|Protein Name||Ras-related protein Rab-7a|
|Ref Sequence ID||NP_001030253.1|
|Protein Existence Status||Reviewed|
|Protein Function||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|
|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. Ullrich, O., Reinsch, S., Urbé, S., Zerial, M., & Parton, R. G. (1996). Rab11 regulates recycling through the pericentriolar recycling endosome. The Journal of Cell Biology, 135(4), 913–924. https://doi.org/10.1083/jcb.135.4.913. |
2. Ueda, T., Kikuchi, A., Ohga, N., Yamamoto, J., & Takai, Y. (1990). Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein. The Journal of Biological Chemistry, 265(16), 9373–9380. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2111820.
3. Wu, Y.-W., Tan, K.-T., Waldmann, H., Goody, R. S., & Alexandrov, K. (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 of the United States of America, 104(30), 12294–12299. https://doi.org/10.1073/pnas.0701817104.
4. Alexandrov, K., Heinemann, I., Durek, T., Sidorovitch, V., Goody, R. S., & Waldmann, H. (2002). Intein-mediated synthesis of geranylgeranylated Rab7 protein in vitro. Journal of the American Chemical Society, 124(20), 5648–5649. https://doi.org/10.1021/ja017799e.
5. Hutagalung, A. H., & Novick, P. J. (2011). Role of Rab GTPases in membrane traffic and cell physiology. Physiological Reviews, 91(1), 119–149. https://doi.org/10.1152/physrev.00059.2009.
|Protein Function||The small GTPase Ras-related protein Rab-7a (Rab7a) serves as a key organizer of the endosomal-lysosomal system as involved in late endocytic trafficking.|
|PTMs||N-Acetylation at Thr, Lipoylation, Methylation, Phosphorylation at Ser, Prenylation|
| Site(s) of PTM(s) |
|>sp|Q3T0F5|RAB7A_BOVIN Ras-related protein Rab-7a OS=Bos taurus OX=9913 GN=RAB7A PE=2 SV=1 MTSRKKVLLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQ IWDTAGQERFQS*72LGVAFYRGADCCVLVFDVTAPNTFKTLDSWRDEFLIQASPRDPENFPF VVLGNKIDLENRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAFQTIVRNALKQETEV ELYNEFPEPIKLDKNDRTKPSAEGCSC|
|Predicted Disorder Regions||NA|
|TM Helix Prediction||No TM helices|
|Bibliography||1.Xie J, Yan Y, Liu F, Kang H, Xu F, Xiao W, Wang H, Wang Y. Knockdown of Rab7a suppresses the proliferation, migration, and xenograft tumor growth of breast cancer cells. Biosci Rep. 2019 Feb 5;39(2):BSR20180480. doi: 10.1042/BSR20180480. PMID: 29769411; PMCID: PMC6361774.|