Melanophilin

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.

MLPH
Identifiers
AliasesMLPH, SLAC2-A, melanophilin
External IDsOMIM: 606526 MGI: 2176380 HomoloGene: 11465 GeneCards: MLPH
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2q37.3Start237,485,428 bp[1]
End237,555,322 bp[1]
Orthologs
SpeciesHumanMouse
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 MbChr 1: 90.92 – 90.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

gollark: I mean, if they got them for free for some unfathomable reason, sure I guess?
gollark: > How is it wastefulMacBooks are very expensive and not particularly worth it.
gollark: How wasteful.
gollark: Or, well, the obvious alternative.
gollark: Maybe. On the one hand I at least like to think I'm vaguely better than average at actually paying attention to explanations for things and won't just immediately consign them to "outgroup → bad" or "not convention → bad". On the other hand probably most people think that since people are bad at comparing things. On the third hand, which I totally have, the alternative is to just assume people doing things are probably right, which seems wrong.

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.
  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.
  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

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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