Melanophilin

MLPH
Identifiers
Aliases	MLPH , SLAC2-A, melanophilin
External IDs	OMIM: 606526 MGI: 2176380 HomoloGene: 11465 GeneCards: MLPH
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2q37.3 Start 237,485,428 bp [1] End 237,555,322 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1 D|1 45.73 cM Start 90,842,807 bp [2] End 90,878,864 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pancreatic ductal cell parotid gland right uterine tube canal of the cervix right lung minor salivary gland prostate pylorus upper lobe of left lung gallbladder Top expressed in pyloric antrum lacrimal gland epithelium of stomach mucous cell of stomach salivary gland submandibular gland parotid gland iris Paneth cell colon More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding metal ion binding actin binding myosin binding protein-macromolecule adaptor activity Cellular component cytoplasm perinuclear region of cytoplasm dendrite extracellular exosome cortical actin cytoskeleton Biological process intracellular protein transport vesicle transport along actin filament melanosome transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79083 171531 Ensembl ENSG00000115648 ENSMUSG00000026303 UniProt Q9BV36 Q91V27 RefSeq (mRNA) NM_001042467 NM_001281473 NM_001281474 NM_024101 NM_053015 RefSeq (protein) NP_001035932 NP_001268402 NP_001268403 NP_077006 NP_443748 Location (UCSC) Chr 2: 237.49 – 237.56 Mb Chr 1: 90.84 – 90.88 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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. ^[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

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]

References

1. GRCh38: Ensembl release 89: ENSG00000115648 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026303 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. 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.
8. "Entrez Gene: MLPH Melanophilin".
9. 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.
10. 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.
11. 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.
12. 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. 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. 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

• melanophilin+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.