Conserved Protein Domain Family
Rab35

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cd04110: Rab35 
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.
Statistics
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PSSM-Id: 133310
View PSSM: cd04110
Aligned: 6 rows
Threshold Bit Score: 370.724
Threshold Setting Gi: 45934561
Created: 9-Aug-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 34784624   3 RDYDHLFKLLIIGDSGVGKSSLLLRFADNTFSGSYITTIGVDFKIRTVEINGEKVKLQIWDTAGQERFRTITSTYYRGTH 82
gi 3024525    3 RDYDHLFKLLIIGDSGVGKSSLLLRFADNTFSGSYITTIGVDFKIRTVEINGEKVKLQIWDTAGQERFRTITSTYYRGTH 82
gi 20129057   3 RGFDHLFKLLIIGDSGVGKSSLLIRFSDDTFSGSYITTIGVDFKIRTVDIEGMRVKLQIWDTAGQERFRTITSTYYRGTH 82
gi 6018411    5 RDYDHLFKLLIIGDSGVGKSSLLLRFADNTFSENYITTIGVDFKIRTMDINGQRVKLQIWDTAGQERFRTITSTYYRGTH 84
gi 45934561   3 REYDHLFKLLIIGDSGVGKSSLLIRFSDNTFSGSYITTIGVDFKIRTVVINGERVKLQIWDTAGQERFRTITNTYYRGTH 82
gi 71897245   3 RDYDHLFKLLIIGDSGVGKSSLLLRFADNTFSGSYITTIGVDFKIRTVEINGEKVKLQIWDTAGQERFRTITSTYYRGTH 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                            ## #                           ###         
gi 34784624  83 GVIVVYDVTSAESFVNVKRWLHEINQNCDDVCRILVGNKNDDPDRKVVETEDAYKFAAQMd-iRLFETSAKDNLNVEEMF 161
gi 3024525   83 GVIVVYDVTSAESFVNVKRWLHEINQNCDDVCRILVGNKNDDPERKVVETEDAYKFAGQMg-iQLFETSAKENVNVEEMF 161
gi 20129057  83 GVIVVYDVTNGESFANVRRWLEEIQNNCDVVKKVLVGNKNDDPDRKVVITEDAQRFAKQMd-iELFETSAKDNINVENMF 161
gi 6018411   85 GVVVVYDVTNGESFGNVKRWLQEIENNCDSVQKVLVGNKCEENERRVVLESDARNYAQSMn-iSFFETSAKEDKNVEPMF 163
gi 45934561  83 GVIVVYDVTNGESFANVKRWLQEIEANCDVVNKVLVGNKNDDPAREGCDHRRRATFCEPDgiySFSKPQPKTNINVEENV 162
gi 71897245  83 GVIVVYDVTSAESFVNVKRWLHEINQNCDDVCRILVGNKNDDPERKVVETEDAYKFAGQMe-iQLFETSAKENINVEEMF 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
Feature 1                                                         
gi 34784624 162 NCITELVLRAKKDNLAKQqqq-----qqnDVVKLNKNs-----KRKKRCC 201
gi 3024525  162 NCITELVLRAKKDNLAKQqqq-----qqnDVVKLTKNs-----KRKKRCC 201
gi 20129057 162 LSITRQVLDHKLRTSPNEqqk-----dtlHLKPNPKGs-----KGGKCCR 201
gi 6018411  164 TCITSLVLTAKLANPQSAskd-----qsrTGGVSLKDnsgstnQKKKCKC 208
gi 45934561 163 SSHPPKQVLRHKKQTPKNrvqsgskanehRSNLAPKG------ASQKKKK 206
gi 71897245 162 NCITELVLRAKKENLAKQqqq-----qqnDVVKLTKNs-----KRKKRCC 201

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