1N6H,1TU3,2EFC,2FG5,1Z0J,1EK0,3CLV


Conserved Protein Domain Family
Rab5_related

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cd01860: Rab5_related 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 206653
Aligned: 52 rows
Threshold Bit Score: 240.531
Created: 6-Jan-2012
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 18 residues -Click on image for an interactive view with Cn3D
Feature 1:GTP/Mg2+ binding site [chemical binding site]
Evidence:
  • Comment:The active conformation of Rab is stabilized by interations between the gamma phosphate of GTP and two critically conserved residues, Thr in switch I and Gly in switch II
  • Structure:1N6H: Human Rab5a binds GppNHp, a GTP analog and Mg2+, defined using 3.5 A contacts
  • Comment:the Thr residue coordinates Mg2+

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                 #######         ##    ##                          #                    
1N6H_A         6 QFKLVLLGESAVGKSSLVLRFVKGQFHefQESTIGAAFLTQTVCld-dtTVKFEIWDTAGQERYHSLAPMYYRGAQAAIV 84  human
NP_001026038   5 ELKVCLLGDTGVGKSSIVWRFVEDSFDpnINPTIGASFMTKTVQyq-neLHKFLIWDTAGQERFRALAPMYYRGSAAAII 83  chicken
AAO42386      33 RVKLVLLGDSGVGKSCIVLRFVRGQFDatSKVTVGASFLSQTIAlqdstTVKFEIWDTAGQERYSALAPLYYRGAGVAVI 112 thale cress
AAG42497      31 RAKLVLLGDSGVGKSCIVLRFVRGQFDptSKVTVGASFLSQTLAledstIVKFEIWDTAGQERYAALAPLYYRGAAAAVV 110 Oryza sativa (i...
AAI00187       5 ELKVCLLGDTGVGKSSIVWRFVEDSFDpnINPTIGASFMTKTVPhq-neLHKFLIWDTAGQERFRALAPMYYRGSTAAII 83  African clawed ...
2FG5_A        23 ELKVCLLGDTGVGKSSIVCRFVQDHFDhnISPTIGASFMTKTVPcg-neLHKFLIWDTAGQERFHSLAPMYYRGSAAAVI 101 human
1Z0J_A         6 ELKVCLLGDTGVGKSSIMWRFVEDSFDpnINPTIGASFMTKTVQyq-neLHKFLIWDTAGLERFRALAPMYYRGSAAAII 84  house mouse
AAY83815      11 EAKVVMLGSTTVGKSSIVTMLTRGSFSesCASTIGAAFLSKTINlg-dqELKLQIWDTGGSERYRAMAPMYFQNANAAII 89  Trichomonas vag...
AAY83816       9 TQKIVLLGAASAGKTSLVFRFAHDRFLpnSESTIGAAFVTKSVIin-nnEVKLEIWDTGGSEKYRSLAPMYYRDAAAAII 87  Trichomonas vag...
AAY83817      10 VEKIVLLGAQSSGKTSIVTRIQNNTFNanAGSTIGAAFTSKIMMvd-dtQVKLDIWDTAGSEKYKSLIPMYYRDARAAII 88  Trichomonas vag...
Feature 1                                          ## #                           ###            
1N6H_A        85 VYDITNEESFARAKNWVKELQRQaspNIVIALSGNKADLankRAVDFQEAQSYADDNs-lLFMETSAKTSMNVNEIFMAI 163 human
NP_001026038  84 VYDITKEETFSTLKNWVKELRQHgppNIVVAIAGNKCDLndvREVMEKDAKDYADSIh-aIFVETSAKNAININELFIEI 162 chicken
AAO42386     113 VYDITSPESFKKAQYWVKELQKHgspDIVMALVGNKADLhekREVPTEDGMELAEKNg-mFFIETSAKTADNINQLFEEI 191 thale cress
AAG42497     111 VYDITSPESFSKAQYWVKELQKHgspDIIMVLVGNKADLhenRHVSSQEAQEYAEKNn-mVFIETSAKTADNINQVFEEI 189 Oryza sativa (i...
AAI00187      84 VYDITKEETFSTLKNWVKELRQHgppNIVVAIAGNKCDLndvREVLEKEAKDYADSIn-aVFVETSAKNAININELFIEI 162 African clawed ...
2FG5_A       102 VYDITKQDSFYTLKKWVKELKEHgpeNIVMAIAGNKCDLsdiREVPLKDAKEYAESIg-aIVVETSAKNAINIEELFQGI 180 human
1Z0J_A        85 VYDITKEETFSTLKNWVRELRQHgppSIVVAIAGNKCDLtdvREVMERDAKDYADSIh-aIFVETSAKNAININELFIEI 163 house mouse
AAY83815      90 VYDITSSTSYNDVESWLKELREKgpaSIIIALAGNKSDLdqqRCVATEDAQSFAQKHgipIFKETSALKGINIQEIFTDV 169 Trichomonas vag...
AAY83816      88 VFDVTTETSLDDAASWLDELKKNgpqEVFLALAANKTDLasiRKISSETIQDFANKNgikIVYETSALTGSNVIQLFEDV 167 Trichomonas vag...
AAY83817      89 VLDVTREETIPAAVEWLNELREHgkqDCVVVCAANKVDLtsqRVITSEQVADFAFSNqvsLYKETSALTGSGIQELFNET 168 Trichomonas vag...
Feature 1             
1N6H_A       164 AKKLP 168 human
NP_001026038 163 SRRIP 167 chicken
AAO42386     192 GKRLP 196 thale cress
AAG42497     190 AKRLP 194 Oryza sativa (indica cultivar-group)
AAI00187     163 SKRIP 167 African clawed frog
2FG5_A       181 SRQIP 185 human
1Z0J_A       164 SRRIP 168 house mouse
AAY83815     170 AVAIA 174 Trichomonas vaginalis
AAY83816     168 TKQVD 172 Trichomonas vaginalis
AAY83817     169 ARLLI 173 Trichomonas vaginalis

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