FE 156

Rab GTPase family 19 (Rab19); Rab19 subfamily. Rab19 proteins are associated with Golgi stacks. Similarity analysis indicated that Rab41 is closely related to Rab19. However, the function of these Rabs is not yet characterized. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:cd01864   5 KIILIGDSNVGKTCVVQRFKSGTFSERQGNTIGVDFTMKTLEIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAIIAYD 84

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 55742336  98 VGLRESFDALDSWLTEMKQEMGSqanmeNIIFVVCANKVDLTKRRVVDESEGRLWAESRG-FHYFETSAQSGEGINEMF 175
Cdd:cd01864  85 ITRRSSFESVPHWIEEVEKYGAS-----NVVLLLIGNKCDLEEQREVLFEEACTLAEHYGiLAVLETSAKESSNVEEAF 158

Rab GTPase family 12 (Rab12); Rab12 was first identified in canine cells, where it was localized to the Golgi complex. The specific function of Rab12 remains unknown, and inconsistent results about its cellular localization have been reported. More recent studies have identified Rab12 associated with post-Golgi vesicles, or with other small vesicle-like structures but not with the Golgi complex. 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. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  18 KVISLGNAEVGKSCIIKRYCEKRFVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVILVYD 97
Cdd:cd04120   2 QVIIIGSRGVGKTSLMERFTDDTFCEACKSTVGVDFKIKTVELRGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336  98 VGLRESFDALDSWLtemkqEMGSQANMENIIFVVCANKVDLTKRRVVDESEGRLWA-ESRGFHYFETSAQSGEGINEMFQ 176
Cdd:cd04120  82 ITKKETFDDLPKWM-----KMIDKYASEDAELLLVGNKLDCETDREITRQQGEKFAqQITGMRFCEASAKDNFNVDEIFL 156

                ....*.
gi 55742336 177 SFFSSI 182
Cdd:cd04120 157 KLVDDI 162

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55742336   15 LRVKVISLGNAEVGKSCIIKRYCEKRfVPKYLATIGIDYGVTKVQVRDREIKVNIFDMAGHPFFYEVRNEFYKDSQGVIL 94
Cdd:PLN03118  13 LSFKILLIGDSGVGKSSLLVSFISSS-VEDLAPTIGVDFKIKQLTVGGKRLKLTIWDTAGQERFRTLTSSYYRNAQGIIL 91