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FLASH GENE
Symbol RAB8A contributors: mct/npt/pgu - updated : 05-02-2020
HGNC name RAB8A, member RAS oncogene family
HGNC id 7007
Location 19p13.11      Physical location : 16.222.489 - 16.244.443
Genatlas name RABIN8
Synonym name
  • guanine nucleotide-exchange factor Rabin8
  • mel transforming oncogene (derived from cell line NK14)-
    • RAB8 homolog
  • ras-associated protein RAB8
  • oncogene c-mel
  • ras-associated protein RAB8
    • Synonym symbol(s) RAB8, MEL
    DNA
    TYPE functioning gene
    STRUCTURE 21.95 kb     8 Exon(s)
    MAPPING cloned Y linked Y status confirmed
    regionally located 800 kb distal to MY09B
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2194 - 207 - 2010 20308558
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     liver   highly
    Endocrinepancreas   highly
    Lymphoid/Immunespleen   highly
    Nervousbrain   highly
    Reproductivemale systemprostate  highly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four GTP/GDP-binding sites
  • a putative effector-binding site
  • a GEF domain (AAs 144-245)
  • AA 262-331 of Rabin8 is important for its interaction with both BBS1 and RAB11A
  • a C terminal CAAX motif
    • conjugated LipoP , Other
    HOMOLOGY
    interspecies homolog to murine Mel and Ypt1/RAB1
    homolog to Drosophila rab8
    homolog to C.elegans rab8
    Homologene
    FAMILY
  • small GTPase superfamily
  • Rab family
    • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • localizes to the primary cilium membrane during ciliogenesis
  • EXOC6 co-localizes with RAB8A in primary cilia
    • basic FUNCTION
  • GTPase activity
  • playing a role in the transport of proteins from endoplasmic reticulum to the Golgi and the plasma membrane
  • involved in neurotransmitter release
  • responsible for the localization of apical proteins in intestinal epithelial cells, necessary role for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine
  • important role for the small GTPase RAB8A in cilia assembly and function
  • involved in polarized trafficking of vesicles from the trans-Golgi network
  • direct downstream effector of RAB11A, which functions in membrane trafficking from the trans-Golgi network and recycling endosomes
  • regulator of membrane traffic from endosomal compartments to the cell surface, essential for primary ciliogenesis
  • RAB13 and RAB8A are Rab-GTPases activated by insulin, and downstream of TBC1D4 they regulate traffic of SLC2A4 vesicles, possibly acting at distinct steps and sites
  • could participate in ciliary membrane assembly
  • both RAB8A and RAB8B are important for ciliation in RPE cells
  • RAB8A and RAB8B are recruited by RAB11A after serum starvation for transport to the pericentriolar compartment
  • RAB6A, RAB8A, and MICAL3 cooperate in controlling docking and fusion of exocytotic carriers
  • RAB8A guanine nucleotide exchange factor-effector interaction is important for exocytosis and primary ciliogenesis
  • OCRL and RAB8A are recruited to the cilia during early ciliogenesis
  • is involved in controlling several trafficking processes, including the trafficking of transferrin receptor from the early endosome to the recycling endosome
  • compensatory effect of RAB8A and RAB8B in apical transport, and neither RAB8A nor RAB8B are required for basolateral and/or dendritic transport
  • unique cascade consisting of GSK3B, DZIP1, and RAB8A that regulates ciliogenesis after mitosis
  • controls Wnt delivery in producing cells and is crucial for Paneth cell maturation
  • RAB8A is a new player in vesicular traffic to the immune synapse and provide insight into the pathways co-opted by different cell types for immune synapse assembly and ciliogenesis
  • is an essential participant in primary cilium formation
  • RAB8A plays a role in exocytosis toward the polarized plasma membrane in eukaryotic cells
  • converging roles of two PD genes TMEM230 and LRRK2 on RAB8A function, suggesting that retromer and secretory dysfunction play an important role in Parkinson disease (PD) pathogenesis
  • small GTPase RAB8A regulates lipid uptake and storage in skeletal muscle
  • small Rab GTPase involved in vesicular trafficking
  • stress-responsive machinery composed of RAB29, LRRK2, phosphorylated RAB8A/RAB10, and their downstream effectors implicated in the maintenance of lysosomal homeostasis
  • Cl- channels regulate lipid droplet formation via RAB8A expression during adipocyte differentiation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text vesicular traffic
    PATHWAY
    metabolism
    signaling
    a component potential RAB11A–RAB8A cascade which may function in primary cilium assembly
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GTP
    • protein
  • interacting with AHI1 (distribution and functioning of RAB8A is regulated by AHI1, not only affecting cilium formation, but also vesicle transport)
  • interaction of MICALL2 with RAB8A and RAB13 coordinates the assembly of adherens junctions and tight junctions
  • RAB8A and RAB11A are associated with the BBS pathway
  • in teracting with TRAPPC3, -C9, and -C10 that are required for RABIN8 centrosome trafficking and ciliogenesis
  • PEBP1 interacting with RAB8A (interacts preferably with the GDP-bound form of RAB8A in the retina)
  • RAB8A8A and ERC1 can be linked by MICAL3
  • TBC1D10A interacts with SYTL1 to coordinate RAB8A and ARF6 membrane trafficking
  • exocyst component EXOC6 directly interacts with RAB8A in its activated conformation
  • through its catalytic activity, TBC1D17 inhibits recruitment of RAB8A to the tubules and reduces colocalisation of transferrin receptor and RAB8A
  • ASAP1 serves as a scaffold that brings together the proteins necessary for transport to the cilia including the GTP-binding protein ARF4 and the two G proteins of the Rab family--RAB11A and RAB8A--linked by the RAB8A guanine nucleotide exchange factor RAB3IP
  • SYTL4 and RAB8A enhance dense granule release and the SYTL4 effect is dependent on RAB8A binding
  • components of the vesicular transport machinery, the GEF RAB3IP and the GTPase RAB8A, are interacting partners of CEP164
  • STK38L-mediated RAB8A phosphorylation is crucial for ciliogenesis by triggering the switch in binding specificity of RAB8A from phosphatidylserine (PS) to EXOC6, thereby promoting local activation of RAB8 and ciliary membrane formation
  • RAB3IL1 is a dual RAB-binding protein that could potentially link RAB3A and RAB11A/RAB11B and/or RAB8A/RAB8B and RAB11-mediated intracellular trafficking processes
  • KIAA0586 affects cilia formation through RAB8A recruitment and/or activation
  • MYO5A mediates RAB8A-regulated SLC2A4 vesicle exocytosis in insulin-stimulated muscle cells
  • RAB8A enhanced SNCA aggregation and reduced SNCA-induced cellular toxicity
  • RAB35 functions as a master RAB that determines the intracellular localization of MICALL1, which in turn functions as a scaffold for RAB8A, RAB13, and RAB36
  • TBC1D4 is the GTPase activating protein (GAP) for RAB8A, which forms a ternary complex with CIDEC and RAB8A to positively regulate Lipid droplets fusion
  • WLS binds to RAB8A
  • small GTPase RAB8A interacts with VAMP3 to regulate the delivery of recycling T-cell receptors to the immune synapse
  • EHBP1L1 links RAB8A and the BIN1-dynamin complex, which generates membrane curvature and excises the vesicle at the ERC for apical transport
  • ARHGAP26 -mediated removal of RAB8A from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis
  • new function of LRRK2 mediated by RAB8A phosphorylation and related to various centrosomal defects
  • LRRK2 mediated RAB8A phosphorylation promotes lipid storage
  • by impairing RAB8A function, pathogenic G2019S LRRK2 deregulates endolysosomal transport and endocytic recycling events
  • BAG6 binds not only RAB8A but also a functionally distinct set of Rab family proteins, and is also required for the correct distribution of Golgi and endosomal markers
  • phosphatase OCRL, located on macropinosomes, interacts with RAB8A, suggesting that RAB8A may operate on multiple levels to modulate phosphoinositides in macropinosomes
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    reduced in intestinal epithelial cells of the microvillus inclusion disease patient
    constitutional   deletion    
    muscle-specific RAB8A deletion caused hyperlipidemia and exacerbated hepatosteatosis induced by a high-fat diet
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • RAB8A might be a new biomarker for endometrial cancer
    • Therapy target
    ANIMAL & CELL MODELS