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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
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