Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol MLPH contributors: mct - updated : 04-12-2018
HGNC name melanophilin
HGNC id 29643
Corresponding disease
VCIPD3 variable combined immunodeficiency and pigmentary dilution 3
Location 2q37.3      Physical location : 238.395.877 - 238.463.960
Synonym name
  • synaptotagmin-like protein SLAC-2
  • exophilin-3
  • Slp homolog lacking C2 domains a
  • Synonym symbol(s) MELPH, SLAC2-A, l1Rk3, l(1)-3Rk, MGC59733, MGC2771
    DNA
    TYPE functioning gene
    STRUCTURE 68.91 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 3703 - 572 - 2002 11980908
    16 - 3787 66 600 - 2002 11980908
    12 - 3508 - 457 - 2002 11980908
    13 - 3427 - 480 - 2002 11980908
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systembreastmammary gland highly
     male systemprostate  highly
    Respiratoryrespiratory tracttrachea  highly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentmelanocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal Slp homology domain (SHD)
  • two alpha helical regions (SHD1, SHD2)
  • two Zn2+ binding sites
  • a short aromatic-rich amino acid region
  • a FYVE-type zinc finger
  • a RabBD (Rab-binding) domain
  • a coiled-coil domain essential for MYO5A recruitment and melanosome transport in melanocytes
  • two Ca2+ dependent targeting domains at the C terminus, and C-terminal actin-binding domain (ABD), that is a target of PRKACA
  • HOMOLOGY
    intraspecies homolog to synaptotagmin
    homolog to gramiphilin
    Homologene
    FAMILY SLP family
    CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nuclear envelope
    text melanosomes
    basic FUNCTION
  • contributing to recognition of its cargo by MYO5A
  • Rab effector protein involved in melanosome transport
  • regulates retention of melanosomes at the peripheral actin cytoskeleton of melanocytes, a process essential for normal mammalian pigmentation
  • MLPH is targeted to and/or stabilised on melanosomes by RAB27A, and then recruits MYO5A
  • MLPH acts as a "tether" that links the motor to the track
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
  • component of a tripartite complex for melanosome transport
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • RAB27A by its Slp N terminal domain
  • MYO5A by its C terminal region
  • in melanocytes, MYO5A tail interacts with its cargo-binding protein melanophilin (MLPH), which associates with melanosome via RAB27A
  • RAB27A is required for actin-based melanosome transport in mammalian skin melanocytes through its interaction with a specific effector MLPH
  • MLPH is the adapter protein that links RAB27A-melanosomes to MYO5A
  • MLPH-dependent changes in MYO5a depend on a positively charged cluster of amino acids in the actin binding domain of MLPH
  • RAB27A mutant (Q78L) is unable to localize on mature melanosomes and its inhibitory activity on melanosome transport is completely dependent on its binding to the RAB27A effector MLPH
  • MLPH/globular tail domain-binding domain (GTBD) is able to bind to the GTD of MYO5A in preactivated state and allosterically inhibits the binding of globular tail domain (GTD) to the head, thus inducing the extended conformation and activating the motor function of MYO5A
  • MLPH interaction with RAB27A is important for MLPH stability and melanosome transport
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) VCIPD3
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS