GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1974326278   1 MLKVKVLFVGPSEAGKSVLANFLSETIEGIGSYIPTQGVRILEYEKPHFNGNSkgpgcRFELWDCGGDQKFETCWPAL-- 78
Cdd:COG1100     1 MGEKKIVVVGTGGVGKTSLVNRLVGDIFSLEKYLSTNGVTIDKKELKLDGLDV-----DLVIWDTPGQDEFRETRQFYar 75

                          90       100
                  ....*....|....*....|....*...
gi 1974326278  79 -MKDSHGVVIIFNPDLPSHVKEIEMWYS 105
Cdd:COG1100    76 qLTGASLYLFVVDGTREETLQSLYELLE 103

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1974326278   1 MLKVKVLFVGPSEAGKSVLANFLSETIEGIGSYIPTQGVRILEYEKPHFNGNSkgpgcRFELWDCGGDQKFETCWPAL-- 78
Cdd:COG1100     1 MGEKKIVVVGTGGVGKTSLVNRLVGDIFSLEKYLSTNGVTIDKKELKLDGLDV-----DLVIWDTPGQDEFRETRQFYar 75

                          90       100
                  ....*....|....*....|....*...
gi 1974326278  79 -MKDSHGVVIIFNPDLPSHVKEIEMWYS 105
Cdd:COG1100    76 qLTGASLYLFVVDGTREETLQSLYELLE 103

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 1974326278   4 VKVLFVGPSEAGKSvlaNFLSETIEGI--GSYIPTQGVRILEyEKPHFNGNSkgpgCRFELWDCGGDQKFETCWPALMKD 81
Cdd:cd04128     1 LKIGLLGDAQIGKT---SLMVKYVEGEfdEEYIQTLGVNFME-KTISIRGTE----ITFSIWDLGGQREFINMLPLVCKD 72

                          90       100
                  ....*....|....*....|....*.
gi 1974326278  82 ShgVVIIFNPDL--PSHVKEIEMWYS 105
Cdd:cd04128    73 A--VAILFMFDLtrKSTLNSIKEWYR 96

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 1974326278   4 VKVLFVGPSEAGKSVLANFLSETIEGIGSYIPTQGvriLEYEKPHFngNSKGPGCRFELWDCGGDQKFETCWPALMKDSH 83
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLGNKGSITEYYPGTT---RNYVTTVI--EEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVE 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1974326278  84 GVVIIFnpDLPSHVKEIEmwyscfvqqqQLLENQCLLIAHHKPG 127
Cdd:TIGR00231  77 RSLRVF--DIVILVLDVE----------EILEKQTKEIIHHADS 108

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1974326278   1 MLKVKVLFVGPSEAGKSVLANFLSETIEGIGSYIPTQGVRILEYEKPHFNGNSkgpgcRFELWDCGGDQKFETCWPAL-- 78
Cdd:COG1100     1 MGEKKIVVVGTGGVGKTSLVNRLVGDIFSLEKYLSTNGVTIDKKELKLDGLDV-----DLVIWDTPGQDEFRETRQFYar 75

                          90       100
                  ....*....|....*....|....*...
gi 1974326278  79 -MKDSHGVVIIFNPDLPSHVKEIEMWYS 105
Cdd:COG1100    76 qLTGASLYLFVVDGTREETLQSLYELLE 103

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 1974326278   4 VKVLFVGPSEAGKSvlaNFLSETIEGI--GSYIPTQGVRILEyEKPHFNGNSkgpgCRFELWDCGGDQKFETCWPALMKD 81
Cdd:cd04128     1 LKIGLLGDAQIGKT---SLMVKYVEGEfdEEYIQTLGVNFME-KTISIRGTE----ITFSIWDLGGQREFINMLPLVCKD 72

                          90       100
                  ....*....|....*....|....*.
gi 1974326278  82 ShgVVIIFNPDL--PSHVKEIEMWYS 105
Cdd:cd04128    73 A--VAILFMFDLtrKSTLNSIKEWYR 96

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 1974326278   7 LFVGPSEAGKSVLANFLSETIEGIGSYIPTQGVRILEYEKPHfngnsKGPGCRFELWDCGG-----DQKFETCWPALMKD 81
Cdd:cd00882     1 VVVGRGGVGKSSLLNALLGGEVGEVSDVPGTTRDPDVYVKEL-----DKGKVKLVLVDTPGldefgGLGREELARLLLRG 75

                          90       100
                  ....*....|....*....|...
gi 1974326278  82 SHGVVIIFNPDLPSHVKEIEMWY 104
Cdd:cd00882    76 ADLILLVVDSTDRESEEDAKLLI 98

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 1974326278   4 VKVLFVGPSEAGKSVLANFLSETIEGIGSYIPTQGvriLEYEKPHFngNSKGPGCRFELWDCGGDQKFETCWPALMKDSH 83
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLGNKGSITEYYPGTT---RNYVTTVI--EEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVE 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1974326278  84 GVVIIFnpDLPSHVKEIEmwyscfvqqqQLLENQCLLIAHHKPG 127
Cdd:TIGR00231  77 RSLRVF--DIVILVLDVE----------EILEKQTKEIIHHADS 108

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 1974326278   5 KVLFVGPSEAGK-SVLANFLSETIEGigSYIPTQGV----RILEYEkphfngnskGPGCRFELWDCGGDQKFETCWPALM 79
Cdd:cd01861     2 KLVFLGDQSVGKtSIITRFMYDTFDN--QYQATIGIdflsKTMYVD---------DKTVRLQLWDTAGQERFRSLIPSYI 70

                          90
                  ....*....|
gi 1974326278  80 KDSHGVVIIF 89
Cdd:cd01861    71 RDSSVAVVVY 80

Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab proteins identified recently which display features that are distinct from other Rabs, and have been termed Rab-like. RabL2 contains RabL2a and RabL2b, two very similar Rab proteins that share > 98% sequence identity in humans. RabL2b maps to the subtelomeric region of chromosome 22q13.3 and RabL2a maps to 2q13, a region that suggests it is also a subtelomeric gene. Both genes are believed to be expressed ubiquitously, suggesting that RabL2s are the first example of duplicated genes in human proximal subtelomeric regions that are both expressed actively. Like other Rab-like proteins, RabL2s lack a prenylation site at the C-terminus. The specific functions of RabL2a and RabL2b remain unknown. 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 1974326278   4 VKVLFVGPSEAGKSVLAN-FLSEtiegigSYIPTQgVRILEYEKPHFNGNSKGPGCRFELWDCGGDQKFETCWPALMKDS 82
Cdd:cd04124     1 VKIILLGDSAVGKSKLVErFLMD------GYEPQQ-LSTYALTLYKHNAKFEGKTILVDFWDTAGQERFQTMHASYYHKA 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1974326278  83 HGVVIIFNPDLPSHVKEIEMWYscfvqqQQLLENQ----CLLIAH 123
Cdd:cd04124    74 HACILVFDVTRKITYKNLSKWY------EELREYRpeipCIVVAN 112

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 1974326278   4 VKVLFVGPSEAGKSvlaNFLSETIEGI--GSYIPTQGV----RILEYekphfNGNSkgpgCRFELWDCGGDQKFETCWPA 77
Cdd:cd00154     1 FKIVLIGDSGVGKT---SLLLRFVDNKfsENYKSTIGVdfksKTIEV-----DGKK----VKLQIWDTAGQERFRSITSS 68

                          90       100       110
                  ....*....|....*....|....*....|
gi 1974326278  78 LMKDSHGVVIIFnpDLPSHV--KEIEMWYS 105
Cdd:cd00154    69 YYRGAHGAILVY--DVTNREsfENLDKWLN 96

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 1974326278   4 VKVLFVGPSEAGKSVLanfLSETIEGIGS--YIPTQGVRILEyeKPHFNgNSKGPGCRFELWDCGGDQKFETCWPALMKD 81
Cdd:cd04106     1 IKVIVVGNGNVGKSSM---IQRFVKGIFTkdYKKTIGVDFLE--KQIFL-RQSDEDVRLMLWDTAGQEEFDAITKAYYRG 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1974326278  82 SHGVVIIFNPDLPSHVKEIEMWYSCfvqqqqlLENQC 118
Cdd:cd04106    75 AQACILVFSTTDRESFEAIESWKEK-------VEAEC 104

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1974326278    4 VKVLFVGPSEAGKSvlaNFLSETIEGI--GSYIPTQGV----RILEYEkphfngnskGPGCRFELWDCGGDQKFETCWPA 77
Cdd:smart00175   1 FKIILIGDSGVGKS---SLLSRFTDGKfsEQYKSTIGVdfktKTIEVD---------GKRVKLQIWDTAGQERFRSITSS 68

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1974326278   78 LMKDSHGVVIIF---NPD----LPSHVKEIEM 102
Cdd:smart00175  69 YYRGAVGALLVYditNREsfenLENWLKELRE 100

Sar1 is an essential component of COPII vesicle coats; Sar1 is an essential component of COPII vesicle coats involved in export of cargo from the ER. The GTPase activity of Sar1 functions as a molecular switch to control protein-protein and protein-lipid interactions that direct vesicle budding from the ER. Activation of the GDP to the GTP-bound form of Sar1 involves the membrane-associated guanine nucleotide exchange factor (GEF) Sec12. Sar1 is unlike all Ras superfamily GTPases that use either myristoyl or prenyl groups to direct membrane association and function, in that Sar1 lacks such modification. Instead, Sar1 contains a unique nine-amino-acid N-terminal extension. This extension contains an evolutionarily conserved cluster of bulky hydrophobic amino acids, referred to as the Sar1-N-terminal activation recruitment (STAR) motif. The STAR motif mediates the recruitment of Sar1 to ER membranes and facilitates its interaction with mammalian Sec12 GEF leading to activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1974326278   5 KVLFVGPSEAGKSVLANFLSEtiEGIGSYIPTQgvrileyekpHFN------GNSKgpgcrFELWDCGGDQKFETCWPAL 78
Cdd:cd00879    21 KIVFLGLDNAGKTTLLHMLKD--DRLAQHVPTL----------HPTseeltiGNVK-----FTTFDLGGHEQARRVWKDY 83

                          90
                  ....*....|
gi 1974326278  79 MKDSHGVVII 88
Cdd:cd00879    84 FPEVDGIVFL 93