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FLASH GENE
Symbol ARL6IP5 contributors: mct/npt/pgu - updated : 06-02-2024
HGNC name ADP-ribosylation-like factor 6 interacting protein 5
HGNC id 16937
DNA
TYPE functioning gene
STRUCTURE 21.15 kb     3 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 2135 21.5 188 - 2002 12119102
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestivepharynx   highly
Endocrineneuroendocrinepituitary  highly
 parathyroid   highly
Nervousnerve   highly
Reproductivemale systemprostate  highly
Respiratorylung   highly
Urinarybladder   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Connectivebone    Homo sapiens
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Skeletonosteoblast Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a Rab-acceptor motif, indicating a function in vesicle formation at the Golgi complex
  • four transmembrane domains
  • cytosolic N and C termini
  • mono polymer polymer
    HOMOLOGY
    interspecies homolog to rattus Jwa
    homolog to rat glutamate transporter-associated protein 3-18 (GTRAP3-18)
    intraspecies homolog to PRAF2
    Homologene
    FAMILY
  • PRA1 family
  • prenylated rab-acceptor-family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • translocated into the nucleus by the carrier protein XRCC1 and co-localized with XRCC1 foci after oxidative DNA damage
  • basic FUNCTION
  • modulating the transport functions ascribed to SLC1A1
  • playing an important role in regulating the metabolic function of SLC1A1
  • involved in regulation of intracellular concentrations of taurine and glutamate
  • actively involved in the signal pathways of oxidative stress in the cells
  • may be involved in membrane trafficKing
  • signaling molecule, involved in the induction of differentiation of myeloid leukemia cells
  • regulator of ER protein trafficking
  • having the ability to regulate the trafficking of selected additional neuron-transmitter transporters and receptors
  • ARL6IP5-regulated-tumor cellular migration might involve MAPK cascades activation and F-actin cytoskeleton rearrangement mechanisms
  • having a unexpected role in tumor cell migration behaviors
  • glutamate transport-associated protein for SLC1A1, interacting with SLC1A1 at the plasma membrane and thereby regulating neuronal glutathione levels
  • dominantly and negatively determining the intracellular glutathione contents in neurons
  • regulator of ER protein trafficking
  • involved in cellular responses to environmental stress including oxidative stress
  • may serve as a novel regulator of XRCC1 in the BER (base excision repair) protein complex to facilitate the repair of DNA single-strand breaks
  • structurally novel microtubule-associated protein, which regulates cancer cell migration via MAPK cascades and mediates differentiation of leukemic cells
  • recruited by XRCC1 to the DNA damage sites, mediates the repair of DNA damage induced by oxidative stress via activating the expression of XRCC1 through MAPK-E2F1 signaling pathway and protecting XRCC1 from ubiquitin-proteasome degradation
  • directly involved in the regulation of chronic morphine dependence
  • ARL6IP5 in the ER controls intracellular TMEFF1 trafficking from the ER to plasma membrane and regulates cell migration through its interaction with TMEFF1
  • has an important role in exocytic protein trafficking, glutathione metabolism and involves in cancer progression
  • function as an ER calcium regulator and control calmodulin signaling for osteoblast proliferation
  • is a novel regulator of bone formation in osteoblasts
  • plays pivotal roles in membrane traffic as a GDI displacement factor via physical interaction with a variety of Rab proteins
  • inhibits tumor progression by suppressing multiple oncogenes or activating tumor suppressor genes
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS
    text glutamate transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to the C-terminal intracellular domain of SLC1A1
  • binding to prenylated RAB1A and RAB3A, and to the ADP- ribosylation like factor ARL6
  • putative negative modulator of Na+-dependent neural glutamate transporter-excitatory amino acid carrier 1 (EAAC1)
  • interact with SLC1A1 at the plasma membrane and thereby regulate neuronal glutathione levels
  • interaction of RAB1A and its regulator ARL6IP5 are involved in trafficking and neuronal differentiation
  • interacts with and reduces the activity of the neuronal specific Na(+)/K(+) glutamate transporter, SLC1A1
  • functioned as a repair protein by multi-interaction with XRCC1
  • regulates XRCC1 expression at both the transcriptional and post-translational levels
  • OPRD1 interacting with ARL6IP5 (ARL6IP5 is required for maintaining the stability of OPRD1 via the ubiquitin-proteasome pathway)
  • ARL6IP5 has an important role in ING4-regulated melanoma angiogenesis
  • tomoregulin-1 (TMEFF1) is a novel addicsin (ARL6IP5)-associated factor
  • ARL6IP5 is a negative modulator of the neural glutamate transporter excitatory amino acid carrier 1 (SLC1A1) (
  • ARL6IP5 was an anti-catabolic factor by binding with TNFSF11 and disturbing its subcellular trafficking in osteoblast
  • ARL6IP5 anchor protein that retains interacting proteins in the endoplasmic reticulum, is a critical regulator of food intake and body weight by interacting with POMC
  • RAB1A can rescue the cytotoxicity caused by ARL6IP5 possibly by "positively" regulating ER-Golgi trafficking, cancelling the "negative" modulation by ARL6IP5
  • potential interacting partner of ARL15, is the ER-localised protein ARL6IP5
  • cell & other
    REGULATION
    activated by upon induced differentiation and in heat stress
    induced by retinoic acid
    methyl-beta-cyclodextrin
    Other responsive to heat shock, and oxidative stress
    not only regulated by ATRA but also by several other differentiation inducers such as phorbol-12-myristate-13-acetate (TPA), and hemin, involved in the mechanisms of differentiation along different lineages of myeloid leukemia cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Arl6ip5 knock-out mice (Arl6ip5 (&
    916;2/&
    916;2)) show marked decrease of bone mineral density, trabecular bone volume and trabecular thickness