Gene Symbol: Mlph
Description: melanophilin
Alias: 2210418F23Rik, 5031433I09Rik, AW228792, D1Wsu84e, Slac-2a, l(1)-3Rk, l1Rk3, melanophilin, exophilin-3, leaden protein, slaC2-a, slp homolog lacking C2 domains a, synaptotagmin-like protein 2a
Species: mouse
Products:     Mlph

Top Publications

  1. 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 ..
  2. Kuroda T, Ariga H, Fukuda M. The actin-binding domain of Slac2-a/melanophilin is required for melanosome distribution in melanocytes. Mol Cell Biol. 2003;23:5245-55 pubmed
    ..Three proteins, Rab27A, myosin Va, and Slac2-a/melanophilin (a linker protein between Rab27A and myosin Va), are known to be essential for proper actin-based melanosome ..
  3. Wu X, Rao K, Zhang H, Wang F, Sellers J, Matesic L, et al. Identification of an organelle receptor for myosin-Va. Nat Cell Biol. 2002;4:271-8 pubmed one of its cargoes, the melanosome, by interacting with a receptor-protein complex containing Rab27a and melanophilin, a postulated Rab27a effector...
  4. 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...
  5. Karolyi I, Dootz G, Halsey K, Beyer L, Probst F, Johnson K, et al. Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice. Mamm Genome. 2007;18:596-608 pubmed
    ..We conclude that TH supplement administered during the critical period of hearing development in mice can prevent deafness associated with congenital hypothyroidism of heterogeneous genetic etiology. ..
  6. Wilcox F, Hirschhorn L, Taylor B, Womack J, Roderick T. Genetic variation in alkaline phosphatase of the house mouse (Mus musculus) with emphasis on a manganese-requiring isozyme. Biochem Genet. 1979;17:1093-107 pubmed
    ..6 +/- 2.9 cM from the M1s locus on the side distal to the centromere. Test-cross data show the following gene order and recombination percentages: Dip-1 19.0 +/- 3.8% Lp 7.4 +/- 2.2% Akp-1. ..
  7. Nadeau J. Modifier genes in mice and humans. Nat Rev Genet. 2001;2:165-74 pubmed
  8. Taylor B, Meier H. Mapping the adrenal lipid depletion gene of the AKR/J mouse strain. Genet Res. 1975;26:307-12 pubmed
  9. 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...

More Information


  1. Szymura J, Taylor B, Klein J. Upg-2: a urinary pepsinogen variant located on chromosome 1 of the mouse. Biochem Genet. 1982;20:1211-9 pubmed
    ..Typing of recombinant inbred strains suggests that the location of the Upg-2 locus is on chromosome 1, in the vicinity of loci coding for other peptidases, namely, Pep-2 and Rnr, and of the Acf-1 locus. ..
  2. 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 ..
  3. Evans E, Beechey C, Burtenshaw M, Searle A. T(In1;5)44H, a complex mouse chromosomal rearrangement with a phenotypic effect. Cytogenet Cell Genet. 1993;63:66-72 pubmed
    ..Analysis of chromatid classes at this stage suggests reasons for both the high embryonic mortality and the shortage of liveborn T44H carriers. ..
  4. Hutton J, Roderick T. Linkage analyses using biochemical variants in mice. 3. Linkage relationships of eleven biochemical markers. Biochem Genet. 1970;4:339-50 pubmed
  5. Provance D, James T, Mercer J. Melanophilin, the product of the leaden locus, is required for targeting of myosin-Va to melanosomes. Traffic. 2002;3:124-32 pubmed
    ..We have utilized primary melanocytes to examine the interdependencies between rab27a, myosin-Va, and melanophilin. The localization of rab27a to melanosomes did not require the function of either myosin-Va or melanophilin, ..
  6. Ogawa Y, Itoh H, Yoshitake Y, Inoue M, Yoshimasa T, Serikawa T, et al. Molecular cloning and chromosomal assignment of the mouse C-type natriuretic peptide (CNP) gene (Nppc): comparison with the human CNP gene (NPPC). Genomics. 1994;24:383-7 pubmed
    ..Using somatic hybrid cell methodology, the CNP gene (NPPC) was assigned to human chromosome 2. The present study has added another locus to the conserved syntenic group in mice and humans. ..
  7. Ward R, Stone B, Raetzman L, Camper S. Cell proliferation and vascularization in mouse models of pituitary hormone deficiency. Mol Endocrinol. 2006;20:1378-90 pubmed
    ..This suggests that Prop1 and/or Pit1 may be necessary for caspase-3 expression. These studies provide further insight as to the mechanisms of Prop1 and Pit1 action in mice. ..
  8. Hume A, Collinson L, Hopkins C, Strom M, Barral D, Bossi G, et al. The leaden gene product is required with Rab27a to recruit myosin Va to melanosomes in melanocytes. Traffic. 2002;3:193-202 pubmed
    ..However, in contrast to melanocytes, we found that neither the leaden gene product (melanophilin) nor myosin Va was detectable in cytotoxic T lymphocytes...
  9. Bradley D, Taylor B, Blackwell J, Evans E, Freeman J. Regulation of Leishmania populations within the host. III. Mapping of the locus controlling susceptibility to visceral leishmaniasis in the mouse. Clin Exp Immunol. 1979;37:7-14 pubmed
    ..The data indicate that the gene order is centromere-Lsh-Id-1-ln-Dip-1. The estimated recombination frequency between Lsh and Id-1 is 0.12 +/- 0.04. This mapping is away from the known histocompatibility loci. ..
  10. Wilson C, Erdos E, Wilson J, Taylor B. Location on chromosome 1 of Rnr, a gene that regulates renin in the submaxillary gland of the mouse. Proc Natl Acad Sci U S A. 1978;75:5623-6 pubmed
    ..Documentation that a single gene can have major effects on renin in the submaxillary gland of the mouse implies that single gene differences might explain known variations in renin in other species. ..
  11. Lyon M, Quinney R, Glenister P, Kerscher S, Guillot P, Boyd Y. Doublefoot: a new mouse mutant affecting development of limbs and head. Genet Res. 1996;68:221-31 pubmed
    ..The gene maps close to the locus of Pax3, but crossovers between Dbf and Pax3 have been found, ruling out the possibility that a gain-of-function mutation in Pax3 might be involved. ..
  12. Moore K, Swing D, Rinchik E, Mucenski M, Buchberg A, Copeland N, et al. The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln. Genetics. 1988;119:933-41 pubmed
    ..These studies provide new insights into the mechanism of action of dsu and into the interrelationships between members of a family of pigment genes. ..
  13. Stephenson D, Glenister P, Hornby J. Site of beige (bg) and leaden (ln) pigment gene expression determined by recombinant embryonic skin grafts and aggregation mouse chimaeras employing sash (Wsh) homozygotes. Genet Res. 1985;46:193-205 pubmed
  14. 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...
  15. Fukuda M, Saegusa C, Mikoshiba K. Novel splicing isoforms of synaptotagmin-like proteins 2 and 3: identification of the Slp homology domain. Biochem Biophys Res Commun. 2001;283:513-9 pubmed
    ..In addition, we show that the Slp2-a/c/d mRNAs are differentially distributed in different mouse tissues and at different stages of development, suggesting that these transcripts may be regulated by different promoters. ..
  16. Fang Q, Giordimaina A, Dolan D, Camper S, Mustapha M. Genetic background of Prop1(df) mutants provides remarkable protection against hypothyroidism-induced hearing impairment. J Assoc Res Otolaryngol. 2012;13:173-184 pubmed publisher
    ..Thus, the genetic background of Prop1(df) mutants is remarkably protective for most functions affected in other hypothyroid mice. The Prop1(df) mutant is an attractive model for identifying the genes that protect against deafness. ..
  17. Singh R, Mizuno K, Wasmeier C, Wavre Shapton S, Recchi C, Catz S, et al. Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion. FEBS J. 2013;280:892-903 pubmed publisher
    ..Rab27 is known to interact with actin via its effectors melanophilin (Mlph) and myosin Va (MyoVa) in other cell types...
  18. McMurtrie E, Barbosa M, Zerial M, Kingsmore S. Rab17 and rab18, small GTPases with specificity for polarized epithelial cells: genetic mapping in the mouse. Genomics. 1997;45:623-5 pubmed
    ..We also discuss some implications of Rab17 and Rab18 mapping, including their candidacy for the mouse mutations ln (leaden), Tw (twirler), and ax (ataxia). ..
  19. 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...
  20. Hume A, Ushakov D, Tarafder A, Ferenczi M, Seabra M. Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes. J Cell Sci. 2007;120:3111-22 pubmed
    ..b>Melanophilin (Mlph) is a Rab27a- and myosin Va (MyoVa)-binding protein that regulates this process...
  21. Kukimoto Niino M, Sakamoto A, Kanno E, Hanawa Suetsugu K, Terada T, Shirouzu M, et al. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure. 2008;16:1478-90 pubmed publisher
    ..melanosome transport in mammalian skin melanocytes through its interaction with a specific effector, Slac2-a/melanophilin. Mutations that disrupt the Rab27A/Slac2-a interaction cause human Griscelli syndrome...
  22. Faulkner Jones B, Godinho L, Reese B, Pasquini G, Ruefli A, Tan S. Cloning and expression of mouse Cadherin-7, a type-II cadherin isolated from the developing eye. Mol Cell Neurosci. 1999;14:1-16 pubmed
    ..This expression pattern suggests a role for Cadherin-7 in mouse retinal development, particularly in the formation and maintenance of the GCL. ..
  23. Kozak C. Susceptibility of wild mouse cells to exogenous infection with xenotropic leukemia viruses: control by a single dominant locus on chromosome 1. J Virol. 1985;55:690-5 pubmed
  24. Hearing V, Phillips P, Lutzner M. The fine structure of melanogenesis in coat color mutants of the mouse. J Ultrastruct Res. 1973;43:88-106 pubmed
  25. Anderson M, Hawes N, Trantow C, Chang B, John S. Iris phenotypes and pigment dispersion caused by genes influencing pigmentation. Pigment Cell Melanoma Res. 2008;21:565-78 pubmed publisher
    ..Combined, these findings illustrate the utility of studying iris phenotypes as a means of discovering new pathways, and re-linking old ones, to processes of pigmented cells in health and disease. ..
  26. Sweet S, Quevedo W. Role of melanocyte morphology in pigmentation of mouse hair. Anat Rec. 1968;162:243-54 pubmed
  27. Borodin P, Gorlov I, Ladygina TYu -. Double insertion of homogeneously staining regions in chromosome 1 of wild Mus musculus musculus: effects on chromosome pairing and recombination. J Hered. 1990;81:91-5 pubmed
    ..The increase in the total chiasma number in the heteromorphic bivalent is due to the addition of double chiasmata located mostly at precentromeric and pretelomeric regions of the chromosome. ..
  28. Seldin M, Roderick T, Paigen B. Mouse chromosome 1. Mamm Genome. 1991;1 Spec No:S1-17 pubmed
  29. 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...
  30. Loster J, Pretsch W, Sandulache R, Schmitt John T, Lyon M, Graw J. Close linkage of the dominant cataract mutations (Cat-2) with Idh-1 and cryge on mouse chromosome 1. Genomics. 1994;23:240-2 pubmed
  31. Sundaresan S, Balasubbu S, Mustapha M. Thyroid hormone is required for the pruning of afferent type II spiral ganglion neurons in the mouse cochlea. Neuroscience. 2016;312:165-78 pubmed publisher
    ..Our data suggest that the state of maturation of hair cells, as determined by OTOF expression, may not regulate the pruning of their afferent innervation. ..
  32. Green S, Steinberg D, Quehenberger O. Cloning and expression in Xenopus oocytes of a mouse homologue of the human acylcoenzyme A: cholesterol acyltransferase and its potential role in metabolism of oxidized LDL. Biochem Biophys Res Commun. 1996;218:924-9 pubmed
    ..Injection of ACAT mRNA into oocytes induced specific binding of OxLDL. ACAT is expressed in mouse macrophages as a approximately 3.6 kB transcript and the expression is upregulated in human THP-1 cells treated with PMA. ..
  33. LaVail J, Nixon R, Sidman R. Genetic control of retinal ganglion cell projections. J Comp Neurol. 1978;182:399-421 pubmed
    ..The few anomalous results suggest that alternative or additional factors may control optic axon projections. ..
  34. Hauschka T, Jacobs B, Holdridge B. Recessive yellow and its interaction with belted in the mouse. J Hered. 1968;59:339-41 pubmed
  35. Dickie M, WOOLLEY G. Fuzzy mice. J Hered. 1950;41:193-6 pubmed
  36. Everett C, Glenister P, Taylor D, Lyon M, Kratochvilova Loester J, Favor J. Mapping of six dominant cataract genes in the mouse. Genomics. 1994;20:429-34 pubmed
    ..A third mutant, provisionally designated Npp, mapped to Chromosome 5, 1.3 +/- 0.9 cM from the locus of W, and thus probably has a homologue on human Chromosome 4. ..
  37. Moore K, Swing D, Copeland N, Jenkins N. Interaction of the murine dilute suppressor gene (dsu) with fourteen coat color mutations. Genetics. 1990;125:421-30 pubmed
    ..These studies have thus identified a second group of genes whose phenotypes are suppressed by dsu and have provided new insights into the mechanism of action of dsu. ..
  38. 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 ..
  39. Taylor B, O Brien A. Position on mouse chromosome 1 of a gene that controls resistance to Salmonella typhimurium. Infect Immun. 1982;36:1257-60 pubmed
    ..The results of a five-point backcross clearly showed that the correct gene order on chromosome 1 is fz-Idh-1-Ity-ln-Pep-3. ..
  40. Markert C, Silvers W. The Effects of Genotype and Cell Environment on Melanoblast Differentiation in the House Mouse. Genetics. 1956;41:429-50 pubmed
  41. Tada N, Kimura S, Liu Lam Y, Hammerling U. Mouse alloantigen system Ly-m22 predominantly expressed on T lymphocytes and controlled by a gene linked to M1s region on chromosome 1. Hybridoma. 1983;2:29-38 pubmed
    ..Analysis of BXD and SWXL recombinant inbred strains revealed close linkage between Ly-m22 and Ltw-4 loci on chromosome 1. The estimated recombination frequency is 0.027 +/- 0.081. ..
  42. Higgins M, Hill R, West J. Dominant hemimelia and En-1 on mouse chromosome 1 are not allelic. Genet Res. 1992;60:53-60 pubmed
    ..The likely gene order and recombination frequencies of these loci are: ln (5.2 +/- 0.9) Emv-17 (1.1 +/- 0.4) Dh (0.7 +/- 0.4) En-1 (3.0 +/- 0.7) Pep-3. This shows that Dh is not a mutant allele of En-1. ..
  43. Buchberg A, Taylor B, Jenkins N, Copeland N. Chromosomal localization of Emv-16 and Emv-17, two closely linked ecotropic proviruses of RF/J mice. J Virol. 1986;60:1175-8 pubmed
  44. Volkmann N, Liu H, Hazelwood L, Krementsova E, Lowey S, Trybus K, et al. The structural basis of myosin V processive movement as revealed by electron cryomicroscopy. Mol Cell. 2005;19:595-605 pubmed
    ..Our findings reveal how the structural elements of myosin V work together to allow myosin V to step along actin for multiple ATPase cycles without dissociating. ..
  45. Martel J, Michael D, Fejes Toth G, NARAY FEJES TOTH A. Melanophilin, a novel aldosterone-induced gene in mouse cortical collecting duct cells. Am J Physiol Renal Physiol. 2007;293:F904-13 pubmed
    ..We report that the transcript levels of melanophilin (MLPH), a protein involved in vesicular trafficking in melanocytes, are rapidly increased by aldosterone in ..
  46. Geething N, Spudich J. Identification of a minimal myosin Va binding site within an intrinsically unstructured domain of melanophilin. J Biol Chem. 2007;282:21518-28 pubmed
    ..The recruitment of myosin Va to the melanosome and proper transport of the melanosome requires melanophilin, which directly binds to myosin Va and is tethered to the melanosome membrane via Rab27a...
  47. Li X, Ikebe R, Ikebe M. Activation of myosin Va function by melanophilin, a specific docking partner of myosin Va. J Biol Chem. 2005;280:17815-22 pubmed
    It is known that melanophilin is a myosin Va-targeting molecule that links myosin Va and the cargo vesicles in cells...
  48. Fukuda M, Itoh T. Slac2-a/melanophilin contains multiple PEST-like sequences that are highly sensitive to proteolysis. J Biol Chem. 2004;279:22314-21 pubmed
    The synaptotagmin-like protein homologue lacking C2 domains-a (Slac2-a)/melanophilin was recently identified as the "missing link" between the small GTPase Rab27A and the actin-based motor protein myosin Va...
  49. Christner P, Siracusa L, Hawkins D, McGrath R, Betz J, Ball S, et al. A high-resolution linkage map of the tight skin 2 (Tsk2) locus: a mouse model for scleroderma (SSc) and other cutaneous fibrotic diseases. Mamm Genome. 1996;7:610-2 pubmed
  50. Wu X, Tsan G, Hammer J. Melanophilin and myosin Va track the microtubule plus end on EB1. J Cell Biol. 2005;171:201-7 pubmed
    ..surface of melanosomes by a receptor complex containing Rab27a that is present in the melanosome membrane and melanophilin (Mlp), which links myosin Va to Rab27a...
  51. Gerrelli D, Sharpe N, Latchman D. Cloning and sequencing of a mouse embryonal carcinoma cell mRNA encoding the tissue specific RNA splicing protein SmN. Nucleic Acids Res. 1991;19:6642 pubmed
  52. Novak E, Hui S, Swank R. Platelet storage pool deficiency in mouse pigment mutations associated with seven distinct genetic loci. Blood. 1984;63:536-44 pubmed
    ..Also, the results emphasize the genetic, morphological, and functional interrelatedness of three organelles: melanosomes, lysosomes, and platelet dense granules. ..
  53. Plant J, Glynn A. Locating salmonella resistance gene on mouse chromosome 1. Clin Exp Immunol. 1979;37:1-6 pubmed
    ..typhimurium without infecting the mice, so permitting experiments on the nature of the inheritance in unsensitized mice. ..
  54. Sckolnick M, Krementsova E, Warshaw D, Trybus K. More than just a cargo adapter, melanophilin prolongs and slows processive runs of myosin Va. J Biol Chem. 2013;288:29313-22 pubmed publisher
    ..b>Melanophilin (Mlph) is the adapter protein that links Rab27a-melanosomes to myoVa...