MLPH

Summary

Gene Symbol: MLPH
Description: melanophilin
Alias: SLAC2-A, melanophilin, exophilin-3, slp homolog lacking C2 domains a, synaptotagmin-like protein 2a
Species: human
Products:     MLPH

Top Publications

  1. Manakhov A, Andreeva T, Trapezov O, Kolchanov N, Rogaev E. Genome analysis identifies the mutant genes for common industrial Silverblue and Hedlund white coat colours in American mink. Sci Rep. 2019;9:4581 pubmed publisher
    ..We identified mutations in splice donor sites of genes coding melanophilin (MLPH) and microphthalmia-associated transcription factor (MITF) that regulate melanosome transport and neural-..
  2. Kassem Youssef H, Ramstein C, Ginglinger E, Chouta Ngaha F, Nojavan H, Michel C. [Griscelli syndrome type 3: A new case]. Ann Dermatol Venereol. 2018;: pubmed publisher
    ..DNA sequencing showed a homozygous C103T (R35W) transition in exon 1 of MLPH, confirming Griscelli syndrome type 3...
  3. Lin L, Chen C, Kuo C, Lin Y, Hwang B, Wang T, et al. 36H: A Novel Potent Inhibitor for Antimelanogenesis. Oxid Med Cell Longev. 2018;2018:6354972 pubmed publisher
    ..MITF, tyrosinase, TRP-1, and TRP-2), melanosome maturation (Rab27a), and melanosome transportation (Myo5a, MLPH and Mreg)...
  4. Figueiredo A, Wasmeier C, Tarafder A, Ramalho J, Baron R, Seabra M. Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J Biol Chem. 2008;283:23209-16 pubmed publisher
    ..In melanocytes, Rab27a regulates peripheral transport of mature melanosomes by recruiting melanophilin and myosin Va. Here, we studied the activation of Rab27a in melanocytes...
  5. Westbroek W, Tuchman M, Tinloy B, De Wever O, Vilboux T, Hertz J, et al. A novel missense mutation (G43S) in the switch I region of Rab27A causing Griscelli syndrome. Mol Genet Metab. 2008;94:248-54 pubmed publisher
    ..Once attached, Rab27A recruits the downstream effector Melanophilin (Mlph) and the actin-dependent motor protein Myosin Va (MyoVa)...
  6. Otręba M, Buszman E, Miliński M, Wrześniok D. [Hypomelanoses transmitted from generation to generation]. Postepy Hig Med Dosw (Online). 2014;68:1081-90 pubmed
    ..and are caused by different mutations of the following genes: TYR, P, TRP1, MATP, HPS, CHS, MYO5A, RAB27A, MLPH, ATP7A and PAH...
  7. Penney K, Sinnott J, Tyekucheva S, Gerke T, Shui I, Kraft P, et al. Association of prostate cancer risk variants with gene expression in normal and tumor tissue. Cancer Epidemiol Biomarkers Prev. 2015;24:255-60 pubmed publisher
    ..05) associations of variants with the expression of nearby genes including C2orf43, ITGA6, MLPH, CHMP2B, BMPR1B, and MTL5...
  8. Demars J, Iannuccelli N, Utzeri V, Auvinet G, Riquet J, Fontanesi L, et al. New Insights into the Melanophilin (MLPH) Gene Affecting Coat Color Dilution in Rabbits. Genes (Basel). 2018;9: pubmed publisher
    ..Candidate gene approaches focused on the melanophilin (MLPH) gene highlighted two variants associated with the dilution phenotype in rabbits: The c...
  9. Hernando B, Peña Chilet M, Ibarrola Villava M, Martin Gonzalez M, Gomez Fernandez C, Ribas G, et al. Genetic 3'UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight. Exp Dermatol. 2017;26:896-903 pubmed publisher
    ..This association is especially noticeable for two of them, rs2325813 in the MLPH gene and rs752107 in the WNT3A gene...

More Information

Publications47

  1. Ramalho J, Lopes V, Tarafder A, Seabra M, Hume A. Myrip uses distinct domains in the cellular activation of myosin VA and myosin VIIA in melanosome transport. Pigment Cell Melanoma Res. 2009;22:461-73 pubmed publisher
    ..recruits and activates MyoVa on skin melanosomes with similar efficiency to the established MyoVa activator Melanophilin (Mlph)...
  2. Hume A, Tarafder A, Ramalho J, Sviderskaya E, Seabra M. A coiled-coil domain of melanophilin is essential for Myosin Va recruitment and melanosome transport in melanocytes. Mol Biol Cell. 2006;17:4720-35 pubmed
    b>Melanophilin (Mlph) regulates retention of melanosomes at the peripheral actin cytoskeleton of melanocytes, a process essential for normal mammalian pigmentation...
  3. Zhan C, Yan L, Wang L, Sun Y, Wang X, Lin Z, et al. Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma. J Thorac Dis. 2015;7:1398-405 pubmed publisher
    ..Then we detected the expression of six of these genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in lung cancer sections using immunohistochemical staining...
  4. Ahn J, Lee J, Park J, Oh K, Hwang S, Lee C, et al. Targeted genome editing in a quail cell line using a customized CRISPR/Cas9 system. Poult Sci. 2017;96:1445-1450 pubmed publisher
    ..Then, guide RNA, which was designed to target 20-base pair (bp) nucleotides in the quail melanophilin (MLPH) locus, was ligated to the modified CRISPR vector and transfected to QM7 cells...
  5. Seberg H, Van Otterloo E, Loftus S, Liu H, Bonde G, Sompallae R, et al. TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF. PLoS Genet. 2017;13:e1006636 pubmed publisher
    ..expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel...
  6. Zhang W, Yao L, Li X. The Globular Tail Domain of Myosin-5a Functions as a Dimer in Regulating the Motor Activity. J Biol Chem. 2016;291:13571-9 pubmed publisher
    ..the inhibitory activity of the GTD but also enhance the activation of myosin-5a by its cargo-binding protein melanophilin (Mlph)...
  7. Laqqan M, Solomayer E, Hammadeh M. Aberrations in sperm DNA methylation patterns are associated with abnormalities in semen parameters of subfertile males. Reprod Biol. 2017;17:246-251 pubmed publisher
    ..highest difference in methylation levels (cg09737095, cg14271023, and cg17662493), which are located in the KCNJ5, MLPH, and SMC1? genes, respectively; these were selected for further analysis using deep bisulfite sequencing in 78 ..
  8. Sckolnick M, Krementsova E, Warshaw D, Trybus K. Tropomyosin isoforms bias actin track selection by vertebrate myosin Va. Mol Biol Cell. 2016;27:2889-97 pubmed publisher
    ..the ability of myosin Va (myoVa) to engage with actin in vitro in the absence or presence of the cargo adapter melanophilin (Mlph), which links myoVa to Rab27a-melanosomes for in vivo transport...
  9. Chen W, Zhang J. Potential molecular characteristics in situ in response to repetitive UVB irradiation. Diagn Pathol. 2016;11:129 pubmed
    ..DEGs were significantly enriched in biological processes related to pigmentation (DCT, SOX10, TYRP1, TYR, MLPH, KIT and GPR143), while the down-regulated DEGs were dramatically related to haemopoiesis and the immune system (..
  10. Tretiakova D, Onishchenko N, Boldyrev I, Mikhalyov I, Tuzikov A, Bovin N, et al. Influence of stabilizing components on the integrity of antitumor liposomes loaded with lipophilic prodrug in the bilayer. Colloids Surf B Biointerfaces. 2018;166:45-53 pubmed publisher
    Previously, we proposed a liposomal formulation of melphalan (Mlph)-a chemotherapeutic alkylating agent-incorporated in a fluid lipid bilayer in the form of dioleoylglyceride ester...
  11. Li W, Sartelet A, Tamma N, Coppieters W, Georges M, Charlier C. Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle. Anim Genet. 2016;47:110-3 pubmed publisher
    ..87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p...
  12. Rossberg W, Saternus R, Wagenpfeil S, Kleber M, März W, Reichrath S, et al. Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes (SNPs) Involved in Skin Pigmentation Are Associated with 25(OH)D Serum Concentration. Anticancer Res. 2016;36:1429-37 pubmed
    ..biogenesis (ATP7A, DTNBP1, BLOC1S5, PLDN, PMEL), melanosomal transport within melanocytes (RAB27A, MYO5A, MLPH); or various melanocyte signaling pathways (MC1R, MITF, PAX3, SOX10, DKK1, RACK1, CNR1) are predictive of serum 25(..
  13. Campana M, Parker L, Hawkins M, Young H, Helgen K, Szykman Gunther M, et al. Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus). BMC Genomics. 2016;17:1013 pubmed
    ..We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage.
  14. Bauer A, Kehl A, Jagannathan V, Leeb T. A novel MLPH variant in dogs with coat colour dilution. Anim Genet. 2018;49:94-97 pubmed publisher
    ..Loss-of-function variants in the melanophilin gene (MLPH) cause a recessively inherited form of coat colour dilution in many mammalian and avian species ..
  15. Fujimoto M, Togashi Y, Matsuzaki I, Baba S, Takeuchi K, Inaba Y, et al. A case report of atypical Spitz tumor harboring a novel MLPH-ALK gene fusion with discordant ALK immunohistochemistry results. Hum Pathol. 2018;80:99-103 pubmed publisher
    ..Herein, we report a case of atypical Spitz tumor with a novel MLPH-ALK fusion, which has not been previously reported to contribute to cancer development...
  16. Koch A, De Meyer T, Jeschke J, Van Criekinge W. MEXPRESS: visualizing expression, DNA methylation and clinical TCGA data. BMC Genomics. 2015;16:636 pubmed publisher
    ..We also used MEXPRESS to reveal the differences in the DNA methylation status of the PAM50 marker gene MLPH between the breast cancer subtypes and how these differences were linked to the expression of MPLH...
  17. Park J, Cai J, McIntosh I, Jabs E, Fallin M, Ingersoll R, et al. High throughput SNP and expression analyses of candidate genes for non-syndromic oral clefts. J Med Genet. 2006;43:598-608 pubmed
    ..the presence of disequilibrium, and ten of these were found to be expressed in relevant embryonic tissues: SP100, MLPH, HDAC4, LEF1, C6orf105, CD44, ALX4, ZNF202, CRHR1, and MAPT...
  18. Wu X, Wang F, Rao K, Sellers J, Hammer J. Rab27a is an essential component of melanosome receptor for myosin Va. Mol Biol Cell. 2002;13:1735-49 pubmed
  19. Bu H, Narisu N, Schlick B, Rainer J, Manke T, Schafer G, et al. Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites. Hum Mutat. 2016;37:52-64 pubmed publisher
    ..Of these, rs11891426:T>G in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of ..
  20. Fukuda M, Kuroda T. 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. 2002;277:43096-103 pubmed
    Slac2-a (synaptotagmin-like protein (Slp) homologue lacking C2 domains-a)/melanophilin is a melanosome-associated protein that links Rab27A on melanosomes with myosin Va, an actin-based motor protein, and formation of the tripartite ..
  21. Lukusa T, Vermeesch J, Holvoet M, Fryns J, Devriendt K. Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder. Genet Couns. 2004;15:293-301 pubmed
    ..3 Mb. Comparison with another well documented autistic patient from the literature results in the same conclusion. These findings represent thus a further step towards identifying genes predisposing to autism. ..
  22. Seabra M, Coudrier E. Rab GTPases and myosin motors in organelle motility. Traffic. 2004;5:393-9 pubmed
    ..Better understood is the case of the melanosome where Rab27a recruits a specific effector called melanophilin, which in turn binds myosin Va...
  23. Bahadoran P, Busca R, Chiaverini C, Westbroek W, Lambert J, Bille K, et al. Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome. J Biol Chem. 2003;278:11386-92 pubmed
    ..In the present report, we evaluated the effect of overexpression of these mutants on melanosome, melanophilin, and myosin-Va localization in B16 melanoma cells...
  24. Wankel B, Ouyang J, Guo X, Hadjiolova K, Miller J, Liao Y, et al. Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells. Mol Biol Cell. 2016;27:1621-34 pubmed publisher
    ..These data support a unifying model in which UP cargoes are targeted for apical insertion via sequential interactions with Rabs and their effectors, SNAREs and MAL, and in which K20 plays a key role in regulating vesicular trafficking. ..
  25. Fukuda M. 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. 2002;277:40118-24 pubmed
    ..In this study, systematic deletion analysis and Ala-based site-directed mutagenesis showed that SHD1 of Slac2-a/melanophilin alone is both necessary and sufficient for high affinity specific recognition of the GTP-bound form of Rab27A...
  26. Matesic L, Yip R, Reuss A, Swing D, O Sullivan T, Fletcher C, et al. 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. 2001;98:10238-43 pubmed
    ..Here we show that ln encodes melanophilin (Mlph), a previously undescribed protein with homology to Rab effectors such as granuphilin, Slp3-a, and ..
  27. Strom M, Hume A, Tarafder A, Barkagianni E, Seabra M. A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport. J Biol Chem. 2002;277:25423-30 pubmed
    ..JFC1/Slp1 and related proteins, including melanophilin, contain a conserved amino-terminal domain similar to the Rab3a-binding domain of Rabphilin-3...
  28. Westbroek W, Klar A, Cullinane A, Ziegler S, Hurvitz H, Ganem A, et al. Cellular and clinical report of new Griscelli syndrome type III cases. Pigment Cell Melanoma Res. 2012;25:47-56 pubmed publisher
    The RAB27A/Melanophilin/Myosin-5a tripartite protein complex is required for capturing mature melanosomes in the peripheral actin network of melanocytes for subsequent transfer to keratinocytes...
  29. Fukuda M, Kuroda T. Missense mutations in the globular tail of myosin-Va in dilute mice partially impair binding of Slac2-a/melanophilin. J Cell Sci. 2004;117:583-91 pubmed
    ..I1510N, M1513K and D1519G) in the globular tail (GT) of myosin-Va partially impair the binding of Slac2-a/melanophilin, a linker protein between myosin-Va and Rab27A on the melanosome...
  30. Nagashima K, Torii S, Yi Z, Igarashi M, Okamoto K, Takeuchi T, et al. Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions. FEBS Lett. 2002;517:233-8 pubmed
    Rab GTPases regulate the membrane transport pathways by recruiting their specific effector proteins. Melanophilin, a putative Rab effector, has recently been identified as a gene that is mutated in leaden mice, in which peripheral ..
  31. Schumacher F, Berndt S, Siddiq A, Jacobs K, Wang Z, Lindstrom S, et al. Genome-wide association study identifies new prostate cancer susceptibility loci. Hum Mol Genet. 2011;20:3867-75 pubmed publisher
    ..72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes. ..
  32. Westbroek W, Lambert J, De Schepper S, Kleta R, Van Den Bossche K, Seabra M, et al. Rab27b is up-regulated in human Griscelli syndrome type II melanocytes and linked to the actin cytoskeleton via exon F-Myosin Va transcripts. Pigment Cell Res. 2004;17:498-505 pubmed
    ..two-hybrid screening studies reveal that Rab27b can form a tripartite complex on the melanosome membrane with Melanophilin, a Rab27a effector, and protein products of Myosin Va transcripts that contain exon F...
  33. Passeron T, Bahadoran P, Bertolotto C, Chiaverini C, Busca R, Valony G, et al. Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2-a and actin association. FASEB J. 2004;18:989-91 pubmed
    ..We demonstrate that cAMP stimulates the expression of Rab27a and rapidly increases the interaction of the melanophilin/Slac2-a with actin...
  34. Menasche G, Ho C, Sanal O, Feldmann J, Tezcan I, Ersoy F, et al. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J Clin Invest. 2003;112:450-6 pubmed
    ..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...
  35. Ishida M, Arai S, Ohbayashi N, Fukuda M. The GTPase-deficient Rab27A(Q78L) mutant inhibits melanosome transport in melanocytes through trapping of Rab27A effector protein Slac2-a/melanophilin in their cytosol: development of a novel melanosome-targetinG tag. J Biol Chem. 2014;289:11059-67 pubmed publisher
    ..activity on melanosome transport is completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin. When we forcibly expressed Rab27A(Q78L) on mature melanosomes by using a novel melanosome-targeting tag that ..
  36. Wu X, Sakamoto T, Zhang F, Sellers J, Hammer J. In vitro reconstitution of a transport complex containing Rab27a, melanophilin and myosin Va. FEBS Lett. 2006;580:5863-8 pubmed
    Rab27a and melanophilin (Mlph) are required in vivo to form a melanosome receptor for myosin Va in which Rab27a anchored in the melanosome membrane recruits Mlph, which in turn recruits myosin Va...
  37. Westbroek W, Lambert J, Bahadoran P, Busca R, Herteleer M, Smit N, et al. Interactions of human Myosin Va isoforms, endogenously expressed in human melanocytes, are tightly regulated by the tail domain. J Invest Dermatol. 2003;120:465-75 pubmed
    ..with and influence melanosome distribution by indirect interaction with rab27a and direct interaction with melanophilin. These results indicate that the myosin Va medial tail domain provides the globular tail domain with organelle-..
  38. Menasche G, Feldmann J, Houdusse A, Desaymard C, Fischer A, Goud B, et al. Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients. Blood. 2003;101:2736-42 pubmed
    ..However, in contrast to Gln78Leu, Trp73Gly mutant construct neither interacts with the Rab27a effector melanophilin nor modifies melanosome distribution and cytotoxic granule exocytosis...