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FLASH GENE
Symbol SPRY2 contributors: mct - updated : 07-01-2018
HGNC name sprouty homolog 2 (Drosophila)
HGNC id 11270
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a SPR (sprouty) domain
  • C terminal cysteine-rich domain, responsible for the localization of the protein to the membrane ruffles
  • conjugated PhosphoP
    HOMOLOGY
    Homologene
    FAMILY
  • sprouty family
  • CATEGORY tumor suppressor , signaling growth factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    text associated with microtubules in unstimulated cells but translocated to the membrane ruffles in cells stimulated by EGF (epidermal growth factor)
    basic FUNCTION
  • palmitoylated phosphoprotein that can attenuate or potentiate numerous growth factor-induced signaling pathways
  • required for growth factor stimulated translocation of the protein to membrane ruffles
  • may be playing a role in alveoli branching during lung development
  • key antagonistic regulator of RTK signalling and suppression of its expression or function may facilitate proliferation and angiogenesis
  • acting as a potential tumour suppressor locus in prostate carcinoma
  • inhibiting growth and migration of vascular smooth muscle cell, and may be decreasing neointimal growth after blood vessel injury
  • playing a role during the final stages of follicle maturation and corpus luteum formation
  • involved in the control of neuritic growth
  • involved in the development of the CNS by inhibiting both neuronal differentiation and survival through a negative-feedback loop that downregulates neurotrophic factors-driven signaling pathways
  • playing a necessary role for tumor formation by H-Ras-transformed fibroblasts
  • both redundant and non-redundant functions for SPRY2 and SPRY4 on embryonic development and FGF signaling
  • playing a crucial, permissive role in the anti-apoptotic actions of serum
  • involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis
  • inhibits apoptosis in response to DNA damage by regulating AKT1, MDM2, and TP53, by a process mediated partly by RAC1
  • acts as an inhibitor of CRKL-RAP1 signaling
  • regulates receptor tyrosine kinase signalling and therefore cell growth and differentiation
  • induces the epithelial-to-mesenchymal transition gene ZEB1
  • potentially regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation
  • SPRY1, SPRY2, SPRY3, SPRY4, are central and complex regulators of the receptor tyrosine kinase (RTK) signalling pathway
  • SPRY1, SPRY2, are targets of FGF signaling in the lens during initiation of fiber differentiation and function redundantly in the corneal epithelial cells to suppress proliferation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with FGF8 (inhibition)
  • interacting with PTEN to inhibit AKT1 activation by epidermal growth factor as well as cell proliferation
  • negative regulators of receptor tyrosine kinase (RTK) signaling
  • interacting with CAV1 (C terminus of CAV1 is the major Sprouty-binding site, whereas Sprouty binds CAV1 via its conserved C-terminal domain, and interaction modulates signaling in a growth factor- and Sprouty isoform-specific manner)
  • TESK1 interacts with SPRY2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling
  • specific relationship between FGF6 and SPRY 2, both being known for their particular involvement in myogenesis
  • interacts with DYRK1A that regulates the phosphorylation status of SPRY2
  • SPRY1 and SPRY2, associate with the HECT domain family E3 ubiquitin ligase, NEDD4 (NEDD4 ubiquitinates SPRY2)
  • with Sprouty1 bind to the adaptor protein CRKL in a stimulus-dependent manner
  • SPRY2 and ERRFI1 are important regulators of wild-type and mutant EGFR trafficking
  • ERBB2 downregulates PERP by activating an ERBB2 effector protein kinase MEK that blocks detachment-induced EGFR loss in a manner that requires the presence of a signaling protein SPRY2
  • cell & other
    REGULATION
    induced by FGF signaling
    inhibited by 1,25(OH)2D3 in colon cancer cells in part due to the induction of CDH1-mediated cell adhesion
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by hypermethylation of CpG island in invasive prostate carcinoma cell lines and high-grade clinical cancer (compared to benign prostatic hyperplasia (BPH) and well-differentiated tumours)
    tumoral     --low  
    in hepatocellular carcinoma
    constitutional     --over  
    induces neuronal cell death, whereas its inhibition favors neuronal survival
    tumoral     --low  
    in breast, lung and prostate cancer, and in melanoma
    tumoral       gain of function
    in undifferentiated high-grade tumours and at the invasive front of low-grade carcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene for cleft lip/palate; for lens cell proliferation and congenital cataract in del 13q
    Marker
  • candidate novel marker for high-grade tumours
  • Therapy target
  • target of therapeutic intervention in colon cancer
  • ANIMAL & CELL MODELS