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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012    4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPE-IPCILVANKIDDIQMTQKNF----SFAKKFSLPLYFVSAADG 78
Cdd:smart00175  68 SYYRGAVGALLVYDITNRESFENLENWLKELREYASPnVVIMLVGNKSDLEEQRQVSReeaeAFAEEHGLPFFETSAKTN 147

                   ....*..
gi 1907114012   79 TNVVKLF 85
Cdd:smart00175 148 TNVEEAF 154

GTP-binding nuclear protein Ran; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   5 YYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPEIPCILVANKID--DIQMTQKNFSFAKKFSLPLYFVSAADGTNVV 82
Cdd:PTZ00132   78 YYIKGQCAIIMFDVTSRITYKNVPNWHRDIVRVCENIPIVLVGNKVDvkDRQVKARQITFHRKKNLQYYDISAKSNYNFE 157

                  ...
gi 1907114012  83 KLF 85
Cdd:PTZ00132  158 KPF 160

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 1907114012   5 YYHKAHACIMVFD-VQRKITYKN-LGTWYAELREFRP-EIPCILVANKIDDIQMTQKN---FSFAKKFSLPLYFVSAADG 78
Cdd:TIGR00231  71 YYPQVERSLRVFDiVILVLDVEEiLEKQTKEIIHHADsGVPIILVGNKIDLKDADLKThvaSEFAKLNGEPIIPLSAETG 150

                  ....*...
gi 1907114012  79 TNVVKLFN 86
Cdd:TIGR00231 151 KNIDSAFK 158

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 1907114012   1 MHASYYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPE-IPCILVANKIDDIQMTQKNF----SFAKKFSLPLYFVSA 75
Cdd:cd00154    65 ITSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPPnIPIILVGNKSDLEDERQVSTeeaqQFAKENGLLFFETSA 144

                          90
                  ....*....|....*
gi 1907114012  76 ADGTNVVKLFNDAIR 90
Cdd:cd00154   145 KTGENVDEAFESLAR 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907114012   1 MHASYYHKAHACIMVFDVQrkiTYKNLGTWYAELREFRPEIPCILVANKID 51
Cdd:pfam08477  67 LHPFYYRGAAAALLVYDSR---TFSNLKYWLRELKKYAGNSPVILVGNKID 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 1907114012   4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPE-IPCILVANKID--DIQM--TQKNFSFAKKFSLPLYFVSAADG 78
Cdd:pfam00071  67 LYYRGADGFLLVYDITSRDSFENVKKWVEEILRHADEnVPIVLVGNKCDleDQRVvsTEEGEALAKELGLPFMETSAKTN 146

                          90
                  ....*....|....
gi 1907114012  79 TNVVKLFNDAIRLA 92
Cdd:pfam00071 147 ENVEEAFEELAREI 160

GTP-binding nuclear protein Ran; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   5 YYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPEIPCILVANKID--DIQMTQKNFSFAKKFSLPLYFVSAADGTNVV 82
Cdd:PLN03071   82 YYIHGQCAIIMFDVTARLTYKNVPTWHRDLCRVCENIPIVLCGNKVDvkNRQVKAKQVTFHRKKNLQYYEISAKSNYNFE 161

                  ...
gi 1907114012  83 KLF 85
Cdd:PLN03071  162 KPF 164

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 1907114012   4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREF-RPEIPCILVANKIDDIQM----TQKNFSFAKKFSLPLYFVSAADG 78
Cdd:cd01868    71 AYYRGAVGALLVYDITKKSTFENVERWLKELRDHaDSNIVIMLVGNKSDLRHLravpTEEAKAFAEKNGLSFIETSALDG 150

                  ....*...
gi 1907114012  79 TNVVKLFN 86
Cdd:cd01868   151 TNVEEAFK 158

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. 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 1907114012   3 ASYYHKAHACIMVFDVQRKITYKNLGTWyaeLREFR-------PE-IPCILVANKIDDIQMTQKNFSFAK-----KFSLP 69
Cdd:cd01862    67 VAFYRGADCCVLVYDVTNPKSFESLDSW---RDEFLiqasprdPEnFPFVVLGNKIDLEEKRQVSTKKAQqwcksKGNIP 143

                          90       100
                  ....*....|....*....|....*....
gi 1907114012  70 LYFVSAADGTNVVKLFNDAIRLAVAYKES 98
Cdd:cd01862   144 YFETSAKEAINVDQAFETIARLALEQEKE 172

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   5 YYHKAHACIMVFDVQRKITYKNLGTWYAELREfRPEIPCILVANKID-----DIQMTQKNFSFAKKFSLPLYFVSAADGT 79
Cdd:cd00882    72 LLRGADLILLVVDSTDRESEEDAKLLILRRLR-KEGIPIILVGNKIDlleerEVEELLRLEELAKILGVPVFEVSAKTGE 150

                          90
                  ....*....|.
gi 1907114012  80 NVVKLFNDAIR 90
Cdd:cd00882   151 GVDELFEKLIE 161

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 1907114012   5 YYHKAHACIMVFDVQRKITYKNLGTWYAEL--REFRPE---IPCILVANKIDDIQMTQKNFS-----FAKKFSLPLYFV- 73
Cdd:cd04107    70 YYKGAVGAIIVFDVTRPSTFEAVLKWKADLdsKVTLPNgepIPALLLANKCDLKKERLAKDPeqmdqFCKENGFIGWFEt 149

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907114012  74 SAADGTNVvklfNDAIRLAVaykessqDFMDEVLQELENFKLEQKEEDTSGQEQSdTTKSPS 135
Cdd:cd04107   150 SAKENINI----EEAMRFLV-------KNILKNDKGLQSPEPDEDNVIDLKQETT-TSKSKS 199

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. 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 1907114012   1 MHASYYHKAHACIMVFDVQRKITYKNLGTWYAELR------EFRPEIpcILVANKIDDIQMTQ----KNFSFAKKFSLPL 70
Cdd:cd04109    66 MLDKYIYGAQAVCLVYDITNSQSFENLEDWLSVVKkvneesETKPKM--VLVGNKTDLEHNRQvtaeKHARFAQENDMES 143

                          90
                  ....*....|....*
gi 1907114012  71 YFVSAADGTNVVKLF 85
Cdd:cd04109   144 IFVSAKTGDRVFLCF 158

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREFR-PEIPCILVANKIDDIQMTQKNF----SFAKKFSLPLYFVSAADG 78
Cdd:cd01861    68 SYIRDSSVAVVVYDITNRQSFDNTDKWIDDVRDERgNDVIIVLVGNKTDLSDKRQVSTeegeKKAKENNAMFIETSAKAG 147

                  ....*...
gi 1907114012  79 TNVVKLFN 86
Cdd:cd01861   148 HNVKQLFK 155

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 1907114012   4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPEIPC-ILVANKIDDIQMTQKNFSFAKKFS----LPLYFVSAADG 78
Cdd:cd01869    70 SYYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYASENVNkLLVGNKCDLTDKKVVDYTEAKEFAdelgIPFLETSAKNA 149

                          90       100
                  ....*....|....*....|
gi 1907114012  79 TNVVKLFndaIRLAVAYKES 98
Cdd:cd01869   150 TNVEEAF---MTMAREIKKR 166

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. 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 1907114012   1 MHASYYHKAHACIMVFDVQRKITYKNLGTWYAELRE--FRPEIPCILVANKID---DIQM-TQKNFSFAKKFSLPLYFVS 74
Cdd:cd04115    68 MVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQhsLPNEVPRILVGNKCDlreQIQVpTDLAQRFADAHSMPLFETS 147

                          90       100
                  ....*....|....*....|....*...
gi 1907114012  75 AADGT---NVVKLFndairLAVAYKESS 99
Cdd:cd04115   148 AKDPSendHVEAIF-----MTLAHKLKS 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 1907114012    6 YHKAHACIMVFDVQRKITYKNLGT-WYAELREFRPEIPCILVANKID---DIQM-------------TQKNFSFAKKFSL 68
Cdd:smart00174  67 YPDTDVFLICFSVDSPASFENVKEkWYPEVKHFCPNVPIILVGTKLDlrnDKSTleelskkkqepvtYEQGQALAKRIGA 146

                           90       100
                   ....*....|....*....|....*.
gi 1907114012   69 PLYF-VSAADGTNVVKLFNDAIRLAV 93
Cdd:smart00174 147 VKYLeCSALTQEGVREVFEEAIRAAL 172

Septum-promoting GTPase (Spg1); Spg1p. Spg1p (septum-promoting GTPase) was first identified in the fission yeast S. pombe, where it regulates septum formation in the septation initiation network (SIN) through the cdc7 protein kinase. Spg1p is an essential gene that localizes to the spindle pole bodies. When GTP-bound, it binds cdc7 and causes it to translocate to spindle poles. Sid4p (septation initiation defective) is required for localization of Spg1p to the spindle pole body, and the ability of Spg1p to promote septum formation from any point in the cell cycle depends on Sid4p. Spg1p is negatively regulated by Byr4 and cdc16, which form a two-component GTPase activating protein (GAP) for Spg1p. The existence of a SIN-related pathway in plants has been proposed. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   9 AHACIMVFDVQRKITYKNLGTWYAELREFRPEIPCILVANKIDD---------IQMTQKNFSFAKKFSLPLYFVSAADGT 79
Cdd:cd04128    73 AVAILFMFDLTRKSTLNSIKEWYRQARGFNKTAIPILVGTKYDLfadlppeeqEEITKQARKYAKAMKAPLIFCSTSHSI 152

                  ....*.
gi 1907114012  80 NVVKLF 85
Cdd:cd04128   153 NVQKIF 158

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. 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 1907114012   4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREF-RPEIPCILVANKID---DIQMTQKNFS-FAKKFSLPLYFVSAADG 78
Cdd:cd04113    68 SYYRGAAGALLVYDITSRESFNALTNWLTDARTLaSPDIVIILVGNKKDledDREVTFLEASrFAQENGLLFLETSALTG 147

                          90
                  ....*....|..
gi 1907114012  79 TNVVKLFNDAIR 90
Cdd:cd04113   148 ENVEEAFLKCAR 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 1907114012   3 ASYYHKAHACIMVFDVQRKITYKNLGTWYAELREF-RPEIPCILVANKIDDIQ----MTQKNFSFAKKFSLPLYFVSAAD 77
Cdd:cd01867    70 TSYYRGAMGIILVYDITDEKSFENIKNWMRNIDEHaSEDVERMLVGNKCDMEEkrvvSKEEGEALAREYGIKFLETSAKA 149

                  ....*...
gi 1907114012  78 GTNVVKLF 85
Cdd:cd01867   150 NINVEEAF 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 1907114012   2 HAsYYHKAHACIMVFDVQRKITYKNLGTWYAELREF-RPEIPCILVANKIDD----IQMTQKNFSFAKKFSLPLYFVSAA 76
Cdd:cd04112    68 HA-YYRDAHALLLLYDVTNKSSFDNIRAWLTEILEYaQSDVVIMLLGNKADMsgerVVKREDGERLAKEYGVPFMETSAK 146

                  ....*
gi 1907114012  77 DGTNV 81
Cdd:cd04112   147 TGLNV 151

Ras homology family 4 (Rho4) of small guanosine triphosphatases (GTPases)-like; Rho4 is a GTPase that controls septum degradation by regulating secretion of Eng1 or Agn1 during cytokinesis. Rho4 also plays a role in cell morphogenesis. Rho4 regulates septation and cell morphology by controlling the actin cytoskeleton and cytoplasmic microtubules. The localization of Rho4 is modulated by Rdi1, which may function as a GDI, and by Rga9, which is believed to function as a GAP. In S. pombe, both Rho4 deletion and Rho4 overexpression result in a defective cell wall, suggesting a role for Rho4 in maintaining cell wall integrity. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   6 YHKAHACIMVFDVQRKITYKN-LGTWYAELREFRPEIPCILVANKIDdiqMTQKNFSFAKKFSLPLYFVSAADGTNVVKL 84
Cdd:cd04132    73 YPDVDVILICYSVDNPTSLDNvEDKWYPEVNHFCPGTPIVLVGLKTD---LRKDKNSVSKLRAQGLEPVTPEQGESVAKS 149

                          90       100
                  ....*....|....*....|..
gi 1907114012  85 FNdairlAVAYKESSQDFMDEV 106
Cdd:cd04132   150 IG-----AVAYIECSAKLMENV 166

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREF-RPEIPCILVANKIDDIQ----MTQKNFSFAKKFSLPLYFVSAADG 78
Cdd:PLN03108   74 SYYRGAAGALLVYDITRRETFNHLASWLEDARQHaNANMTIMLIGNKCDLAHrravSTEEGEQFAKEHGLIFMEASAKTA 153

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1907114012  79 TNVVKLFndaIRLAVAYKESSQDFMDEVLQELENFKL 115
Cdd:PLN03108  154 QNVEEAF---IKTAAKIYKKIQDGVFDVSNESYGIKV 187

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   5 YYHKAHACIMVFDVQRKITYKNLGTWYAELREF------RPEIPCILVANKIDDIQM------TQKNFSFAKKFslpLYF 72
Cdd:cd04119    69 FYKDTQGVLLVYDVTDRQSFEALDSWLKEMKQEggphgnMENIVVVVCANKIDLTKHravsedEGRLWAESKGF---KYF 145

                          90
                  ....*....|....*.
gi 1907114012  73 -VSAADGTNVVKLFND 87
Cdd:cd04119   146 eTSACTGEGVNEMFQT 161

Double Era-like domain GTPase Der [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   8 KAHACIMVFDVQRKITY--KNLGtWYAeLREFRPeipCILVANK---IDDIQMTQKNF--SFAKKFS----LPLYFVSAA 76
Cdd:COG1160   257 RADVVLLVIDATEGITEqdLKIA-GLA-LEAGKA---LVIVVNKwdlVEKDRKTREELekEIRRRLPfldyAPIVFISAL 331

                          90       100
                  ....*....|....*....|....
gi 1907114012  77 DGTNVVKLFNDAIRlavAYKESSQ 100
Cdd:COG1160   332 TGQGVDKLLEAVDE---VYESANK 352

Rab GTPase family 12 (Rab12); Rab12 was first identified in canine cells, where it was localized to the Golgi complex. The specific function of Rab12 remains unknown, and inconsistent results about its cellular localization have been reported. More recent studies have identified Rab12 associated with post-Golgi vesicles, or with other small vesicle-like structures but not with the Golgi complex. 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. 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 1907114012   3 ASYYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPE-IPCILVANKID---DIQMT-QKNFSFAKKFS-LPLYFVSAA 76
Cdd:cd04120    67 SAYYRSAKGIILVYDITKKETFDDLPKWMKMIDKYASEdAELLLVGNKLDcetDREITrQQGEKFAQQITgMRFCEASAK 146

                  ....*....
gi 1907114012  77 DGTNVVKLF 85
Cdd:cd04120   147 DNFNVDEIF 155

Rab GTPase family 15 (Rab15); Rab15 colocalizes with the transferrin receptor in early endosome compartments, but not with late endosomal markers. It codistributes with Rab4 and Rab5 on early/sorting endosomes, and with Rab11 on pericentriolar recycling endosomes. It is believed to function as an inhibitory GTPase that regulates distinct steps in early endocytic trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   5 YYHKAHACIMVFDVQRKITYKNLGTWYAELREFRPE-IPCILVANKIDDIQMTQ----KNFSFAKKFSLPLYFVSAADGT 79
Cdd:cd04117    69 YYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEgVQKILIGNKADEEQKRQvgdeQGNKLAKEYGMDFFETSACTNK 148

                  ....*.
gi 1907114012  80 NVVKLF 85
Cdd:cd04117   149 NIKESF 154

Rab GTPase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   3 ASYYHKAHACIMVFDVQRKITYKNLGTWYAELREFR-PEIPCILVANKIDDIQM----TQKNFSFAKKFSLPLYFVSAAD 77
Cdd:PLN03110   79 SAYYRGAVGALLVYDITKRQTFDNVQRWLRELRDHAdSNIVIMMAGNKSDLNHLrsvaEEDGQALAEKEGLSFLETSALE 158

                  ....*...
gi 1907114012  78 GTNVVKLF 85
Cdd:PLN03110  159 ATNVEKAF 166

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 1907114012   5 YYHKAHACIMVFDVQRKITYKNLGTW------YAELREfrPE-IPCILVANKIDdiqMTQKNFSF-------AKKFSLPL 70
Cdd:cd04116    74 FYRGSDCCLLTFSVDDSQSFQNLSNWkkefiyYADVKE--PEsFPFVILGNKID---IPERQVSTeeaqawcRDNGDYPY 148

                          90       100
                  ....*....|....*....|
gi 1907114012  71 YFVSAADGTNVVKLFNDAIR 90
Cdd:cd04116   149 FETSAKDATNVAAAFEEAVR 168

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. 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 1907114012   3 ASYYHKAHACIMVFDVQRKITYKNLGTWYAELRE-FRPEIPC-ILVANKIDDIQMTQKNFSFAKKFS--LPLYFV--SAA 76
Cdd:cd04111    70 RSYYRNSVGVLLVFDITNRESFEHVHDWLEEARShIQPHRPVfILVGHKCDLESQRQVTREEAEKLAkdLGMKYIetSAR 149

                  ....*....
gi 1907114012  77 DGTNVVKLF 85
Cdd:cd04111   150 TGDNVEEAF 158

EngA2 GTPase contains the second domain of EngA; This EngA2 subfamily CD represents the second GTPase domain of EngA and its orthologs, which are composed of two adjacent GTPase domains. Since the sequences of the two domains are more similar to each other than to other GTPases, it is likely that an ancient gene duplication, rather than a fusion of evolutionarily distinct GTPases, gave rise to this family. Although the exact function of these proteins has not been elucidated, studies have revealed that the E. coli EngA homolog, Der, and Neisseria gonorrhoeae EngA are essential for cell viability. A recent report suggests that E. coli Der functions in ribosome assembly and stability.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907114012   8 KAHACIMVFDVQRKITY--KNLGTwYAeLREFRPeipCILVANK---IDDIQMTQKNF-----------SFAkkfslPLY 71
Cdd:cd01895    84 RADVVLLVLDASEGITEqdLRIAG-LI-LEEGKA---LIIVVNKwdlVEKDEKTMKEFekelrrklpflDYA-----PIV 153

                          90       100
                  ....*....|....*....|
gi 1907114012  72 FVSAADGTNVVKLFNDAIRL 91
Cdd:cd01895   154 FISALTGQGVDKLFDAIKEV 173

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. 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 1907114012   4 SYYHKAHACIMVFDVQRKITYKNLGTWYAELREF----RPEIpcILVANKIDDIQMTQKNFS----FAKKFSLPLYFVSA 75
Cdd:cd04127    82 AFFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHayceNPDI--VLIGNKADLPDQREVSERqareLADKYGIPYFETSA 159

                  ....*...
gi 1907114012  76 ADGTNVVK 83
Cdd:cd04127   160 ATGQNVEK 167