Melanophilin
| MLPH | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||||||
| Aliases | MLPH, SLAC2-A, melanophilin | ||||||||||||||||
| External IDs | OMIM: 606526 MGI: 2176380 HomoloGene: 11465 GeneCards: MLPH | ||||||||||||||||
| Genetically Related Diseases | |||||||||||||||||
| prostate cancer[1] | |||||||||||||||||
| |||||||||||||||||
| Orthologs | |||||||||||||||||
| Species | Human | Mouse | |||||||||||||||
| Entrez | |||||||||||||||||
| Ensembl | |||||||||||||||||
| UniProt | |||||||||||||||||
| RefSeq (mRNA) | |||||||||||||||||
| RefSeq (protein) | |||||||||||||||||
| Location (UCSC) | Chr 2: 237.49 – 237.56 Mb | Chr 1: 90.92 – 90.95 Mb | |||||||||||||||
| PubMed search | [2] | [3] | |||||||||||||||
| Wikidata | |||||||||||||||||
| View/Edit Human | View/Edit Mouse |
Melanophilin is a carrier protein which in humans is encoded by the MLPH gene.[4][5] 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.[6] 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.[7]
In melanocytic cells MLPH gene expression may be regulated by MITF.[8]
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[9] and cats.[10] 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.[11]
References
- ↑ "Diseases that are genetically associated with MLPH view/edit references on wikidata".
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Matesic LE, Yip R, Reuss AE, Swing DA, O'Sullivan TN, Fletcher CF, Copeland NG, Jenkins NA (August 2001). "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. doi:10.1073/pnas.181336698. PMC 56945
. PMID 11504925. - ↑ 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. PMID 11980908.
- ↑ 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. PMID 12062444.
- ↑ "Entrez Gene: MLPH Melanophilin".
- ↑ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ 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. PMID 17519392.
- ↑ 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. PMID 16860533.
- ↑ Pickrell JK, Coop G, Novembre J, Kudaravalli S, Li JZ, Absher D, Srinivasan BS, Barsh GS, Myers RM, Feldman MW, Pritchard JK (May 2009). "Signals of recent positive selection in a worldwide sample of human populations". Genome Res. 19 (5): 826–37. doi:10.1101/gr.087577.108. PMC 2675971. PMID 19307593.
Further reading
- 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. 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.
- 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. PMID 12221080.
- 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. PMID 12603861.
- 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. PMID 14730011.
- Seabra MC, Coudrier E (2004). "Rab GTPases and myosin motors in organelle motility". Traffic. 5 (6): 393–9. doi:10.1111/j.1398-9219.2004.00190.x. PMID 15117313.
- 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. PMID 12531900.
- Wu X, Sakamoto T, Zhang F, et al. (2006). "In vitro reconstitution of a transport complex containing Rab27a, melanophilin and myosin Va". FEBS Lett. 580 (25): 5863–8. doi:10.1016/j.febslet.2006.09.047. PMID 17045265.
- Ménasché G, Ho CH, Sanal O, Feldmann J, Tezcan I, Ersoy F, Houdusse A, Fischer A, de Saint Basile G (August 2003). "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. doi:10.1172/JCI18264. PMC 166299. PMID 12897212.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- 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. PMID 11856727.
- 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. PMID 14702039.
- 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. PMID 15517821.
- Clark HF, Gurney AL, Abaya E, et al. (2003). "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. doi:10.1101/gr.1293003. PMC 403697. 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.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Park JW, Cai J, McIntosh I, et al. (2006). "High throughput SNP and expression analyses of candidate genes for non‐syndromic oral clefts". J. Med. Genet. 43 (7): 598–608. doi:10.1136/jmg.2005.040162. PMC 2564555. 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.
This article is issued from Wikipedia - version of the 6/17/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.