|Protein Name||Ras-related protein Rab-8A|
|Milk Fraction||MFGM, Exosome|
|Ref Sequence Id||NP_001098951.1|
|Protein Existence Status||Reviewed: Experimental evidence at transcript level|
|Protein Function||TGN-plasma membrane trafficking, GLUT4 vesicle translocation, cilial transport, adherens junction assembly; Rab proteins are GTPases that act as key regulators in intracellular vesicular transport; belong to Ras family; switch between the inactive (GDP-bound) and active (GTP-bound) forms; associate with membranes via their C-terminal isoprenoid moieties; interact with motor proteins involved in transport; contribute to the structural and functional identity of intracellular organelles; master regulators of organelle biogenesis and cellular homeostasis; The ubiquitous Rab GTPases Rab5, Rab4, and Rab11 function on the early endocytic pathway, whereas Rab7 and Rab9 function on the late endocytic pathway|
|Biochemical Properties||Rabs are inactivated by GTP hydrolysis catalyzed by GAPs (GTP activating proteins), before extraction of GDP-bound Rabs by GDB dissociation inhibitor (GDI); C-terminally lipidmodified GTPases; high affinity for Rab escort protein and GDI; REP has high affinity for unprenylated Rabs; GDI binds unprenylated Rabs weakly but prenylated Rabs very strongly; Rab GTPases behave both as soluble and specifically localized, integral-membrane proteins; kept soluble in the cytosol and in the inactive (GDP-bound) conformation through association with GDI;|
|Significance in milk||important for proper mammary gland development|
|PTMs||Prenylation—addition of one or two geranyl- geranyl groups—on conserved carboxyterminal cysteine residues; mammalian Rab GTPases undergoes adenylation or phosphocholination by bacterial enzymes that can occur on the membrane-bound, inactive Rab and preclude GDI rebinding|
| Site(s) of PTM(s) |
|Predicted Disorder Regions||NA|
|TM Helix Prediction||No TM helices|
|Significance of PTMs||prenylation serves together with upstream hypervariable regions in promoting specific and stable membrane association; adenylation or phosphocholination occurs in the absence of infection as an alternative to GDI displacement and membrane stabilization;|
|Bibliography||1. Wu, Y.-W. et al. (2007) ‘Interaction analysis of prenylated Rab GTPase with Rab escort protein and GDP dissociation inhibitor explains the need for both regulators’, Proceedings of the National Academy of Sciences, 104(30), pp. 12294–12299. doi: 10.1073/pnas.0701817104. |
2. Hutagalung, A. H. and Novick, P. J. (2011) ‘Role of Rab GTPases in Membrane Traffic and Cell Physiology’, Physiological Reviews, 91(1), pp. 119–149. doi: 10.1152/physrev.00059.2009.
3. Ullrich, S. J. et al. (1993) ‘Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from human tumors is altered compared to wild-type p53.’, Proceedings of the National Academy of Sciences, 90(13), pp. 5954–5958. doi: 10.1073/pnas.90.13.5954.
4. Gavriljuk, K. et al. (2013) ‘Membrane extraction of Rab proteins by GDP dissociation inhibitor characterized using attenuated total reflection infrared spectroscopy.’, Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 110(33), pp. 13380–5. doi: 10.1073/pnas.1307655110.
5. Oesterlin, L. K., Goody, R. S. and Itzen, A. (2012) ‘Posttranslational modifications of Rab proteins cause effective displacement of GDP dissociation inhibitor’, Proceedings of the National Academy of Sciences, 109(15), pp. 5621–5626. doi: 10.1073/pnas.1121161109.