Melanophilin is a carrier protein which in humans is encoded by the MLPHgene. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.
This gene encodes a member of the exophilin subfamily of Rab effector proteins. The protein forms a ternary complex with the small Ras-related GTPase Rab27A in its GTP-bound form and the motor protein myosin Va. A similar protein complex in mouse functions to tether pigment-producing organelles called melanosomes to the actincytoskeleton in melanocytes, and is required for visible pigmentation in the hair and skin.
In melanocytic cells MLPH gene expression may be regulated by MITF.
A mutation in this gene results in Griscelli syndrome type 3, which is characterized by a silver-gray hair color and abnormal pigment distribution in the hair shaft.
Mutations in melanophilin cause the "dilute" coat color phenotype in dogs and cats. Variation in this gene appears to have been a target for recent natural selection in humans, and it has been hypothesized that this is due to a role in human pigmentation.
^Strom M, Hume AN, Tarafder AK, Barkagianni E, Seabra MC (July 2002). "A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport". J. Biol. Chem. 277 (28): 25423–30. doi:10.1074/jbc.M202574200. PMID11980908.
^Nagashima K, Torii S, Yi Z, Igarashi M, Okamoto K, Takeuchi T, Izumi T (April 2002). "Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions". FEBS Lett. 517 (1–3): 233–8. doi:10.1016/S0014-5793(02)02634-0. PMID12062444.
^Drögemüller C, Philipp U, Haase B, Günzel-Apel AR, Leeb T (2007). "A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs". J. Hered. 98 (5): 468–73. doi:10.1093/jhered/esm021. PMID17519392.
^Ishida Y, David VA, Eizirik E, Schäffer AA, Neelam BA, Roelke ME, Hannah SS, O'brien SJ, Menotti-Raymond M (December 2006). "A homozygous single-base deletion in MLPH causes the dilute coat color phenotype in the domestic cat". Genomics. 88 (6): 698–705. doi:10.1016/j.ygeno.2006.06.006. PMID16860533.
Passeron T, Bahadoran P, Bertolotto C, et al. (2004). "Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2-a and actin association". FASEB J. 18 (9): 989–91. doi:10.1096/fj.03-1240fje. PMID15059972.
Fukuda M (2003). "Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2". J. Biol. Chem. 278 (17): 15373–80. doi:10.1074/jbc.M212341200. PMID12578829.
Fukuda M, Kuroda TS (2002). "Slac2-c (synaptotagmin-like protein homologue lacking C2 domains-c), a novel linker protein that interacts with Rab27, myosin Va/VIIa, and actin". J. Biol. Chem. 277 (45): 43096–103. doi:10.1074/jbc.M203862200. PMID12221080.
Westbroek W, Lambert J, Bahadoran P, et al. (2003). "Interactions of human Myosin Va isoforms, endogenously expressed in human melanocytes, are tightly regulated by the tail domain". J. Invest. Dermatol. 120 (3): 465–75. doi:10.1046/j.1523-1747.2003.12068.x. PMID12603861.
Fukuda M, Kuroda TS (2004). "Missense mutations in the globular tail of myosin-Va in dilute mice partially impair binding of Slac2-a/melanophilin". J. Cell. Sci. 117 (Pt 4): 583–91. doi:10.1242/jcs.00891. PMID14730011.
Bahadoran P, Busca R, Chiaverini C, et al. (2003). "Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome". J. Biol. Chem. 278 (13): 11386–92. doi:10.1074/jbc.M211996200. PMID12531900.
Fukuda M, Kuroda TS, Mikoshiba K (2002). "Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport". J. Biol. Chem. 277 (14): 12432–6. doi:10.1074/jbc.C200005200. PMID11856727.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Lukusa T, Vermeesch JR, Holvoet M, et al. (2004). "Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder". Genet. Couns. 15 (3): 293–301. PMID15517821.
Fukuda M (2002). "Synaptotagmin-like protein (Slp) homology domain 1 of Slac2-a/melanophilin is a critical determinant of GTP-dependent specific binding to Rab27A". J. Biol. Chem. 277 (42): 40118–24. doi:10.1074/jbc.M205765200. PMID12189142.