Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases; Ran is involved in the active transport of proteins through nuclear pores.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A          18 VGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMFDVTSR 97
Cdd:smart00176   1 VGDGGTGKTTFVKRHLTGEFEKKYVATLGVEVHPLVFHTNRGPIRFNVWDTAGQEKFGGLRDGYYIQGQCAIIMFDVTAR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A          98 ITYKNVPNWHRDLVRVCENIPIVLCGNKVDVKERKVKAKTITFHRKKNLQYYDISAKSNYNFEKPFLWLARKLAGNPQLE 177
Cdd:smart00176  81 VTYKNVPNWHRDLVRVCENIPIVLCGNKVDVKDRKVKAKSITFHRKKNLQYYDISAKSNYNFEKPFLWLARKLIGDPNLE 160

                   ....*
3WYG_A         178 FVASP 182
Cdd:smart00176 161 FVAMP 165

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A         14 KLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMFD 93
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A         94 VTSRITYKNVPNWHRDLVRVC-ENIPIVLCGNKVDVKE-RKVKAKT-ITFHRKKNLQYYDISAKSNYNFEKPFLWLARKL 170
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHAdENVPIVLVGNKCDLEDqRVVSTEEgEALAKELGLPFMETSAKTNENVEEAFEELAREI 160

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A         12 TFKLVLVGDGGTGKTTFVKRHLTGE-FEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAII 90
Cdd:TIGR00231   1 DIKIVIVGHPNVGKSTLLNSLLGNKgSITEYYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLR 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
3WYG_A         91 MFDVTSR-ITYKNVPN-WHRDLVRVCE-NIPIVLCGNKVDVKERKVKAKTIT-FHRKKNLQYYDISAKSNYNFEKPF 163
Cdd:TIGR00231  81 VFDIVILvLDVEEILEkQTKEIIHHADsGVPIILVGNKIDLKDADLKTHVASeFAKLNGEPIIPLSAETGKNIDSAF 157

GTP-binding nuclear protein Ran; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A         1 MSAPA-ANGEVPTFKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRD 79
Cdd:PLN03071   1 MALPNqQTVDYPSFKLVIVGDGGTGKTTFVKRHLTGEFEKKYEPTIGVEVHPLDFFTNCGKIRFYCWDTAGQEKFGGLRD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A        80 GYYINAQCAIIMFDVTSRITYKNVPNWHRDLVRVCENIPIVLCGNKVDVKERKVKAKTITFHRKKNLQYYDISAKSNYNF 159
Cdd:PLN03071  81 GYYIHGQCAIIMFDVTARLTYKNVPTWHRDLCRVCENIPIVLCGNKVDVKNRQVKAKQVTFHRKKNLQYYEISAKSNYNF 160

                        170       180
                 ....*....|....*....|...
3WYG_A       160 EKPFLWLARKLAGNPQLEFVASP 182
Cdd:PLN03071 161 EKPFLYLARKLAGDPNLHFVESP 183

Ras-related nuclear proteins (Ran)/TC4 family of small GTPases; Ran GTPase is involved in diverse biological functions, such as nuclear transport, spindle formation during mitosis, DNA replication, and cell division. Among the Ras superfamily, Ran is a unique small G protein. It does not have a lipid modification motif at the C-terminus to bind to the membrane, which is often observed within the Ras superfamily. Ran may therefore interact with a wide range of proteins in various intracellular locations. Like other GTPases, Ran exists in GTP- and GDP-bound conformations that interact differently with effectors. Conversion between these forms and the assembly or disassembly of effector complexes requires the interaction of regulator proteins. The intrinsic GTPase activity of Ran is very low, but it is greatly stimulated by a GTPase-activating protein (RanGAP1) located in the cytoplasm. By contrast, RCC1, a guanine nucleotide exchange factor that generates RanGTP, is bound to chromatin and confined to the nucleus. Ran itself is mobile and is actively imported into the nucleus by a mechanism involving NTF-2. Together with the compartmentalization of its regulators, this is thought to produce a relatively high concentration of RanGTP in the nucleus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:cd00877   1 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYVATLGVEVHPLDFHTNRGKIRFNVWDTAGQEKFGGLRDGYYIQGQCAIIMF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       93 DVTSRITYKNVPNWHRDLVRVCENIPIVLCGNKVDVKERKVKAKTITFHRKKNLQYYDISAKSNYNFEKPFLWLARKLAG 172
Cdd:cd00877  81 DVTSRVTYKNVPNWHRDLVRVCENIPIVLCGNKVDIKDRKVKPKQITFHRKKNLQYYEISAKSNYNFEKPFLWLARKLLG 160

                ....*.
3WYG_A      173 NPQLEF 178
Cdd:cd00877 161 NPNLEF 166

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
3WYG_A       93 DVTSRITYKNVPNWHRDLVRVC-ENIPIVLCGNKVD-VKERKV-KAKTITFHRKKNLQYYDISAKSNYNFEKPFLWLAR 168
Cdd:cd00154  81 DVTNRESFENLDKWLNELKEYApPNIPIILVGNKSDlEDERQVsTEEAQQFAKENGLLFFETSAKTGENVDEAFESLAR 159

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A          13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEvhplsFYTNFGE-----IKFDVWDTAGLEKFGGLRDGYYINAQC 87
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGVD-----FKTKTIEvdgkrVKLQIWDTAGQERFRSITSSYYRGAVG 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A          88 AIIMFDVTSRITYKNVPNWHRDLVRVC-ENIPIVLCGNKVDVKE-RKVK---AKtiTFHRKKNLQYYDISAKSNYNFEKP 162
Cdd:smart00175  76 ALLVYDITNRESFENLENWLKELREYAsPNVVIMLVGNKSDLEEqRQVSreeAE--AFAEEHGLPFFETSAKTNTNVEEA 153

                   ....*...
3WYG_A         163 FLWLARKL 170
Cdd:smart00175 154 FEELAREI 161

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       14 KLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGvevhplSFY---TNFG--EIKFDVWDTAGLEKFGGLRDGYYINAQCA 88
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIE------DSYrkqIVVDgeTYTLDILDTAGQEEFSAMRDQYIRNGDGF 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       89 IIMFDVTSRITYKNVPNWHRDLVRV--CENIPIVLCGNKVD-VKERKV-KAKTITFHRKKNLQYYDISAKSNYNFEKPFL 164
Cdd:cd00876  75 ILVYSITSRESFEEIKNIREQILRVkdKEDVPIVLVGNKCDlENERQVsTEEGEALAEEWGCPFLETSAKTNINIDELFN 154

                ....*.
3WYG_A      165 WLARKL 170
Cdd:cd00876 155 TLVREI 160

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       14 KLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFG--EIKFDVWDTAGLEKFGGLRDGYYINAQCAIIM 91
Cdd:cd04106   2 KVIVVGNGNVGKSSMIQRFVKGIFTKDYKKTIGVDFLEKQIFLRQSdeDVRLMLWDTAGQEEFDAITKAYYRGAQACILV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       92 FDVTSRITYKNVPNWHRDLVRVCENIPIVLCGNKVDVKERKV--KAKTITFHRKKNLQYYDISAKSNYNFEKPFLWLARK 169
Cdd:cd04106  82 FSTTDRESFEAIESWKEKVEAECGDIPMVLVQTKIDLLDQAVitNEEAEALAKRLQLPLFRTSVKDDFNVTELFEYLAEK 161

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHplSFYTNFGEIKFDV--WDTAGLEKFGGLRDGYYINAQCAII 90
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTDDTFDEDLSSTIGVDFK--VKTVTVDGKKVKLaiWDTAGQERFRTLTSSYYRGAQGVIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       91 MFDVTSRITYKNVPNWHRDLVRVC--ENIPIVLCGNKVDVKERKV-KAKTITFHRKKNLQYYDISAKSNYNFEKPFLWLA 167
Cdd:cd01863  79 VYDVTRRDTFDNLDTWLNELDTYStnPDAVKMLVGNKIDKENREVtREEGQKFARKHNMLFIETSAKTRIGVQQAFEELV 158

                ...
3WYG_A      168 RKL 170
Cdd:cd01863 159 EKI 161

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEvhplsFYTNfgEIKFD-------VWDTAGLEKFGGLRDGYYINA 85
Cdd:cd01862   1 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGAD-----FLTK--EVTVDdrlvtlqIWDTAGQERFQSLGVAFYRGA 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       86 QCAIIMFDVTSRITYKNVPNWHRD-LVRVC----ENIPIVLCGNKVDVKERKVkaktITFHR-------KKNLQYYDISA 153
Cdd:cd01862  74 DCCVLVYDVTNPKSFESLDSWRDEfLIQASprdpENFPFVVLGNKIDLEEKRQ----VSTKKaqqwcksKGNIPYFETSA 149

                       170
                ....*....|....*.
3WYG_A      154 KSNYNFEKPFLWLARK 169
Cdd:cd01862 150 KEAINVDQAFETIARL 165

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:cd01867   4 FKLLLIGDSGVGKSCLLLRFSEDSFNPSFISTIGIDFKIRTIELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGIILVY 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
3WYG_A       93 DVTSRITYKNVPNWHRDLVR-VCENIPIVLCGNKVDVKERKV--KAKTITFHRKKNLQYYDISAKSNYNFEKPFLWLAR 168
Cdd:cd01867  84 DITDEKSFENIKNWMRNIDEhASEDVERMLVGNKCDMEEKRVvsKEEGEALAREYGIKFLETSAKANINVEEAFLTLAK 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVE----VHPLSFYTNfgeIKFDVWDTAGLEKFGGLRDGYYINAQCA 88
Cdd:cd04107   1 FKVLVIGDLGVGKTSIIKRYVHGVFSQHYKATIGVDfalkVIEWDPNTV---VRLQLWDIAGQERFGGMTRVYYKGAVGA 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       89 IIMFDVTSRITYKNVPNWHRDL---VRVC--ENIPIVLCGNKVDVKERKVKAKTITFHR--KKN--LQYYDISAKSNYNF 159
Cdd:cd04107  78 IIVFDVTRPSTFEAVLKWKADLdskVTLPngEPIPALLLANKCDLKKERLAKDPEQMDQfcKENgfIGWFETSAKENINI 157

                       170
                ....*....|.
3WYG_A      160 EKPFLWLARKL 170
Cdd:cd04107 158 EEAMRFLVKNI 168

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A          13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIgvEvhplSFYTNFGEI-----KFDVWDTAGLEKFGGLRDGYYINAQC 87
Cdd:smart00173   1 YKLVVLGSGGVGKSALTIQFIQGHFVDDYDPTI--E----DSYRKQIEIdgevcLLDILDTAGQEEFSAMRDQYMRTGEG 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A          88 AIIMFDVTSRITYKNVPNWHRDLVRV--CENIPIVLCGNKVDVK-ERKV-KAKTITFHRKKNLQYYDISAKSNYNFEKPF 163
Cdd:smart00173  75 FLLVYSITDRQSFEEIKKFREQILRVkdRDDVPIVLVGNKCDLEsERVVsTEEGKELARQWGCPFLETSAKERVNVDEAF 154

                   ....*
3WYG_A         164 LWLAR 168
Cdd:smart00173 155 YDLVR 159

Rab GTPase family 30 (Rab30); Rab30 subfamily. Rab30 appears to be associated with the Golgi stack. It is expressed in a wide variety of tissue types and in humans maps to chromosome 11. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:cd04114   8 FKIVLIGNAGVGKTCLVRRFTQGLFPPGQGATIGVDFMIKTVEIKGEKIKLQIWDTAGQERFRSITQSYYRSANALILTY 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       93 DVTSRITYKNVPNWHRDLVRVCEN-IPIVLCGNKVDVKERKVKAKTIT--FHRKKNLQYYDISAKSNYNFEKPFLWLARK 169
Cdd:cd04114  88 DITCEESFRCLPEWLREIEQYANNkVITILVGNKIDLAERREVSQQRAeeFSDAQDMYYLETSAKESDNVEKLFLDLACR 167

                .
3WYG_A      170 L 170
Cdd:cd04114 168 L 168

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:cd01861   1 HKLVFLGDQSVGKTSIITRFMYDTFDNQYQATIGIDFLSKTMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       93 DVTSRITYKNVPNWHRDLVRVCENIP-IVLCGNKVDVKERKVKAKTI--TFHRKKNLQYYDISAKSNYNFEKpflwLARK 169
Cdd:cd01861  81 DITNRQSFDNTDKWIDDVRDERGNDViIVLVGNKTDLSDKRQVSTEEgeKKAKENNAMFIETSAKAGHNVKQ----LFKK 156

                ....*
3WYG_A      170 LAGNP 174
Cdd:cd01861 157 IAQAL 161

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       14 KLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVE------VHPLSFYTNFGEIKFDV----WDTAGLEKFGGLRDGYYI 83
Cdd:cd04127   6 KLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDfrekrvVYNSQGPDGTSGKAFRVhlqlWDTAGQERFRSLTTAFFR 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       84 NAQCAIIMFDVTSRITYKNVPNWHRDLVR--VCENIPIVLCGNKVDV-KERKVKAKTI-TFHRKKNLQYYDISAKSNYNF 159
Cdd:cd04127  86 DAMGFLLMFDLTSEQSFLNVRNWMSQLQAhaYCENPDIVLIGNKADLpDQREVSERQArELADKYGIPYFETSAATGQNV 165

                ..
3WYG_A      160 EK 161
Cdd:cd04127 166 EK 167

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A        13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:PLN03110  13 FKIVLIGDSGVGKSNILSRFTRNEFCLESKSTIGVEFATRTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGALLVY 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
3WYG_A        93 DVTSRITYKNVPNWHRDLVRVCE-NIPIVLCGNKVDVKE-RKVKAKTI-TFHRKKNLQYYDISAKSNYNFEKPF 163
Cdd:PLN03110  93 DITKRQTFDNVQRWLRELRDHADsNIVIMMAGNKSDLNHlRSVAEEDGqALAEKEGLSFLETSALEATNVEKAF 166

Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:cd04116   6 LKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERFRSLRTPFYRGSDCCLLTF 85

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
3WYG_A       93 DVTSRITYKNVPNWHRDL-----VRVCENIPIVLCGNKVDVKERKVKAKTIT--FHRKKNLQYYDISAKSNYNFEKPF 163
Cdd:cd04116  86 SVDDSQSFQNLSNWKKEFiyyadVKEPESFPFVILGNKIDIPERQVSTEEAQawCRDNGDYPYFETSAKDATNVAAAF 163

Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap subfamily of the Ras family. It consists of Rap2a, Rap2b, and Rap2c. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGvevhplSFYTNfgEIKFD-------VWDTAGLEKFGGLRDGYYINA 85
Cdd:cd04176   2 YKVVVLGSGGVGKSALTVQFVSGTFIEKYDPTIE------DFYRK--EIEVDsspsvleILDTAGTEQFASMRDLYIKNG 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       86 QCAIIMFDVTSRITYKNVPNWHRDLVRV--CENIPIVLCGNKVDVK-ERKVK-AKTITFHRKKNLQYYDISAKSNYNFEK 161
Cdd:cd04176  74 QGFIVVYSLVNQQTFQDIKPMRDQIVRVkgYEKVPIILVGNKVDLEsEREVSsAEGRALAEEWGCPFMETSAKSKTMVNE 153

                ....*....
3WYG_A      162 PFLWLARKL 170
Cdd:cd04176 154 LFAEIVRQM 162

Rab GTPase family 15 (Rab15); Rab15 colocalizes with the transferrin receptor in early endosome compartments, but not with late endosomal markers. It codistributes with Rab4 and Rab5 on early/sorting endosomes, and with Rab11 on pericentriolar recycling endosomes. It is believed to function as an inhibitory GTPase that regulates distinct steps in early endocytic 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3WYG_A       13 FKLVLVGDGGTGKTTFVKRHLTGEFEKKYIATIGVEVHPLSFYTNFGEIKFDVWDTAGLEKFGGLRDGYYINAQCAIIMF 92
Cdd:cd04117   1 FRLLLIGDSGVGKTCLLCRFTDNEFHSSHISTIGVDFKMKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVY 80