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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B           9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVF 88
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B          89 DVTAPNTFKTLDSWRDEFLIQASPrdpeNFPFVVLGNKIDFEN-RQVATKRAQAWCySKNNIPYFETSAKEAINVEQAFQ 167
Cdd:smart00175  81 DITNRESFENLENWLKELREYASP----NVVIMLVGNKSDLEEqRQVSREEAEAFA-EEHGLPFFETSAKTNTNVEEAFE 155

                   ....*....
3LAW_B         168 TIARNALKQ 176
Cdd:smart00175 156 ELAREILKR 164

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B         8 LLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLV 87
Cdd:PLN03110  12 LFKIVLIGDSGVGKSNILSRFTRNEFCLESKSTIGVEFATRTLQVEGKTVKAQIWDTAGQERYRAITSAYYRGAVGALLV 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        88 FDVTAPNTFKTLDSWRDEFliqaspRDPENFPFVVL--GNKIDFEN-RQVATKRAQAWCySKNNIPYFETSAKEAINVEQ 164
Cdd:PLN03110  92 YDITKRQTFDNVQRWLREL------RDHADSNIVIMmaGNKSDLNHlRSVAEEDGQALA-EKEGLSFLETSALEATNVEK 164

                 ....*
3LAW_B       165 AFQTI 169
Cdd:PLN03110 165 AFQTI 169

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B         10 KVIILGDSGVGKTSLMNQYV-NKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVF 88
Cdd:TIGR00231   3 KIVIVGHPNVGKSTLLNSLLgNKGSITEYYPGTTRNYVTTVIEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVF 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B         89 DVTAP--NTFKTLDSWRDEFLIQAsprdPENFPFVVLGNKIDFENR----QVATKRAQAwcyskNNIPYFETSAKEAINV 162
Cdd:TIGR00231  83 DIVILvlDVEEILEKQTKEIIHHA----DSGVPIILVGNKIDLKDAdlktHVASEFAKL-----NGEPIIPLSAETGKNI 153

                  ....*..
3LAW_B        163 EQAFQTI 169
Cdd:TIGR00231 154 DSAFKIV 160

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B           9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVF 88
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGVDFKTKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B          89 DVTAPNTFKTLDSWRDEFLIQASPrdpeNFPFVVLGNKIDFEN-RQVATKRAQAWCySKNNIPYFETSAKEAINVEQAFQ 167
Cdd:smart00175  81 DITNRESFENLENWLKELREYASP----NVVIMLVGNKSDLEEqRQVSREEAEAFA-EEHGLPFFETSAKTNTNVEEAFE 155

                   ....*....
3LAW_B         168 TIARNALKQ 176
Cdd:smart00175 156 ELAREILKR 164

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVF 88
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTIGVDFKSKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       89 DVTAPNTFKTLDSWRDEFLIQAsprdPENFPFVVLGNKIDFE-NRQVATKRAQAWCySKNNIPYFETSAKEAINVEQAFQ 167
Cdd:cd00154  81 DVTNRESFENLDKWLNELKEYA----PPNIPIILVGNKSDLEdERQVSTEEAQQFA-KENGLLFFETSAKTGENVDEAFE 155

                ....
3LAW_B      168 TIAR 171
Cdd:cd00154 156 SLAR 159

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        8 LLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLV 87
Cdd:cd01868   3 LFKIVLIGDSGVGKSNLLSRFTRNEFNLDSKSTIGVEFATRTIQIDGKTIKAQIWDTAGQERYRAITSAYYRGAVGALLV 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       88 FDVTAPNTFKTLDSWRDEFliqaspRD--PENFPFVVLGNKIDFEN-RQVATKRAQAWCySKNNIPYFETSAKEAINVEQ 164
Cdd:cd01868  83 YDITKKSTFENVERWLKEL------RDhaDSNIVIMLVGNKSDLRHlRAVPTEEAKAFA-EKNGLSFIETSALDGTNVEE 155

                ....*
3LAW_B      165 AFQTI 169
Cdd:cd01868 156 AFKQL 160

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDD-RLVTMQIWDTAGQERFQSLGVAFYRGADCCVLV 87
Cdd:cd04107   1 FKVLVIGDLGVGKTSIIKRYVHGVFSQHYKATIGVDFALKVIEWDPnTVVRLQLWDIAGQERFGGMTRVYYKGAVGAIIV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       88 FDVTAPNTFKTLDSWRDEFLIQASPRDPENFPFVVLGNKIDFENRQVATKRAQAWCYSKNN--IPYFETSAKEAINVEQA 165
Cdd:cd04107  81 FDVTRPSTFEAVLKWKADLDSKVTLPNGEPIPALLLANKCDLKKERLAKDPEQMDQFCKENgfIGWFETSAKENINIEEA 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
3LAW_B      166 FQTIARNALKQETevELYNEFPEPIKLDKNDRAKASAESCSC 207
Cdd:cd04107 161 MRFLVKNILKNDK--GLQSPEPDEDNVIDLKQETTTSKSKSC 200

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       10 KVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVFD 89
Cdd:cd01861   2 KLVFLGDQSVGKTSIITRFMYDTFDNQYQATIGIDFLSKTMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVVYD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       90 VTAPNTFKTLDSWRDEFLIQASprdpENFPFVVLGNKIDF-ENRQVATKRAQAWcYSKNNIPYFETSAKEAINVEQAFQT 168
Cdd:cd01861  82 ITNRQSFDNTDKWIDDVRDERG----NDVIIVLVGNKTDLsDKRQVSTEEGEKK-AKENNAMFIETSAKAGHNVKQLFKK 156

                ..
3LAW_B      169 IA 170
Cdd:cd01861 157 IA 158

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        8 LLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLV 87
Cdd:cd01867   3 LFKLLLIGDSGVGKSCLLLRFSEDSFNPSFISTIGIDFKIRTIELDGKKIKLQIWDTAGQERFRTITTSYYRGAMGIILV 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       88 FDVTAPNTFKTLDSWRDEFLIQASprdpENFPFVVLGNKIDFEN-RQVATKRAQAWCySKNNIPYFETSAKEAINVEQAF 166
Cdd:cd01867  83 YDITDEKSFENIKNWMRNIDEHAS----EDVERMLVGNKCDMEEkRVVSKEEGEALA-REYGIKFLETSAKANINVEEAF 157

                       170
                ....*....|
3LAW_B      167 QTIARNALKQ 176
Cdd:cd01867 158 LTLAKDILKK 167

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B         10 KVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDD---RLVTMQIWDTAGQERFQSLGVAFYRGADCCVL 86
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKSTIGVDFKTKTVLENDdngKKIKLNIWDTAGQERFRSLHPFYYRGAAAALL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
3LAW_B         87 VFDVTapnTFKTLDSWRDEfLIQASPRDpenfPFVVLGNKID 128
Cdd:pfam08477  81 VYDSR---TFSNLKYWLRE-LKKYAGNS----PVILVGNKID 114

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        8 LLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLV 87
Cdd:cd01866   4 LFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGALLV 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       88 FDVTAPNTFKTLDSWRDEFLIQASPrdpeNFPFVVLGNKIDFENRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAFQ 167
Cdd:cd01866  84 YDITRRETFNHLTSWLEDARQHSNS----NMTIMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAKTASNVEEAFI 159

                ....
3LAW_B      168 TIAR 171
Cdd:cd01866 160 NTAK 163

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        8 LLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRL----------VTMQIWDTAGQERFQSLGVAF 77
Cdd:cd04127   4 LIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYNSQGpdgtsgkafrVHLQLWDTAGQERFRSLTTAF 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       78 YRGADCCVLVFDVTAPNTFKTLDSWRDEFLIQASPRDPEnfpFVVLGNKIDFEN-RQVATKRAQAWCySKNNIPYFETSA 156
Cdd:cd04127  84 FRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAYCENPD---IVLIGNKADLPDqREVSERQARELA-DKYGIPYFETSA 159

                       170
                ....*....|...
3LAW_B      157 KEAINVEQAFQTI 169
Cdd:cd04127 160 ATGQNVEKAVETL 172

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVF 88
Cdd:cd04113   1 FKFLIIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKSVKLQIWDTAGQERFRSVTRSYYRGAAGALLVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       89 DVTAPNTFKTLDSWRDEFLIQASPrdpeNFPFVVLGNKIDF-ENRQVATKRAQAWCySKNNIPYFETSAKEAINVEQAFQ 167
Cdd:cd04113  81 DITSRESFNALTNWLTDARTLASP----DIVIILVGNKKDLeDDREVTFLEASRFA-QENGLLFLETSALTGENVEEAFL 155

                ....
3LAW_B      168 TIAR 171
Cdd:cd04113 156 KCAR 159

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        9 LKVIILGDSGVGKTSLMNQYVNKKFSN-QYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLG---VAFYRGADCC 84
Cdd:COG1100   4 KKIVVVGTGGVGKTSLVNRLVGDIFSLeKYLSTNGVTIDKKELKLDGLDVDLVIWDTPGQDEFRETRqfyARQLTGASLY 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       85 VLVFDVTAPNTFKTLDSWRdEFLIQASPrdpeNFPFVVLGNKIDF--ENRQVATKRAQAWCYSKNNIPYFETSAKEAINV 162
Cdd:COG1100  84 LFVVDGTREETLQSLYELL-ESLRRLGK----KSPIILVLNKIDLydEEEIEDEERLKEALSEDNIVEVVATSAKTGEGV 158

                       170       180
                ....*....|....*....|
3LAW_B      163 EQAFQTIARnALKQETEVEL 182
Cdd:COG1100 159 EELFAALAE-ILRGEGDSLD 177

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        8 LLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLV 87
Cdd:cd04110   6 LFKLLIIGDSGVGKSSLLLRFADNTFSGSYITTIGVDFKIRTVEINGERVKLQIWDTAGQERFRTITSTYYRGTHGVIVV 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       88 FDVTAPNTFKTLDSWRDEflIQASPRDPENfpfVVLGNKIDFENRQVA-TKRAQAWCYSkNNIPYFETSAKEAINVEQAF 166
Cdd:cd04110  86 YDVTNGESFVNVKRWLQE--IEQNCDDVCK---VLVGNKNDDPERKVVeTEDAYKFAGQ-MGISLFETSAKENINVEEMF 159

                ....*...
3LAW_B      167 QTIARNAL 174
Cdd:cd04110 160 NCITELVL 167

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDR--LVTMQIWDTAGQERFQSLGVAFYRGADCCVL 86
Cdd:cd04106   1 IKVIVVGNGNVGKSSMIQRFVKGIFTKDYKKTIGVDFLEKQIFLRQSdeDVRLMLWDTAGQEEFDAITKAYYRGAQACIL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       87 VFDVTAPNTFKTLDSWRDefliqASPRDPENFPFVVLGNKIDFENRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAF 166
Cdd:cd04106  81 VFSTTDRESFEAIESWKE-----KVEAECGDIPMVLVQTKIDLLDQAVITNEEAEALAKRLQLPLFRTSVKDDFNVTELF 155

                ....
3LAW_B      167 QTIA 170
Cdd:cd04106 156 EYLA 159

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B          10 KVIILGDSGVGKTSLMNQYVNKKFSNQYKATIgADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVFD 89
Cdd:smart00173   2 KLVVLGSGGVGKSALTIQFIQGHFVDDYDPTI-EDSYRKQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B          90 VTAPNTFKTLDSWRDEFLiqaSPRDPENFPFVVLGNKIDFEN-RQVAT----KRAQAWcysknNIPYFETSAKEAINVEQ 164
Cdd:smart00173  81 ITDRQSFEEIKKFREQIL---RVKDRDDVPIVLVGNKCDLESeRVVSTeegkELARQW-----GCPFLETSAKERVNVDE 152

                          170
                   ....*....|..
3LAW_B         165 AFQTIARNALKQ 176
Cdd:smart00173 153 AFYDLVREIRKK 164

Rab GTPase family 19 (Rab19); Rab19 subfamily. Rab19 proteins are associated with Golgi stacks. Similarity analysis indicated that Rab41 is closely related to Rab19. However, the function of these Rabs is not yet characterized. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        8 LLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLV 87
Cdd:cd01864   3 LFKIILIGDSNVGKTCVVQRFKSGTFSERQGNTIGVDFTMKTLEIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAIIA 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       88 FDVTAPNTFKTLDSWRDEFLIQASPrdpeNFPFVVLGNKIDF-ENRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAF 166
Cdd:cd01864  83 YDITRRSSFESVPHWIEEVEKYGAS----NVVLLLIGNKCDLeEQREVLFEEACTLAEHYGILAVLETSAKESSNVEEAF 158

                ....*
3LAW_B      167 QTIAR 171
Cdd:cd01864 159 LLMAT 163

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVF 88
Cdd:cd04120   1 LQVIIIGSRGVGKTSLMERFTDDTFCEACKSTVGVDFKIKTVELRGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B       89 DVTAPNTFKTLDSWRDEFLIQASprdpENFPFVVLGNKIDFE-NRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAFQ 167
Cdd:cd04120  81 DITKKETFDDLPKWMKMIDKYAS----EDAELLLVGNKLDCEtDREITRQQGEKFAQQITGMRFCEASAKDNFNVDEIFL 156

                       170       180       190
                ....*....|....*....|....*....|
3LAW_B      168 TIARNALKQETEVELYNEF--------PEP 189
Cdd:cd04120 157 KLVDDILKKMPLDILRNELsnsilslqPEP 186

R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, and related members of the Ras family. M-Ras is expressed in lympho-hematopoetic cells. It interacts with some of the known Ras effectors, but appears to also have its own effectors. Expression of mutated M-Ras leads to transformation of several types of cell lines, including hematopoietic cells, mammary epithelial cells, and fibroblasts. Overexpression of M-Ras is observed in carcinomas from breast, uterus, thyroid, stomach, colon, kidney, lung, and rectum. In addition, expression of a constitutively active M-Ras mutant in murine bone marrow induces a malignant mast cell leukemia that is distinct from the monocytic leukemia induced by H-Ras. TC21, along with H-Ras, has been shown to regulate the branching morphogenesis of ureteric bud cell branching in mice. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LAW_B        9 LKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIgADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVF 88
Cdd:cd04145   3 YKLVVVGGGGVGKSALTIQFIQSYFVTDYDPTI-EDSYTKQCEIDGQWARLDILDTAGQEEFSAMREQYMRTGEGFLLVF 81