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Gene Review

PLIN3  -  perilipin 3

Homo sapiens

Synonyms: 47 kDa MPR-binding protein, 47 kDa mannose 6-phosphate receptor-binding protein, Cargo selection protein TIP47, M6PRBP1, Mannose-6-phosphate receptor-binding protein 1, ...
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Disease relevance of M6PRBP1


High impact information on M6PRBP1


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


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].


  1. Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for env incorporation into virions and infectivity. Blot, G., Janvier, K., Le Panse, S., Benarous, R., Berlioz-Torrent, C. J. Virol. (2003) [Pubmed]
  2. In vitro selection and prediction of TIP47 protein-interaction interfaces. Burguete, A.S., Harbury, P.B., Pfeffer, S.R. Nat. Methods (2004) [Pubmed]
  3. Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus. Murray, J.L., Mavrakis, M., McDonald, N.J., Yilla, M., Sheng, J., Bellini, W.J., Zhao, L., Le Doux, J.M., Shaw, M.W., Luo, C.C., Lippincott-Schwartz, J., Sanchez, A., Rubin, D.H., Hodge, T.W. J. Virol. (2005) [Pubmed]
  4. Is placental tissue protein 17b/TIP47 a new factor in cervical cancer genesis? Than, N.G., Sumegi, B., Than, G.N., Kispal, G., Bohn, H. Anticancer Res. (1999) [Pubmed]
  5. TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking. Díaz, E., Pfeffer, S.R. Cell (1998) [Pubmed]
  6. Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Carroll, K.S., Hanna, J., Simon, I., Krise, J., Barbero, P., Pfeffer, S.R. Science (2001) [Pubmed]
  7. Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor. Nair, P., Schaub, B.E., Rohrer, J. J. Biol. Chem. (2003) [Pubmed]
  8. Spatial integration of TIP47 and adipophilin in macrophage lipid bodies. Robenek, H., Lorkowski, S., Schnoor, M., Troyer, D. J. Biol. Chem. (2005) [Pubmed]
  9. Cloning and sequence analysis of cDNAs encoding human placental tissue protein 17 (PP17) variants. Than, N.G., Sumegi, B., Than, G.N., Kispal, G., Bohn, H. Eur. J. Biochem. (1998) [Pubmed]
  10. Lipid droplet and milk lipid globule membrane associated placental protein 17b (PP17b) is involved in apoptotic and differentiation processes of human epithelial cervical carcinoma cells. Than, N.G., Sumegi, B., Bellyei, S., Berki, T., Szekeres, G., Janaky, T., Szigeti, A., Bohn, H., Than, G.N. Eur. J. Biochem. (2003) [Pubmed]
  11. TIP47 is not a component of lipid droplets. Barbero, P., Buell, E., Zulley, S., Pfeffer, S.R. J. Biol. Chem. (2001) [Pubmed]
  12. TIP47 associates with lipid droplets. Wolins, N.E., Rubin, B., Brasaemle, D.L. J. Biol. Chem. (2001) [Pubmed]
  13. S3-12, Adipophilin, and TIP47 package lipid in adipocytes. Wolins, N.E., Quaynor, B.K., Skinner, J.R., Schoenfish, M.J., Tzekov, A., Bickel, P.E. J. Biol. Chem. (2005) [Pubmed]
  14. Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein. Orsel, J.G., Sincock, P.M., Krise, J.P., Pfeffer, S.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  15. Rab9 GTPase regulates late endosome size and requires effector interaction for its stability. Ganley, I.G., Carroll, K., Bittova, L., Pfeffer, S. Mol. Biol. Cell (2004) [Pubmed]
  16. Purification and characterization of two new soluble placental tissue proteins (PP13 and PP17). Bohn, H., Kraus, W., Winckler, W. Oncodev. Biol. Med. (1983) [Pubmed]
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