The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Mlph  -  melanophilin

Mus musculus

Synonyms: 2210418F23Rik, 5031433I09Rik, AW228792, D1Wsu84e, Exophilin-3, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Mlph

  • In the present report, we evaluated the effect of overexpression of these mutants on melanosome, melanophilin, and myosin-Va localization in B16 melanoma cells [1].
  • We herein present genetic and functional evidence that a third form of GS (GS3), whose expression is restricted to the characteristic hypopigmentation of GS, results from mutation in the gene that encodes melanophilin (Mlph), the ortholog of the gene mutated in leaden mice [2].

Psychiatry related information on Mlph


High impact information on Mlph

  • By contrast, knockdown of Slac2-a (also called melanophilin), another Rab27A-binding protein in melanocytes, caused perinuclear aggregation of melanosomes alone without altering cell shape [4].
  • Rab27a binds to the melanosome first and then recruits melanophilin, which in turn recruits myosin-Va [5].
  • In this study, we show that Mlp is also a microtubule plus end-tracking protein or +TIP [6].
  • Collectively, our data show that Mlph is a critical component of the melanosome transport machinery and suggest that Mlph might function as part of a transport complex with Rab27a and MyoVa [7].
  • However, Mlph does not contain the two Ca(2+)-binding C(2) domains found in these and other proteins involved in vesicle transport, suggesting that it represents a previously unrecognized class of Rab effectors [7].

Biological context of Mlph


Anatomical context of Mlph


Associations of Mlph with chemical compounds


Physical interactions of Mlph

  • Although Slac2-a directly interacts with Rab27A and myosin Va via its N-terminal region (amino acids 1 to 146) and the middle region (amino acids 241 to 405), respectively, the functional importance of the putative actin-binding domain of the Slac2-a C terminus (amino acids 401 to 590) in melanosome transport has never been elucidated [16].

Regulatory relationships of Mlph


Other interactions of Mlph

  • The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln [11].
  • Site of beige (bg) and leaden (ln) pigment gene expression determined by recombinant embryonic skin grafts and aggregation mouse chimaeras employing sash (Wsh) homozygotes [17].
  • We found that the C-terminal domain of Slac2-a is highly sensitive to low concentrations of proteases, such as trypsin and calpain, in vitro, whereas the N-terminal Rab27A-binding domain is highly resistant to these proteases [18].
  • In this study, we discovered that Slac2-a and a closely related isoform, Slac2-c/MyRIP, contain multiple PEST-like sequences (potential signals for rapid protein degradation) in the myosin Va- and actin-binding domains at the C terminus [18].
  • Using the Mlph R35W mutant that blocks Mlph-Rab27a interaction and Rab27a siRNA we show this interaction is required for melanosome targeting and stability of Mlph [19].

Analytical, diagnostic and therapeutic context of Mlph


  1. Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome. Bahadoran, P., Busca, R., Chiaverini, C., Westbroek, W., Lambert, J., Bille, K., Valony, G., Fukuda, M., Naeyaert, J.M., Ortonne, J.P., Ballotti, R. J. Biol. Chem. (2003) [Pubmed]
  2. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). Ménasché, G., Ho, C.H., Sanal, O., Feldmann, J., Tezcan, I., Ersoy, F., Houdusse, A., Fischer, A., de Saint Basile, G. J. Clin. Invest. (2003) [Pubmed]
  3. Activation of myosin Va function by melanophilin, a specific docking partner of myosin Va. Li, X.D., Ikebe, R., Ikebe, M. J. Biol. Chem. (2005) [Pubmed]
  4. Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes. Kuroda, T.S., Fukuda, M. Nat. Cell Biol. (2004) [Pubmed]
  5. Identification of an organelle receptor for myosin-Va. Wu, X.S., Rao, K., Zhang, H., Wang, F., Sellers, J.R., Matesic, L.E., Copeland, N.G., Jenkins, N.A., Hammer, J.A. Nat. Cell Biol. (2002) [Pubmed]
  6. Melanophilin and myosin Va track the microtubule plus end on EB1. Wu, X.S., Tsan, G.L., Hammer, J.A. J. Cell Biol. (2005) [Pubmed]
  7. Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice. Matesic, L.E., Yip, R., Reuss, A.E., Swing, D.A., O'Sullivan, T.N., Fletcher, C.F., Copeland, N.G., Jenkins, N.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients. Menasche, G., Feldmann, J., Houdusse, A., Desaymard, C., Fischer, A., Goud, B., de Saint Basile, G. Blood (2003) [Pubmed]
  9. Missense mutations in the globular tail of myosin-Va in dilute mice partially impair binding of Slac2-a/melanophilin. Fukuda, M., Kuroda, T.S. J. Cell. Sci. (2004) [Pubmed]
  10. Interaction of the murine dilute suppressor gene (dsu) with fourteen coat color mutations. Moore, K.J., Swing, D.A., Copeland, N.G., Jenkins, N.A. Genetics (1990) [Pubmed]
  11. The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln. Moore, K.J., Swing, D.A., Rinchik, E.M., Mucenski, M.L., Buchberg, A.M., Copeland, N.G., Jenkins, N.A. Genetics (1988) [Pubmed]
  12. Mapping of six dominant cataract genes in the mouse. Everett, C.A., Glenister, P.H., Taylor, D.M., Lyon, M.F., Kratochvilova-Loester, J., Favor, J. Genomics (1994) [Pubmed]
  13. Melanophilin, the product of the leaden locus, is required for targeting of myosin-Va to melanosomes. Provance, D.W., James, T.L., Mercer, J.A. Traffic (2002) [Pubmed]
  14. The leaden gene product is required with Rab27a to recruit myosin Va to melanosomes in melanocytes. Hume, A.N., Collinson, L.M., Hopkins, C.R., Strom, M., Barral, D.C., Bossi, G., Griffiths, G.M., Seabra, M.C. Traffic (2002) [Pubmed]
  15. Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2-a and actin association. Passeron, T., Bahadoran, P., Bertolotto, C., Chiaverini, C., Buscà, R., Valony, G., Bille, K., Ortonne, J.P., Ballotti, R. FASEB J. (2004) [Pubmed]
  16. The actin-binding domain of Slac2-a/melanophilin is required for melanosome distribution in melanocytes. Kuroda, T.S., Ariga, H., Fukuda, M. Mol. Cell. Biol. (2003) [Pubmed]
  17. Site of beige (bg) and leaden (ln) pigment gene expression determined by recombinant embryonic skin grafts and aggregation mouse chimaeras employing sash (Wsh) homozygotes. Stephenson, D.A., Glenister, P.H., Hornby, J.E. Genet. Res. (1985) [Pubmed]
  18. Slac2-a/melanophilin contains multiple PEST-like sequences that are highly sensitive to proteolysis. Fukuda, M., Itoh, T. J. Biol. Chem. (2004) [Pubmed]
  19. Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes. Hume, A.N., Ushakov, D.S., Tarafder, A.K., Ferenczi, M.A., Seabra, M.C. J. Cell. Sci. (2007) [Pubmed]
  20. Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. Fukuda, M., Kuroda, T.S., Mikoshiba, K. J. Biol. Chem. (2002) [Pubmed]
WikiGenes - Universities