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FLASH GENE
Symbol CYTH2 contributors: np/mct - updated : 23-10-2019
HGNC name cytohesin 2
HGNC id 9502
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal coiled coil, contributing to the specificity of apical localization through association with components of the apical plasma membrane, and protein-protein interactions mediated by the coiled-coil domain are required for CYTH2 induced motility
  • a central SEC7 domain (61–252 amino acids) promoting guanine-nucleotide exchange on the small G protein ARF1 (coiled-coil and parts of the SEC7 domain are required for serum-mediated transcriptional activation in nonimmune cells)
  • a C terminal pleckstrin-homology (PH) domain, that binds phosphoinositides , with a polybasic region that participates in interacting directly with the EFh2 domain of ACTN1
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to yeast Sec7
    Homologene
    FAMILY
  • PSCD family, cytohesin (CYTH) family
    • CATEGORY motor/contractile , signaling , transport
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    text
  • recruited from the cytosol to the plasma membrane in order to activate ARF6
  • found to colocalize with the adhesive rings of podosomes
    • basic FUNCTION
  • a cytosolic guanine nucleotide-exchange factor for ADP-ribosylation factor ARF6, acting on ADP-ribosylation factors
  • promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6 and the activation of ARF through replacement of GDP with GTP
  • acting together with ARF6 to regulate apical endocytosis
  • required to support the alternative, heterotrimeric G protein-independent, signaling pathway of ADORA2A, which is stimulation of MAP kinase
  • guanine nucleotide-exchange factor (GEF) for ARF, and, at the plasma membrane, it can activate ARF6 to regulate actin reorganization and membrane ruffling
  • involved in neurite formation through ARL4D and ARF6
  • guanine-nucleotide exchange factor (GEF) for small GTPases of the Arf family, which regulates many aspects of cellular functions including morphological changes
  • ARF-activating protein that promotes cell migration and cell shape changes
  • through a complex formation with paxillin, regulates preadipocyte migration
  • cytohesin 2 is required for integrin beta1 recycling, whereas GRP1/cytohesin 3 is dispensable for this process
  • CYTH2 recently emerged as an essential modulator of the insulin receptor
  • novel function of ATP6V1H as a signaling receptor that modulates activity of CYTH2 and Arf GTP-binding proteins
  • CYTH2 is transported along neurites by vesicles containing CCDC120, and it mediates neurite growth
  • signaling through CYTH2 is required for myelination by Schwann cells
  • TBC1D10A, CYTH2 regulate endocytosis at distinct stages
    • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text mediated vesicle transport, actin cytoskeleton reorganization, control of Golgi structure and function
    PATHWAY
    metabolism
    signaling
    a component
  • forms a complex with PXN
  • MYD88-CYTH2-ARF6 is a valid target for inflammatory conditions confirming a relevant role for manipulation of this pathway to modulate inflammatory processes and in the treatment of disease
  • CYTH2-ARF1 regulates formation of podosomes by inhibition of RHOA/myosin-II and promotion of actin core assembly
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CRTAP
  • with the a2-isoform of V-ATPase (ATP6V0A2)(role in the regulation of the endocytic degradative pathway)
  • interacts with ARL4D, through its C-terminal pleckstrin homology (PH) and polybasic c domains in a GTP-dependent manner
  • coupled through ELMO and ARF6 to the cytoskeleton (required for CASR-dependent morphological changes and translocated to the plasma membrane ruffles)
  • interacting with ADORA2A
  • GRASP and IPCEF1 promote ARF-to-RAC1 signaling and cell migration by coordinating the association of CYTH2 with DOCK1
  • interaction between ATP6V0A2 and CYTH2 is a complex process involving various binding sites on both proteins
  • interacting with ACTN1, and this interaction is implicated in the regulation of cellular ARF6 activity involved in neurite extension
  • CYTH2 binds directly to the adaptor protein MYD88, and likely MYD88-CYTH2-ARF6 is a proximal IL1B signalling pathway distinct from that mediated by NFKB1
  • GRASP binds directly both CYTH2 and DOCK1 to coordinate their activities, and by doing so promotes crosstalk between ARF and RAC1
  • binds to CCDC120, which contains three coiled-coil domains, and is transported along neurites
  • activates ARF6 in a PI3K dependent manner and then the active ARF6 causes phosphorylation of ERK1/2 during preadipocyte migration
  • CYTH2 interaction with the RALBP1 N-terminus regulates cell spreading and motility via PI3K and ARF6, independent of RALBP1 control of RAC1
  • RALBP1 acts as a scaffold at recycling endosomes by binding activated RRAS, recruiting CYTH2 to activate ARF6, thereby contributing to cell spreading and migration
  • peripheral CYTH2 recruits TBC1D10A to the same area and the interaction requires glucose-induced endocytosis in pancreatic beta-cells
  • interaction between BLOC1S6 and CYTH2 may participate in various neuronal functions such as endosomal trafficking and dendritic formation in hippocampal neurons
    • cell & other
    REGULATION
    Other regulated by ARL4D (ARL4D acts as a novel upstream regulator of CYTH2 to promote ARF6 activation and modulate actin remodeling)
    recruited by ARL4A, ARL4C, ARL4D and other cytohesins to the plasma membrane
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Cyth2 knockout mice exhibit decreased Arf6 activity and reduced myelin thickness in the sciatic nerves, with decreased expression levels of myelin protein zero (MPZ), the major myelin marker protein