Disease relevance of RAB11FIP5

• Incubation of plasma membranes isolated from cultured human melanoma cells with [gamma-32P]ATP in the presence of Ca2+ and ethylene-bis-(oxyethylenenitrilo)-tetraacetic acid (EGTA) resulted in specific phosphorylation of serine and threonine residues on a 75kDa protein (pp75) [1].

High impact information on RAB11FIP5

• The association of Rip11 with membranes is regulated by a phosphorylation and dephosphorylation cycle [2].
• Using various transport assays, we demonstrate that Rip11 is important for protein trafficking from ARE to the apical plasma membrane [2].
• By yeast 2-hybrid screening, we identified a novel 75-kDa protein (pp75) that interacts with the carboxyl 70% of 60-kDa SS-A/Ro [3].
• Immunoprecipitation with radiolabeled HeLa cell extracts showed that pp75 was phosphorylated and associated with 2 other phosphoproteins of 64 kDa [3].
• Rather, Gaf-1/Rip11 was capable of serving a link between gamma-SNAP and Rab11 [4].

Biological context of RAB11FIP5

• The open reading frame of Gaf1 predicts a protein of Mr 32 kDa consisting of 290 intronless amino acids [5].
• These results demonstrate that Gaf1 may function as a transcriptional activator consisting of DNA-binding and transactivation domains [5].
• The predicted amino acid (aa) sequence of Gaf1 reveals a single zinc finger domain typical of fungal GATA factors, and the zinc finger exhibits 60% aa identity to that of human GATA-1 [5].

Anatomical context of RAB11FIP5

• Overexpression of Gaf-1b, like that of Gaf-1/Rip11, affected the morphology of recycling endosomes [6].
• Gaf-1, a gamma -SNAP-binding protein associated with the mitochondria [7].
• Subcellular fractionation and immunofluorescence analysis show that Gaf-1 is peripherally associated with the outer mitochondrial membrane [7].
• This reticular structure colocalizes with Gaf-1 and mitochondria as well as with microtubules but not with other cytoskeletal elements [7].
• Subcellular fractionation and detergent solubility properties of pp75/85 are consistent with its association with the cytoskeleton [8].

Associations of RAB11FIP5 with chemical compounds

• Phosphoamino acid analysis demonstrates that the pp75/85 complex is phosphorylated on both tyrosine and serine residues [8].
• The C. trachomatis-induced tyrosine phosphorylation of pp75/85 and pp100 is observed in several cell lines, including epithelial cells, fibroblasts, and macrophages [8].
• 3. Neither Ca2+ or EGTA alone, nor any other divalent metal ion tested could induce phosphorylation of pp75 [1].

Physical interactions of RAB11FIP5

• This binding is distinct from other SNAP interactions since no alpha-SNAP or NSF coprecipitated with Gaf-1 [7].

Other interactions of RAB11FIP5

• Our two-hybrid analysis revealed that gamma-SNAP, unlike alpha-SNAP, interacts directly with NSF, as well as Gaf-1/Rip11, but not with SNAREs [4].
• RCP is a homologue of Rip11 and therefore belongs to the recently described Rab11-FIP family [9].
• We now demonstrate that two of the family members-pp75/Rip11 and Rab11-FIP3 do not bind Rab4 and show that several members of the family can self-interact and interact with each other [10].

Analytical, diagnostic and therapeutic context of RAB11FIP5

• Based on immunofluorescence of transfected HeLa cells, pp75 is localized predominantly in the cytoplasm, an observation confirmed by immunohistochemistry in untransfected cells [3].
• In Northern blot analysis, pp75 was expressed in all tissues analyzed; the highest expression was in the human heart [3].

References