P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   2 VQVWDTAGQERFRKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd04115    53 VQLWDTAGQERFRKSMVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSLPNEVPRILVGNKCDLREQIQVPTDLA 132

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907203038  82 LKFADAHNMLLFETSAKDPKESQNVESIFMCLACRLKA 119
Cdd:cd04115   133 QRFADAHSMPLFETSAKDPSENDHVEAIFMTLAHKLKS 170

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. 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 1907203038   2 VQVWDTAGQERFRKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd04115    53 VQLWDTAGQERFRKSMVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSLPNEVPRILVGNKCDLREQIQVPTDLA 132

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907203038  82 LKFADAHNMLLFETSAKDPKESQNVESIFMCLACRLKA 119
Cdd:cd04115   133 QRFADAHSMPLFETSAKDPSENDHVEAIFMTLAHKLKS 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 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLAL 82
Cdd:pfam00071  51 QIWDTAGQERFR-ALRPLYYRGADGFLLVYDITSRDSFENVKKWVEEILRHA-DENVPIVLVGNKCDLEDQRVVSTEEGE 128

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907203038  83 KFADAHNMLLFETSAKDpkeSQNVESIFMCLA 114
Cdd:pfam00071 129 ALAKELGLPFMETSAKT---NENVEEAFEELA 157

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   2 VQVWDTAGQERFRKS--MVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECngHAVPPLVPKVLVGNKCDLR--EQIQVP 77
Cdd:COG1100    55 LVIWDTPGQDEFRETrqFYARQLTGASLYLFVVDGTREETLQSLYELLESL--RRLGKKSPIILVLNKIDLYdeEEIEDE 132

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1907203038  78 SNLALKFADAHNMLLFETSAKDPKesqNVESIF 110
Cdd:COG1100   133 ERLKEALSEDNIVEVVATSAKTGE---GVEELF 162

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. 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 1907203038   2 VQVWDTAGQERFRKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd04115    53 VQLWDTAGQERFRKSMVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSLPNEVPRILVGNKCDLREQIQVPTDLA 132

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907203038  82 LKFADAHNMLLFETSAKDPKESQNVESIFMCLACRLKA 119
Cdd:cd04115   133 QRFADAHSMPLFETSAKDPSENDHVEAIFMTLAHKLKS 170

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 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd00154    51 LQIWDTAGQERFR-SITSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYA-PPNIPIILVGNKSDLEDERQVSTEEA 128

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1907203038  82 LKFADAHNMLLFETSAKDpkeSQNVESIFMCLA 114
Cdd:cd00154   129 QQFAKENGLLFFETSAKT---GENVDEAFESLA 158

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLAL 82
Cdd:cd01869    54 QIWDTAGQERFR-TITSSYYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYA-SENVNKLLVGNKCDLTDKKVVDYTEAK 131

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1907203038  83 KFADAHNMLLFETSAKDpkeSQNVESIFMCLACRLK 118
Cdd:cd01869   132 EFADELGIPFLETSAKN---ATNVEEAFMTMAREIK 164

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPlVPKVLVGNKCDLREQIQVPSNLAL 82
Cdd:cd01867    55 QIWDTAGQERFR-TITTSYYRGAMGIILVYDITDEKSFENIKNWMRNIDEHASED-VERMLVGNKCDMEEKRVVSKEEGE 132

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907203038  83 KFADAHNMLLFETSAKDpkeSQNVESIFMCLACRLKAQ 120
Cdd:cd01867   133 ALAREYGIKFLETSAKA---NINVEEAFLTLAKDILKK 167

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 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvPPLVPKVLVGNKCDLREQIQVPSNLAL 82
Cdd:cd01868    55 QIWDTAGQERYR-AITSAYYRGAVGALLVYDITKKSTFENVERWLKELRDHA-DSNIVIMLVGNKSDLRHLRAVPTEEAK 132

                          90       100
                  ....*....|....*....|....*....
gi 1907203038  83 KFADAHNMLLFETSAKDpkeSQNVESIFM 111
Cdd:cd01868   133 AFAEKNGLSFIETSALD---GTNVEEAFK 158

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 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd01864    54 LQIWDTAGQERFR-TITQSYYRSANGAIIAYDITRRSSFESVPHWIEEVEKYGASNVV-LLLIGNKCDLEEQREVLFEEA 131

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1907203038  82 LKFADAHNML-LFETSAkdpKESQNVESIFMCLACRL 117
Cdd:cd01864   132 CTLAEHYGILaVLETSA---KESSNVEEAFLLMATEL 165

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHA-VPPLVpkVLVGNKCDLREQIQVPSNLA 81
Cdd:cd01861    52 QLWDTAGQERFR-SLIPSYIRDSSVAVVVYDITNRQSFDNTDKWIDDVRDERgNDVII--VLVGNKTDLSDKRQVSTEEG 128

                          90       100
                  ....*....|....*....|....*....
gi 1907203038  82 LKFADAHNMLLFETSAkdpKESQNVESIF 110
Cdd:cd01861   129 EKKAKENNAMFIETSA---KAGHNVKQLF 154

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   2 VQVWDTAGQERFrKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPL---VPKVLVGNKCDLREQIQVPS 78
Cdd:cd01862    51 LQIWDTAGQERF-QSLGVAFYRGADCCVLVYDVTNPKSFESLDSWRDEFLIQASPRDpenFPFVVLGNKIDLEEKRQVST 129

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907203038  79 NLALKFADAH-NMLLFETSAkdpKESQNVESIFMCLACRLKAQKS 122
Cdd:cd01862   130 KKAQQWCKSKgNIPYFETSA---KEAINVDQAFETIARLALEQEK 171

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 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLAL 82
Cdd:cd04111    55 QLWDTAGQERFR-SITRSYYRNSVGVLLVFDITNRESFEHVHDWLEEARSHIQPHRPVFILVGHKCDLESQRQVTREEAE 133

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907203038  83 KFADAHNMLLFETSAKDpkeSQNVESIFMCLA 114
Cdd:cd04111   134 KLAKDLGMKYIETSART---GDNVEEAFELLT 162

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQE---CNGHAVPPlvpkVLVGNKCDLREQIQVPSN 79
Cdd:cd04123    52 AIWDTAGQERYH-ALGPIYYRDADGAILVYDITDADSFQKVKKWIKElkqMRGNNISL----VIVGNKIDLERQRVVSKS 126

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907203038  80 LALKFADAHNMLLFETSAKDpkeSQNVESIFMCLACRL 117
Cdd:cd04123   127 EAEEYAKSVGAKHFETSAKT---GKGIEELFLSLAKRM 161

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 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd04122    53 LQIWDTAGQERFR-AVTRSYYRGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPNTV-IFLIGNKADLEAQRDVTYEEA 130

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907203038  82 LKFADAHNMLLFETSAKDpkeSQNVESIFM 111
Cdd:cd04122   131 KQFADENGLLFLECSAKT---GENVEDAFL 157

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 1907203038   3 QVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPL---VPKVLVGNKCDL-REQIQVPS 78
Cdd:cd04107    53 QLWDIAGQERFG-GMTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLDSKVTLPNgepIPALLLANKCDLkKERLAKDP 131

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907203038  79 NLALKFADAHNML-LFETSAkdpKESQNVESIFMCLACRLKAQKSLLYRDAERQQGKVQKLEFSQEANGKASC 150
Cdd:cd04107   132 EQMDQFCKENGFIgWFETSA---KENINIEEAMRFLVKNILKNDKGLQSPEPDEDNVIDLKQETTTSKSKSCC 201

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. 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 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd04112    52 LQIWDTAGQERFR-SVTHAYYRDAHALLLLYDVTNKSSFDNIRAWLTEILEYAQSDVV-IMLLGNKADMSGERVVKREDG 129

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038  82 LKFADAHNMLLFETSAkdpKESQNVESIFMCLACRLKaqksllYRDAER-QQGKVQKLEFSQEANGKASC 150
Cdd:cd04112   130 ERLAKEYGVPFMETSA---KTGLNVELAFTAVAKELK------HRSVEQpDEPKFKIQDYVEKQKKSSGC 190

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 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd04127    65 LQLWDTAGQERFR-SLTTAFFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAYCENPDIVLIGNKADLPDQREVSERQA 143

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907203038  82 LKFADAHNMLLFETSAKDpkeSQNVESIFMCL 113
Cdd:cd04127   144 RELADKYGIPYFETSAAT---GQNVEKAVETL 172

Rab GTPase family 40 (Rab40) contains Rab40a, Rab40b and Rab40c; The Rab40 subfamily contains Rab40a, Rab40b, and Rab40c, which are all highly homologous. In rat, Rab40c is localized to the perinuclear recycling compartment (PRC), and is distributed in a tissue-specific manor, with high expression in brain, heart, kidney, and testis, low expression in lung and liver, and no expression in spleen and skeletal muscle. Rab40c is highly expressed in differentiated oligodendrocytes but minimally expressed in oligodendrocyte progenitors, suggesting a role in the vesicular transport of myelin components. Unlike most other Ras-superfamily proteins, Rab40c was shown to have a much lower affinity for GTP, and an affinity for GDP that is lower than for GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. 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 1907203038   2 VQVWDTAGQERFrKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAvpPLVPKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd04121    57 LQLWDTSGQGRF-CTIFRSYSRGAQGIILVYDITNRWSFDGIDRWIKEIDEHA--PGVPKILVGNRLHLAFKRQVATEQA 133

                          90
                  ....*....|....*
gi 1907203038  82 LKFADAHNMLLFETS 96
Cdd:cd04121   134 QAYAERNGMTFFEVS 148

Rab GTPase-like family 4 (Rab-like4); RabL4 (Rab-like4) subfamily. RabL4s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL4 lacks a prenylation site at the C-terminus. The specific function of RabL4 remains unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   4 VWDTAGQERFrKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALK 83
Cdd:cd04101    57 IFDSAGQELF-SDMVENVWEQPAVVCVVYDVTNEVSFNNCSRWINRVRTHSHGLHTPGVLVGNKCDLTDRREVDAAQAQA 135

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907203038  84 FADAHNMLLFETSAkdpKESQNVESIFMCLA 114
Cdd:cd04101   136 LAQANTLKFYETSA---KEGVGYEAPFLSLA 163

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038    1 MVQVWDTAGQERFrKSMVEHYYRNVHAVVFVYDVTKMTSFT---NLKMWIQECNGHAVpplVPKVLVGNKCDLREQIQVP 77
Cdd:smart00173  49 LLDILDTAGQEEF-SAMRDQYMRTGEGFLLVYSITDRQSFEeikKFREQILRVKDRDD---VPIVLVGNKCDLESERVVS 124

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1907203038   78 SNLALKFADAHNMLLFETSAkdpKESQNVESIF 110
Cdd:smart00173 125 TEEGKELARQWGCPFLETSA---KERVNVDEAF 154

rab6; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPLVpKVLVGNKCDLREQIQVPSNLA 81
Cdd:PTZ00099   31 LQLWDTAGQERFR-SLIPSYIRDSAAAIVVYDITNRQSFENTTKWIQDILNERGKDVI-IALVGNKTDLGDLRKVTYEEG 108

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907203038  82 LKFADAHNMLLFETSAkdpKESQNVESIFMCLACRLKAQKSLLYRDAERQQGKVQKLEFSQEANGKASCPC 152
Cdd:PTZ00099  109 MQKAQEYNTMFHETSA---KAGHNIKVLFKKIAAKLPNLDNSNSNDANVVDIQLTNNSNANDKNMLSKCMC 176

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHAVPPlVPKVLVGNKCDLREQIQVPSNLA 81
Cdd:cd01865    52 LQIWDTAGQERYR-TITTAYYRGAMGFILMYDITNEESFNAVQDWSTQIKTYSWDN-AQVILVGNKCDMEDERVVSAERG 129

                          90       100
                  ....*....|....*....|....*....
gi 1907203038  82 LKFADAHNMLLFETSAkdpKESQNVESIF 110
Cdd:cd01865   130 RQLADQLGFEFFEASA---KENINVKQVF 155

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   2 VQVWDTAGQERF----RKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIqecNGHAVPPLVPKVLVGNKCDLREQIQVP 77
Cdd:cd00882    49 LVLVDTPGLDEFgglgREELARLLLRGADLILLVVDSTDRESEEDAKLLI---LRRLRKEGIPIILVGNKIDLLEEREVE 125

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907203038  78 SNLALKFADAHNML-LFETSAKDPkesQNVESIFMCLA 114
Cdd:cd00882   126 ELLRLEELAKILGVpVFEVSAKTG---EGVDELFEKLI 160

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 1907203038   2 VQVWDTAGQERFRKsMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQ---ECNGHAV-PPLVpkVLVGNKCDLREQIQVP 77
Cdd:cd04109    52 LQVWDIGGQQIGGK-MLDKYIYGAQAVCLVYDITNSQSFENLEDWLSvvkKVNEESEtKPKM--VLVGNKTDLEHNRQVT 128

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1907203038  78 SNLALKFADAHNMLLFETSAKDPkesqnvESIFMC 112
Cdd:cd04109   129 AEKHARFAQENDMESIFVSAKTG------DRVFLC 157

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 1907203038   2 VQVWDTAGQERFRKsMVEHYYRNVHAVVFVYDVTKMT-SFTNLKM-WIQECNGHAvPPLVPKVLVGNKCDLReQIQVPSN 79
Cdd:TIGR00231  53 FNLLDTAGQEDYDA-IRRLYYPQVERSLRVFDIVILVlDVEEILEkQTKEIIHHA-DSGVPIILVGNKIDLK-DADLKTH 129

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907203038  80 LALKFADAHNMLLFETSAKDpkeSQNVESIF 110
Cdd:TIGR00231 130 VASEFAKLNGEPIIPLSAET---GKNIDSAF 157

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   4 VWDTAGQERFrKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNghAVPPLVPKVLVGNKCDLREQIQVPSnlALK 83
Cdd:cd00877    53 VWDTAGQEKF-GGLRDGYYIQGQCAIIMFDVTSRVTYKNVPNWHRDLV--RVCENIPIVLCGNKVDIKDRKVKPK--QIT 127

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1907203038  84 FADAHNMLLFETSAkdpKESQNVESIFMCLACRLKAQKSLLY 125
Cdd:cd00877   128 FHRKKNLQYYEISA---KSNYNFEKPFLWLARKLLGNPNLEF 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907203038   2 VQVWDTAGQERFRkSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQECNGHA---VPPLVPKVLVGNKCDLrEQIQVPS 78
Cdd:cd04116    56 LQIWDTAGQERFR-SLRTPFYRGSDCCLLTFSVDDSQSFQNLSNWKKEFIYYAdvkEPESFPFVILGNKIDI-PERQVST 133

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1907203038  79 NLALKF-ADAHNMLLFETSAKDpkeSQNVESIF 110
Cdd:cd04116   134 EEAQAWcRDNGDYPYFETSAKD---ATNVAAAF 163

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 1907203038   4 VWDTAGQERFrKSMVEHYYRNVHAVVFVYDVTKMTSFTNLKMWIQ----ECNGhavpplVPKVLVGNKCDLREQIQVPSN 79
Cdd:cd04106    55 LWDTAGQEEF-DAITKAYYRGAQACILVFSTTDRESFEAIESWKEkveaECGD------IPMVLVQTKIDLLDQAVITNE 127

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1907203038  80 LALKFADAHNMLLFETSAKDpkeSQNVESIFMCLA 114
Cdd:cd04106   128 EAEALAKRLQLPLFRTSVKD---DFNVTELFEYLA 159