Melanophilin is a carrier protein which in humans is encoded by the MLPHgene.[5][6] 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.[7] 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.[8]
In melanocytic cells MLPH gene expression may be regulated by MITF.[9]
Clinical significanceedit
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[10] and cats.[11] 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.[12]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000115648 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000026303 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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. Bibcode:2001PNAS...9810238M. doi:10.1073/pnas.181336698. PMC56945. 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. S2CID 14844547.
^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. S2CID 24698373.
^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. PMC2675971. PMID 19307593.
Further readingedit
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. S2CID 24564755.
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. S2CID 46201875.
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. S2CID 23921179.
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. PMC166299. 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. PMC528928. 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. PMC403697. 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. 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. PMC2564555. PMID 16415175.
External linksedit
melanophilin+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
melanophilin, carrier, protein, which, humans, encoded, mlph, gene, several, alternatively, spliced, transcript, variants, this, gene, have, been, described, full, length, nature, some, these, variants, been, determined, mlphidentifiersaliasesmlph, slac2, mela. Melanophilin is a carrier protein which in humans is encoded by the MLPH gene 5 6 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 MLPHIdentifiersAliasesMLPH SLAC2 A melanophilinExternal IDsOMIM 606526 MGI 2176380 HomoloGene 11465 GeneCards MLPHGene location Human Chr Chromosome 2 human 1 Band2q37 3Start237 485 428 bp 1 End237 555 322 bp 1 Gene location Mouse Chr Chromosome 1 mouse 2 Band1 D 1 45 73 cMStart90 842 807 bp 2 End90 878 864 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inpancreatic ductal cellparotid glandright uterine tubecanal of the cervixright lungminor salivary glandprostatepylorusupper lobe of left lunggallbladderTop expressed inpyloric antrumlacrimal glandepithelium of stomachmucous cell of stomachsalivary glandsubmandibular glandparotid glandirisPaneth cellcolonMore reference expression dataBioGPSn aGene ontologyMolecular functionprotein binding metal ion binding actin binding myosin binding protein macromolecule adaptor activityCellular componentcytoplasm perinuclear region of cytoplasm dendrite extracellular exosome cortical actin cytoskeletonBiological processintracellular protein transport vesicle transport along actin filament melanosome transportSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez79083171531EnsemblENSG00000115648ENSMUSG00000026303UniProtQ9BV36Q91V27RefSeq mRNA NM 001042467NM 001281473NM 001281474NM 024101NM 053015RefSeq protein NP 001035932NP 001268402NP 001268403NP 077006NP 443748Location UCSC Chr 2 237 49 237 56 MbChr 1 90 84 90 88 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 References 4 Further reading 5 External linksFunction editThis 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 7 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 8 In melanocytic cells MLPH gene expression may be regulated by MITF 9 Clinical significance editA 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 10 and cats 11 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 12 References edit a b c GRCh38 Ensembl release 89 ENSG00000115648 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000026303 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 Bibcode 2001PNAS 9810238M 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 S2CID 14844547 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 S2CID 24698373 Drogemuller C Philipp U Haase B Gunzel 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 Schaffer 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 editPasseron 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 S2CID 24564755 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 S2CID 46201875 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 S2CID 23921179 Menasche 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 Bibcode 2002PNAS 9916899M 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 editmelanophilin protein human at the U S 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 nbsp This article on a gene on human chromosome 2 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Melanophilin amp oldid 1170984711, wikipedia, wiki, book, books, library,
