Arf-like 9 (Arl9) and 10 (Arl10) GTPases; Arl10-like subfamily. Arl9/Arl10 was identified from a human cancer-derived EST dataset. No functional information about the subfamily is available at the current time, but crystal structures of human Arl10b and Arl10c have been solved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVL 80
Cdd:cd04159    28 TIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADREKLEVAKNELHDLLEKPSLEGIPLLVL 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907070223  81 GNKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQH 132
Cdd:cd04159   108 GNKNDLPGALSVDELIEQMNLKSITDREVSCYSISAKEKTNIDIVLDWLIKH 159

Arf-like 9 (Arl9) and 10 (Arl10) GTPases; Arl10-like subfamily. Arl9/Arl10 was identified from a human cancer-derived EST dataset. No functional information about the subfamily is available at the current time, but crystal structures of human Arl10b and Arl10c have been solved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVL 80
Cdd:cd04159    28 TIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADREKLEVAKNELHDLLEKPSLEGIPLLVL 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907070223  81 GNKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQH 132
Cdd:cd04159   108 GNKNDLPGALSVDELIEQMNLKSITDREVSCYSISAKEKTNIDIVLDWLIKH 159

ARF-like small GTPases; ARF, ADP-ribosylation factor; Ras homologues involved in vesicular transport. Activator 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. Contains ATP/GTP-binding motif (P-loop).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223    2 IPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVLG 81
Cdd:smart00177  42 IPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFA 121

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907070223   82 NKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQHSKS 135
Cdd:smart00177 122 NKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNNLKN 175

GTPase SAR1 family domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223  11 KITKGNVTIKLWDIGGQPRFRSMWERYCR---GVSAIVYMVDAADQEKIEASKNELHNLLdkpQLQG-IPVLVLGNKRDL 86
Cdd:COG1100    47 KLDGLDVDLVIWDTPGQDEFRETRQFYARqltGASLYLFVVDGTREETLQSLYELLESLR---RLGKkSPIILVLNKIDL 123

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907070223  87 agaLDEKELIEKMNL-SAIQDREICC-YSISCKEKDNID 123
Cdd:COG1100   124 ---YDEEEIEDEERLkEALSEDNIVEvVATSAKTGEGVE 159

Arf-like 9 (Arl9) and 10 (Arl10) GTPases; Arl10-like subfamily. Arl9/Arl10 was identified from a human cancer-derived EST dataset. No functional information about the subfamily is available at the current time, but crystal structures of human Arl10b and Arl10c have been solved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVL 80
Cdd:cd04159    28 TIPTVGFNMRKVTKGNVTIKVWDLGGQPRFRSMWERYCRGVNAIVYVVDAADREKLEVAKNELHDLLEKPSLEGIPLLVL 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907070223  81 GNKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQH 132
Cdd:cd04159   108 GNKNDLPGALSVDELIEQMNLKSITDREVSCYSISAKEKTNIDIVLDWLIKH 159

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVL 80
Cdd:pfam00025  28 TIPTIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSADRDRIEEAKEELHALLNEEELADAPLLIL 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907070223  81 GNKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQ 131
Cdd:pfam00025 108 ANKQDLPGAMSEAEIRELLGLHELKDRPWEIQGCSAVTGEGLDEGLDWLSN 158

Arf-like 3 (Arl3) GTPase; Arl3 (Arf-like 3) is an Arf family protein that differs from most Arf family members in the N-terminal extension. In is inactive, GDP-bound form, the N-terminal extension forms an elongated loop that is hydrophobically anchored into the membrane surface; however, it has been proposed that this region might form a helix in the GTP-bound form. The delta subunit of the rod-specific cyclic GMP phosphodiesterase type 6 (PDEdelta) is an Arl3 effector. Arl3 binds microtubules in a regulated manner to alter specific aspects of cytokinesis via interactions with retinitis pigmentosa 2 (RP2). It has been proposed that RP2 functions in concert with Arl3 to link the cell membrane and the cytoskeleton in photoreceptors as part of the cell signaling or vesicular transport machinery. In mice, the absence of Arl3 is associated with abnormal epithelial cell proliferation and cyst formation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   3 PTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVLGN 82
Cdd:cd04155    45 PTQGFNIKNVQADGFKLNVWDIGGQRKIRPYWRNYFENTDVLIYVIDSADRKRFEEAGQELVELLEEEKLAGVPVLVFAN 124

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1907070223  83 KRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQ 131
Cdd:cd04155   125 KQDLLTAAPAEEVAEALNLHDIRDRSWHIQACSAKTGEGLQEGMNWVCK 173

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 1907070223   1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVL 80
Cdd:cd00879    47 HVPTLHPTSEELTIGNVKFTTFDLGGHEQARRVWKDYFPEVDGIVFLVDAADPERFQESKEELDSLLNDEELANVPILIL 126

                          90       100
                  ....*....|....*....|.
gi 1907070223  81 GNKRDLAGALDEKELIEKMNL 101
Cdd:cd00879   127 GNKIDKPGAVSEEELREALGL 147

ARF-like small GTPases; ARF, ADP-ribosylation factor; Ras homologues involved in vesicular transport. Activator 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. Contains ATP/GTP-binding motif (P-loop).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223    2 IPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVLG 81
Cdd:smart00177  42 IPTIGFNVETVTYKNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDSNDRDRIDEAREELHRMLNEDELRDAVILVFA 121

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1907070223   82 NKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQHSKS 135
Cdd:smart00177 122 NKQDLPDAMKAAEITEKLGLHSIRDRNWYIQPTCATSGDGLYEGLTWLSNNLKN 175

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 1907070223   1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQL--QGIPVL 78
Cdd:cd04157    29 IVPTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSSDRLRMVVAKDELELLLNHPDIkhRRIPIL 108

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907070223  79 VLGNKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQ 131
Cdd:cd04157   109 FYANKMDLPDALTAVKITQLLCLENIKDKPWHIFASSALTGEGLDEGVDWLQA 161

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 1907070223   3 PTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVLGN 82
Cdd:cd04160    37 PTVGLNIGTIEVGKARLMFWDLGGQEELRSLWDKYYAESHGVIYVIDSTDRERFNESKSAFEKVINNEALEGVPLLVLAN 116

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907070223  83 KRDLAGALDEKELIEKMNLSA--IQDREICCYSISCKEKDNIDITLQWLI 130
Cdd:cd04160   117 KQDLPDALSVAEIKEVFDDCIalIGRRDCLVQPVSALEGEGVEEGIEWLV 166

ADP-ribosylation factor; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   2 IPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVLG 81
Cdd:PLN00223   46 IPTIGFNVETVEYKNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRDRVVEARDELHRMLNEDELRDAVLLVFA 125

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907070223  82 NKRDLAGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQHSKSR 136
Cdd:PLN00223  126 NKQDLPNAMNAAEITDKLGLHSLRQRHWYIQSTCATSGEGLYEGLDWLSNNIANK 180

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 1907070223   2 IPTVGFNMRKI--TKGN---VTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIP 76
Cdd:cd04152    32 VPTKGFNTEKIkvSLGNakgVTFHFWDVGGQEKLRPLWKSYTRCTDGIVFVVDSVDVERMEEAKTELHKITKFSENQGVP 111

                          90       100
                  ....*....|....*....|...
gi 1907070223  77 VLVLGNKRDLAGALDEKElIEKM 99
Cdd:cd04152   112 VLVLANKQDLPNALPVSE-VEKL 133

Arl2-like protein 1 (Arl2l1) and Arl13; Arl2l1 (Arl2-like protein 1) and Arl13 form a subfamily of the Arf family of small GTPases. Arl2l1 was identified in human cells during a search for the gene(s) responsible for Bardet-Biedl syndrome (BBS). Like Arl6, the identified BBS gene, Arl2l1 is proposed to have cilia-specific functions. Arl13 is found on the X chromosome, but its expression has not been confirmed; it may be a pseudogene.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVL 80
Cdd:cd04161    27 VAPTVGFTPTKLRLDKYEVCIFDLGGGANFRGIWVNYYAEAHGLVFVVDSSDDDRVQEVKEILRELLQHPRVSGKPILVL 106

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907070223  81 GNKRDLAGALDEKELIEKMNLSAIQDREICCYSI-SCKEKDN--------IDITLQWLI 130
Cdd:cd04161   107 ANKQDKKNALLGADVIEYLSLEKLVNENKSLCHIePCSAIEGlgkkidpsIVEGLRWLL 165

Sar1p-like members of the Ras-family of small GTPases; Yeast SAR1 is an essential gene required for transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223    1 MIPTVGFNMRKITKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVL 80
Cdd:smart00178  45 HQPTQHPTSEELAIGNIKFTTFDLGGHQQARRLWKDYFPEVNGIVYLVDAYDKERFAESKRELDALLSDEELATVPFLIL 124

                           90
                   ....*....|....*
gi 1907070223   81 GNKRDLAGALDEKEL 95
Cdd:smart00178 125 GNKIDAPYAASEDEL 139

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 1907070223   2 IPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDAADQ---EKIEASKNELHNLLDkpqlQG 74
Cdd:cd00154    30 KSTIGvdFKSKTIEVDGKKVKLqiWDTAGQERFRSITSSYYRGAHGAILVYDVTNResfENLDKWLNELKEYAP----PN 105

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907070223  75 IPVLVLGNKRDLAgalDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQ 131
Cdd:cd00154   106 IPIILVGNKSDLE---DERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESLAR 159

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 1907070223   2 IPTVG--FNMRKITKGNVTIK-----LWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKpqlqg 74
Cdd:pfam08477  29 KSTIGvdFKTKTVLENDDNGKkiklnIWDTAGQERFRSLHPFYYRGAAAALLVYDSRTFSNLKYWLRELKKYAGN----- 103

                          90
                  ....*....|.
gi 1907070223  75 IPVLVLGNKRD 85
Cdd:pfam08477 104 SPVILVGNKID 114

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. 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 1907070223   3 PTVG--FNMRKIT---KGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQL---QG 74
Cdd:cd04107    31 ATIGvdFALKVIEwdpNTVVRLQLWDIAGQERFGGMTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLDSKVTLpngEP 110

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907070223  75 IPVLVLGNKRDLAGAlDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQH 132
Cdd:cd04107   111 IPALLLANKCDLKKE-RLAKDPEQMDQFCKENGFIGWFETSAKENINIEEAMRFLVKN 167

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 1907070223   1 MIPTVGFNMRKITKGNVtIKLWDIGGQPRFRSM-WERYCRGVSAIVYMVD-AADQEKIEASKNELHNLLDKPQL--QGIP 76
Cdd:cd04105    32 IEPNVASFYSNSSKGKK-LTLVDVPGHEKLRDKlLEYLKASLKAIVFVVDsATFQKNIRDVAEFLYDILTDLEKikNKIP 110

                          90       100
                  ....*....|....*....|....*
gi 1907070223  77 VLVLGNKRDLAGALDE---KELIEK 98
Cdd:cd04105   111 ILIACNKQDLFTAKPAkkiKELLEK 135

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   2 IPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELhNLLDKPQLQGIPV 77
Cdd:cd01869    32 ISTIGvdFKIRTIELDGKTVKLqiWDTAGQERFRTITSSYYRGAHGIIIVYDVTDQESFNNVKQWL-QEIDRYASENVNK 110

                          90
                  ....*....|
gi 1907070223  78 LVLGNKRDLA 87
Cdd:cd01869   111 LLVGNKCDLT 120

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 1907070223   3 PTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSA--IVYmvDAADQEKIEASK---NELHNlldkpqlQ 73
Cdd:cd01860    32 STIGaaFLTQTVNLDDTTVKFeiWDTAGQERYRSLAPMYYRGAAAaiVVY--DITSEESFEKAKswvKELQE-------H 102

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907070223  74 GIP--VLVL-GNKRDLAG-----ALDEKELIEKMNLSAIQdreiccysISCKEKDNI 122
Cdd:cd01860   103 GPPniVIALaGNKADLESkrqvsTEEAQEYADENGLLFME--------TSAKTGENV 151

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 1907070223   2 IPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNlLDKPQLQGIPV 77
Cdd:cd01867    33 ISTIGidFKIRTIELDGKKIKLqiWDTAGQERFRTITTSYYRGAMGIILVYDITDEKSFENIKNWMRN-IDEHASEDVER 111

                          90
                  ....*....|
gi 1907070223  78 LVLGNKRDLA 87
Cdd:cd01867   112 MLVGNKCDME 121

Rab GTPase families 34 (Rab34) and 36 (Rab36); Rab34/Rab36 subfamily. Rab34, found primarily in the Golgi, interacts with its effector, Rab-interacting lysosomal protein (RILP). This enables its participation in microtubular dynenin-dynactin-mediated repositioning of lysosomes from the cell periphery to the Golgi. A Rab34 (Rah) isoform that lacks the consensus GTP-binding region has been identified in mice. This isoform is associated with membrane ruffles and promotes macropinosome formation. Rab36 has been mapped to human chromosome 22q11.2, a region that is homozygously deleted in malignant rhabdoid tumors (MRTs). However, experimental assessments do not implicate Rab36 as a tumor suppressor that would enable tumor formation through a loss-of-function mechanism. 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 1907070223   5 VGFNMRKITKGNV--TIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQLQGIPVLVLGN 82
Cdd:cd04108    35 VDFEMERFEVLGVpfSLQLWDTAGQERFKCIASTYYRGAQAIIIVFDLTDVASLEHTRQWLEDALKENDPSSVLLFLVGT 114

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907070223  83 KRDLAGAlDEKELIEKMNLSAIQDREICCYSISCKEKDNI 122
Cdd:cd04108   115 KKDLSSP-AQYALMEQDAIKLAREMKAEYWAVSALTGENV 153

Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. 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 1907070223  17 VTIKLWDIGGQPRFRSMWERYCRG--VSAIVYMVDAADQ-EKIEASKNELHNLLDKPQLQGIPVLVLGNKRDlagaLDEK 93
Cdd:cd04116    54 VTLQIWDTAGQERFRSLRTPFYRGsdCCLLTFSVDDSQSfQNLSNWKKEFIYYADVKEPESFPFVILGNKID----IPER 129

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907070223  94 ELIEKMNLSAIQDREICCYsISCKEKDNIDIT 125
Cdd:cd04116   130 QVSTEEAQAWCRDNGDYPY-FETSAKDATNVA 160

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 1907070223   3 PTVG--FNMRKITKGNVTIK--LWDIGGQPRFRSMWERYCRG-VSA-IVYmvDAADQ---EKIEASKNELHNLLDkpqlQ 73
Cdd:cd01868    34 STIGveFATRTIQIDGKTIKaqIWDTAGQERYRAITSAYYRGaVGAlLVY--DITKKstfENVERWLKELRDHAD----S 107

                          90
                  ....*....|....
gi 1907070223  74 GIPVLVLGNKRDLA 87
Cdd:cd01868   108 NIVIMLVGNKSDLR 121

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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 1907070223   2 IPTVG--FNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNL----LDKPQlq 73
Cdd:cd01865    31 VSTVGidFKVKTVYRNDKRIKLqiWDTAGQERYRTITTAYYRGAMGFILMYDITNEESFNAVQDWSTQIktysWDNAQ-- 108

                          90
                  ....*....|...
gi 1907070223  74 gipVLVLGNKRDL 86
Cdd:cd01865   109 ---VILVGNKCDM 118

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223   5 VGFNMRKITKGNVTIKL--WDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIeaskNELHNLLDKPQLQGIP---VLV 79
Cdd:PLN03108   41 VEFGARMITIDNKPIKLqiWDTAGQESFRSITRSYYRGAAGALLVYDITRRETF----NHLASWLEDARQHANAnmtIML 116

                  ....*...
gi 1907070223  80 LGNKRDLA 87
Cdd:PLN03108  117 IGNKCDLA 124

trmE is a tRNA modification GTPase; TrmE (MnmE, ThdF, MSS1) is a 3-domain protein found in bacteria and eukaryotes. It controls modification of the uridine at the wobble position (U34) of tRNAs that read codons ending with A or G in the mixed codon family boxes. TrmE contains a GTPase domain that forms a canonical Ras-like fold. It functions a molecular switch GTPase, and apparently uses a conformational change associated with GTP hydrolysis to promote the tRNA modification reaction, in which the conserved cysteine in the C-terminal domain is thought to function as a catalytic residue. In bacteria that are able to survive in extremely low pH conditions, TrmE regulates glutamate-dependent acid resistance.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907070223  44 IVYMVDAADQEKIEasknelhNLLDKPQLQGIPVLVLGNKRDLAGALDEKELIEKMNlsaiqdreicCYSISCKEKDNID 123
Cdd:cd04164    86 VLLVVDASEGLDEE-------DLEILELPAKKPVIVVLNKSDLLSDAEGISELNGKP----------IIAISAKTGEGID 148

                  ....*...
gi 1907070223 124 ITLQWLIQ 131
Cdd:cd04164   149 ELKEALLE 156