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 145558870   57 KIFVSGKSGVGKTALVAKLAGLEVPIVHHETTGIQttvvFWPAKLKASDCVVmfRFEFWDcgeSA-LKKFDHMLPACKEN 135
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVD----FYTKTIEVDGKTV--KLQIWD---TAgQERFRALRPLYYRG 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 145558870  136 ADAFLFLFSFTDRASFEDLP---GQLTRVAGEapGLVKIVIGSKFD 178
Cdd:pfam00071  72 ADGFLLVYDITSRDSFENVKkwvEEILRHADE--NVPIVLVGNKCD 115

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145558870    56 YKIFVSGKSGVGKTALVAKLAGLEVPIVHHETTGI--QTTVVFWPAKLkasdcvvmFRFEFWD-CGEsalKKFDHMLPAC 132
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGVdfKTKTIEVDGKR--------VKLQIWDtAGQ---ERFRSITSSY 69

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 145558870   133 KENADAFLFLFSFTDRASFEDLPGQLTRVAGEA-PGLVKIVIGSKFD 178
Cdd:smart00175  70 YRGAVGALLVYDITNRESFENLENWLKELREYAsPNVVIMLVGNKSD 116

NTPase;

                         10        20
                 ....*....|....*....|..
gi 145558870  57 KIFVSGKSGVGKTALVAKLAGL 78
Cdd:PRK13695   2 KIGITGPPGVGKTTLVLKIAEL 23

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 145558870  57 KIFVSGKSGVGKTALVAKLAGLEvpivhHETTGIQTT-VVFWPAKLKASDCVVMFrfEFWDCGESalKKFDHMLPACKEN 135
Cdd:cd04128    2 KIGLLGDAQIGKTSLMVKYVEGE-----FDEEYIQTLgVNFMEKTISIRGTEITF--SIWDLGGQ--REFINMLPLVCKD 72

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145558870 136 ADAFLFLFSFTDRASFEDLPGQLTRVAGEAPGLVKIVIGSKFDQYMHTDVP-----ARDLTAFRQAWELPLF 202
Cdd:cd04128   73 AVAILFMFDLTRKSTLNSIKEWYRQARGFNKTAIPILVGTKYDLFADLPPEeqeeiTKQARKYAKAMKAPLI 144

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 145558870  56 YKIFVSGKSGVGKTALVAKLAGLEVPIVHHETTGIQT---TVVfwpAKLKASDCVVMfrfEFWDCGESalkkfdHMLPA- 131
Cdd:cd04148    1 YRVVLLGDSGVGKSSLANIFTAGVYEDSAYEASGDDTyerTVS---VDGEEATLVVY---DHWEQEDG------MWLEDs 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 145558870 132 CKENADAFLFLFSFTDRASFE---DLPGQLtRVAGEAPGLVKIVIGSKFD 178
Cdd:cd04148   69 CMQVGDAYVIVYSVTDRSSFEkasELRIQL-RRARQAEDIPIILVGNKSD 117

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 145558870  56 YKIFVSGKSGVGKTALVAKLAGLEVPIVHHETTGI--QTTVVFWPAKlkasdcvvMFRFEFWD-CG-EsalkKFDHMLPA 131
Cdd:cd00154    1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVdfKSKTIEVDGK--------KVKLQIWDtAGqE----RFRSITSS 68

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145558870 132 CKENADAFLFLFSFTDRASFEDLPG---QLTRVAGeaPGLVKIVIGSKFDQYMHTDVPARDLTAFRQAWELPLF 202
Cdd:cd00154   69 YYRGAHGAILVYDVTNRESFENLDKwlnELKEYAP--PNIPIILVGNKSDLEDERQVSTEEAQQFAKENGLLFF 140

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145558870   57 KIFVSGKSGVGKTALVAKLAGLEVPIVHHETTGIqtTVVFWPAkLKASDCVVMFRFEFWDCG--EsalkKFDHMLPACKE 134
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKSTIGV--DFKTKTV-LENDDNGKKIKLNIWDTAgqE----RFRSLHPFYYR 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 145558870  135 NADAFLFLFsftDRASFEDLP---GQLTRVAGEAPglvKIVIGSKFD 178
Cdd:pfam08477  74 GAAAALLVY---DSRTFSNLKywlRELKKYAGNSP---VILVGNKID 114

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145558870  57 KIFVSGKSGVGKTALVAKLAGLEVPIVHHETTGIQttvvFWPAKLKASDCVVMFRFEFWDCgeSALKKFDHMLPACKENA 136
Cdd:cd04106    2 KVIVVGNGNVGKSSMIQRFVKGIFTKDYKKTIGVD----FLEKQIFLRQSDEDVRLMLWDT--AGQEEFDAITKAYYRGA 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145558870 137 DAFLFLFSFTDRASFEDLPGQLTRVAGEAPGLVKIVIGSKFDQYMHTDVPARDLTAFRQAWELPLFRVKS 206
Cdd:cd04106   76 QACILVFSTTDRESFEAIESWKEKVEAECGDIPMVLVQTKIDLLDQAVITNEEAEALAKRLQLPLFRTSV 145

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 145558870  57 KIFVSGKSGVGKTALVAKL--AGLEVPIVHHETTGIQTTVVFWPAKlkasdcvvMFRFEFWDCgeSALKKFDHMLPACKE 134
Cdd:cd04121    8 KFLLVGDSDVGKGEILASLqdGSTESPYGYNMGIDYKTTTILLDGR--------RVKLQLWDT--SGQGRFCTIFRSYSR 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145558870 135 NADAFLFLFSFTDRASFEDLPGQLTRVAGEAPGLVKIVIGSKFDQYMHTDVPARDLTAFRQAWELPLFRV 204
Cdd:cd04121   78 GAQGIILVYDITNRWSFDGIDRWIKEIDEHAPGVPKILVGNRLHLAFKRQVATEQAQAYAERNGMTFFEV 147

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145558870  57 KIFVSGKSGVGKTALVAKLAGLEVPIVHHETtgIQ----TTVVFwpaklkasDCVvMFRFEFWD-CGE---SALKkFDHM 128
Cdd:cd00876    1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPT--IEdsyrKQIVV--------DGE-TYTLDILDtAGQeefSAMR-DQYI 68

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 145558870 129 LpackeNADAFLFLFSFTDRASFEDLPG---QLTRVAGEAPglVKIVI-GSKFDQYMHTDVPARDLTAFRQAWELPLF 202
Cdd:cd00876   69 R-----NGDGFILVYSITSRESFEEIKNireQILRVKDKED--VPIVLvGNKCDLENERQVSTEEGEALAEEWGCPFL 139

NTPase;

                         10        20
                 ....*....|....*....|..
gi 145558870  57 KIFVSGKSGVGKTALVAKLAGL 78
Cdd:PRK13695   2 KIGITGPPGVGKTTLVLKIAEL 23