Melanophilin

From Wikipedia, the free encyclopedia
Jump to: navigation, search
MLPH
Identifiers
Aliases MLPH, SLAC2-A, melanophilin
External IDs OMIM: 606526 MGI: 2176380 HomoloGene: 11465 GeneCards: 79083
Genetically Related Diseases
Disease Name References
prostate cancer
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001042467
NM_001281473
NM_001281474
NM_024101

NM_053015

RefSeq (protein)

NP_001035932.1
NP_001268402.1
NP_001268403.1
NP_077006.1

NP_443748.2

Location (UCSC) Chr 2: 237.49 – 237.56 Mb Chr 1: 90.92 – 90.95 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Melanophilin is a carrier protein which in humans is encoded by the MLPH gene.[1][2] 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[edit]

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.[3] 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.[4]

In melanocytic cells MLPH gene expression may be regulated by MITF.[5]

Clinical significance[edit]

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[6] and cats.[7] 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.[8]

References[edit]

  1. ^ 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. doi:10.1073/pnas.181336698. PMC 56945. PMID 11504925. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ "Entrez Gene: MLPH Melanophilin". 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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[edit]

External links[edit]

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