Rab GTPase-like family 3 (Rab-like3); RabL3 (Rab-like3) subfamily. RabL3s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL3 lacks a prenylation site at the C-terminus. The specific function of RabL3 remains unknown.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYREGTPEEKAFYIELWDVGGSVGSASSVKSTRAVFYN 86
Cdd:cd04102   1 VKVLVLGDSGVGKSSLVHLLCKNQVLGNPSWTVGCSVDVRHHTYGEGTPEEKTFYVELWDVGGSVGSAESVKSTRAVFYN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487  87 SVNGIILVHDLTNKKSSQNLYRWSLEALSKDSSPTGIIVSNGDYDREQFAENAVPLLLIGTKFDQIPENKRNDVLTRTAF 166
Cdd:cd04102  81 QINGIIFVHDLTNKKSSQNLYRWSLEALNRDTFPAGLLVTNGDYDSEQFAGNPVPLLVIGTKLDQIPEAKRNWVLTRTAF 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 82187487 167 LSEDFNAEEINLDCTNPRYLAAGSSNAVKLSRFFDKVIEKRYFT 210
Cdd:cd04102 161 LSEDFNAEEINLDCTNGRLLAAGSSNAVKLSRFFDKVIEKRYFS 204

Rab GTPase-like family 3 (Rab-like3); RabL3 (Rab-like3) subfamily. RabL3s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL3 lacks a prenylation site at the C-terminus. The specific function of RabL3 remains unknown.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYREGTPEEKAFYIELWDVGGSVGSASSVKSTRAVFYN 86
Cdd:cd04102   1 VKVLVLGDSGVGKSSLVHLLCKNQVLGNPSWTVGCSVDVRHHTYGEGTPEEKTFYVELWDVGGSVGSAESVKSTRAVFYN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487  87 SVNGIILVHDLTNKKSSQNLYRWSLEALSKDSSPTGIIVSNGDYDREQFAENAVPLLLIGTKFDQIPENKRNDVLTRTAF 166
Cdd:cd04102  81 QINGIIFVHDLTNKKSSQNLYRWSLEALNRDTFPAGLLVTNGDYDSEQFAGNPVPLLVIGTKLDQIPEAKRNWVLTRTAF 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 82187487 167 LSEDFNAEEINLDCTNPRYLAAGSSNAVKLSRFFDKVIEKRYFT 210
Cdd:cd04102 161 LSEDFNAEEINLDCTNGRLLAAGSSNAVKLSRFFDKVIEKRYFS 204

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487      7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGcsVDVRVhdyREGTPEEKAFYIELWDVGG-----SVGSAssvkstr 81
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIG--VDFKT---KTIEVDGKRVKLQIWDTAGqerfrSITSS------- 68

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 82187487     82 avFYNSVNGIILVHDLTNKKSSQNLYRWSLEAlskdssptgiivsngdydrEQFAENAVPLLLIGTKFDQipENKR 157
Cdd:smart00175  69 --YYRGAVGALLVYDITNRESFENLENWLKEL-------------------REYASPNVVIMLVGNKSDL--EEQR 121

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487   6 RVKVLVLGDSGVGKSSLVHLLCQNQV-----LGnpswTVGcsVDVRVHDYregTPEEKAFYIELWDVGGSVGsassVKST 80
Cdd:COG1100   3 EKKIVVVGTGGVGKTSLVNRLVGDIFslekyLS----TNG--VTIDKKEL---KLDGLDVDLVIWDTPGQDE----FRET 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487  81 RAVFYNSVNG---IILVHDLTNKKSSQNLYRW--SLEALSKDSsptgiivsngdydreqfaenavPLLLIGTKFDQIPEN 155
Cdd:COG1100  70 RQFYARQLTGaslYLFVVDGTREETLQSLYELleSLRRLGKKS----------------------PIILVLNKIDLYDEE 127

                       170
                ....*....|....*
gi 82187487 156 KRNDVLTRTAFLSED 170
Cdd:COG1100 128 EIEDEERLKEALSED 142

Rab GTPase-like family 3 (Rab-like3); RabL3 (Rab-like3) subfamily. RabL3s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL3 lacks a prenylation site at the C-terminus. The specific function of RabL3 remains unknown.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYREGTPEEKAFYIELWDVGGSVGSASSVKSTRAVFYN 86
Cdd:cd04102   1 VKVLVLGDSGVGKSSLVHLLCKNQVLGNPSWTVGCSVDVRHHTYGEGTPEEKTFYVELWDVGGSVGSAESVKSTRAVFYN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487  87 SVNGIILVHDLTNKKSSQNLYRWSLEALSKDSSPTGIIVSNGDYDREQFAENAVPLLLIGTKFDQIPENKRNDVLTRTAF 166
Cdd:cd04102  81 QINGIIFVHDLTNKKSSQNLYRWSLEALNRDTFPAGLLVTNGDYDSEQFAGNPVPLLVIGTKLDQIPEAKRNWVLTRTAF 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 82187487 167 LSEDFNAEEINLDCTNPRYLAAGSSNAVKLSRFFDKVIEKRYFT 210
Cdd:cd04102 161 LSEDFNAEEINLDCTNGRLLAAGSSNAVKLSRFFDKVIEKRYFS 204

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 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYregtpEEKAFYIELWDVGGSvgsaSSVKSTRAVFYN 86
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSKTIEV-----DGKKVKLQIWDTAGQ----ERFRSITSSYYR 71

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 82187487  87 SVNGIILVHDLTNKKSSQNLYRWSLEAlskdssptgiivsngdydrEQFAENAVPLLLIGTKFDQIPE 154
Cdd:cd00154  72 GAHGAILVYDVTNRESFENLDKWLNEL-------------------KEYAPPNIPIILVGNKSDLEDE 120

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 82187487     8 KVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGcsVDVRVHDYREGTPEEKAFYIELWDVGGsvgsASSVKSTRAVFYNS 87
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKSTIG--VDFKTKTVLENDDNGKKIKLNIWDTAG----QERFRSLHPFYYRG 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 82187487    88 VNGIILVHDltnKKSSQNLYRWSLEAlskdssptgiivsngdydrEQFAENAvPLLLIGTKFD 150
Cdd:pfam08477  75 AAAALLVYD---SRTFSNLKYWLREL-------------------KKYAGNS-PVILVGNKID 114

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 82187487   8 KVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCsvdvrvhDYREGTPE---EKaFYIELWDvggSVGSASSVKSTRAVF 84
Cdd:cd04115   4 KIIVIGDSNVGKTCLTYRFCAGRFPERTEATIGV-------DFRERTVEidgER-IKVQLWD---TAGQERFRKSMVQHY 72

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 82187487  85 YNSVNGIILVHDLTNKKSSQNLYRWsLEALSKDSSPtgiivsngdydreqfaeNAVPLLLIGTKFD-----QIPEN 155
Cdd:cd04115  73 YRNVHAVVFVYDVTNMASFHSLPSW-IEECEQHSLP-----------------NEVPRILVGNKCDlreqiQVPTD 130

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 82187487     8 KVLVLGDSGVGKSSLVHLLCQNQVlgNPSW--TVGC---SVDVRVHDyregtpeeKAFYIELWDVGGSvgsaSSVKSTRA 82
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKF--PEEYipTIGVdfyTKTIEVDG--------KTVKLQIWDTAGQ----ERFRALRP 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487    83 VFYNSVNGIILVHDLTNKKSSQNLYRWSLEALskdssptgiivsngdydreQFAENAVPLLLIGTKFDQipENKRnDVLT 162
Cdd:pfam00071  67 LYYRGADGFLLVYDITSRDSFENVKKWVEEIL-------------------RHADENVPIVLVGNKCDL--EDQR-VVST 124

                         170
                  ....*....|....*.
gi 82187487   163 RTAflsEDFnAEEINL 178
Cdd:pfam00071 125 EEG---EAL-AKELGL 136

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 82187487   8 KVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYREGtpeeKAFYIELWDVGGSvgsaSSVKS-TRAVFYN 86
Cdd:cd04111   4 RLIVIGDSTVGKSSLLKRFTEGRFAEVSDPTVGVDFFSRLIEIEPG----VRIKLQLWDTAGQ----ERFRSiTRSYYRN 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 82187487  87 SVnGIILVHDLTNKKSSQNLYRWSLEALS--KDSSPTGIIV 125
Cdd:cd04111  76 SV-GVLLVFDITNRESFEHVHDWLEEARShiQPHRPVFILV 115

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 82187487   8 KVLVLGDSGVGKSSLVHLLCQNQVlgNPSW--TVGCSVDVRVHDYregtpEEKAFYIELWDVGGSvgsaSSVKSTRAVFY 85
Cdd:cd01867   5 KLLLIGDSGVGKSCLLLRFSEDSF--NPSFisTIGIDFKIRTIEL-----DGKKIKLQIWDTAGQ----ERFRTITTSYY 73

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 82187487  86 NSVNGIILVHDLTNKKSSQNLYRWSLEAlskdssptgiivsngdydrEQFAENAVPLLLIGTKFDQipENKR 157
Cdd:cd01867  74 RGAMGIILVYDITDEKSFENIKNWMRNI-------------------DEHASEDVERMLVGNKCDM--EEKR 124

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 82187487   6 RVKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGC---SVDVRVHDyregtpeeKAFYIELWDVGGSvgsaSSVKSTRA 82
Cdd:cd01860   1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQESTIGAaflTQTVNLDD--------TTVKFEIWDTAGQ----ERYRSLAP 68

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 82187487  83 VFYNSVNGIILVHDLTNKKSSQNLYRWsLEALSKDSSPTGIIV 125
Cdd:cd01860  69 MYYRGAAAAIVVYDITSEESFEKAKSW-VKELQEHGPPNIVIA 110

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 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVlgNPSWTVGCSVDVRVHD--YREGTPEEKA-----FYIELWDVGGSvgsaSSVKS 79
Cdd:cd04127   5 IKLLALGDSGVGKTTFLYRYTDNKF--NPKFITTVGIDFREKRvvYNSQGPDGTSgkafrVHLQLWDTAGQ----ERFRS 78

                        90       100       110
                ....*....|....*....|....*....|
gi 82187487  80 TRAVFYNSVNGIILVHDLTNKKSSQNLYRW 109
Cdd:cd04127  79 LTTAFFRDAMGFLLMFDLTSEQSFLNVRNW 108

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 82187487   8 KVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCsvdvrvhDYREGTPEEKAF--YIELWDVGGSVGSASSVKStravFY 85
Cdd:cd04117   2 RLLLIGDSGVGKTCLLCRFTDNEFHSSHISTIGV-------DFKMKTIEVDGIkvRIQIWDTAGQERYQTITKQ----YY 70

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 82187487  86 NSVNGIILVHDLTNKKSSQNLYRWslealskdssptgiiVSngdyDREQFAENAVPLLLIGTKFDqiPENKR 157
Cdd:cd04117  71 RRAQGIFLVYDISSERSYQHIMKW---------------VS----DVDEYAPEGVQKILIGNKAD--EEQKR 121

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 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRvhdyREGTPEEKAFYIELWDVGG-SVGSASSVKstravFY 85
Cdd:cd04109   1 IKIVVLGDGASGKTSLIRRFAQEGFGKSYKQTIGLDFFSR----RITLPGSLNVTLQVWDIGGqQIGGKMLDK-----YI 71

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 82187487  86 NSVNGIILVHDLTNKKSSQNLYRW--SLEALSKDSsptgiivsngdydreqfaENAVPLLLIGTKFDqIPENK 156
Cdd:cd04109  72 YGAQAVCLVYDITNSQSFENLEDWlsVVKKVNEES------------------ETKPKMVLVGNKTD-LEHNR 125

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487   6 RVKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGcsvdVRVHDYREGTPEEKAFYIELWDVGGS---VGSASSVKSTRA 82
Cdd:cd09914   1 EAKLMLVGQGGVGKTSLCKQLIGEKFDGDESSTHG----INVQDWKIPAPERKKIRLNVWDFGGQeiyHATHQFFLTSRS 76

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 82187487  83 VFynsvngiILVHDLTNKKSSQNLYRW--SLEALSKDSsptgiivsngdydreqfaenavPLLLIGTKFDQIPENK 156
Cdd:cd09914  77 LY-------LLVFDLRTGDEVSRVPYWlrQIKAFGGVS----------------------PVILVGTHIDESCDED 123

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 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGcsVDVRVhdyREGTPEEKAFYIELWDVGGSvgsaSSVKSTRAVFYN 86
Cdd:cd04119   1 IKVISMGNSGVGKSCIIKRYCEGRFVSKYLPTIG--IDYGV---KKVSVRNKEVRVNFFDLSGH----PEYLEVRNEFYK 71

                        90       100
                ....*....|....*....|....*..
gi 82187487  87 SVNGIILVHDLTNKKSSQNLYRWSLEA 113
Cdd:cd04119  72 DTQGVLLVYDVTDRQSFEALDSWLKEM 98

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487    8 KVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYregtpEEKAFYIELWDVGGSvgsaSSVKSTRAVFYNS 87
Cdd:PLN03110  14 KIVLIGDSGVGKSNILSRFTRNEFCLESKSTIGVEFATRTLQV-----EGKTVKAQIWDTAGQ----ERYRAITSAYYRG 84

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 82187487   88 VNGIILVHDLTNKKSSQNLYRWSLEAlsKDSSPTGIIV 125
Cdd:PLN03110  85 AVGALLVYDITKRQTFDNVQRWLREL--RDHADSNIVI 120

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of phagocytosis. 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 82187487   8 KVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYregtpEEKAFYIELWDVGGSvgsassvKSTRAV---F 84
Cdd:cd04122   4 KYIIIGDMGVGKSCLLHQFTEKKFMADCPHTIGVEFGTRIIEV-----NGQKIKLQIWDTAGQ-------ERFRAVtrsY 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 82187487  85 YNSVNGIILVHDLTNKKSSQNLYRWSLEALSKDSSPTGIIVSNGDYDRE 133
Cdd:cd04122  72 YRGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPNTVIFLIGNKADLE 120

Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab proteins identified recently which display features that are distinct from other Rabs, and have been termed Rab-like. RabL2 contains RabL2a and RabL2b, two very similar Rab proteins that share > 98% sequence identity in humans. RabL2b maps to the subtelomeric region of chromosome 22q13.3 and RabL2a maps to 2q13, a region that suggests it is also a subtelomeric gene. Both genes are believed to be expressed ubiquitously, suggesting that RabL2s are the first example of duplicated genes in human proximal subtelomeric regions that are both expressed actively. Like other Rab-like proteins, RabL2s lack a prenylation site at the C-terminus. The specific functions of RabL2a and RabL2b remain unknown. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487   7 VKVLVLGDSGVGKSSLVH-LLCQNQVlgnPSWTVGCSVDVRVHDYregTPEEKAFYIELWDVGGSvgsaSSVKSTRAVFY 85
Cdd:cd04124   1 VKIILLGDSAVGKSKLVErFLMDGYE---PQQLSTYALTLYKHNA---KFEGKTILVDFWDTAGQ----ERFQTMHASYY 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487  86 NSVNGIILVHDLTNKKSSQNLYRWSLEAlsKDSSPTgiivsngdydreqfaenaVPLLLIGTKFDQIPEnkrndvLTRTA 165
Cdd:cd04124  71 HKAHACILVFDVTRKITYKNLSKWYEEL--REYRPE------------------IPCIVVANKIDLDPS------VTQKK 124

                       170       180       190
                ....*....|....*....|....*....|...
gi 82187487 166 FlseDFnAEEINLdctnPRYL--AAGSSNAVKL 196
Cdd:cd04124 125 F---NF-AEKHNL----PLYYvsAADGTNVVKL 149

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 82187487   8 KVLVLGDSGVGKSS-LVHLLCQNQVLGNPSWTVGCSVDVRVHdyregTPEEKAFYIELWDVGGSvgsaSSVKSTRAVFYN 86
Cdd:cd04112   2 KVMLVGDSGVGKTClLVRFKDGAFLAGSFIATVGIQFTNKVV-----TVDGVKVKLQIWDTAGQ----ERFRSVTHAYYR 72

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 82187487  87 SVNGIILVHDLTNKKSSQNLYRWSLEALSKDSSPTGIIV 125
Cdd:cd04112  73 DAHALLLLYDVTNKSSFDNIRAWLTEILEYAQSDVVIML 111

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82187487   8 KVLVLGDSGVGKSSLVHLLCQNQVlGNPSWTVGCSV-DVRVHDYRegtpeekafyIELWDVGGSvgsassvKSTRAV--- 83
Cdd:cd00878   1 RILMLGLDGAGKTTILYKLKLGEV-VTTIPTIGFNVeTVEYKNVK----------FTVWDVGGQ-------DKIRPLwkh 62

                        90
                ....*....|....*..
gi 82187487  84 FYNSVNGIILVHDLTNK 100
Cdd:cd00878  63 YYENTDGLIFVVDSSDR 79

Rab GTPase family 2 (Rab2); Rab2 is localized on cis-Golgi membranes and interacts with Golgi matrix proteins. Rab2 is also implicated in the maturation of vesicular tubular clusters (VTCs), which are microtubule-associated intermediates in transport between the ER and Golgi apparatus. In plants, Rab2 regulates vesicle trafficking between the ER and the Golgi bodies and is important to pollen tube growth. 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 82187487   8 KVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHdyregTPEEKAFYIELWDVGGSvgsaSSVKSTRAVFYNS 87
Cdd:cd01866   6 KYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMI-----TIDGKQIKLQIWDTAGQ----ESFRSITRSYYRG 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 82187487  88 VNGIILVHDLTNKKSSQNLYRWSLEALSKDSSPTGIIVSNGDYDRE 133
Cdd:cd01866  77 AAGALLVYDITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDLE 122

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 82187487   7 VKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTV--GCSVDVRVhdyregtpEEKAFYIELWDVGGSvgsaSSVKSTRAVF 84
Cdd:cd00157   1 IKIVVVGDGAVGKTCLLISYTTNKFPTEYVPTVfdNYSANVTV--------DGKQVNLGLWDTAGQ----EEYDRLRPLS 68

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 82187487  85 YNSVNGIILVHDLTNKKSSQNLYR-WSLEalskdssptgIIvsngdydreQFAENaVPLLLIGTKFDQIPENKRNDVL 161
Cdd:cd00157  69 YPQTDVFLLCFSVDSPSSFENVKTkWYPE----------IK---------HYCPN-VPIILVGTKIDLRDDGNTLKKL 126