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 2217338743   7 KCILAGDPAVGKTALAQIFRSDgaHFQKSYTLTTGMDLVVKTVPVPdtGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQN--KFPEEYIPTIGVDFYTKTIEVD--GKTVKLQIWDTAGQERFRALRPLYYRGADGFL 76

                          90       100
                  ....*....|....*....|....*.
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKARSQAP 112
Cdd:pfam00071  77 LVYDITSRDSFENVKKWVEEILRHAD 102

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   7 KCILAGDPAVGKTALAQIFRSDgaHFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:PLN03108    8 KYIIIGDTGVGKSCLLLQFTDK--RFQPVHDLTIGVEFGARMITI--DNKPIKLQIWDTAGQESFRSITRSYYRGAAGAL 83

                          90       100
                  ....*....|....*....|....*
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKARSQA 111
Cdd:PLN03108   84 LVYDITRRETFNHLASWLEDARQHA 108

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 2217338743   6 AKCILAGDPAVGKTALAQIFRSDgAHFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVL 85
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLGN-KGSITEYYPGTTRNYVTTVIEE--DGKTYKFNLLDTAGQEDYDAIRRLYYPQVERS 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217338743  86 CLVYDVTN-EESFNNC-SKWLEKARSQAPG 113
Cdd:TIGR00231  79 LRVFDIVIlVLDVEEIlEKQTKEIIHHADS 108

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 2217338743   7 KCILAGDPAVGKTALAQIFRSDgaHFQKSYTLTTGMDLVVKTVPVPDTgdSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd00154     2 KIVLIGDSGVGKTSLLLRFVDN--KFSENYKSTIGVDFKSKTIEVDGK--KVKLQIWDTAGQERFRSITSSYYRGAHGAI 77

                          90       100
                  ....*....|....*....|....*.
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKARSQAP 112
Cdd:cd00154    78 LVYDVTNRESFENLDKWLNELKEYAP 103

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 2217338743   7 KCILAGDPAVGKTALAQIFRSDGahFQKSYTLTTGMDLVVKTVPVPDTgDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04109     2 KIVVLGDGASGKTSLIRRFAQEG--FGKSYKQTIGLDFFSRRITLPGS-LNVTLQVWDIGGQQIGGKMLDKYIYGAQAVC 78

                          90
                  ....*....|....*....
gi 2217338743  87 LVYDVTNEESFNNCSKWLE 105
Cdd:cd04109    79 LVYDITNSQSFENLEDWLS 97

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 2217338743   6 AKCILAGDPAVGKTALAQIFRSDgaHFQKSYTLTTGMDLVVKTVPVPDTgdSVELFIFDSAGKELFSEMLDKLWESPNVL 85
Cdd:cd01861     1 HKLVFLGDQSVGKTSIITRFMYD--TFDNQYQATIGIDFLSKTMYVDDK--TVRLQLWDTAGQERFRSLIPSYIRDSSVA 76

                          90       100
                  ....*....|....*....|...
gi 2217338743  86 CLVYDVTNEESFNNCSKWLEKAR 108
Cdd:cd01861    77 VVVYDITNRQSFDNTDKWIDDVR 99

Rab GTPase family 30 (Rab30); Rab30 subfamily. Rab30 appears to be associated with the Golgi stack. It is expressed in a wide variety of tissue types and in humans maps to chromosome 11. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   7 KCILAGDPAVGKTALAQIFRSdgAHFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04114     9 KIVLIGNAGVGKTCLVRRFTQ--GLFPPGQGATIGVDFMIKTVEI--KGEKIKLQIWDTAGQERFRSITQSYYRSANALI 84

                          90       100
                  ....*....|....*....|....*
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKARSQA 111
Cdd:cd04114    85 LTYDITCEESFRCLPEWLREIEQYA 109

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 2217338743   7 KCILAGDPAVGKTALAQIFRSdGAHFQKSYTlTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd01864     5 KIILIGDSNVGKTCVVQRFKS-GTFSERQGN-TIGVDFTMKTLEI--QGKRVKLQIWDTAGQERFRTITQSYYRSANGAI 80

                          90       100
                  ....*....|....*....|..
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKAR 108
Cdd:cd01864    81 IAYDITRRSSFESVPHWIEEVE 102

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 2217338743   7 KCILAGDPAVGKTALaqIFR-SDGAhFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVL 85
Cdd:cd01867     5 KLLLIGDSGVGKSCL--LLRfSEDS-FNPSFISTIGIDFKIRTIEL--DGKKIKLQIWDTAGQERFRTITTSYYRGAMGI 79

                          90
                  ....*....|....*....
gi 2217338743  86 CLVYDVTNEESFNNCSKWL 104
Cdd:cd01867    80 ILVYDITDEKSFENIKNWM 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 2217338743   7 KCILAGDPAVGKTALAQIFRSDgaHFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd01863     2 KILLIGDSGVGKSSLLLRFTDD--TFDEDLSSTIGVDFKVKTVTV--DGKKVKLAIWDTAGQERFRTLTSSYYRGAQGVI 77

                          90       100
                  ....*....|....*....|...
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKARS 109
Cdd:cd01863    78 LVYDVTRRDTFDNLDTWLNELDT 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   9 ILAGDPAVGKTALAQIFRSDGahFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLCLV 88
Cdd:cd04120     4 IIIGSRGVGKTSLMERFTDDT--FCEACKSTVGVDFKIKTVEL--RGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILV 79

                          90
                  ....*....|....*..
gi 2217338743  89 YDVTNEESFNNCSKWLE 105
Cdd:cd04120    80 YDITKKETFDDLPKWMK 96

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 2217338743   7 KCILAGDPAVGKTALAqiFRSDGAHFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSE-MLDKLWESPNVL 85
Cdd:cd04115     4 KIIVIGDSNVGKTCLT--YRFCAGRFPERTEATIGVDFRERTVEI--DGERIKVQLWDTAGQERFRKsMVQHYYRNVHAV 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2217338743  86 CLVYDVTNEESFNNCSKWLEKARSQAPGISLP 117
Cdd:cd04115    80 VFVYDVTNMASFHSLPSWIEECEQHSLPNEVP 111

Rab GTPase family 15 (Rab15); Rab15 colocalizes with the transferrin receptor in early endosome compartments, but not with late endosomal markers. It codistributes with Rab4 and Rab5 on early/sorting endosomes, and with Rab11 on pericentriolar recycling endosomes. It is believed to function as an inhibitory GTPase that regulates distinct steps in early endocytic trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   7 KCILAGDPAVGKTALAQIFRSDgaHFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04117     2 RLLLIGDSGVGKTCLLCRFTDN--EFHSSHISTIGVDFKMKTIEV--DGIKVRIQIWDTAGQERYQTITKQYYRRAQGIF 77

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKARSQAP-GISLP 117
Cdd:cd04117    78 LVYDISSERSYQHIMKWVSDVDEYAPeGVQKI 109

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 2217338743   7 KCILAGDPAVGKTALaqIFRSDGAHFQKSYTLTTGMDLVVKTVPVPDTgdSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd01865     3 KLLIIGNSSVGKTSF--LFRYADDSFTSAFVSTVGIDFKVKTVYRNDK--RIKLQIWDTAGQERYRTITTAYYRGAMGFI 78

                          90       100
                  ....*....|....*....|...
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKARS 109
Cdd:cd01865    79 LMYDITNEESFNAVQDWSTQIKT 101

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 2217338743   7 KCILAGDPAVGKTALAQIFRSDgaHFQKSYTLTTGMDLVVKTVPVpDTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04107     2 KVLVIGDLGVGKTSIIKRYVHG--VFSQHYKATIGVDFALKVIEW-DPNTVVRLQLWDIAGQERFGGMTRVYYKGAVGAI 78

                          90
                  ....*....|....*..
gi 2217338743  87 LVYDVTNEESFNNCSKW 103
Cdd:cd04107    79 IVFDVTRPSTFEAVLKW 95

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. 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 2217338743   6 AKCILAGDPAVGKTALAQIF-RSDGAHFQKSytlTTGMDLVVKTVPVPDTgdSVELFIFDSAGKELFSEMLDKLWESPNV 84
Cdd:cd01860     2 FKLVLLGDSSVGKSSIVLRFvKNEFSENQES---TIGAAFLTQTVNLDDT--TVKFEIWDTAGQERYRSLAPMYYRGAAA 76

                          90       100
                  ....*....|....*....|....*....
gi 2217338743  85 LCLVYDVTNEESFNNCSKWLEKARSQAPG 113
Cdd:cd01860    77 AIVVYDITSEESFEKAKSWVKELQEHGPP 105

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   4 LAAKCILAGDPAVGKTALAQIFRSDGAhfqKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPN 83
Cdd:PLN03118   13 LSFKILLIGDSGVGKSSLLVSFISSSV---EDLAPTIGVDFKIKQLTV--GGKRLKLTIWDTAGQERFRTLTSSYYRNAQ 87

                          90
                  ....*....|....*...
gi 2217338743  84 VLCLVYDVTNEESFNNCS 101
Cdd:PLN03118   88 GIILVYDVTRRETFTNLS 105

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 2217338743   9 ILAGDPAVGKTALAQIFrSDGAHFQKSyTLTTGMDLVVKTVPVPDtGDSVELFIFDSAGKELFSEMLDKLWE-SPNVLcL 87
Cdd:cd04111     6 IVIGDSTVGKSSLLKRF-TEGRFAEVS-DPTVGVDFFSRLIEIEP-GVRIKLQLWDTAGQERFRSITRSYYRnSVGVL-L 81

                          90       100
                  ....*....|....*....|..
gi 2217338743  88 VYDVTNEESFNNCSKWLEKARS 109
Cdd:cd04111    82 VFDITNRESFEHVHDWLEEARS 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   7 KCILAGDPAVGKTALaqIFRSDGAHFQKSYTLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04119     2 KVISMGNSGVGKSCI--IKRYCEGRFVSKYLPTIGIDYGVKKVSV--RNKEVRVNFFDLSGHPEYLEVRNEFYKDTQGVL 77

                          90       100
                  ....*....|....*....|.
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKA 107
Cdd:cd04119    78 LVYDVTDRQSFEALDSWLKEM 98

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 2217338743   7 KCILAGDPAVGKTALaqIFRSDGAHFQKSYTLTTGMDLVVKTVPVPDTgdSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04128     2 KIGLLGDAQIGKTSL--MVKYVEGEFDEEYIQTLGVNFMEKTISIRGT--EITFSIWDLGGQREFINMLPLVCKDAVAIL 77

                          90       100
                  ....*....|....*....|..
gi 2217338743  87 LVYDVTNEESFNNCSKWLEKAR 108
Cdd:cd04128    78 FMFDLTRKSTLNSIKEWYRQAR 99

Rab GTPase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   7 KCILAGDPAVGKT-ALAQIFRSDGAHFQKSytlTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVL 85
Cdd:PLN03110   14 KIVLIGDSGVGKSnILSRFTRNEFCLESKS---TIGVEFATRTLQV--EGKTVKAQIWDTAGQERYRAITSAYYRGAVGA 88

                          90       100
                  ....*....|....*....|....*.
gi 2217338743  86 CLVYDVTNEESFNNCSKWLEKARSQA 111
Cdd:PLN03110   89 LLVYDITKRQTFDNVQRWLRELRDHA 114

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 2217338743   7 KCILAGDPAVGKtalAQIFRS--DGAHfQKSYTLTTGMDLvvKTVPVPDTGDSVELFIFDSAGKELFSEMLDKLWESPNV 84
Cdd:cd04121     8 KFLLVGDSDVGK---GEILASlqDGST-ESPYGYNMGIDY--KTTTILLDGRRVKLQLWDTSGQGRFCTIFRSYSRGAQG 81

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217338743  85 LCLVYDVTNEESFNNCSKWLEKARSQAPGI 114
Cdd:cd04121    82 IILVYDITNRWSFDGIDRWIKEIDEHAPGV 111

Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C-terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro. The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways. 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 2217338743   6 AKCILAGDPAVGKTALAQIFRSdGAHFQKSYTLTTGMDLVVKTVPVPDTgdSVELFIFDSAGKELFSEMLDKLWESPNVL 85
Cdd:cd04118     1 VKVVMLGKESVGKTSLVERYVH-HRFLVGPYQNTIGAAFVAKRMVVGER--VVTLGIWDTAGSERYEAMSRIYYRGAKAA 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2217338743  86 CLVYDVTNEESFNNCSKWLEKARSQAPGISL 116
Cdd:cd04118    78 IVCYDLTDSSSFERAKFWVKELQNLEEHCKI 108

Rho GTPase TC10 (Tc10); TC10 is a Rho family protein that has been shown to induce microspike formation and neurite outgrowth in vitro. Its expression changes dramatically after peripheral nerve injury, suggesting an important role in promoting axonal outgrowth and regeneration. TC10 regulates translocation of insulin-stimulated GLUT4 in adipocytes and has also been shown to bind directly to Golgi COPI coat proteins. GTP-bound TC10 in vitro can bind numerous potential effectors. Depending on its subcellular localization and distinct functional domains, TC10 can differentially regulate two types of filamentous actin in adipocytes. TC10 mRNAs are highly expressed in three types of mouse muscle tissues: leg skeletal muscle, cardiac muscle, and uterus; they were also present in brain, with higher levels in adults than in newborns. TC10 has also been shown to play a role in regulating the expression of cystic fibrosis transmembrane conductance regulator (CFTR) through interactions with CFTR-associated ligand (CAL). The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated DFTR degradation in the lysosome. 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 2217338743   7 KCILAGDPAVGKTALAQIFRSDGahFQKSYTLTTgMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04135     2 KCVVVGDGAVGKTCLLMSYANDA--FPEEYVPTV-FDHYAVSVTV--GGKQYLLGLYDTAGQEDYDRLRPLSYPMTDVFL 76

                          90       100
                  ....*....|....*....|....*....
gi 2217338743  87 LVYDVTNEESFNNC-SKWLEKARSQAPGI 114
Cdd:cd04135    77 ICFSVVNPASFQNVkEEWVPELKEYAPNV 105

Rho-related protein from plants (Rop)-like; The Rop (Rho-related protein from plants) subfamily plays a role in diverse cellular processes, including cytoskeletal organization, pollen and vegetative cell growth, hormone responses, stress responses, and pathogen resistance. Rops are able to regulate several downstream pathways to amplify a specific signal by acting as master switches early in the signaling cascade. They transmit a variety of extracellular and intracellular signals. Rops are involved in establishing cell polarity in root-hair development, root-hair elongation, pollen-tube growth, cell-shape formation, responses to hormones such as abscisic acid (ABA) and auxin, responses to abiotic stresses such as oxygen deprivation, and disease resistance and disease susceptibility. An individual Rop can have a unique function or an overlapping function shared with other Rop proteins; in addition, a given Rop-regulated function can be controlled by one or multiple Rop proteins. For example, Rop1, Rop3, and Rop5 are all involved in pollen-tube growth; Rop2 plays a role in response to low-oxygen environments, cell-morphology, and root-hair development; root-hair development is also regulated by Rop4 and Rop6; Rop6 is also responsible for ABA response, and ABA response is also regulated by Rop10. Plants retain some of the regulatory mechanisms that are shared by other members of the Rho family, but have also developed a number of unique modes for regulating Rops. Unique RhoGEFs have been identified that are exclusively active toward Rop proteins, such as those containing the domain PRONE (plant-specific Rop nucleotide exchanger). 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 2217338743   7 KCILAGDPAVGKTALAQIFRSDgaHFQKSYtLTTGMDLVVKTVPVpdTGDSVELFIFDSAGKELFSEMLDKLWESPNVLC 86
Cdd:cd04133     3 KCVTVGDGAVGKTCMLISYTSN--TFPTDY-VPTVFDNFSANVVV--DGNTVNLGLWDTAGQEDYNRLRPLSYRGADVFL 77

                          90       100
                  ....*....|....*....|....*....
gi 2217338743  87 LVYDVTNEESFNNCS-KWLEKARSQAPGI 114
Cdd:cd04133    78 LAFSLISKASYENVLkKWIPELRHYAPGV 106

Mitochondrial Rho family 2 (Miro2), C-terminal; Miro2 subfamily. Miro (mitochondrial Rho) proteins have tandem GTP-binding domains separated by a linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins were found in several eukaryotic organisms. This CD represents the putative GTPase domain in the C terminus of Miro proteins. These atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. Most Rho proteins contain a lipid modification site at the C-terminus; however, Miro is one of few Rho subfamilies that lack this feature.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338743   7 KCILAGDPAVGKTALAQIF--RSDGahfQKSYTLTTGMDLVVKTVPVPDTGDSVELFIFDSagKELFSEMLDKLWESPNV 84
Cdd:cd01892     6 LCFVLGAKGSGKSALLQAFlgRSFS---QNAYSPTIKPRYAVNTVEVPGQEKYLILREVGE--DEEAILLNDAELAACDV 80

                          90
                  ....*....|....*..
gi 2217338743  85 LCLVYDVTNEESFNNCS 101
Cdd:cd01892    81 ACLVYDSSDPNSFSYCA 97