Disease relevance of M6PRBP1

• These data support the view that binding of TIP47 to HIV-1 Env facilitates its delivery to the TGN [1].
• Cysteine mutations were incorporated randomly into TIP47 by expression in Escherichia coli cells harboring specific misincorporator tRNAs [2].
• Although Rab9 has not been implicated in human immunodeficiency virus (HIV) replication, previous reports suggested that the late endosome is an initiation site for HIV assembly and that TIP47-dependent trafficking out of the late endosome to the trans-Golgi network facilitates the sorting of HIV Env into virions budding at the plasma membrane [3].
• Due to its oncodevelopmental function, PP17b/TIP47 is more than likely to be connected to HSV-2 infection, which is probably one of the main etiopathogenic agents of cervical carcinoma along with the HPV virus, and may open a new trend in the research of pathological processes in human uterine cervical cancer [4].

High impact information on M6PRBP1

• TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo [5].
• TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking [5].
• TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway [5].
• These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi [5].
• A functional Rab9 binding site was required for TIP47 stimulation of MPR transport in vivo [6].

Biological context of M6PRBP1

• This raises the possibility of two separate binding sites on Tip47 because both receptors require binding to Tip47 for endosomal sorting [7].
• Because TIP47 and adipophilin also localize to lipid sails, lipid sails are intimately involved in intracellular lipid metabolism [8].
• 13 cDNAs with three different insert lengths encoding PP17 variants were isolated by screening a human placental cDNA library [9].
• Sequence analysis of the shortest clones showed that the inserts contain the same open reading frame encoding PP17a variant (28,129 kDa) consisting of 251 residues, which is identical to the previously isolated and characterised PP17 antigen described in 1983 [9].
• The similarity between the amino acid sequences of PP17 variants, adipophilin and perilipins, and between their gene structures indicate that PP17b as well as other alternatively spliced PP17 variants belong to the lipid storage droplet protein family, containing also some differentiation factors [10].

Anatomical context of M6PRBP1

• Decreasing hydrophobicity of residues at position 19 resulted in further impairment of Tip47 binding and an increase of receptor accumulation in lysosomes [7].
• TIP47 functions in the delivery of mannose 6-phosphate receptors from endosomes to the trans-Golgi network both in vitro and in vivo [11].
• TIP47 was found primarily in the cytosolic fractions of HeLa cells and murine MA10 Leydig cells grown in low lipid-containing culture medium, while ADRP was undetectable in these fractionated cell homogenates [12].
• We studied the distribution of the PAT family proteins TIP47 and adipophilin in lipid bodies of THP-1 cell-derived macrophages using freeze-fracture immunolabeling and other techniques [8].
• Lipid bodies in macrophages comprise lipid droplets and extensive, previously scantily characterized sheet-like organelles, which we descriptively call "lipid sails." TIP47 and adipophilin are components of many, but not all, the lipid droplets [8].

Associations of M6PRBP1 with chemical compounds

• Mutant constructs with bulky hydrophobic residues (valine, isoleucine, or leucine) instead of Trp19 exhibited 30-60% decreases in binding to the tail interacting protein of 47 kDa (Tip47), a protein mediating this transport step, and partially prevented receptor delivery to lysosomes [7].
• We found that the cytoplasmic domain of TMgp41 binds to TIP47, a protein required for the transport of mannose-6-phosphate receptors from endosomes to the TGN [1].
• We made use of the ability of the native TIP47 protein to protect 48 cysteine probes from chemical modification by iodoacetamide as a means to obtain a surface map of TIP47, revealing the identity of surface-localized, hydrophobic residues that are likely to participate in protein-protein interactions [2].
• Here we show that TIP47 also bound directly to the Rab9 guanosine triphosphatase (GTPase) in its active, GTP-bound conformation [6].
• After 100 min of oleate treatment, the nascent lipid droplets are more heterogeneous: S3-12 and TIP47 coat smaller, peripheral droplets and adipophilin coats a more medial population of droplets [13].

Physical interactions of M6PRBP1

• Tail-interacting protein of 47 kDa (TIP47) binds Rab9 GTPase and the cytoplasmic domains of mannose 6-phosphate receptors and is required for their transport from endosomes to the Golgi apparatus [2].
• Independent competition binding experiments confirm that TIP47 interacts with the membrane-proximal portion of the CI-MPR cytoplasmic domain [14].

Other interactions of M6PRBP1

• Surprisingly, Rab9 stability on late endosomes required interaction with TIP47 [15].
• From one human term placenta an average of 3.7 mg PP13 and 2.5 mg PP17 could be extracted [16].
• Thus, we conclude that TIP47 associates with nascent lipid droplets and can be classified as a lipid droplet-associated protein [12].
• Although crystallography will be needed to define the precise interaction interface, these data provide an initial structural basis for TIP47-CI-MPR association [14].
• TIP47 recognizes a phenylalanine-tryptophan signal in the CD-MPR [14].

Analytical, diagnostic and therapeutic context of M6PRBP1

• In HeLa cells grown in standard low lipid-containing culture media, immunofluorescence microscopy revealed that the cells had few lipid droplets; however, TIP47 and ADRP were found on the surfaces of the small lipid droplets present [12].
• Cloning and sequence analysis of cDNAs encoding human placental tissue protein 17 (PP17) variants [9].
• Using monospecific anti-PP17 serum with chemiluminescence Western-blot analysis, we detected different molecular-mass variants of human soluble placental tissue protein 17 (PP17) in different normal adult and fetal human tissues besides term placenta [9].
• Using a specific antibody, PP17b was detected in lipid droplet fractions and co-localized with neutral lipid droplets stained by Nile red, and fluorescently labelled PP17 antibody in HeLa cells with confocal microscopy [10].
• TIP47 mutants with enhanced or diminished affinities were also selected by affinity chromatography [2].

References