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 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTADLD---TPRNCERYLNWAHAFLVVYSVDSRQSFDSSSS 100
Cdd:cd04146    14 ALTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQqneDPESLERSLRWADGFVLVYSITDRSSFDVVSQ 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1827625722 101 YLELLALHAKeTQRSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDFEHVQHVFHEAVREARR 174
Cdd:cd04146    94 LLQLIREIKK-RDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNVFHELCREVRR 166

Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like families; RERG (Ras-related and Estrogen- Regulated Growth inhibitor) and Ras-like 11 are members of a novel subfamily of Ras that were identified based on their behavior in breast and prostate tumors, respectively. RERG expression was decreased or lost in a significant fraction of primary human breast tumors that lack estrogen receptor and are correlated with poor clinical prognosis. Elevated RERG expression correlated with favorable patient outcome in a breast tumor subtype that is positive for estrogen receptor expression. In contrast to most Ras proteins, RERG overexpression inhibited the growth of breast tumor cells in vitro and in vivo. RasL11 was found to be ubiquitously expressed in human tissue, but down-regulated in prostate tumors. Both RERG and RasL11 lack the C-terminal CaaX prenylation motif, where a = an aliphatic amino acid and X = any amino acid, and are localized primarily in the cytoplasm. Both are believed to have tumor suppressor activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTADLD---TPRNCERYLNWAHAFLVVYSVDSRQSFDSSSS 100
Cdd:cd04146    14 ALTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQqneDPESLERSLRWADGFVLVYSITDRSSFDVVSQ 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1827625722 101 YLELLALHAKeTQRSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDFEHVQHVFHEAVREARR 174
Cdd:cd04146    94 LLQLIREIKK-RDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNVFHELCREVRR 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 1827625722  24 ALTVKFLTKRFISEYDPNL-EDTYSSEETVDHQPVHLRVMDTADLdtprncER--------YLNwAHAFLVVYSVDSRQS 94
Cdd:pfam00071  14 SLLIRFTQNKFPEEYIPTIgVDFYTKTIEVDGKTVKLQIWDTAGQ------ERfralrplyYRG-ADGFLLVYDITSRDS 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722  95 FDSSSSYLELLALHAKEtqrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDfEHVQHVFHEAVREARR 174
Cdd:pfam00071  87 FENVKKWVEEILRHADE---NVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTN-ENVEEAFEELAREILK 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 1827625722  24 ALTVKFL-TKRFISEYDPNLEDTYSSE-ETVDHQPVHLRVMDTADLDTPRNCER-YLNWAHAFLVVYSVDSRQSFDS--S 98
Cdd:TIGR00231  16 TLLNSLLgNKGSITEYYPGTTRNYVTTvIEEDGKTYKFNLLDTAGQEDYDAIRRlYYPQVERSLRVFDIVILVLDVEeiL 95

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1827625722  99 SSYLELLALHAKetqRSIPALLLGNKLDMAQYRQVTKaEGVALAGRFGCLFFEVSA 154
Cdd:TIGR00231  96 EKQTKEIIHHAD---SGVPIILVGNKIDLKDADLKTH-VASEFAKLNGEPIIPLSA 147

Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like families; RERG (Ras-related and Estrogen- Regulated Growth inhibitor) and Ras-like 11 are members of a novel subfamily of Ras that were identified based on their behavior in breast and prostate tumors, respectively. RERG expression was decreased or lost in a significant fraction of primary human breast tumors that lack estrogen receptor and are correlated with poor clinical prognosis. Elevated RERG expression correlated with favorable patient outcome in a breast tumor subtype that is positive for estrogen receptor expression. In contrast to most Ras proteins, RERG overexpression inhibited the growth of breast tumor cells in vitro and in vivo. RasL11 was found to be ubiquitously expressed in human tissue, but down-regulated in prostate tumors. Both RERG and RasL11 lack the C-terminal CaaX prenylation motif, where a = an aliphatic amino acid and X = any amino acid, and are localized primarily in the cytoplasm. Both are believed to have tumor suppressor activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTADLD---TPRNCERYLNWAHAFLVVYSVDSRQSFDSSSS 100
Cdd:cd04146    14 ALTVRFLTKRFIGEYEPNLESLYSRQVTIDGEQVSLEIQDTPGQQqneDPESLERSLRWADGFVLVYSITDRSSFDVVSQ 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1827625722 101 YLELLALHAKeTQRSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDFEHVQHVFHEAVREARR 174
Cdd:cd04146    94 LLQLIREIKK-RDGEIPVILVGNKADLLHSRQVSTEEGQKLALELGCLFFEVSAAENYLEVQNVFHELCREVRR 166

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 1827625722    1 MVIMGPELVGswsdfKNeaadprALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTA---DLDTPRncERYL 77
Cdd:smart00173   3 LVVLGSGGVG-----KS------ALTIQFIQGHFVDDYDPTIEDSYRKQIEIDGEVCLLDILDTAgqeEFSAMR--DQYM 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722   78 NWAHAFLVVYSVDSRQSFDSSSSYLELLaLHAKETQrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLD 157
Cdd:smart00173  70 RTGEGFLLVYSITDRQSFEEIKKFREQI-LRVKDRD-DVPIVLVGNKCDLESERVVSTEEGKELARQWGCPFLETSAKER 147

                          170
                   ....*....|....*..
gi 1827625722  158 fEHVQHVFHEAVREARR 174
Cdd:smart00173 148 -VNVDEAFYDLVREIRK 163

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 1827625722  24 ALTVKFLTKRFISEYDPNL-EDTYSSEETVDHQPVHLRVMDTADLdtprncER--------YLNwAHAFLVVYSVDSRQS 94
Cdd:pfam00071  14 SLLIRFTQNKFPEEYIPTIgVDFYTKTIEVDGKTVKLQIWDTAGQ------ERfralrplyYRG-ADGFLLVYDITSRDS 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722  95 FDSSSSYLELLALHAKEtqrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDfEHVQHVFHEAVREARR 174
Cdd:pfam00071  87 FENVKKWVEEILRHADE---NVPIVLVGNKCDLEDQRVVSTEEGEALAKELGLPFMETSAKTN-ENVEEAFEELAREILK 162

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTA---DLDTPRncERYLNWAHAFLVVYSVDSRQSFDSSSS 100
Cdd:PTZ00369   20 ALTIQFIQNHFIDEYDPTIEDSYRKQCVIDEETCLLDILDTAgqeEYSAMR--DQYMRTGQGFLCVYSITSRSSFEEIAS 97

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1827625722 101 YLELLaLHAKETQRsIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDFeHVQHVFHEAVREARRELE 177
Cdd:PTZ00369   98 FREQI-LRVKDKDR-VPMILVGNKCDLDSERQVSTGEGQELAKSFGIPFLETSAKQRV-NVDEAFYELVREIRKYLK 171

Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap subfamily of the Ras family. It consists of Rap2a, Rap2b, and Rap2c. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. 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 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTADLDTPRNC-ERYLNWAHAFLVVYSVDSRQSFDSSSSYL 102
Cdd:cd04176    16 ALTVQFVSGTFIEKYDPTIEDFYRKEIEVDSSPSVLEILDTAGTEQFASMrDLYIKNGQGFIVVYSLVNQQTFQDIKPMR 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1827625722 103 ELLaLHAKETQrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSAcLDFEHVQHVFHEAVRE 171
Cdd:cd04176    96 DQI-VRVKGYE-KVPIILVGNKVDLESEREVSSAEGRALAEEWGCPFMETSA-KSKTMVNELFAEIVRQ 161

Ras Homolog Enriched in Brain (RheB) is a small GTPase; Rheb (Ras Homolog Enriched in Brain) subfamily. Rheb was initially identified in rat brain, where its expression is elevated by seizures or by long-term potentiation. It is expressed ubiquitously, with elevated levels in muscle and brain. Rheb functions as an important mediator between the tuberous sclerosis complex proteins, TSC1 and TSC2, and the mammalian target of rapamycin (TOR) kinase to stimulate cell growth. TOR kinase regulates cell growth by controlling nutrient availability, growth factors, and the energy status of the cell. TSC1 and TSC2 form a dimeric complex that has tumor suppressor activity, and TSC2 is a GTPase activating protein (GAP) for Rheb. The TSC1/TSC2 complex inhibits the activation of TOR kinase through Rheb. Rheb has also been shown to induce the formation of large cytoplasmic vacuoles in a process that is dependent on the GTPase cycle of Rheb, but independent of the TOR kinase, suggesting Rheb plays a role in endocytic trafficking that leads to cell growth and cell-cycle progression. 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 1827625722   2 VIMGPELVGSWSdfkneaadpraLTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTADLDT----PRnceRYL 77
Cdd:cd04137     5 AVLGSRSVGKSS-----------LTVQFVEGHFVESYYPTIENTFSKIITYKGQEYHLEIVDTAGQDEysilPQ---KYS 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722  78 NWAHAFLVVYSVDSRQS-FDSSSSYLELLALHAKEtqrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACL 156
Cdd:cd04137    71 IGIHGYILVYSVTSRKSfEVVKVIYDKILDMLGKE---SVPIVLVGNKSDLHMERQVSAEEGKKLAESWGAAFLESSAKE 147

                         170
                  ....*....|....*...
gi 1827625722 157 DfEHVQHVFHEAVREARR 174
Cdd:cd04137   148 N-ENVEEAFELLIEEIEK 164

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 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTA---------DLdtprncerYLNWAHAFLVVYSVdsrqs 94
Cdd:cd04175    16 ALTVQFVQGIFVEKYDPTIEDSYRKQVEVDGQQCMLEILDTAgteqftamrDL--------YMKNGQGFVLVYSI----- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722  95 fDSSSSYLELLALH-----AKETQrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDFeHVQHVFHEAV 169
Cdd:cd04175    83 -TAQSTFNDLQDLReqilrVKDTE-DVPMILVGNKCDLEDERVVGKEQGQNLARQWGCAFLETSAKAKI-NVNEIFYDLV 159

                  ....*
gi 1827625722 170 REARR 174
Cdd:cd04175   160 RQINR 164

RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that is found in fungi. In budding yeasts, RSR1 is involved in selecting a site for bud growth on the cell cortex, which directs the establishment of cell polarization. The Rho family GTPase cdc42 and its GEF, cdc24, then establish an axis of polarized growth by organizing the actin cytoskeleton and secretory apparatus at the bud site. It is believed that cdc42 interacts directly with RSR1 in vivo. In filamentous fungi, polar growth occurs at the tips of hypha and at novel growth sites along the extending hypha. In Ashbya gossypii, RSR1 is a key regulator of hyphal growth, localizing at the tip region and regulating in apical polarization of the actin cytoskeleton. 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 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTADLD---TPRncERYLNWAHAFLVVYSVDSRQSFDssss 100
Cdd:cd04177    16 ALTVQFVQNVFIESYDPTIEDSYRKQVEIDGRQCDLEILDTAGTEqftAMR--ELYIKSGQGFLLVYSVTSEASLN---- 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1827625722 101 ylELLALHA-----KETQRsIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCL-FFEVSACLDfEHVQHVFHEAVREAR 173
Cdd:cd04177    90 --ELGELREqvlriKDSDN-VPMVLVGNKADLEDDRQVSREDGVSLSQQWGNVpFYETSARKR-TNVDEVFIDLVRQII 164

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 1827625722  36 SEYDPNLEDTYSSEETVDHQPVHLRVMDTADLDTPRNCERY-LNWAHAFLVVYSV-DSRQSFDSSSSYLELLALHAKEtq 113
Cdd:cd04148    28 SAYEASGDDTYERTVSVDGEEATLVVYDHWEQEDGMWLEDScMQVGDAYVIVYSVtDRSSFEKASELRIQLRRARQAE-- 105

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722 114 rSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDfEHVQHVFHEAVREAR 173
Cdd:cd04148   106 -DIPIILVGNKSDLVRSREVSVQEGRACAVVFDCKFIETSAALQ-HNVDELFEGIVRQVR 163

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722   25 LTVKFLTKRFISEYDPNLE-DTYSSEETVDHQPVHLRVMDTAdldtprNCERYLNW-------AHAFLVVYSVDSRQSFD 96
Cdd:smart00175  16 LLSRFTDGKFSEQYKSTIGvDFKTKTIEVDGKRVKLQIWDTA------GQERFRSItssyyrgAVGALLVYDITNRESFE 89

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1827625722   97 SSSSYLELLALHAKETqrsIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSAcLDFEHVQHVFHEAVREA 172
Cdd:smart00175  90 NLENWLKELREYASPN---VVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSA-KTNTNVEEAFEELAREI 161

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 1827625722  29 FLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTA---DLDTPRNCeRYLNwAHAFLVVYSVDSRQSFDSSSS--YLE 103
Cdd:cd00157    20 YTTNKFPTEYVPTVFDNYSANVTVDGKQVNLGLWDTAgqeEYDRLRPL-SYPQ-TDVFLLCFSVDSPSSFENVKTkwYPE 97

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1827625722 104 LlalhaKETQRSIPALLLGNKLDM-----------AQYRQVTKAEGVALAGRFGCL-FFEVSAcLDFEHVQHVFHEAVR 170
Cdd:cd00157    98 I-----KHYCPNVPIILVGTKIDLrddgntlkkleKKQKPITPEEGEKLAKEIGAVkYMECSA-LTQEGLKEVFDEAIR 170

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 1827625722   24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTA---DLDTPRNceryLNW--AHAFLVVYSVDSRQSFDSS 98
Cdd:smart00174  13 CLLIVYTTNAFPEDYVPTVFENYSADVEVDGKPVELGLWDTAgqeDYDRLRP----LSYpdTDVFLICFSVDSPASFENV 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722   99 SS--YLELlalhaKETQRSIPALLLGNKLDMAQYRQ------------VTKAEGVALAGRFGCL-FFEVSAcLDFEHVQH 163
Cdd:smart00174  89 KEkwYPEV-----KHFCPNVPIILVGTKLDLRNDKStleelskkkqepVTYEQGQALAKRIGAVkYLECSA-LTQEGVRE 162

                   ....*....
gi 1827625722  164 VFHEAVREA 172
Cdd:smart00174 163 VFEEAIRAA 171

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 1827625722  30 LTKRFIS-EYDPNLEDTY-----SSEETVDHQPVHLRVMDTADLDTPRN-CERYLNWAHAFLVVYSVDSRQSFDSSSSYL 102
Cdd:cd01863    16 LLLRFTDdTFDEDLSSTIgvdfkVKTVTVDGKKVKLAIWDTAGQERFRTlTSSYYRGAQGVILVYDVTRRDTFDNLDTWL 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1827625722 103 ELLALHAkeTQRSIPALLLGNKLDMAQyRQVTKAEGVALAGRFGCLFFEVSACLDfEHVQHVFHEAVR 170
Cdd:cd01863    96 NELDTYS--TNPDAVKMLVGNKIDKEN-REVTREEGQKFARKHNMLFIETSAKTR-IGVQQAFEELVE 159

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 1827625722  52 VDHQPVHLRVMDTADLDTPRN-CERYLNWAHAFLVVYSVDSRQSFDSSSSYLELLALHAKEtqrSIPALLLGNKLDMAQY 130
Cdd:cd01867    47 LDGKKIKLQIWDTAGQERFRTiTTSYYRGAMGIILVYDITDEKSFENIKNWMRNIDEHASE---DVERMLVGNKCDMEEK 123

                          90       100
                  ....*....|....*....|....
gi 1827625722 131 RQVTKAEGVALAGRFGCLFFEVSA 154
Cdd:cd01867   124 RVVSKEEGEALAREYGIKFLETSA 147

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 1827625722  33 RFI-SEYDPNLEDT-----YSSEETVDHQPVHLRVMDTAdldtprNCERYLNWAH-------AFLVVYSVDSRQSFDSSS 99
Cdd:cd01860    20 RFVkNEFSENQESTigaafLTQTVNLDDTTVKFEIWDTA------GQERYRSLAPmyyrgaaAAIVVYDITSEESFEKAK 93

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1827625722 100 SYLELLALHAKEtqrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSAcLDFEHVQHVFHE 167
Cdd:cd01860    94 SWVKELQEHGPP---NIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSA-KTGENVNELFTE 157

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 1827625722  28 KFLTKRFISEYDPNLEDTYSseeTVDHQPVHLRVMDTADLDTPRNCER-YLNWAHAFLVVYSVDSRQSFDSSSSYLELLA 106
Cdd:cd04112    24 AFLAGSFIATVGIQFTNKVV---TVDGVKVKLQIWDTAGQERFRSVTHaYYRDAHALLLLYDVTNKSSFDNIRAWLTEIL 100

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1827625722 107 LHAKETQRsipALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDFeHVQHVFHEAVRE 171
Cdd:cd04112   101 EYAQSDVV---IMLLGNKADMSGERVVKREDGERLAKEYGVPFMETSAKTGL-NVELAFTAVAKE 161

Rab GTPase family 11 (Rab11)-like includes Rab11a, Rab11b, and Rab25; Rab11a, Rab11b, and Rab25 are closely related, evolutionary conserved Rab proteins that are differentially expressed. Rab11a is ubiquitously synthesized, Rab11b is enriched in brain and heart and Rab25 is only found in epithelia. Rab11/25 proteins seem to regulate recycling pathways from endosomes to the plasma membrane and to the trans-Golgi network. Furthermore, Rab11a is thought to function in the histamine-induced fusion of tubulovesicles containing H+, K+ ATPase with the plasma membrane in gastric parietal cells and in insulin-stimulated insertion of GLUT4 in the plasma membrane of cardiomyocytes. Overexpression of Rab25 has recently been observed in ovarian cancer and breast cancer, and has been correlated with worsened outcomes in both diseases. In addition, Rab25 overexpression has also been observed in prostate cancer, transitional cell carcinoma of the bladder, and invasive breast tumor cells. 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 1827625722  80 AHAFLVVYSVDSRQSFDSSSSYLELLALHAKEtqrSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSAcLDFE 159
Cdd:cd01868    76 AVGALLVYDITKKSTFENVERWLKELRDHADS---NIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSA-LDGT 151

                          90
                  ....*....|..
gi 1827625722 160 HVQHVFHEAVRE 171
Cdd:cd01868   152 NVEEAFKQLLTE 163

Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - dorsal-ventral anterior localization) subfamily consists of a set of proteins characterized only in Xenopus leavis, to date. In Xenopus Ras-dva expression is activated by the transcription factor Otx2 and begins during gastrulation throughout the anterior ectoderm. Ras-dva expression is inhibited in the anterior neural plate by factor Xanf1. Downregulation of Ras-dva results in head development abnormalities through the inhibition of several regulators of the anterior neural plate and folds patterning, including Otx2, BF-1, Xag2, Pax6, Slug, and Sox9. Downregulation of Ras-dva also interferes with the FGF-8a signaling within the anterior ectoderm. 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 1827625722  24 ALTVKFLTKRFISEYDPNLEDTYSSEETVDHQPVHLRVMDTA-DLDTPRNCERYLNWAHAFLVVYSVDSRQSFDSSSSYL 102
Cdd:cd04147    14 ALIQRFLYDTFEPKHRRTVEELHSKEYEVAGVKVTIDILDTSgSYSFPAMRKLSIQNGDAFALVYSVDDPESFEEVKRLR 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1827625722 103 ELLaLHAKETqRSIPALLLGNKLDMAQYRQVTKAEGVALAG-RFGCLFFEVSACLDfEHVQHVFHEAVREARRELEKSPL 181
Cdd:cd04147    94 EEI-LEVKED-KFVPIVVVGNKIDSLAERQVEAADALSTVElDWNNGFVEASAKDN-ENVTEVFKELLQQANLPSWLSPA 170

                         170       180
                  ....*....|....*....|....*...
gi 1827625722 182 TRPLFISEERALPHQAPLTARHglaSCT 209
Cdd:cd04147   171 LRRRRESAPSEIQRRPPMNKTN---SCS 195