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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   3 GKSLLLKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADC 82
Cdd:cd04116     1 GKSSLLKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERFRSLRTPFYRGSDC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  83 CLLTFSVDDRQSFENLSNWQKEFIYYADVKDPDHFPFVVLGNKVDKVERQVTTEEAKAWCLEHGDYPYLETSAKDDTNVT 162
Cdd:cd04116    81 CLLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFVILGNKIDIPERQVSTEEAQAWCRDNGDYPYFETSAKDATNVA 160

                         170
                  ....*....|
gi 1788942529 163 VAFEEAVRQV 172
Cdd:cd04116   161 AAFEEAVRRV 170

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   3 GKSLLLKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADC 82
Cdd:cd04116     1 GKSSLLKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERFRSLRTPFYRGSDC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  83 CLLTFSVDDRQSFENLSNWQKEFIYYADVKDPDHFPFVVLGNKVDKVERQVTTEEAKAWCLEHGDYPYLETSAKDDTNVT 162
Cdd:cd04116    81 CLLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFVILGNKIDIPERQVSTEEAQAWCRDNGDYPYFETSAKDATNVA 160

                         170
                  ....*....|
gi 1788942529 163 VAFEEAVRQV 172
Cdd:cd04116   161 AAFEEAVRRV 170

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 1788942529   9 KVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTFS 88
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVDFYTKTIEVDGKTVKLQIWDTAGQERFRALRPLYYRGADGFLLVYD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  89 VDDRQSFENLSNWQKEFIYYADvkdpDHFPFVVLGNKVD-KVERQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAFEE 167
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHAD----ENVPIVLVGNKCDlEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEEAFEE 155

                  ....*.
gi 1788942529 168 AVRQVL 173
Cdd:pfam00071 156 LAREIL 161

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   8 LKVILLGDGGVGKSSLMNRYVTNKFDSQAFH-TIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRtPFY----RGADC 82
Cdd:COG1100     4 KKIVVVGTGGVGKTSLVNRLVGDIFSLEKYLsTNGVTIDKKELKLDGLDVDLVIWDTPGQDEFRETR-QFYarqlTGASL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  83 CLLTFSVDDRQSFENLSNWQKEFIYYAdvkdpDHFPFVVLGNKVDKV--ERQVTTEEAKAWCLEHGDYPYLETSAKDDTN 160
Cdd:COG1100    83 YLFVVDGTREETLQSLYELLESLRRLG-----KKSPIILVLNKIDLYdeEEIEDEERLKEALSEDNIVEVVATSAKTGEG 157

                         170       180
                  ....*....|....*....|
gi 1788942529 161 VTVAFEEAVRQVLAVEEQLE 180
Cdd:COG1100   158 VEELFAALAEILRGEGDSLD 177

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   3 GKSLLLKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADC 82
Cdd:cd04116     1 GKSSLLKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERFRSLRTPFYRGSDC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  83 CLLTFSVDDRQSFENLSNWQKEFIYYADVKDPDHFPFVVLGNKVDKVERQVTTEEAKAWCLEHGDYPYLETSAKDDTNVT 162
Cdd:cd04116    81 CLLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFVILGNKIDIPERQVSTEEAQAWCRDNGDYPYFETSAKDATNVA 160

                         170
                  ....*....|
gi 1788942529 163 VAFEEAVRQV 172
Cdd:cd04116   161 AAFEEAVRRV 170

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529    8 LKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTF 87
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   88 SVDDRQSFENLSNWQKEFIYYADvkdpDHFPFVVLGNKVDKVE-RQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAFE 166
Cdd:smart00175  81 DITNRESFENLENWLKELREYAS----PNVVIMLVGNKSDLEEqRQVSREEAEAFAEEHG-LPFFETSAKTNTNVEEAFE 155

                   ....*...
gi 1788942529  167 EAVRQVLA 174
Cdd:smart00175 156 ELAREILK 163

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 1788942529   8 LKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTF 87
Cdd:cd00154     1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  88 SVDDRQSFENLSNWQKEFIYYAdvkdPDHFPFVVLGNKVDKV-ERQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAFE 166
Cdd:cd00154    81 DVTNRESFENLDKWLNELKEYA----PPNIPIILVGNKSDLEdERQVSTEEAQQFAKENG-LLFFETSAKTGENVDEAFE 155

                  ....
gi 1788942529 167 EAVR 170
Cdd:cd00154   156 SLAR 159

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 1788942529   7 LLKVILLGDGGVGKSSLMNRYVTNKF--DSQAfhTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCL 84
Cdd:cd01868     3 LFKIVLIGDSGVGKSNLLSRFTRNEFnlDSKS--TIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGAL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  85 LTFSVDDRQSFENLSNWQKEFIYYADvkdpDHFPFVVLGNKVD-KVERQVTTEEAKAWCLEHGDYpYLETSAKDDTNVTV 163
Cdd:cd01868    81 LVYDITKKSTFENVERWLKELRDHAD----SNIVIMLVGNKSDlRHLRAVPTEEAKAFAEKNGLS-FIETSALDGTNVEE 155

                  ....*....
gi 1788942529 164 AFEEAVRQV 172
Cdd:cd01868   156 AFKQLLTEI 164

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 1788942529   9 KVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGvEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTFS 88
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIE-DSYRKQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  89 VDDRQSFENLSNWQKEfIYyaDVKDPDHFPFVVLGNKVDKV-ERQVTTEEAKAWClEHGDYPYLETSAKDDTNVTVAFEE 167
Cdd:cd00876    80 ITSRESFEEIKNIREQ-IL--RVKDKEDVPIVLVGNKCDLEnERQVSTEEGEALA-EEWGCPFLETSAKTNINIDELFNT 155

                  ....*
gi 1788942529 168 AVRQV 172
Cdd:cd00876   156 LVREI 160

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 1788942529   9 KVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEV-DGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTF 87
Cdd:cd04111     4 RLIVIGDSTVGKSSLLKRFTEGRFAEVSDPTVGVDFFSRLIEIePGVRIKLQLWDTAGQERFRSITRSYYRNSVGVLLVF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  88 SVDDRQSFENLSNWQKEFIYYAdvkDPDHFPFVVLGNKVDKV-ERQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAFE 166
Cdd:cd04111    84 DITNRESFEHVHDWLEEARSHI---QPHRPVFILVGHKCDLEsQRQVTREEAEKLAKDLG-MKYIETSARTGDNVEEAFE 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1788942529 167 EAVRQVLAVEEQLEHCLL--------GHT---------VDLNSSSKAGSSCC 201
Cdd:cd04111   160 LLTQEIYERIKRGELCALdgwdgvksGFPagrafsleeRSPTFASPEKSCCC 211

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. 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 1788942529   8 LKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTF 87
Cdd:cd04113     1 FKFLIIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  88 SVDDRQSFENLSNWQKEFIYYADvkdpDHFPFVVLGNKVDKVE-RQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAFE 166
Cdd:cd04113    81 DITSRESFNALTNWLTDARTLAS----PDIVIILVGNKKDLEDdREVTFLEASRFAQENG-LLFLETSALTGENVEEAFL 155

                  ....*.
gi 1788942529 167 EAVRQV 172
Cdd:cd04113   156 KCARSI 161

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   8 LKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVD-GRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLT 86
Cdd:cd04107     1 FKVLVIGDLGVGKTSIIKRYVHGVFSQHYKATIGVDFALKVIEWDpNTVVRLQLWDIAGQERFGGMTRVYYKGAVGAIIV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  87 FSVDDRQSFENLSNWqKEFIyyaDVK----DPDHFPFVVLGNKVD--KVERQVTTEEAKAWCLEHGDYPYLETSAKDDTN 160
Cdd:cd04107    81 FDVTRPSTFEAVLKW-KADL---DSKvtlpNGEPIPALLLANKCDlkKERLAKDPEQMDQFCKENGFIGWFETSAKENIN 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1788942529 161 VTVAFEEAVRQVLAVEEQLEHCL----LGHTVDLNSSSKAGSSCC 201
Cdd:cd04107   157 IEEAMRFLVKNILKNDKGLQSPEpdedNVIDLKQETTTSKSKSCC 201

Rab GTPase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   7 LLKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLT 86
Cdd:PLN03110   12 LFKIVLIGDSGVGKSNILSRFTRNEFCLESKSTIGVEFATRTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGALLV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  87 FSVDDRQSFENLSNWQKEFIYYADvkdpDHFPFVVLGNKVD-KVERQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAF 165
Cdd:PLN03110   92 YDITKRQTFDNVQRWLRELRDHAD----SNIVIMMAGNKSDlNHLRSVAEEDGQALAEKEG-LSFLETSALEATNVEKAF 166

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 1788942529 166 EEAV--------RQVLAVEEQLEHCLL---GHTVDLNSSSKAGS-SCC 201
Cdd:PLN03110  167 QTILleiyhiisKKALAAQEAAANSGLpgqGTTINVADTSGNNKrGCC 214

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   2 SGKSLLLKVILLGDGGVGKSSLMNRYVTNKFDSQAfHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGAD 81
Cdd:PLN03118    9 SGYDLSFKILLIGDSGVGKSSLLVSFISSSVEDLA-PTIGVDFKIKQLTVGGKRLKLTIWDTAGQERFRTLTSSYYRNAQ 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  82 CCLLTFSVDDRQSFENLSN-WQKEFIYYADVKDPDHfpfVVLGNKVDK-VERQVTTEEAKAWCLEHGdYPYLETSAKDDT 159
Cdd:PLN03118   88 GIILVYDVTRRETFTNLSDvWGKEVELYSTNQDCVK---MLVGNKVDReSERDVSREEGMALAKEHG-CLFLECSAKTRE 163

                         170       180
                  ....*....|....*....|.
gi 1788942529 160 NVTVAFEEAVRQVLAVEEQLE 180
Cdd:PLN03118  164 NVEQCFEELALKIMEVPSLLE 184

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 1788942529    9 KVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGvEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTFS 88
Cdd:smart00010   4 KLVVLGGGGVGKSALTIQFVQGHFVDEYDPTIE-DSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   89 VDDRQSFENLSNWqKEFIYyaDVKDPDHFPFVVLGNKVD-KVERQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAFEE 167
Cdd:smart00010  83 ITDRQSFEEIAKF-REQIL--RVKDRDDVPIVLVGNKCDlENERVVSTEEGKELARQWG-CPFLETSAKERINVDEAFYD 158

                   ....*
gi 1788942529  168 AVRQV 172
Cdd:smart00010 159 LVREI 163

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 1788942529   7 LLKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLT 86
Cdd:cd04122     2 IFKYIIIGDMGVGKSCLLHQFTEKKFMADCPHTIGVEFGTRIIEVNGQKIKLQIWDTAGQERFRAVTRSYYRGAAGALMV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  87 FSVDDRQSFENLSNWQKEfiyYADVKDPDHFPFVVlGNKVD-KVERQVTTEEAKAWCLEHGdYPYLETSAKDDTNVTVAF 165
Cdd:cd04122    82 YDITRRSTYNHLSSWLTD---ARNLTNPNTVIFLI-GNKADlEAQRDVTYEEAKQFADENG-LLFLECSAKTGENVEDAF 156

                  ....*..
gi 1788942529 166 EEAVRQV 172
Cdd:cd04122   157 LETAKKI 163

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 1788942529   7 LLKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLT 86
Cdd:cd01864     3 LFKIILIGDSNVGKTCVVQRFKSGTFSERQGNTIGVDFTMKTLEIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAIIA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  87 FSVDDRQSFENLSNWQKEFIYYAdvkdPDHFPFVVLGNKVDKVE-RQVTTEEAKAWCLEHGDYPYLETSAKDDTNVTVAF 165
Cdd:cd01864    83 YDITRRSSFESVPHWIEEVEKYG----ASNVVLLLIGNKCDLEEqREVLFEEACTLAEHYGILAVLETSAKESSNVEEAF 158

                  ....*..
gi 1788942529 166 EEAVRQV 172
Cdd:cd01864   159 LLMATEL 165

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   7 LLKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVD----------GRFVTLQIWDTAGQERFKSLRTPF 76
Cdd:cd04127     4 LIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYNsqgpdgtsgkAFRVHLQLWDTAGQERFRSLTTAF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  77 YRGADCCLLTFSVDDRQSFENLSNWQKEFIYYADVKDPDhfpFVVLGNKVD-KVERQVTTEEAKAWCLEHGdYPYLETSA 155
Cdd:cd04127    84 FRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAYCENPD---IVLIGNKADlPDQREVSERQARELADKYG-IPYFETSA 159

                         170
                  ....*....|.
gi 1788942529 156 KDDTNVTVAFE 166
Cdd:cd04127   160 ATGQNVEKAVE 170

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 1788942529   8 LKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLNRDLEVDGR--FVTLQIWDTAGQERFKSLRTPFYRGADCCLL 85
Cdd:cd04106     1 IKVIVVGNGNVGKSSMIQRFVKGIFTKDYKKTIGVDFLEKQIFLRQSdeDVRLMLWDTAGQEEFDAITKAYYRGAQACIL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  86 TFSVDDRQSFENLSNWQKefiyyADVKDPDHFPFVVLGNKVDKVERQ-VTTEEAKAWCLEHgDYPYLETSAKDDTNVTVA 164
Cdd:cd04106    81 VFSTTDRESFEAIESWKE-----KVEAECGDIPMVLVQTKIDLLDQAvITNEEAEALAKRL-QLPLFRTSVKDDFNVTEL 154

                  ..
gi 1788942529 165 FE 166
Cdd:cd04106   155 FE 156

R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, and related members of the Ras family. M-Ras is expressed in lympho-hematopoetic cells. It interacts with some of the known Ras effectors, but appears to also have its own effectors. Expression of mutated M-Ras leads to transformation of several types of cell lines, including hematopoietic cells, mammary epithelial cells, and fibroblasts. Overexpression of M-Ras is observed in carcinomas from breast, uterus, thyroid, stomach, colon, kidney, lung, and rectum. In addition, expression of a constitutively active M-Ras mutant in murine bone marrow induces a malignant mast cell leukemia that is distinct from the monocytic leukemia induced by H-Ras. TC21, along with H-Ras, has been shown to regulate the branching morphogenesis of ureteric bud cell branching in mice. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   8 LKVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGVEFLnRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTF 87
Cdd:cd04145     3 YKLVVVGGGGVGKSALTIQFIQSYFVTDYDPTIEDSYT-KQCEIDGQWARLDILDTAGQEEFSAMREQYMRTGEGFLLVF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529  88 SVDDRQSFENLSNWQKEFIyyaDVKDPDHFPFVVLGNKVDKV-ERQVTTEEAKAWCLEHgDYPYLETSAKDDTNVTVAFE 166
Cdd:cd04145    82 SVTDRGSFEEVDKFHTQIL---RVKDRDEFPMILVGNKADLEhQRQVSREEGQELARQL-KIPYIETSAKDRVNVDKAFH 157

                  ....*.
gi 1788942529 167 EAVRQV 172
Cdd:cd04145   158 DLVRVI 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1788942529   9 KVILLGDGGVGKSSLMNRYVTNKFDSQAFHTIGvEFLNRDLEVDGRFVTLQIWDTAGQERFKSLRTPFYRGADCCLLTFS 88
Cdd:cd04176     3 KVVVLGSGGVGKSALTVQFVSGTFIEKYDPTIE-DFYRKEIEVDSSPSVLEILDTAGTEQFASMRDLYIKNGQGFIVVYS 81