GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   1 MLKAKILFVGPCESGKTVLAN-FLTESSDITEYNPTQGVRILEFENPHvtsnnKGTGCEFELWDCGGDSKFESCWPAL-- 77
Cdd:COG1100   1 MGEKKIVVVGTGGVGKTSLVNrLVGDIFSLEKYLSTNGVTIDKKELKL-----DGLDVDLVIWDTPGQDEFRETRQFYar 75

                        90       100
                ....*....|....*....|....*...
gi 21313026  78 -MKDAHGVVIVFNADIPSHLKEIEMWYS 104
Cdd:COG1100  76 qLTGASLYLFVVDGTREETLQSLYELLE 103

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   1 MLKAKILFVGPCESGKTVLAN-FLTESSDITEYNPTQGVRILEFENPHvtsnnKGTGCEFELWDCGGDSKFESCWPAL-- 77
Cdd:COG1100   1 MGEKKIVVVGTGGVGKTSLVNrLVGDIFSLEKYLSTNGVTIDKKELKL-----DGLDVDLVIWDTPGQDEFRETRQFYar 75

                        90       100
                ....*....|....*....|....*...
gi 21313026  78 -MKDAHGVVIVFNADIPSHLKEIEMWYS 104
Cdd:COG1100  76 qLTGASLYLFVVDGTREETLQSLYELLE 103

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 21313026   5 KILFVGPCESGKTVLANFLTESSDITEYNPTQGVrilEFENPHVTSNNKgtGCEFELWDCGGDSKFESCWPALMKDAHGV 84
Cdd:cd00154   2 KIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGV---DFKSKTIEVDGK--KVKLQIWDTAGQERFRSITSSYYRGAHGA 76

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 21313026  85 VIVFnaDIPSH--LKEIEMWYScFVQQQFLQDSHCMLVA 121
Cdd:cd00154  77 ILVY--DVTNResFENLDKWLN-ELKEYAPPNIPIILVG 112

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 21313026     4 AKILFVGPCESGKTVLAN-FLTESSDITEYNPTQGvriLEFENPHVTSNnkGTGCEFELWDCGGDSKFESCWPALMKDAH 82
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNsLLGNKGSITEYYPGTT---RNYVTTVIEED--GKTYKFNLLDTAGQEDYDAIRRLYYPQVE 76

                          90
                  ....*....|.
gi 21313026    83 GVVIVFNADIP 93
Cdd:TIGR00231  77 RSLRVFDIVIL 87

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   1 MLKAKILFVGPCESGKTVLAN-FLTESSDITEYNPTQGVRILEFENPHvtsnnKGTGCEFELWDCGGDSKFESCWPAL-- 77
Cdd:COG1100   1 MGEKKIVVVGTGGVGKTSLVNrLVGDIFSLEKYLSTNGVTIDKKELKL-----DGLDVDLVIWDTPGQDEFRETRQFYar 75

                        90       100
                ....*....|....*....|....*...
gi 21313026  78 -MKDAHGVVIVFNADIPSHLKEIEMWYS 104
Cdd:COG1100  76 qLTGASLYLFVVDGTREETLQSLYELLE 103

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 21313026   5 KILFVGPCESGKTVLANFLTESSDITEYNPTQGVrilEFENPHVTSNNKgtGCEFELWDCGGDSKFESCWPALMKDAHGV 84
Cdd:cd00154   2 KIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGV---DFKSKTIEVDGK--KVKLQIWDTAGQERFRSITSSYYRGAHGA 76

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 21313026  85 VIVFnaDIPSH--LKEIEMWYScFVQQQFLQDSHCMLVA 121
Cdd:cd00154  77 ILVY--DVTNResFENLDKWLN-ELKEYAPPNIPIILVG 112

Septum-promoting GTPase (Spg1); Spg1p. Spg1p (septum-promoting GTPase) was first identified in the fission yeast S. pombe, where it regulates septum formation in the septation initiation network (SIN) through the cdc7 protein kinase. Spg1p is an essential gene that localizes to the spindle pole bodies. When GTP-bound, it binds cdc7 and causes it to translocate to spindle poles. Sid4p (septation initiation defective) is required for localization of Spg1p to the spindle pole body, and the ability of Spg1p to promote septum formation from any point in the cell cycle depends on Sid4p. Spg1p is negatively regulated by Byr4 and cdc16, which form a two-component GTPase activating protein (GAP) for Spg1p. The existence of a SIN-related pathway in plants has been proposed. 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 21313026   5 KILFVGPCESGKTVLANFLTESSDITEYNPTQGVRILEfenphVTSNNKGTGCEFELWDCGGDSKFESCWPALMKDAhgV 84
Cdd:cd04128   2 KIGLLGDAQIGKTSLMVKYVEGEFDEEYIQTLGVNFME-----KTISIRGTEITFSIWDLGGQREFINMLPLVCKDA--V 74

                        90       100
                ....*....|....*....|..
gi 21313026  85 VIVFNADI--PSHLKEIEMWYS 104
Cdd:cd04128  75 AILFMFDLtrKSTLNSIKEWYR 96

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   2 LKAKILFVGPCESGKTVLANFLTESSDITEYNPTQgvrileFENPHVTSNNKGTGCEFELWDCGGDSKFESCWPALMKDA 81
Cdd:cd04172   4 VKCKIVVVGDSQCGKTALLHVFAKDCFPENYVPTV------FENYTASFEIDTQRIELSLWDTSGSPYYDNVRPLSYPDS 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 21313026  82 HGVVIVFNADIPSHLKEI-EMWYSCFvqQQFLQDSHCMLVA 121
Cdd:cd04172  78 DAVLICFDISRPETLDSVlKKWKGEI--QEFCPNTKMLLVG 116

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 21313026   5 KILFVGPCESGKTVLANFLTESSDITEYNPTQGVRILEfenPHVTSNNKGTGCEFELWDCGGDSKFESCWPALMKDAHGV 84
Cdd:cd04106   2 KVIVVGNGNVGKSSMIQRFVKGIFTKDYKKTIGVDFLE---KQIFLRQSDEDVRLMLWDTAGQEEFDAITKAYYRGAQAC 78

                        90       100
                ....*....|....*....|.
gi 21313026  85 VIVFNADIPSHLKEIEMWYSC 105
Cdd:cd04106  79 ILVFSTTDRESFEAIESWKEK 99

Ras of complex proteins (Roc) C-terminal of Roc (COR) domain family; RocCOR (or Roco) protein family is characterized by a superdomain containing a Ras-like GTPase domain, called Roc (Ras of complex proteins), and a characteristic second domain called COR (C-terminal of Roc). A kinase domain and diverse regulatory domains are also often found in Roco proteins. Their functions are diverse; in Dictyostelium discoideum, which encodes 11 Roco proteins, they are involved in cell division, chemotaxis and development, while in human, where 4 Roco proteins (LRRK1, LRRK2, DAPK1, and MFHAS1) are encoded, these proteins are involved in epilepsy and cancer. Mutations in LRRK2 (leucine-rich repeat kinase 2) are known to cause familial Parkinson's disease.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   3 KAKILFVGPCESGKTVLANFLTESsditEYNP----TQGVRILEFENPhvtsNNKGTGCEFELWDCGGDSKFESCWPALM 78
Cdd:cd09914   1 EAKLMLVGQGGVGKTSLCKQLIGE----KFDGdessTHGINVQDWKIP----APERKKIRLNVWDFGGQEIYHATHQFFL 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 21313026  79 KDAHGVVIVFNADIPSHLKEIEMWYSCFvqQQFLQDSHCMLVAHHK 124
Cdd:cd09914  73 TSRSLYLLVFDLRTGDEVSRVPYWLRQI--KAFGGVSPVILVGTHI 116

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 21313026     4 AKILFVGPCESGKTVLAN-FLTESSDITEYNPTQGvriLEFENPHVTSNnkGTGCEFELWDCGGDSKFESCWPALMKDAH 82
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNsLLGNKGSITEYYPGTT---RNYVTTVIEED--GKTYKFNLLDTAGQEDYDAIRRLYYPQVE 76

                          90
                  ....*....|.
gi 21313026    83 GVVIVFNADIP 93
Cdd:TIGR00231  77 RSLRVFDIVIL 87

Signal recognition particle receptor, beta subunit (SR-beta), together with SR-alpha, forms the heterodimeric signal recognition particle (SRP); Signal recognition particle receptor, beta subunit (SR-beta). SR-beta and SR-alpha form the heterodimeric signal recognition particle (SRP or SR) receptor that binds SRP to regulate protein translocation across the ER membrane. Nascent polypeptide chains are synthesized with an N-terminal hydrophobic signal sequence that binds SRP54, a component of the SRP. SRP directs targeting of the ribosome-nascent chain complex (RNC) to the ER membrane via interaction with the SR, which is localized to the ER membrane. The RNC is then transferred to the protein-conducting channel, or translocon, which facilitates polypeptide translation across the ER membrane or integration into the ER membrane. SR-beta is found only in eukaryotes; it is believed to control the release of the signal sequence from SRP54 upon binding of the ribosome to the translocon. High expression of SR-beta has been observed in human colon cancer, suggesting it may play a role in the development of this type of cancer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   6 ILFVGPCESGKTVLANFLTESsditEYNPTQgVRILEFENPHVTSNNKGTGceFELWDCGGDSKF-ESCWPALMKDAHGV 84
Cdd:cd04105   3 VLLLGPSDSGKTALFTKLTTG----KVRSTV-TSIEPNVASFYSNSSKGKK--LTLVDVPGHEKLrDKLLEYLKASLKAI 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026  85 VIVFN-ADIPSHLKEI-EMWYSCFVQQQFLQDSHCMLVAHHKPGSggergSLALSPplnklKLVHSNLEEDPEEVRVEFI 162
Cdd:cd04105  76 VFVVDsATFQKNIRDVaEFLYDILTDLEKIKNKIPILIACNKQDL-----FTAKPA-----KKIKELLEKEINTLRESRS 145

                ....*....
gi 21313026 163 KYLKSIINS 171
Cdd:cd04105 146 KSLESLDGD 154

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 21313026   5 KILFVGPCESGKTVLANFLTESSDITEYNPTQGVrilEFENPHVTSNNKGTG--------CEFELWDCGGDSKFESCWPA 76
Cdd:cd04127   6 KLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGI---DFREKRVVYNSQGPDgtsgkafrVHLQLWDTAGQERFRSLTTA 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 21313026  77 LMKDAHGVVIVFNADIPSHLKEIEMWYSCFVQQQFLQDSHCMLV 120
Cdd:cd04127  83 FFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAYCENPDIVLI 126

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   5 KILFVGPCESGKTVLANFLTESSDITEYNPTQGV-----RILEFENPHVTsnnkgtgceFELWDCGGDSKFESCWPALMK 79
Cdd:cd04109   2 KIVVLGDGASGKTSLIRRFAQEGFGKSYKQTIGLdffsrRITLPGSLNVT---------LQVWDIGGQQIGGKMLDKYIY 72

                        90       100
                ....*....|....*....|....*.
gi 21313026  80 DAHGVVIVFNADIPSHLKEIEMWYSC 105
Cdd:cd04109  73 GAQAVCLVYDITNSQSFENLEDWLSV 98

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 21313026   5 KILFVGPCESGKTVLANFLTESSDITEYNPTQGVrilEFENPHVTSNnkGTGCEFELWDCGGDSKFESCWPALMKDAHGV 84
Cdd:cd01863   2 KILLIGDSGVGKSSLLLRFTDDTFDEDLSSTIGV---DFKVKTVTVD--GKKVKLAIWDTAGQERFRTLTSSYYRGAQGV 76

                        90
                ....*....|....*...
gi 21313026  85 VIVFNADIPSHLKEIEMW 102
Cdd:cd01863  77 ILVYDVTRRDTFDNLDTW 94

Arf-like 6 (Arl6) GTPase; Arl6 (Arf-like 6) forms a subfamily of the Arf family of small GTPases. Arl6 expression is limited to the brain and kidney in adult mice, but it is expressed in the neural plate and somites during embryogenesis, suggesting a possible role for Arl6 in early development. Arl6 is also believed to have a role in cilia or flagella function. Several proteins have been identified that bind Arl6, including Arl6 interacting protein (Arl6ip), and SEC61beta, a subunit of the heterotrimeric conducting channel SEC61p. Based on Arl6 binding to these effectors, Arl6 is also proposed to play a role in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. At least three specific homozygous Arl6 mutations in humans have been found to cause Bardet-Biedl syndrome, a disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   6 ILFVGPCESGKTVLANFL----TESSDITeynPTQGVRILEFEnphvTSNNKgtgceFELWDCGGDSKFESCWPALMKDA 81
Cdd:cd04157   2 ILVLGLDNSGKTTIINQLkpsnAQSQNIV---PTVGFNVESFK----KGNLS-----FTAFDMSGQGKYRGLWEHYYKNI 69

                ....*.
gi 21313026  82 HGVVIV 87
Cdd:cd04157  70 QGIIFV 75

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 21313026   5 KILFVGPCESGKT------VLANFlteSSDiteYNPTQGVrilEFENpHVTSNNKGTGCEFELWDCGGDSKFESCWPALM 78
Cdd:cd04107   2 KVLVIGDLGVGKTsiikryVHGVF---SQH---YKATIGV---DFAL-KVIEWDPNTVVRLQLWDIAGQERFGGMTRVYY 71

                        90       100
                ....*....|....*....|....
gi 21313026  79 KDAHGVVIVFNADIPSHLKEIEMW 102
Cdd:cd04107  72 KGAVGAIIVFDVTRPSTFEAVLKW 95

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313026   5 KILFVGPCESGKTVLANFLtESSDITEYNPTQG--VRILEFENPHVTsnnkgtgcefeLWDCGGDSKFESCWPALMKDAH 82
Cdd:cd00878   1 RILMLGLDGAGKTTILYKL-KLGEVVTTIPTIGfnVETVEYKNVKFT-----------VWDVGGQDKIRPLWKHYYENTD 68

                        90       100       110
                ....*....|....*....|....*....|...
gi 21313026  83 GVVIVFNADIPSHLKEIEMWYSCFVQQQFLQDS 115
Cdd:cd00878  69 GLIFVVDSSDRERIEEAKNELHKLLNEEELKGA 101