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 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSA 80
Cdd:cd04138    65 MRDQYMRTGEGFLCVFAINSRKSFEDIHTYREQIKRVKDSDDVPMVLVGNKCDLAARTVSTRQGQDLAKSYGIPYIETSA 144

                          90
                  ....*....|....*...
gi 2186152442  81 KTRQRVEDAFYTLVREIR 98
Cdd:cd04138   145 KTRQGVEEAFYTLVREIR 162

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSA 80
Cdd:cd04138    65 MRDQYMRTGEGFLCVFAINSRKSFEDIHTYREQIKRVKDSDDVPMVLVGNKCDLAARTVSTRQGQDLAKSYGIPYIETSA 144

                          90
                  ....*....|....*...
gi 2186152442  81 KTRQRVEDAFYTLVREIR 98
Cdd:cd04138   145 KTRQGVEEAFYTLVREIR 162

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 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDsEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETS 79
Cdd:pfam00071  64 LRPLYYRGADGFLLVYDITSRDSFENVKKWVEEILRHAD-ENVPIVLVGNKCDLEDqRVVSTEEGEALAKELGLPFMETS 142

                          90       100
                  ....*....|....*....|
gi 2186152442  80 AKTRQRVEDAFYTLVREIRQ 99
Cdd:pfam00071 143 AKTNENVEEAFEELAREILK 162

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 2186152442   1 MRDQYMRTGEGFLCVFAINN-TKSFEDI-HHYREQIKRVKDSeDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIET 78
Cdd:TIGR00231  67 IRRLYYPQVERSLRVFDIVIlVLDVEEIlEKQTKEIIHHADS-GVPIILVGNKIDLKDADLKTHVASEFAKLNGEPIIPL 145

                          90
                  ....*....|....*..
gi 2186152442  79 SAKTRQRVEDAFYTLVR 95
Cdd:TIGR00231 146 SAETGKNIDSAFKIVEA 162

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSA 80
Cdd:cd04138    65 MRDQYMRTGEGFLCVFAINSRKSFEDIHTYREQIKRVKDSDDVPMVLVGNKCDLAARTVSTRQGQDLAKSYGIPYIETSA 144

                          90
                  ....*....|....*...
gi 2186152442  81 KTRQRVEDAFYTLVREIR 98
Cdd:cd04138   145 KTRQGVEEAFYTLVREIR 162

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442    1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETS 79
Cdd:smart00010  66 MRDQYMRTGEGFLLVYSITDRQSFEEIAKFREQILRVKDRDDVPIVLVGNKCDLENeRVVSTEEGKELARQWGCPFLETS 145

                           90       100
                   ....*....|....*....|.
gi 2186152442   80 AKTRQRVEDAFYTLVREIRQY 100
Cdd:smart00010 146 AKERINVDEAFYDLVREIRKS 166

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 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDsEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETS 79
Cdd:pfam00071  64 LRPLYYRGADGFLLVYDITSRDSFENVKKWVEEILRHAD-ENVPIVLVGNKCDLEDqRVVSTEEGEALAKELGLPFMETS 142

                          90       100
                  ....*....|....*....|
gi 2186152442  80 AKTRQRVEDAFYTLVREIRQ 99
Cdd:pfam00071 143 AKTNENVEEAFEELAREILK 162

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLP-SRTVDTKQAQDLARSYGIPFIETS 79
Cdd:cd04139    64 IRDNYFRSGEGFLLVFSITDMESFTALAEFREQILRVKEDDNVPLLLVGNKCDLEdKRQVSVEEAANLAEQWGVNYVETS 143

                          90       100
                  ....*....|....*....|
gi 2186152442  80 AKTRQRVEDAFYTLVREIRQ 99
Cdd:cd04139   144 AKTRANVDKVFFDLVREIRQ 163

Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap subfamily of the Ras family. It can be further divided into the Rap1a and Rap1b isoforms. In humans, Rap1a and Rap1b share 95% sequence homology, but are products of two different genes located on chromosomes 1 and 12, respectively. Rap1a is sometimes called smg p21 or Krev1 in the older literature. Rap1 proteins are believed to perform different cellular functions, depending on the isoform, its subcellular localization, and the effector proteins it binds. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and the microsomal membrane of pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. High expression of Rap1 has been observed in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines; interestingly, in the SCCs, the active GTP-bound form localized to the nucleus, while the inactive GDP-bound form localized to the cytoplasm. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap1a, which is stimulated by T-cell receptor (TCR) activation, is a positive regulator of T cells by directing integrin activation and augmenting lymphocyte responses. In murine hippocampal neurons, Rap1b determines which neurite will become the axon and directs the recruitment of Cdc42, which is required for formation of dendrites and axons. In murine platelets, Rap1b is required for normal homeostasis in vivo and is involved in integrin activation. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETS 79
Cdd:cd04175    65 MRDLYMKNGQGFVLVYSITAQSTFNDLQDLREQILRVKDTEDVPMILVGNKCDLEDeRVVGKEQGQNLARQWGCAFLETS 144

                          90
                  ....*....|....*...
gi 2186152442  80 AKTRQRVEDAFYTLVREI 97
Cdd:cd04175   145 AKAKINVNEIFYDLVRQI 162

Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, and RSR1. Rap subfamily proteins perform different cellular functions, depending on the isoform and its subcellular localization. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and microsomal membrane of the pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. Rap1 localizes in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap2 is involved in multiple functions, including activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton and activation of the Wnt/beta-catenin signaling pathway in embryonic Xenopus. A number of effector proteins for Rap2 have been identified, including isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK), and the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. RSR1 is the fungal homolog of Rap1 and Rap2. In budding yeasts, it is involved in selecting a site for bud growth, which directs the establishment of cell polarization. The Rho family GTPase Cdc42 and its GEF, Cdc24, then establish an axis of polarized growth. It is believed that Cdc42 interacts directly with RSR1 in vivo. In filamentous fungi such as Ashbya gossypii, RSR1 is a key regulator of polar growth in the hypha. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYG-IPFIET 78
Cdd:cd04136    65 MRDLYIKNGQGFALVYSITAQQSFNDLQDLREQILRVKDTEDVPMILVGNKCDLEDeRVVSKEEGQNLARQWGnCPFLET 144

                          90
                  ....*....|....*....
gi 2186152442  79 SAKTRQRVEDAFYTLVREI 97
Cdd:cd04136   145 SAKSKINVDEIFYDLVRQI 163

Ras-like protein in all tissues (Rit), Ras-like protein in neurons (Rin) and Ras-related protein which interacts with calmodulin (Ric); Rit (Ras-like protein in all tissues), Rin (Ras-like protein in neurons) and Ric (Ras-related protein which interacts with calmodulin) form a subfamily with several unique structural and functional characteristics. These proteins all lack a the C-terminal CaaX lipid-binding motif typical of Ras family proteins, and Rin and Ric contain calmodulin-binding domains. Rin, which is expressed only in neurons, induces neurite outgrowth in rat pheochromocytoma cells through its association with calmodulin and its activation of endogenous Rac/cdc42. Rit, which is ubiquitously expressed in mammals, inhibits growth-factor withdrawl-mediated apoptosis and induces neurite extension in pheochromocytoma cells. Rit and Rin are both able to form a ternary complex with PAR6, a cell polarity-regulating protein, and Rac/cdc42. This ternary complex is proposed to have physiological function in processes such as tumorigenesis. Activated Ric is likely to signal in parallel with the Ras pathway or stimulate the Ras pathway at some upstream point, and binding of calmodulin to Ric may negatively regulate Ric activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETS 79
Cdd:cd04141    66 MRDQYMRCGEGFIICYSVTDRHSFQEASEFKELITRVRLTEDIPLVLVGNKVDLEQqRQVTTEEGRNLAREFNCPFFETS 145

                          90       100
                  ....*....|....*....|
gi 2186152442  80 AKTRQRVEDAFYTLVREIRQ 99
Cdd:cd04141   146 AALRFYIDDAFHGLVREIRR 165

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442    5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIkRVKDSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:smart00175  69 YYRGAVGALLVYDITNRESFENLENWLKEL-REYASPNVVIMLVGNKSDLEEqRQVSREEAEAFAEEHGLPFFETSAKTN 147

                           90
                   ....*....|....
gi 2186152442   84 QRVEDAFYTLVREI 97
Cdd:smart00175 148 TNVEEAFEELAREI 161

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 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKdSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd01867    72 YYRGAMGIILVYDITDEKSFENIKNWMRNIDEHA-SEDVERMLVGNKCDMEEkRVVSKEEGEALAREYGIKFLETSAKAN 150

                          90
                  ....*....|....*.
gi 2186152442  84 QRVEDAFYTLVREIRQ 99
Cdd:cd01867   151 INVEEAFLTLAKDILK 166

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 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKdSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd01869    71 YYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYA-SENVNKLLVGNKCDLTDkKVVDYTEAKEFADELGIPFLETSAKNA 149

                          90
                  ....*....|....*
gi 2186152442  84 QRVEDAFYTLVREIR 98
Cdd:cd01869   150 TNVEEAFMTMAREIK 164

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 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQ 84
Cdd:cd01863    69 YYRGAQGVILVYDVTRRDTFDNLDTWLNELDTYSTNPDAVKMLVGNKIDKENREVTREEGQKFARKHNMLFIETSAKTRI 148

                          90
                  ....*....|...
gi 2186152442  85 RVEDAFYTLVREI 97
Cdd:cd01863   149 GVQQAFEELVEKI 161

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd04127    83 FFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAYCENPDIVLIGNKADLPDqREVSERQARELADKYGIPYFETSAATG 162

                          90
                  ....*....|.
gi 2186152442  84 QRVEDAFYTLV 94
Cdd:cd04127   163 QNVEKAVETLL 173

Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, Gem/Kir) subfamily of Ras GTPases are expressed in a tissue-specific manner and are dynamically regulated by transcriptional and posttranscriptional mechanisms in response to environmental cues. RGK proteins bind to the beta subunit of L-type calcium channels, causing functional down-regulation of these voltage-dependent calcium channels, and either termination of calcium-dependent secretion or modulation of electrical conduction and contractile function. Inhibition of L-type calcium channels by Rem2 may provide a mechanism for modulating calcium-triggered exocytosis in hormone-secreting cells, and has been proposed to influence the secretion of insulin in pancreatic beta cells. RGK proteins also interact with and inhibit the Rho/Rho kinase pathway to modulate remodeling of the cytoskeleton. Two characteristics of RGK proteins cited in the literature are N-terminal and C-terminal extensions beyond the GTPase domain typical of Ras superfamily members. The N-terminal extension is not conserved among family members; the C-terminal extension is reported to be conserved among the family and lack the CaaX prenylation motif typical of membrane-associated Ras proteins. However, a putative CaaX motif has been identified in the alignment of the C-terminal residues of this CD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   2 RDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLP-SRTVDTKQAQDLARSYGIPFIETSA 80
Cdd:cd04148    66 EDSCMQVGDAYVIVYSVTDRSSFEKASELRIQLRRARQAEDIPIILVGNKSDLVrSREVSVQEGRACAVVFDCKFIETSA 145

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2186152442  81 KTRQRVEDAFYTLVreiRQYRLKKISKEEKT 111
Cdd:cd04148   146 ALQHNVDELFEGIV---RQVRLRRDSKEKNT 173

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 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVpMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd01860    70 YYRGAAAAIVVYDITSEESFEKAKSWVKELQEHGPPNIV-IALAGNKADLESkRQVSTEEAQEYADENGLLFMETSAKTG 148

                          90
                  ....*....|....
gi 2186152442  84 QRVEDAFYTLVREI 97
Cdd:cd01860   149 ENVNELFTEIARKL 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 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKdSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd04123    69 YYRDADGAILVYDITDADSFQKVKKWIKELKQMR-GNNISLVIVGNKIDLERqRVVSKSEAEEYAKSVGAKHFETSAKTG 147

                          90
                  ....*....|....
gi 2186152442  84 QRVEDAFYTLVREI 97
Cdd:cd04123   148 KGIEELFLSLAKRM 161

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 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRV-KDSEDVP-MVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIE 77
Cdd:cd04109    66 MLDKYIYGAQAVCLVYDITNSQSFENLEDWLSVVKKVnEESETKPkMVLVGNKTDLEHnRQVTAEKHARFAQENDMESIF 145

                          90       100
                  ....*....|....*....|....*..
gi 2186152442  78 TSAKTRQRVEDAFYTLVREIRQYRLKK 104
Cdd:cd04109   146 VSAKTGDRVFLCFQRIAAELLGVKLSQ 172

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 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRvkdSEDVPMVLVGNKCDLPSRTVDT--KQAQDLARSYGIPFIET 78
Cdd:cd00882    68 LARLLLRGADLILLVVDSTDRESEEDAKLLILRRLR---KEGIPIILVGNKIDLLEEREVEelLRLEELAKILGVPVFEV 144

                          90
                  ....*....|....*..
gi 2186152442  79 SAKTRQRVEDAFYTLVR 95
Cdd:cd00882   145 SAKTGEGVDELFEKLIE 161

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2186152442  15 VFAINNTKSFEDIHHYreqIKRVKD--SEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAF 90
Cdd:cd01861    79 VYDITNRQSFDNTDKW---IDDVRDerGNDVIIVLVGNKTDLSDkRQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLF 154

Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); This subfamily includes Rhes (Ras homolog enriched in striatum) and Dexras1/AGS1 (activator of G-protein signaling 1). These proteins are homologous, but exhibit significant differences in tissue distribution and subcellular localization. Rhes is found primarily in the striatum of the brain, but is also expressed in other areas of the brain, such as the cerebral cortex, hippocampus, inferior colliculus, and cerebellum. Rhes expression is controlled by thyroid hormones. In rat PC12 cells, Rhes is farnesylated and localizes to the plasma membrane. Rhes binds and activates PI3K, and plays a role in coupling serpentine membrane receptors with heterotrimeric G-protein signaling. Rhes has recently been shown to be reduced under conditions of dopamine supersensitivity and may play a role in determining dopamine receptor sensitivity. Dexras1/AGS1 is a dexamethasone-induced Ras protein that is expressed primarily in the brain, with low expression levels in other tissues. Dexras1 localizes primarily to the cytoplasm, and is a critical regulator of the circadian master clock to photic and nonphotic input. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQI--------KRVKDSEDVPMVLVGNKCDLPS-RTVDTKQA-QDLARS 70
Cdd:cd04143    64 MRRLSILTGDVFILVFSLDNRESFEEVCRLREQIletksclkNKTKENVKIPMVICGNKADRDFpREVQRDEVeQLVGGD 143

                          90       100
                  ....*....|....*....|...
gi 2186152442  71 YGIPFIETSAKTRQRVEDAFYTL 93
Cdd:cd04143   144 ENCAYFEVSAKKNSNLDEMFRAL 166

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. 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 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKrvKDSEDVPMVLVGNKCDLPSR-TVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd04110    75 YYRGTHGVIVVYDVTNGESFVNVKRWLQEIE--QNCDDVCKVLVGNKNDDPERkVVETEDAYKFAGQMGISLFETSAKEN 152

                          90       100
                  ....*....|....*....|....*..
gi 2186152442  84 QRVEDAFYTLVREIRQYRLKKISKEEK 110
Cdd:cd04110   153 INVEEMFNCITELVLRAKKDNLAKQQQ 179

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 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKdSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd04112    70 YYRDAHALLLLYDVTNKSSFDNIRAWLTEILEYA-QSDVVIMLLGNKADMSGeRVVKREDGERLAKEYGVPFMETSAKTG 148

                          90
                  ....*....|....*
gi 2186152442  84 QRVEDAFYTLVREIR 98
Cdd:cd04112   149 LNVELAFTAVAKELK 163

Ras homology family (Rho) of small guanosine triphosphatases (GTPases); Members of the Rho (Ras homology) family include RhoA, Cdc42, Rac, Rnd, Wrch1, RhoBTB, and Rop. There are 22 human Rho family members identified currently. These proteins are all involved in the reorganization of the actin cytoskeleton in response to external stimuli. They also have roles in cell transformation by Ras in cytokinesis, in focal adhesion formation and in the stimulation of stress-activated kinase. These various functions are controlled through distinct effector proteins and mediated through a GTP-binding/GTPase cycle involving three classes of regulating proteins: GAPs (GTPase-activating proteins), GEFs (guanine nucleotide exchange factors), and GDIs (guanine nucleotide dissociation inhibitors). 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. Since crystal structures often lack C-terminal residues, this feature is not available for annotation in many of the CDs in the hierarchy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442  12 FLCVFAINNTKSFEDIHH--YREqIKrvKDSEDVPMVLVGNKCDL------------PSRTVDTKQAQDLARSYG-IPFI 76
Cdd:cd00157    75 FLLCFSVDSPSSFENVKTkwYPE-IK--HYCPNVPIILVGTKIDLrddgntlkklekKQKPITPEEGEKLAKEIGaVKYM 151

                          90
                  ....*....|....*....
gi 2186152442  77 ETSAKTRQRVEDAFYTLVR 95
Cdd:cd00157   152 ECSALTQEGLKEVFDEAIR 170

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 2186152442   1 MRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRT-VDTKQAQDLARSYGIPFIETS 79
Cdd:cd04101    69 MVENVWEQPAVVCVVYDVTNEVSFNNCSRWINRVRTHSHGLHTPGVLVGNKCDLTDRReVDAAQAQALAQANTLKFYETS 148

                          90
                  ....*....|....*.
gi 2186152442  80 AKTRQRVEDAFYTLVR 95
Cdd:cd04101   149 AKEGVGYEAPFLSLAR 164

Rho (Ras homology) subfamily of Ras-like small GTPases; Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   12 FLCVFAINNTKSFEDI-HHYREQIKrvKDSEDVPMVLVGNKCDLPSRT-------------VDTKQAQDLARSYG-IPFI 76
Cdd:smart00174  73 FLICFSVDSPASFENVkEKWYPEVK--HFCPNVPIILVGTKLDLRNDKstleelskkkqepVTYEQGQALAKRIGaVKYL 150

                           90
                   ....*....|....*....
gi 2186152442   77 ETSAKTRQRVEDAFYTLVR 95
Cdd:smart00174 151 ECSALTQEGVREVFEEAIR 169

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKdSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKTR 83
Cdd:cd04113    69 YYRGAAGALLVYDITSRESFNALTNWLTDARTLA-SPDIVIILVGNKKDLEDdREVTFLEASRFAQENGLLFLETSALTG 147

                          90
                  ....*....|....
gi 2186152442  84 QRVEDAFYTLVREI 97
Cdd:cd04113   148 ENVEEAFLKCARSI 161

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2186152442   5 YMRTGEGFLCVFAINNTKSFEDIHH-YREQIKRVKDSEDVPMVLVGNKCDLPS-RTVDTKQAQDLARSYGIPFIETSAKT 82
Cdd:PLN03118   82 YYRNAQGIILVYDVTRRETFTNLSDvWGKEVELYSTNQDCVKMLVGNKVDRESeRDVSREEGMALAKEHGCLFLECSAKT 161

                          90
                  ....*....|....*..
gi 2186152442  83 RQRVEDAFYTLVREIRQ 99
Cdd:PLN03118  162 RENVEQCFEELALKIME 178