ADP-ribosylation factor family; Pfam combines a number of different Prosite families together

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597   98 ILVLGLDGAGKTSVLYSLASNRVQHSVaPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVDSADHN 177
Cdd:pfam00025   3 ILILGLDNAGKTTILYKLKLGEIVTTI-PTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADRD 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 830014597  178 RLPEAKKYLHQLIG--ANPVLPLVVFANKQDLETAYHITDIHEALALSEVgNDRKMFLFGTHLTK 240
Cdd:pfam00025  82 RIEEAKEELHALLNeeELADAPLLILANKQDLPGAMSEAEIRELLGLHEL-KDRPWEIQGCSAVT 145

ADP-ribosylation factor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  93 EKNKQILVLGLDGAGKTSVLYSLASNRVQHSVaPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVD 172
Cdd:PTZ00133  15 KKEVRILMVGLDAAGKTTILYKLKLGEVVTTI-PTIGFNVETVEYKNLKFTMWDVGGQDKLRPLWRHYYQNTNGLIFVVD 93

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 830014597 173 SADHNRLPEAKKYLHQLIGANPV--LPLVVFANKQDLETAYHITDIHEALALSEVGNdRKMFLFGT 236
Cdd:PTZ00133  94 SNDRERIGDAREELERMLSEDELrdAVLLVFANKQDLPNAMSTTEVTEKLGLHSVRQ-RNWYIQGC 158

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 830014597   96 KQILVLGLDGAGKTSVLYSLASN-RVQHSVAP--TQGFNAVCINI--EDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFV 170
Cdd:TIGR00231   2 IKIVIVGHPNVGKSTLLNSLLGNkGSITEYYPgtTRNYVTTVIEEdgKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRV 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 830014597  171 VDSADH-NRLPEAK-KYLHQLIGANPV-LPLVVFANKQDLETA 210
Cdd:TIGR00231  82 FDIVILvLDVEEILeKQTKEIIHHADSgVPIILVGNKIDLKDA 124

ADP-ribosylation factor family; Pfam combines a number of different Prosite families together

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597   98 ILVLGLDGAGKTSVLYSLASNRVQHSVaPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVDSADHN 177
Cdd:pfam00025   3 ILILGLDNAGKTTILYKLKLGEIVTTI-PTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADRD 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 830014597  178 RLPEAKKYLHQLIG--ANPVLPLVVFANKQDLETAYHITDIHEALALSEVgNDRKMFLFGTHLTK 240
Cdd:pfam00025  82 RIEEAKEELHALLNeeELADAPLLILANKQDLPGAMSEAEIRELLGLHEL-KDRPWEIQGCSAVT 145

ADP-ribosylation factor(Arf)/Arf-like (Arl) small GTPases; Arf (ADP-ribosylation factor)/Arl (Arf-like) small GTPases. Arf proteins are activators of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. Arfs are N-terminally myristoylated. Members of the Arf family are regulators of vesicle formation in intracellular traffic that interact reversibly with membranes of the secretory and endocytic compartments in a GTP-dependent manner. They depart from other small GTP-binding proteins by a unique structural device, interswitch toggle, that implements front-back communication from N-terminus to the nucleotide binding site. Arf-like (Arl) proteins are close relatives of the Arf, but only Arl1 has been shown to function in membrane traffic like the Arf proteins. Arl2 has an unrelated function in the folding of native tubulin, and Arl4 may function in the nucleus. Most other Arf family proteins are so far relatively poorly characterized. Thus, despite their significant sequence homologies, Arf family proteins may regulate unrelated functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  97 QILVLGLDGAGKTSVLYSLASNRVQhSVAPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVDSADH 176
Cdd:cd00878    1 RILMLGLDGAGKTTILYKLKLGEVV-TTIPTIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSSDR 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 830014597 177 NRLPEAKKYLHQLIGANPV--LPLVVFANKQDLETAYHITDIHEALALSEVGnDRKMFLFGT 236
Cdd:cd00878   80 ERIEEAKNELHKLLNEEELkgAPLLILANKQDLPGALTESELIELLGLESIK-GRRWHIQPC 140

Arf-like 5 (Arl5) and 8 (Arl8) GTPases; Arl5/Arl8 subfamily. Arl5 (Arf-like 5) and Arl8, like Arl4 and Arl7, are localized to the nucleus and nucleolus. Arl5 is developmentally regulated during embryogenesis in mice. Human Arl5 interacts with the heterochromatin protein 1-alpha (HP1alpha), a nonhistone chromosomal protein that is associated with heterochromatin and telomeres, and prevents telomere fusion. Arl5 may also play a role in embryonic nuclear dynamics and/or signaling cascades. Arl8 was identified from a fetal cartilage cDNA library. It is found in brain, heart, lung, cartilage, and kidney. No function has been assigned for Arl8 to date.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  93 EKNKQILVLGLDGAGKTSVLYSLASNRVQHSvAPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVD 172
Cdd:cd04153   13 RKEYKVIIVGLDNAGKTTILYQFLLGEVVHT-SPTIGSNVEEIVYKNIRFLMWDIGGQESLRSSWNTYYTNTDAVILVID 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 830014597 173 SADHNRLPEAKKYLHQLIGANPV--LPLVVFANKQDLETAYHITDIHEALALSEVgNDRKMFLFG 235
Cdd:cd04153   92 STDRERLPLTKEELYKMLAHEDLrkAVLLVLANKQDLKGAMTPAEISESLGLTSI-RDHTWHIQG 155

Arf-like 4 (Arl4) and 7 (Arl7) GTPases; Arl4 (Arf-like 4) is highly expressed in testicular germ cells, and is found in the nucleus and nucleolus. In mice, Arl4 is developmentally expressed during embryogenesis, and a role in somite formation and central nervous system differentiation has been proposed. Arl7 has been identified as the only Arf/Arl protein to be induced by agonists of liver X-receptor and retinoid X-receptor and by cholesterol loading in human macrophages. Arl7 is proposed to play a role in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  98 ILVLGLDGAGKTSVLYSLASNRVQHSVaPTQGFNAVCI-----NIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVD 172
Cdd:cd04152    6 IVMLGLDSAGKTTVLYRLKFNEFVNTV-PTKGFNTEKIkvslgNAKGVTFHFWDVGGQEKLRPLWKSYTRCTDGIVFVVD 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 830014597 173 SADHNRLPEAKKYLHQL--IGANPVLPLVVFANKQDLETAYHITDIHEALALSEVGNDRKMFLFGT 236
Cdd:cd04152   85 SVDVERMEEAKTELHKItkFSENQGVPVLVLANKQDLPNALPVSEVEKLLALHELSSSTPWHVQPA 150

Arf-related protein 1 (Arfrp1); Arfrp1 (Arf-related protein 1), formerly known as ARP, is a membrane-associated Arf family member that lacks the N-terminal myristoylation motif. Arfrp1 is mainly associated with the trans-Golgi compartment and the trans-Golgi network, where it regulates the targeting of Arl1 and the GRIP domain-containing proteins, golgin-97 and golgin-245, onto Golgi membranes. It is also involved in the anterograde transport of the vesicular stomatitis virus G protein from the Golgi to the plasma membrane, and in the retrograde transport of TGN38 and Shiga toxin from endosomes to the trans-Golgi network. Arfrp1 also inhibits Arf/Sec7-dependent activation of phospholipase D. Deletion of Arfrp1 in mice causes embryonic lethality at the gastrulation stage and apoptosis of mesodermal cells, indicating its importance in development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  98 ILVLGLDGAGKTSVL------YSLASNRVQHS-VAPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFV 170
Cdd:cd04160    2 VLILGLDNAGKTTFLeqtktkFSKNYKGLNPSkITPTVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAESHGVIYV 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 830014597 171 VDSADHNRLPEAKKYLHQLIgANPVL---PLVVFANKQDLETAYHITDIHEALALSEVGNDRKMFLF 234
Cdd:cd04160   82 IDSTDRERFNESKSAFEKVI-NNEALegvPLLVLANKQDLPDALSVAEIKEVFDDCIALIGRRDCLV 147

Arf-like tumor suppressor gene 1 (ARLTS1 or Arl11); ARLTS1 (Arf-like tumor suppressor gene 1), also known as Arl11, is a member of the Arf family of small GTPases that is believed to play a major role in apoptotic signaling. ARLTS1 is widely expressed and functions as a tumor suppressor gene in several human cancers. ARLTS1 is a low-penetrance suppressor that accounts for a small percentage of familial melanoma or familial chronic lymphocytic leukemia (CLL). ARLTS1 inactivation seems to occur most frequently through biallelic down-regulation by hypermethylation of the promoter. In breast cancer, ARLTS1 alterations were typically a combination of a hypomorphic polymorphism plus loss of heterozygosity. In a case of thyroid adenoma, ARLTS1 alterations were polymorphism plus promoter hypermethylation. The nonsense polymorphism Trp149Stop occurs with significantly greater frequency in familial cancer cases than in sporadic cancer cases, and the Cys148Arg polymorphism is associated with an increase in high-risk familial breast cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  97 QILVLGLDGAGKTSVLYSLaSNRVQHSVAPTQGFNAVCINIEDS-QMEFLEIGGSEPFRSYWETYLSRGLLLIFVVDSAD 175
Cdd:cd04156    1 QVLLLGLDSAGKSTLLYKL-KHAELVTTIPTVGFNVEMLQLEKHlSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVDSSD 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 830014597 176 HNRLPEAKKYLHQLIgANPVL---PLVVFANKQDLETAYHITDIHEALALSEVGNDRKMFL 233
Cdd:cd04156   80 EARLDESQKELKHIL-KNEHIkgvPVVLLANKQDLPGALTAEEITRRFKLKKYCSDRDWYV 139

ADP-ribosylation factor-1 (Arf1) and ADP-ribosylation factor-5 (Arf5); The Arf1-Arf5-like subfamily contains Arf1, Arf2, Arf3, Arf4, Arf5, and related proteins. Arfs1-5 are soluble proteins that are crucial for assembling coat proteins during vesicle formation. Each contains an N-terminal myristoylated amphipathic helix that is folded into the protein in the GDP-bound state. GDP/GTP exchange exposes the helix, which anchors to the membrane. Following GTP hydrolysis, the helix dissociates from the membrane and folds back into the protein. A general feature of Arf1-5 signaling may be the cooperation of two Arfs at the same site. Arfs1-5 are generally considered to be interchangeable in function and location, but some specific functions have been assigned. Arf1 localizes to the early/cis-Golgi, where it is activated by GBF1 and recruits the coat protein COPI. It also localizes to the trans-Golgi network (TGN), where it is activated by BIG1/BIG2 and recruits the AP1, AP3, AP4, and GGA proteins. Humans, but not rodents and other lower eukaryotes, lack Arf2. Human Arf3 shares 96% sequence identity with Arf1 and is believed to generally function interchangeably with Arf1. Human Arf4 in the activated (GTP-bound) state has been shown to interact with the cytoplasmic domain of epidermal growth factor receptor (EGFR) and mediate the EGF-dependent activation of phospholipase D2 (PLD2), leading to activation of the activator protein 1 (AP-1) transcription factor. Arf4 has also been shown to recognize the C-terminal sorting signal of rhodopsin and regulate its incorporation into specialized post-Golgi rhodopsin transport carriers (RTCs). There is some evidence that Arf5 functions at the early-Golgi and the trans-Golgi to affect Golgi-associated alpha-adaptin homology Arf-binding proteins (GGAs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  97 QILVLGLDGAGKTSVLYSLASNRVQHSVaPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVDSADH 176
Cdd:cd04150    2 RILMVGLDAAGKTTILYKLKLGEIVTTI-PTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDR 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 830014597 177 NRLPEAKKYLHQLIGANPVLP--LVVFANKQDLETAYHITDIHEALALSEVGNdRKMFLFGT 236
Cdd:cd04150   81 ERIGEAREELQRMLNEDELRDavLLVFANKQDLPNAMSAAEVTDKLGLHSLRN-RNWYIQAT 141

Arf-like 2 (Arl2) GTPase; Arl2 (Arf-like 2) GTPases are members of the Arf family that bind GDP and GTP with very low affinity. Unlike most Arf family proteins, Arl2 is not myristoylated at its N-terminal helix. The protein PDE-delta, first identified in photoreceptor rod cells, binds specifically to Arl2 and is structurally very similar to RhoGDI. Despite the high structural similarity between Arl2 and Rho proteins and between PDE-delta and RhoGDI, the interactions between the GTPases and their effectors are very different. In its GTP bound form, Arl2 interacts with the protein Binder of Arl2 (BART), and the complex is believed to play a role in mitochondrial adenine nucleotide transport. In its GDP bound form, Arl2 interacts with tubulin- folding Cofactor D; this interaction is believed to play a role in regulation of microtubule dynamics that impact the cytoskeleton, cell division, and cytokinesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  93 EKNKQILVLGLDGAGKTSVLYSLASNRVQhSVAPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVD 172
Cdd:cd04154   12 EREMRILMLGLDNAGKTTILKKFNGEDIS-TISPTLGFNIKTLEYNGYKLNIWDVGGQKSLRSYWRNYFESTDALIWVVD 90

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597 173 SADHNRLPEAKKYLHQLI------GANpvlpLVVFANKQDLETAYHITDIHEALALSEVgNDRKMFLFGT 236
Cdd:cd04154   91 SSDRARLEDCKRELQKLLveerlaGAT----LLIFANKQDLPGALSPEEIREVLELDSI-KSHHWRIFGC 155

Arf-like 6 (Arl6) GTPase; Arl6 (Arf-like 6) forms a subfamily of the Arf family of small GTPases. Arl6 expression is limited to the brain and kidney in adult mice, but it is expressed in the neural plate and somites during embryogenesis, suggesting a possible role for Arl6 in early development. Arl6 is also believed to have a role in cilia or flagella function. Several proteins have been identified that bind Arl6, including Arl6 interacting protein (Arl6ip), and SEC61beta, a subunit of the heterotrimeric conducting channel SEC61p. Based on Arl6 binding to these effectors, Arl6 is also proposed to play a role in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. At least three specific homozygous Arl6 mutations in humans have been found to cause Bardet-Biedl syndrome, a disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  97 QILVLGLDGAGKTSVLYSLA-SNRVQHSVAPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVDSAD 175
Cdd:cd04157    1 NILVLGLDNSGKTTIINQLKpSNAQSQNIVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSD 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 830014597 176 HNRLPEAKKYLHQLIG----ANPVLPLVVFANKQDLETAYHITDIHEALALSEVGnDRKMFLFGT 236
Cdd:cd04157   81 RLRMVVAKDELELLLNhpdiKHRRIPILFYANKMDLPDALTAVKITQLLCLENIK-DKPWHIFAS 144

(ADP-ribosylation factor domain protein 1 (ARD1); ARD1 (ADP-ribosylation factor domain protein 1) is an unusual member of the Arf family. In addition to the C-terminal Arf domain, ARD1 has an additional 46-kDa N-terminal domain that contains a RING finger domain, two predicted B-Boxes, and a coiled-coil protein interaction motif. This domain belongs to the TRIM (tripartite motif) or RBCC (RING, B-Box, coiled-coil) family. Like most Arfs, the ARD1 Arf domain lacks detectable GTPase activity. However, unlike most Arfs, the full-length ARD1 protein has significant GTPase activity due to the GAP (GTPase-activating protein) activity exhibited by the 46-kDa N-terminal domain. The GAP domain of ARD1 is specific for its own Arf domain and does not bind other Arfs. The rate of GDP dissociation from the ARD1 Arf domain is slowed by the adjacent 15 amino acids, which act as a GDI (GDP-dissociation inhibitor) domain. ARD1 is ubiquitously expressed in cells and localizes to the Golgi and to the lysosomal membrane. Two Tyr-based motifs in the Arf domain are responsible for Golgi localization, while the GAP domain controls lysosomal localization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  97 QILVLGLDGAGKTSVLYSLASNRVQHSVaPTQGFNAVCINIEDSQMEFLEIGGSEPFRSYWETYLSRGLLLIFVVDSADH 176
Cdd:cd04158    1 RVVTLGLDGAGKTTILFKLKQDEFMQPI-PTIGFNVETVEYKNLKFTIWDVGGKHKLRPLWKHYYLNTQAVVFVIDSSHR 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 830014597 177 NRLPEAKKYLHQLIGANPVLP--LVVFANKQDLETAYHITDIHEALALSEVGNDRKMFLFG 235
Cdd:cd04158   80 DRVSEAHSELAKLLTEKELRDalLLIFANKQDVAGALSVEEMTELLSLHKLCCGRSWYIQG 140

Signal recognition particle receptor, beta subunit (SR-beta), together with SR-alpha, forms the heterodimeric signal recognition particle (SRP); Signal recognition particle receptor, beta subunit (SR-beta). SR-beta and SR-alpha form the heterodimeric signal recognition particle (SRP or SR) receptor that binds SRP to regulate protein translocation across the ER membrane. Nascent polypeptide chains are synthesized with an N-terminal hydrophobic signal sequence that binds SRP54, a component of the SRP. SRP directs targeting of the ribosome-nascent chain complex (RNC) to the ER membrane via interaction with the SR, which is localized to the ER membrane. The RNC is then transferred to the protein-conducting channel, or translocon, which facilitates polypeptide translation across the ER membrane or integration into the ER membrane. SR-beta is found only in eukaryotes; it is believed to control the release of the signal sequence from SRP54 upon binding of the ribosome to the translocon. High expression of SR-beta has been observed in human colon cancer, suggesting it may play a role in the development of this type of cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  98 ILVLGLDGAGKTSVLYSLASNRVQHSVaPTQGFNAVCINIEDSQ---MEFLEIGGSEPFRS-YWETYLSRGLLLIFVVDS 173
Cdd:cd04105    3 VLLLGPSDSGKTALFTKLTTGKVRSTV-TSIEPNVASFYSNSSKgkkLTLVDVPGHEKLRDkLLEYLKASLKAIVFVVDS 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 830014597 174 AD-HNRLPEAKKYLHQLI----GANPVLPLVVFANKQDLETAYHITDIHEAL 220
Cdd:cd04105   82 ATfQKNIRDVAEFLYDILtdleKIKNKIPILIACNKQDLFTAKPAKKIKELL 133

GTPase SAR1 family domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  94 KNKQILVLGLDGAGKTSVLYSLASNRV-QHSVAPTQGFNAVCINIE----DSQMEFLEIGGSEPFRSYWETYLsRGL--- 165
Cdd:COG1100    2 GEKKIVVVGTGGVGKTSLVNRLVGDIFsLEKYLSTNGVTIDKKELKldglDVDLVIWDTPGQDEFRETRQFYA-RQLtga 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 830014597 166 -LLIFVVDSADHNRLPEAKKYLHQLIGANPVLPLVVFANKQDLETAYHITDIHE 218
Cdd:COG1100   81 sLYLFVVDGTREETLQSLYELLESLRRLGKKSPIILVLNKIDLYDEEEIEDEER 134

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 830014597   98 ILVLGLDGAGKTSVLYSLASNRVQHSVAPTQGFNAVCINIEDSQMEFLEI-------GGSEPFRSYWETYLSRGLLLIFV 170
Cdd:pfam08477   2 VVLLGDSGVGKTSLLKRFVDDTFDPKYKSTIGVDFKTKTVLENDDNGKKIklniwdtAGQERFRSLHPFYYRGAAAALLV 81

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 830014597  171 VDSADHNRLPEAKKYLHQLIGANPVlplVVFANKQD 206
Cdd:pfam08477  82 YDSRTFSNLKYWLRELKKYAGNSPV---ILVGNKID 114

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 830014597   98 ILVLGLDGAGKTSVLYSLASNRVQHSVAPTQGFN----AVCINIEDSQMEFLEIGGSEPFRSYWETYL--SRGLLLIFVV 171
Cdd:pfam00071   2 LVLVGDGGVGKSSLLIRFTQNKFPEEYIPTIGVDfytkTIEVDGKTVKLQIWDTAGQERFRALRPLYYrgADGFLLVYDI 81

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 830014597  172 DSADhnRLPEAKKYLHQLIG-ANPVLPLVVFANKQDLET 209
Cdd:pfam00071  82 TSRD--SFENVKKWVEEILRhADENVPIVLVGNKCDLED 118

Ras of complex proteins (Roc) C-terminal of Roc (COR) domain family; RocCOR (or Roco) protein family is characterized by a superdomain containing a Ras-like GTPase domain, called Roc (Ras of complex proteins), and a characteristic second domain called COR (C-terminal of Roc). A kinase domain and diverse regulatory domains are also often found in Roco proteins. Their functions are diverse; in Dictyostelium discoideum, which encodes 11 Roco proteins, they are involved in cell division, chemotaxis and development, while in human, where 4 Roco proteins (LRRK1, LRRK2, DAPK1, and MFHAS1) are encoded, these proteins are involved in epilepsy and cancer. Mutations in LRRK2 (leucine-rich repeat kinase 2) are known to cause familial Parkinson's disease.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597  98 ILVLGLDGAGKTSVLYSLASNRVQHSVAPTQGFNAVCINIEDSQMEFLEI-----GGSEPFRSYWETYLSRGLLLIFVVD 172
Cdd:cd09914    4 LMLVGQGGVGKTSLCKQLIGEKFDGDESSTHGINVQDWKIPAPERKKIRLnvwdfGGQEIYHATHQFFLTSRSLYLLVFD 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 830014597 173 SADHNRLPEAKKYLHQLIGANPVLPLVVFANKQDLETAYHIT 214
Cdd:cd09914   84 LRTGDEVSRVPYWLRQIKAFGGVSPVILVGTHIDESCDEDIL 125

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 830014597  97 QILVLGLDGAGKTSVLYSLASNRVQHSVAPT-QGFNAVCINI--EDSQMEFLEIGGSEPFRSYWETYLSRG--LLLIFVV 171
Cdd:cd04143    2 RMVVLGASKVGKTAIVSRFLGGRFEEQYTPTiEDFHRKLYSIrgEVYQLDILDTSGNHPFPAMRRLSILTGdvFILVFSL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597 172 DSADhnRLPEAKKYLHQLIGA----------NPVLPLVVFANKQDLEtAYHITDIHEALALseVGNDRKMFLFGTHLTKN 241
Cdd:cd04143   82 DNRE--SFEEVCRLREQILETksclknktkeNVKIPMVICGNKADRD-FPREVQRDEVEQL--VGGDENCAYFEVSAKKN 156

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 830014597    98 ILVLGLDGAGKTSVLYSLASNRVQHSVAPTqgfnavcinIEDS------------QMEFLEIGGSEPFRSYWETYLS--R 163
Cdd:smart00173   3 LVVLGSGGVGKSALTIQFIQGHFVDDYDPT---------IEDSyrkqieidgevcLLDILDTAGQEEFSAMRDQYMRtgE 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 830014597   164 GLLLIFVVDsaDHNRLPEAKKYLHQLI---GANPVlPLVVFANKQDLETAYHITdIHEALALSE 224
Cdd:smart00173  74 GFLLVYSIT--DRQSFEEIKKFREQILrvkDRDDV-PIVLVGNKCDLESERVVS-TEEGKELAR 133

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 830014597  98 ILVLGLDGAGKTSVLYSLASNRVQHSVAPTQG--FNAVCINIEDSQMEFlEI---GGSEPFRSYWETYL--SRGLLLIFV 170
Cdd:cd01860    4 LVLLGDSSVGKSSIVLRFVKNEFSENQESTIGaaFLTQTVNLDDTTVKF-EIwdtAGQERYRSLAPMYYrgAAAAIVVYD 82

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 830014597 171 VDSADhnRLPEAKKYLHQL-IGANPVLPLVVFANKQDLE 208
Cdd:cd01860   83 ITSEE--SFEKAKSWVKELqEHGPPNIVIALAGNKADLE 119

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 830014597  98 ILVLGLDGAGKTSVLYSLASNRVQHSVAPTQG--FNAVCINIEDSQMEfLEI---GGSEPFRSYWETYL--SRGLLLIFV 170
Cdd:cd00154    3 IVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGvdFKSKTIEVDGKKVK-LQIwdtAGQERFRSITSSYYrgAHGAILVYD 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 830014597 171 VDSAD-----HNRLPEAKKYlhqligANPVLPLVVFANKQDLETAYHITdIHEALALSEVGN 227
Cdd:cd00154   82 VTNREsfenlDKWLNELKEY------APPNIPIILVGNKSDLEDERQVS-TEEAQQFAKENG 136