2F7S,2F7S,2IEZ,2IF0


Conserved Protein Domain Family
Rab27A

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cd04127: Rab27A 
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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.
Statistics
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PSSM-Id: 206700
Aligned: 9 rows
Threshold Bit Score: 332.157
Created: 24-Jan-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 10 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:2F7S: Human Rab27b binds GDP and Mg2+, defined using 3.5 A contacts

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                     ######                                                             
2F7S_B        22 YDYLIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYnaqgpngssGKAFKVHLQLWDTAGQERFRSLT 101 human
2F7S_A        22 YDYLIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYnaqgpngssGKAFKVHLQLWDTAGQERFRSLT 101 human
2IEZ_A         8 YDYLIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYdtqgadgasGKAFKVHLQLWDTAGLERFRSLT 87  house mouse
2IF0_A         8 YDYLIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYdtqgadgasGKAFKVHLQLWDTAGLERFRSLT 87  house mouse
NP_493376      4 YDYLIKFLALGDSGVGKTSFLHRYTDNTFTGQFISTVGIDFKEKKVVYkssr-ggfgGRGQRVLLQLWDTAGQERFRSLT 82  Caenorhabditis ...
NP_569921      8 YDYLLKFLVLGDSGVGKTCLLYQYTDGRFHTQFISTVGIDFREKRLLYns------rGRRHRIHLQIWDTAGQERFRSLT 81  fruit fly
AAH72158       6 YDYLIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYsnagpgnthGKTFKVHLQLWDTAGQERFRSLT 85  African clawed ...
NP_001025428   6 YDYLIKFLALGDSGVGKTSFLYQYTDSKFNSKFITTVGIDFREKRVVYkssgpdgtaGRGQRIHIQLWDTAGQERFRSLT 85  zebrafish
AAX27619       8 YDYLIKLLALGDSNVGKTSLLYQYTDNIFNPRFTTTVGVDFRQKRLVResrdsegllGPKQRLHLQLWDTAGQERYRSLC 87  Schistosoma jap...
Feature 1                                                        # #                           ##
2F7S_B       102 TAFFRDAMGFLLMFDLTSQQSFLNVRNWMSQLQANAYCENPDIVLIGNKADLPDQREVNERQARELADKYGIPYFETSAA 181 human
2F7S_A       102 TAFFRDAMGFLLMFDLTSQQSFLNVRNWMSQLQANAYCENPDIVLIGNKADLPDQREVNERQARELADKYGIPYFETSAA 181 human
2IEZ_A        88 TAFFRDAMGFLLMFDLTSQQSFLNVRNWMSQLQANAYCENPDIVLIGNKADLPDQREVNERQARELAEKYGIPYFETSAA 167 house mouse
2IF0_A        88 TAFFRDAMGFLLMFDLTSQQSFLNVRNWMSQLQANAYCENPDIVLIGNKADLPDQREVNERQARELAEKYGIPYFETSAA 167 house mouse
NP_493376     83 TAFFRDAMGFILIFDITNEQSFLNIRDWLSQLKVHAYCEQPDIIICGNKADLENRRQVSTARAKQLADQLGLPYFETSAC 162 Caenorhabditis ...
NP_569921     82 TAFYRDAMGFLLIFDLTSEKSFLETANWLSQLRTHAYSEDPDVVLCGNKCDLLQLRVVSRDQVAALCRRYRLPYIETSAC 161 fruit fly
AAH72158      86 TAFFRDAMGFLLMFDLTSQQSFLNVRNWMSQLQANAYCENPDMVLIGNKADLSDQREVNERQAKELADKYGIPYFETSAA 165 African clawed ...
NP_001025428  86 TAFFRDAMGFLLLFDLTNEQSFLNVRNWMSQLQTHAYCENPDIVLCGNKSDLEEQRAVKAENARELAEKYGVPYFETSAA 165 zebrafish
AAX27619      88 TVFLRDAMGFLLVFDLTNESSLQSCREWMNLLCQHAYCDRPDVVLVGNKFDLTKERQVSMSAANAMARELDVPYIETSAA 167 Schistosoma jap...
Feature 1                            
2F7S_B       182 TGQNVEKAVETLLDLIMKRM 201 human
2F7S_A       182 TGQNVEKAVETLLDLIMKRM 201 human
2IEZ_A       168 TGQNVEKSVETLLDLIMKRM 187 house mouse
2IF0_A       168 TGQNVEKSVETLLDLIMKRM 187 house mouse
NP_493376    163 TSTNVEKSVDCLLDLVMQRI 182 Caenorhabditis elegans
NP_569921    162 TGANVKEAVELLVGRVMERI 181 fruit fly
AAH72158     166 SGQDVEKSVDILLDLIMKRM 185 African clawed frog
NP_001025428 166 NGENVSRAVEVLLDLIMKRM 185 zebrafish
AAX27619     168 TGYQVTAAVDRLLDLVMTRI 187 Schistosoma japonicum

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