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FLASH GENE
Symbol SPRED1 contributors: npt/pgu - updated : 19-03-2019
HGNC name sprouty-related, EVH1 domain containing 1
HGNC id 20249
DNA
TYPE functioning gene
STRUCTURE 121.67 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 7255 - 444 - 2001 11493923
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivepharynx   highly
Hearing/Equilibriumearinnercochlea highly
Nervousbrain    
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text all fetal tissues
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a cys-rich domain responsible for the localization of the protein to the membrane ruffles, highly homolog to the CRD of the Sprouty family of proteins
  • one EVH1 domain (enabled/vasodilatator-stimulated phosphoprotein homology 1), that binds to the noncatalytic (GAPex) portion of the GAP-related domain (GRD) of neurofibromin
  • a Sprouty domain not required to block MAPK (mitogen-activated protein kinase) activation
  • a cysteine-rich (CR) domain at the C-terminus, which is thought to be palmitoylated like CAV1 and necessary for membrane anchoring
  • HOMOLOGY
    Homologene
    FAMILY
  • sprouty family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text in the cytoplasm in unstimulated cells but translocated to the membrane ruffles in cells stimulated with egf (epidermal growth factor)
    basic FUNCTION
  • may be functioning as an antagonist of fibroblast growth factor (FGF) pathways and may be negatively modulating respiratory organogenesis
  • key regulator of RhoA-mediated cell motility and signal transduction
  • inhibiting ERK activation in collaboration with CAV1
  • modulate Ras-Raf interaction and MAP kinase signalling
  • SPRED1, SPRED2, SPRED3 modulate growth factor receptor signaling by inhibiting the RAS-MAPK cascade
  • the three-way interaction between SPRED1, TAOK1, and TESK1 represents a pathway that links regulation of both the microtubule- and F-actin cytoskeleton (Johne 2008)
  • membrane associated negative regulators of growth factor induced extracellular signal regulated kinases (ERK) activation
  • negatively regulates haematopoiesis by suppressing stem cell factor (SCF) and interleukin 3 (IL3) induced ERK activation
  • inhibit the Ras/ERK pathway downstream of RAS
  • diet-induced stress disrupts fine-tuning of SPRED1-mediated signals to govern hematopoietic stem cell homeostasis
  • SPRED1, SPRED2 negatively regulates lens growth by modulating epithelial cell proliferation and fiber differentiation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with TAOK1 (two new interaction partners of TAOK1, SPRED1 and the testis-specific protein kinase (TESK1)
  • direct and endogenous interaction of SPRED1 and SPRED2 with the novel kinase DYRK1A (bind to a similar domain on DYRK1A as Tau, and possibly other substrates, and the hierarchy of binding will depend on the concentration of the competing proteins and the relative affinity for the DYRK1A-binding site)
  • both SPRED1 and SPRED2 inhibit the ability of DYRK1A to phosphorylate its substrates
  • GPM6A, and the Sprouty domain-containing proteins SPRED1 and SPRED3, are indeed palmitoylated by ZDHHC17
  • SPRED1 negatively regulates cytokines from group 2 innate lymphoid cells (ILC2s) development and functions through the suppression of the Ras-ERK pathway
  • SPRED1 has previously been demonstrated to interact with NF1 via its N-terminal Ena/VASP Homology 1 (EVH1) domain and to mediate membrane translocation of its target dependent on its C-terminal Sprouty domain
  • cell & other
    REGULATION
    induced by FGF signaling.
    ASSOCIATED DISORDERS
    corresponding disease(s) NFLS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in hepatocellular carcinoma is one of the causes of the acquisition of malignant features
    tumoral     --low  
    significantly decreased at RNA and protein levels in the majority of acute myeloblastic leukaemias (AMLs) at diagnosis compared with normal or paired complete remission bone marrows
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS