Biology:Melanophilin
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Melanophilin is a carrier protein which in humans is encoded by the MLPH gene.[1][2] 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.
Function
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.[3] A similar protein complex in mouse functions to tether pigment-producing organelles called melanosomes to the actin cytoskeleton in melanocytes, and is required for visible pigmentation in the hair and skin.[4]
In melanocytic cells MLPH gene expression may be regulated by MITF.[5]
Clinical significance
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[6] and cats.[7] 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.[8]
References
- ↑ "Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10238–43. August 2001. doi:10.1073/pnas.181336698. PMID 11504925. Bibcode: 2001PNAS...9810238M.
- ↑ "A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport". J. Biol. Chem. 277 (28): 25423–30. July 2002. doi:10.1074/jbc.M202574200. PMID 11980908.
- ↑ "Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions". FEBS Lett. 517 (1–3): 233–8. April 2002. doi:10.1016/S0014-5793(02)02634-0. PMID 12062444.
- ↑ "Entrez Gene: MLPH Melanophilin". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=79083.
- ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ "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. 2007. doi:10.1093/jhered/esm021. PMID 17519392.
- ↑ "A homozygous single-base deletion in MLPH causes the dilute coat color phenotype in the domestic cat". Genomics 88 (6): 698–705. December 2006. doi:10.1016/j.ygeno.2006.06.006. PMID 16860533.
- ↑ "Signals of recent positive selection in a worldwide sample of human populations". Genome Res. 19 (5): 826–37. May 2009. doi:10.1101/gr.087577.108. PMID 19307593.
Further reading
- "Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2-a and actin association". FASEB J. 18 (9): 989–91. 2004. doi:10.1096/fj.03-1240fje. PMID 15059972.
- 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. PMID 12578829.
- "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. 2002. doi:10.1074/jbc.M203862200. PMID 12221080.
- "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. 2003. doi:10.1046/j.1523-1747.2003.12068.x. PMID 12603861.
- "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. 2004. doi:10.1242/jcs.00891. PMID 14730011.
- "Rab GTPases and myosin motors in organelle motility". Traffic 5 (6): 393–9. 2004. doi:10.1111/j.1398-9219.2004.00190.x. PMID 15117313.
- "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. 2003. doi:10.1074/jbc.M211996200. PMID 12531900.
- "In vitro reconstitution of a transport complex containing Rab27a, melanophilin and myosin Va". FEBS Lett. 580 (25): 5863–8. 2006. doi:10.1016/j.febslet.2006.09.047. PMID 17045265.
- "Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1)". J. Clin. Invest. 112 (3): 450–6. August 2003. doi:10.1172/JCI18264. PMID 12897212.
- "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "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. 2002. doi:10.1074/jbc.C200005200. PMID 11856727.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder". Genet. Couns. 15 (3): 293–301. 2004. PMID 15517821.
- "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. 2003. doi:10.1101/gr.1293003. PMID 12975309.
- 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. PMID 12189142.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "High throughput SNP and expression analyses of candidate genes for non‐syndromic oral clefts". J. Med. Genet. 43 (7): 598–608. 2006. doi:10.1136/jmg.2005.040162. PMID 16415175.
External links
- melanophilin+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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