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FLASH GENE
Symbol ARL3 contributors: mct/npt - updated : 26-10-2018
HGNC name ADP-ribosylation factor-like 3
HGNC id 694
Corresponding disease
JBTS35 Joubert syndrome 35
Location 10q24.32      Physical location : 104.433.489 - 104.474.190
Synonym name ARF-like 3
Synonym symbol(s) ARFL3
DNA
TYPE functioning gene
STRUCTURE 40.70 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status provisional
Map cen - D10S603 - D10S1697 - ARL3 - D10S540 - qter
Authors GeneMap (99)
Physical map
NPM3 10q24.31 nucleophosmin/nucleoplasmin, 3 MGEA5 10q24.1-q24.3 meningioma expressed antigen 5 (hyaluronidase) KCNIP2 10q24 Kv channel interacting protein 2 FLJ13114 10q24.32 hypothetical protein FLJ13114 HPS6 10q24.32 hypothetical protein FLJ13114 LDB1 10q24-q25 LIM domain binding 1 PRC 10q24.32 PGC-1 related co-activator NOLC1 10q22-q25 nucleolar and coiled-body phosphoprotein 1 ELOVL3 10q24.32 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 PITX3 10q25 paired-like homeodomain transcription factor 3 GBF1 10q24 golgi-specific brefeldin A resistance factor 1 NFKB2 10q24 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100) PSD 10q24 pleckstrin and Sec7 domain protein MGC11279 10q24.32 hypothetical protein MGC11279 MGC2491 FLJ14280 10q24.32 hypothetical protein FLJ14280 FLJ22529 10q24.32-q24.33 hypothetical protein FLJ22529 ACTR1A 10q24 ARP1 actin-related protein 1 homolog A, centractin alpha (yeast) SUFU 10q24.32 suppressor of fused homolog (Drosophila) TRIM8 10q24.3 tripartite motif-containing 8 ARL3 10q24.1 ADP-ribosylation factor-like 3 SFXN2 10q24.32 sideroflexin 2 C10orf26 10q24.33 chromosome 10 open reading frame 26 CYP17A1 10q24.3 cytochrome P450, family 17, subfamily A, polypeptide 1 LOC390000 10 similar to Tebp-pending-prov protein C10orf32 10q24.33 chromosome 10 open reading frame 32 CYT19 10q24.33 Cyt19 protein CNNM2 10q24.32 cyclin M2 NT5C2 10q24.32 5'-nucleotidase, cytosolic II LOC90470 10q24.33 similar to Ribulose-phosphate 3-epimerase (Ribulose-5-phosphate-3-epimerase) (HUSSY-17) INA 10q24.33 internexin neuronal intermediate filament protein, alpha RNF134 10q24.33 ring finger protein 134 TAF5 10q24 TAF5 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 100kDa MGC14697 10q24.33 upregulated during skeletal muscle growth 5 LOC51063 10pter-q26.12 hypothetical protein LOC51063 LOC119395 10q24.33 hypothetical protein LOC119395 NEURL 10q25.1 neuralized-like (Drosophila)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 3891 20.4 182 - 2016 27481943
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain    
Visualeyeretina    Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connective    
Epithelial    
cells
SystemCellPubmedSpeciesStageRna symbol
Visualcone photoreceptor Homo sapiens
cell lineage
cell lines choriocarcinoma and lung carcinoma cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Arl3
intraspecies paralog to ARL2
Homologene
FAMILY
  • small GTPase superfamily
  • ADP-ribosylation factors (ARF) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • mainly localized to the mitochondria, endosomes, lysosomes, and proteasome
  • basic FUNCTION
  • without intrinsic or ARF stimulated GTPase activity
  • playing roles in microtubule-dependent processes
  • binds microtubules in a regulated manner to alter specific aspects of cytokinesis
  • having roles at centrosomes and in regulating microtubule-dependent processes
  • localizes to the cilium and is crucial for ciliogenesis and axoneme formation, as well as cargo displacement of lipidated proteins in the cilium
  • ARL3 is a novel manchette-related protein with an important role in spermiogenesis
  • ARL3 and DYNLL1 regulate dissociation of dynactin from dynein
  • role for ARL3 in the migration of photoreceptor nuclei
  • is a key player in prenylated protein trafficking in rod photoreceptor cells
  • 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
  • RP2 and ARL3 regulate the trafficking of specific kinesins to cilia tips
  • binary functions of ARL3-GTP as a key molecule in late-stage photoreceptor ciliogenesis and cargo displacement factor
  • plays important role in regulating ciliary trafficking, ans is likely necessary for autophagy
  • small GTP-binding protein that is involved in directing lipid-modified proteins into the cilium in a GTP-dependent manner
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • low molecular weight GTP binding
  • RP2 (to link the cell membrane with the cytoskeleton in photoreceptors)
  • RP2 may co-operate with ARL3 and its effectors in the cilia-associated traffic of G proteins
  • 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
  • ARL13B is the GEF for ARL3, and GEF activity of ARL13B is mediated by the G-domain plus an additional C-terminal helix
  • ARL3 is a novel STAT3-binding partner (ARL3 recognizes the DNA-binding domain as well as the C-terminal region of STAT3, and their binding was the strongest when both proteins were activated
  • ARL3 interacts with STAT3 and regulates the transcriptional activation of STAT3 by influencing its nuclear accumulation of STAT3
  • ciliary tip kinesins KIF7 and KIF17 are novel interaction partners of the small GTPase ARL3 and its regulatory GTPase activating protein (GAP) Retinitis Pigmentosa 2 (RP2)
  • ARL13B is a small GTPase that functions as a guanosine nucleotide exchange factor (GEF) for ARL3-GDP
  • cell & other
    REGULATION
    Other RP2 regulation of ARL3 is important for maintaining Golgi cohesion, facilitating the transport and docking of vesicles and thereby carrying proteins to the base of the photoreceptor connecting cilium for transport to the outer segment
    ASSOCIATED DISORDERS
    corresponding disease(s) JBTS35
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Arl3-/- mice, which represent a null allele, developed a severe ciliopathy phenotype with pronounced cystic kidney disease, pancreatic hypoplasia, ductal plate malformation within the liver, and retinal dystrophy with impaired photoreceptor