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FLASH GENE
Symbol SPRY2 contributors: mct - updated : 07-01-2011
HGNC name sprouty homolog 2 (Drosophila)
HGNC id 11270
Location 13q31.1      Physical location : 80.910.113 - 80.915.086
Synonym name sprouty 2
Synonym symbol(s) MGC23039, Spry-2
DNA
TYPE functioning gene
STRUCTURE 4.98 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
Binding site   transcription factor
text structure
  • stimulated expression through BDNF by regulating its promoter through cooperation between CREB and SP1
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC122145 13q21.33 suppressor of bimD6 homolog pseudogene LOC387936 13 hypothetical gene supported by AL133018 LOC387937 13 LOC387937 TBC1D4 13q22 TBC1 domain family, member 4 AK000009  Acrg embryonic lethality (mouse) minimal region ortholog UCHL3 13q22 ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase) LMO7 13q22 LIM domain only 7 KCTD12 13q21 potassium channel tetramerisation domain containing 12 BTF3L1 13q22 basic transcription factor 3, like 1 LOC341720 13q22.1 similar to immune-responsive gene 1 LOC390413 13 similar to 60S ribosomal protein L7 DHX9P 13q21 DEAH (Asp-Glu-Ala-His) box polypeptide 9 pseudogene CLN5 13q22 ceroid-lipofuscinosis, neuronal 5 FBXL3A 13q22 F-box and leucine-rich repeat protein 3A PAM 5q15 peptidylglycine alpha-amidating monooxygenase SCEL 13q22 sciellin LOC390414 13 similar to chromosome 15 open reading frame 2 FLJ30046 13q22.1 hypothetical protein FLJ30046 EDNRB 13q22 endothelin receptor type B POU4F1 13q21.1-q22 POU domain, class 4, transcription factor 1 C13orf7 13q22.2 chromosome 13 open reading frame 7 LOC341732 13q22.2 similar to 60 kDa heat shock protein, mitochondrial precursor (Hsp60) (60 kDa chaperonin) (CPN60) (Heat shock protein 60) (HSP-60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) (HuCHA60) LOC390415 13 similar to T-complex protein 1, epsilon subunit (TCP-1-epsilon) (CCT-epsilon) C13orf10 13q22.1 chromosome 13 open reading frame 10 NDFIP2 13q22.1 Nedd4 family interacting protein 2 SPRY2 13q31-q32 sprouty homolog 2 (Drosophila) LOC150928 13q22.3 hypothetical LOC150928 SLITRK1 13q31.1 SLIT and NTRK-like family, member 1 VENTX2P2 13q31.1 VENT-like homeobox 2 pseudogene 2 LOC387939 13 LOC387939 SLITRK6 13q31.1 SLIT and NTRK-like family, member 6
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2126 34 315 - 2005 16126775
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     mouthtooth   
     stomach   highly
    Nervousnerve   highly
    Reproductivemale systemtestis   
    Respiratorylung    
    Urinarykidney    
    Visualeyeuveachoroid  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialbarrier/liningretinal pigment epithelium (RPE)  
    Epithelialsecretoryglandularendocrine 
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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)
  • 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
  • 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