Conserved Protein Domain Family
Rab36_Rab34

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cd04108: Rab36_Rab34 
Rab GTPase families 34 (Rab34) and 36 (Rab36)
Rab34/Rab36 subfamily. Rab34, found primarily in the Golgi, interacts with its effector, Rab-interacting lysosomal protein (RILP). This enables its participation in microtubular dynenin-dynactin-mediated repositioning of lysosomes from the cell periphery to the Golgi. A Rab34 (Rah) isoform that lacks the consensus GTP-binding region has been identified in mice. This isoform is associated with membrane ruffles and promotes macropinosome formation. Rab36 has been mapped to human chromosome 22q11.2, a region that is homozygously deleted in malignant rhabdoid tumors (MRTs). However, experimental assessments do not implicate Rab36 as a tumor suppressor that would enable tumor formation through a loss-of-function mechanism. 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: 206693
View PSSM: cd04108
Aligned: 5 rows
Threshold Bit Score: 311.427
Threshold Setting Gi: 47221819
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 33348830 102 HFHGQVSAACQRRNTGTVGFCKNVFDRDYKATIGVDFEIERFEIAGIPYSLQIWDTAGQEKFKCIASAYYRGAQVIITAF 181
gi 20139693  53 SKVIVVGDLSVGKTCLINRFCKDTFDKNYKATIGVDFEMERFEVLGIPFSLQLWDTAGQERFKCIASTYYRGAQAIIIVF 132
gi 55742330  53 SKVIVVGDLSVGKTCLINRFCKDTFDKNYKATIGVDFEMERFEILGVPFSLQLWDTAGQERFKCIASTYYRGAQAIIIAF 132
gi 54400690  54 SKVIVVGDLAVGKTCLINRFCKDVFDKNYKATIGVDFEMERFEVLGVPFSLQLWDTAGQERFKCIASTYYRGAQAVIIVF 133
gi 47221819  36 AKVIVVGDVSVGKTCLISRFCKGFFEKNYKATIGVDFEMERFEVLGVPFSVQLWDTAGQERFKCIASTYYRGAQAIIVVF 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                        ## #                            ###            
gi 33348830 182 DLTDVQTLEHTRQWLEDALRENEAGSCFIFLVGTKKDLlSGAACEQAEADAVHLAREMQAEYWSVSAKt----------- 250
gi 20139693 133 NLNDVASLEHTKQWLADALKENDPSSVLLFLVGSKKDLsTPAQYALMEKDALQVAQEMKAEYWAVSSLt----------- 201
gi 55742330 133 DLTDVSSLEHTKQWLQDALKENDPSSALLFLVGSKKDLsPPAQYALMEKDAIKVAKEMQAEYWSVSSLt----------- 201
gi 54400690 134 DLTDVASLEHTRQWLEDAMKENDPTSVLLFLVGTKKDLsSPAQYSLIEQDAIKIADQMKAEYWALSALs----------- 202
gi 47221819 116 DLSSVTSLAHARQWLEDAMKENDPSSVLLFLVGTKKDLsSPDQLYQTEQEAIRLSEEIKAEYWAVSAKsggssagahars 195
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
Feature 1                                                                                 
gi 33348830 251 -------------GENVKAFFSRVAALAFEqsvlqdlerqssarlqvgngdliqmegsppetqeskrpssLGCC 311
gi 20139693 202 -------------GENVREFFFRVAALTFEanvlaeleksgarrigdv----vrinsddsnlyltaskkkPTCC 258
gi 55742330 202 -------------GENVKEFFFRVASLTFEssvlaelektnarrigev----vrinsndrnlyqcskknkTNCC 258
gi 54400690 203 -------------GENVRDFFFRVASLTFEanvlaeleksgsrrigev----vqissnsnnlyatskkkqSNCC 259
gi 47221819 196 sapatlisssgvpGDGVRDFFFRVASLTFEaivlsel--------------------------etggskhVGDI 243

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