Conserved Protein Domain Family
Rab40

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cd04121: Rab40 
Rab GTPase family 40 (Rab40) contains Rab40a, Rab40b and Rab40c
The Rab40 subfamily contains Rab40a, Rab40b, and Rab40c, which are all highly homologous. In rat, Rab40c is localized to the perinuclear recycling compartment (PRC), and is distributed in a tissue-specific manor, with high expression in brain, heart, kidney, and testis, low expression in lung and liver, and no expression in spleen and skeletal muscle. Rab40c is highly expressed in differentiated oligodendrocytes but minimally expressed in oligodendrocyte progenitors, suggesting a role in the vesicular transport of myelin components. Unlike most other Ras-superfamily proteins, Rab40c was shown to have a much lower affinity for GTP, and an affinity for GDP that is lower than for 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. 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.
Statistics
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PSSM-Id: 133321
View PSSM: cd04121
Aligned: 4 rows
Threshold Bit Score: 358.478
Threshold Setting Gi: 16769094
Created: 14-Nov-2005
Updated: 17-Jan-2013
Structure
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Aligned Rows:
  next features
Feature 1:GTP/Mg2+ binding site [chemical binding site]
Evidence:
  • Comment:Based on sequence similarity with other Rab isoforms.
  • 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

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                      #######         #      #                         #                
gi 27734457    9 KSYDYLLKFLLVGDSDVGKGEILESLQDGAAESPYaySNGIDYKTTTILLDGRRVKLELWDTSGQGRFCTIFRSYSRGAQ 88
gi 51593537    9 KAYDFLLKFLLVGDSDVGKGEILASLQDGSTESPYgyNMGIDYKTTTILLDGRRIKLQLWDTSGQGRFCTIFRSYSRGAQ 88
gi 16769094    3 KDYDYLLKVLLVGDSDVGKHEILSNLEDPSTESPF--CSGNAYKTTTILLEGKRVKLQLWDTSGQGRFCTIIRSYSRGAQ 80
gi 349501036  17 KAYDFLLKFLLVGDSDVGKGEILASLQDGSSESPYgyNMGIDYKTTTILLDGRRVKLQLWDTSGQGRFCTIFRSYSRGAQ 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                             ## #                          ###          
gi 27734457   89 GILLVYDITNRWSFDGIDRWIKEIDEHAPGVPRILVGNRLHLAFKRQVPTEQARAYAEKNCMTFFEVSPLCNFNVIESFT 168
gi 51593537   89 GVILVYDITNRWSFDGIDRWIKEIDEHAPGVPKILVGNRLHLAFKRQVSTDQAQNFAERLGMTFFEVSPLCNFNITESFT 168
gi 16769094   81 GIILVYDITNKWSFDGIDRWLKEVDEHAPGIPKVLVGNRLHLAFKRQVAAKQAETYASRNNMSCFEISPLCNFNIRESFC 160
gi 349501036  97 GVILVYDITNRWSFDGIDRWIKEIDEHAPGVPKILVGNRLHLAYKRQVTTEHTQAFVERLGVTFFEVSPLCNFNITESFT 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 27734457  169 ELSRIVLMRHGmekiwrpnrvfslqdlccraivsctpvhlidklplpvtikshlksfsmangmnavmmhgrsyslasgag 248
gi 51593537  169 ELARIVLMRHGmdrlwrpnkvlslqdlccraivsctpvhlvdklplpvalrs---hlksfsmanglnarmmhgrsyslta 245
gi 16769094  161 ELARMALHRNGmehiwrsnkvlslqelccrtivrrtsvyaids---------------------lplppsvkstlksyal 219
gi 349501036 177 ELARIVLMRHGmerlwrpnkvlslqdlccrsivsctpvhlvdklplpvalks--hlksfsmanglvntrmmhgrsysvip 254
                        250       260       270
                 ....*....|....*....|....*....|...
Feature 1                                         
gi 27734457  249 gggskgnslkrsksiRPPQSPPQNCSRSNCKIS 281
gi 51593537  246 nntnkrnslkkakiiRPPQSPPKNCTRNSCKIS 278
gi 16769094  220 ttsqcfnsltqssksKNRCKTPTSSSRNSCAIA 252
gi 349501036 255 ssakkrngtkkskiiYPPLSPSQHCARTSCKIS 287

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