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FLASH GENE
Symbol RAB27A contributors: mct/pgu - updated : 05-02-2015
HGNC name RAB27A, member RAS oncogene family
HGNC id 9766
Corresponding disease
VCIPD2 variable combined immunodeficiency and pigmentary dilution 2
Location 15q21.3      Physical location : 55.495.801 - 55.582.001
Synonym name
  • RAS-related gene from megakaryocyte
  • GTP-binding protein Ram
  • Synonym symbol(s) RAB27, RAM, GS2, HsT18676, MGC117246
    DNA
    TYPE functioning gene
    STRUCTURE 86.21 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • two E-boxes in the proximal region of the promoter
  • MAPPING cloned Y linked N status provisional
    Map cen - D15S1032 - [D15S1003 ] - D15S209 - D15S1049 - D15S121 - D15S1029 ) - D15S962 - pter
    RNA
    TRANSCRIPTS type messenger
    text long and short forms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2824 - 221 - 2007 17352418
    7 - 2812 - 221 - 2007 17352418
    7 - 2809 - 221 - 2007 17352418
    7 - 2772 - 221 - 2007 17352418
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Lymphoid/Immunelymph node   highly
     thymus   lowly
    Reproductivefemale systemplacenta  lowly
     male systemprostate  highly
    Skin/Tegumentskin   highly
    Urinarykidney   lowly
    Visualeyeanterior segmentiris  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
     mast cell
    Blood/Hematopoieticeosinophil
    Blood/Hematopoieticmegakaryocyte
    Blood/Hematopoieticplatelet
    Lymphoid/Immunelymphocyte
    Skin/Tegumentmelanocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a GTP binding site motif A (P-loop)
  • two consensus C terminal cysteine residues (C2) to be anchored to membrane
  • conjugated LipoP , PhosphoP
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to rattus Rab27a (96.4pc)
    homolog to murine Rab27a (95.9pc)
    intraspecies paralog to RAB27B
    Homologene
    FAMILY
  • small GTPase superfamily, Rab family
  • CATEGORY immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,granule
    text membrane bound, colocalizing with melanosomes
    basic FUNCTION
  • being a small GTPase, key effector of cytotoxic granule exocytosis, vesicle transport and organelles dynamics, targeting transport and fusion of vesicles with their appropriate membrane acceptors
  • RAB27A, MYRIP and MYO7A bridges retinal melanosomes to the actin cytoskeleton and thereby mediates the local trafficking of these organelles
  • involved in the transport of melanosomes to the cell periphery
  • involved in other fundamental physiological functions, such as the transport of lytic granules and insulin secretion
  • required for both granule maturation and granule docking and priming at the immunologic synapse
  • involved in terminal phases of cytotoxic granule/melanosome exocytosis
  • may facilitate degranulation at an early step
  • may regulate with MYRIP the amount and multimeric state of VWF released from endothelial cells
  • functions in the multivesicular endosome docking at the plasma membrane and secretion pathway
  • RAB27A and RAB27B control different steps of the exosome secretion pathway
  • RAB27A, RAB27B play independent roles in neutrophil exocytosis
  • distinct role of RAB27A in granule movement at the plasma membrane and in the cytosol of NK cells
  • is involved in the exocytosis of secretory granules in melanocytes and cytotoxic T-cells
  • plays a direct regulatory role in the nascent process of phagocytosis by prolongation of the stage of actin coating via suppression of CORO1A
  • RAB27A, RAB38 and RAB32 function in melanosome maturation or trafficking in melanocyte
  • regulates motility of lysosome-related organelles and secretory granules
  • RAB27A/MYRIP/MYO5A complex is involved in linking Weibel-Palade bodies (WPB) to the peripheral actin cytoskeleton of endothelial cells to allow full maturation and prevent premature secretion of VWF
  • RAB3A and RAB27A regulate late steps during dense-core vesicle exocytosis in neuroendocrine cells
  • intrinsically essential role of RAB27A in human ethnic skin color determination
  • RAB27A and RAB27B regulate exocytosis of multivesicular endosomes
  • supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression
  • mediates insulin exocytosis not only through SYTL4, but also through other effectors expressed in pancreatic beta cells
  • GTPase activity of RAB27A is required for its melanosome localization but is not required for melanosome transport
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text melanosome transport in melanocytes
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • forming a complex with MYO5A and MLPH
  • RAB27A/RAB3A constitutes a Rab-GEF cascade in dense-core vesicle exocytosis
  • MYO5A forms a tripartite complex with RAB27A and its effector MYRIP
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GTP binding
  • protein
  • interacting with PI3K (play a central role in the exocytosis of prostate-specific markers)
  • binding SYTL1, SLAC2B, MYRIP, SYTL3, SYTL4, SYTL5, MLPH, SYTL2
  • close relationship in the expression of RAB27A, RAB27B and VPS36, with RAB27A and RAB27B being dependent on VPS36
  • interacting with UNC13D
  • MLPH is targeted to and/or stabilised on melanosomes by RAB27A, and then recruits MYO5A
  • RAB27A is required for actin-based melanosome transport in mammalian skin melanocytes through its interaction with a specific effector MLPH
  • RAB27A and RAB27B are involved in the stimulation-dependent TNFSF11 release pathway in osteoblastic cells
  • RAB17 acts on melanosomes downstream of RAB27A
  • MADD is the non-redundant RAB27A GEF in melanocytes
  • SYTL2 is required for targeting of the signaling molecule podocalyxin to the apical membrane in a RAB27A-dependent manner
  • UNC13D is a RAB27A effector that coordinates exocytosis in hematopoietic cells
  • putative RAB27A effector family proteins, SYTL1/JFC1/Slp1, is expressed in beta cells
  • two RAB27A effectors, SYTL4 and SYTL1, differentially regulate the exocytosis of either stably or minimally docked granules, respectively
  • MLPH is the adapter protein that links RAB27A-melanosomes to MYO5A
  • SYTL2 is a RAB27A effector protein that regulates transport of RAB27A-bearing vesicles and organelles through its N-terminal RAB27A-binding domain and a phospholipid-binding C2A domain
  • 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
  • RAB27A-SYTL4 complex on WPB (Weibel-Palade body) promotes exocytosis through an interaction with STXBP1, thereby controlling the release of vaso-active substances in the vasculature
  • ATP1A1 plays an essential role in RAB27A-dependent melanosome transport
  • MLPH interaction with RAB27A is important for MLPH stability and melanosome transport
  • cell & other
    REGULATION
    induced by MITF
    Other prenylated by REP1 and unprenylated in CHM (choroidemia) patients with an alternatively polyadenylation site
    ASSOCIATED DISORDERS
    corresponding disease(s) VCIPD2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in advanced prostate cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    mutated in ashen mice