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FLASH GENE
Symbol ARL2 contributors: mct/npt - updated : 31-08-2017
HGNC name ADP-ribosylation factor-like 2
HGNC id 693
Location 11q13.1      Physical location : 64.781.585 - 64.789.655
Synonym symbol(s) ARFL2
DNA
TYPE functioning gene
STRUCTURE 8.07 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 993 20 184 - 2016 27400436
4 - 912 - 157 - 2016 27400436
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestine   highly
Endocrineparathyroid   highly
Visualeyeretina    Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Visualcone photoreceptor Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N myristylation site
  • a conserved GTP-binding domains, lacking the cysteine (near C terminus) present in most members of RAS superfamily
  • HOMOLOGY
    interspecies homolog to murine Arl2
    intraspecies paralog to ARL3
    Homologene
    FAMILY
  • small GTPase superfamily
  • ADP-ribosylation factors (ARF) family
  • ARF family and RAS superfamily of regulatory GTPases
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleolus
    text
  • localize specifically to mitochondria, where it also plays essential roles
  • both ARL2 and TBCD also localize to centrosomes
  • basic FUNCTION
  • having related but distinct roles at centrosomes and in regulating microtubule-dependent processes
  • beta-tubulin cofactor D (TBCD) participate in apical junctional complex disassembly and epithelial depolarization
  • involved in the folding of tubulin peptides
  • plays essential roles in the biogenesis of tubulin and in microtubule dynamics, as well as traffic of farnesylated proteins
  • is essential to a number of mitochondrial functions, including mitochondrial morphology, motility, and maintenance of ATP levels
  • plays likely essential roles inside mitochondria along with other cellular functions, at least in part to provide coupling of regulation between these essential cell processes
  • ARL2, and its cytosolic binding partner cofactor D (TBCD), is important in tubulin folding and microtubule dynamics
  • roles for ARL2, in concert with its closest paralog ARL3, in the traffic of farnesylated cargos between membranes and specifically to cilia and photoreceptor cells
  • ARL2 and ARL3 play a fundamental role as regulators of trafficking of lipid modified proteins between different compartments
  • plays a role in the regulation of mitochondrial fusion
  • ARL2 and its GAP, ELMOD2, regulate mitofusins and mitochondrial fusion and are themselves regulated in abundance at mitochondria
  • ARL2 and ELMOD2 are changing in a highly specific and regulated fashion in response to specific cellular demands and signals
  • is the first regulatory (small) GTPase shown to act inside mitochondria or in the fusion pathway
  • ARL2 plays likely a regulatory role in mitochondrial fusion, acting from the intermembrane space (IMS) and requiring at least one of the mitofusins in their canonical role in fusion of the outer membranes
  • ARL2 plays a key role in regulating the dynamics of microtubules and mitochondrial functions
  • ARL2 inhibits the proliferation, migration and tumorigenicity of glioma cells by regulating the expression of AXL
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • complexing the tumor suppressor protein phosphatase 2Ac in adenocarcinoma cells (cell cycle progression was modified particularly in regard to duration of telophase)
  • although ARL3 and ARL2 bind UNC119 with similar affinities, only ARL3 allosterically displaces cargo by accelerating its release by three orders of magnitude
  • ELMOD2 exhibited GAP activity against ARL2, ARL3, and ARF1
  • in photoreceptors, ARL2 and ARL3 participate in the trafficking of lipidated membrane-associated proteins and colocalize in the inner segment with UNC119 and PDE6D
  • ARL2-TBCD interaction is critical for proper maintenance of microtubule densities in cells
  • ELMOD2 co-localized and interacted with ARL2, a GTPase that is known to maintain mitochondrial dynamics and ATP levels in oocytes
  • ARL2 having at least two distinguishable actions in mitochondria: one leading to regulation of ATP production and a separate one that involves ELMOD2 and impacting fusion and motility
  • ARL2 and ELMOD2 staining in mitochondria are each specifically increased in cells deleted for MFN2
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in glioma, and was inversely associated with poor prognosis in glioma patients
    constitutional       loss of function
    results in a decreased rate of mitochondrial fusion
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • new prognostic marker for glioma
  • Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    new therapeutic target for glioma
    ANIMAL & CELL MODELS