Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SPRY4 contributors: mct/npt/pgu - updated : 22-10-2015
HGNC name sprouty homolog 4 (Drosophila)
HGNC id 15533
Location 5q31.3      Physical location : 141.689.991 - 141.704.620
Synonym symbol(s) Spry-4
DNA
TYPE functioning gene
STRUCTURE 14.63 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure double TCF/LEF-binding sites were identified within the 5'-promoter region
MAPPING cloned Y linked N status provisional
Physical map
PCDHGC3 5q31.3 protocadherin gamma subfamily C, 3 PCDHGC4 5q31.3 protocadherin gamma subfamily C, 4 PCDHGC5 5q31.3 protocadherin gamma subfamily C, 5 DIAPH1 5q31-q32 diaphanous homolog 1 (Drosophila) HDAC3 5q31.3 histone deacetylase 3 FLJ90583 FLJ00007 5q31.3 hypothetical protein FLJ00007 ARAP3 5q31.3 ARF-GAP, RHO-GAP, ankyrin repeat and plekstrin homology domains-containing protein 3 PCDH1 5q31-q32 protocadherin 1 (cadherin-like 1) LOC285615 5q31.3 similar to dJ702J19.1 (glycine cleavage system protein H (aminomethyl carrier)) KIAA0141 5q31.3 similar to dJ702J19.1 (glycine cleavage system protein H (aminomethyl carrier)) PCDH12 5q31.3 protocadherin 12 RNF14 5q23.3-q31.1 ring finger protein 14 GNPDA1 5q21 glucosamine-6-phosphate deaminase 1 MRPL11P2 5q31.3 glucosamine-6-phosphate deaminase 1 NDFIP1 5q31.3 Nedd4 family interacting protein 1 SPRY4 5q31.3 sprouty homolog 4 (Drosophila) FGF1 5q31.3 fibroblast growth factor 1 (acidic) GRAF 5q31 fibroblast growth factor 1 (acidic)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 4992 - 322 - 2006 16877379
2 - 4941 - 299 - 2006 16877379
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestiveintestinelarge intestinecolon highly
Endocrinepancreas   highly
 thyroid   highly
Skin/Tegumentskin   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
 fibroblast
cell lineage
cell lines colon cancer, head and neck tumor, melanoma, and pancreatic cancer
fluid/secretion
at STAGE
physiological period embryo, fetal, pregnancy
Text eye, placenta, in embryonic stem (ES) cells, brain, pancreatic islet
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a prototypic cysteine-rich region, responsible for the localization of the protein to the membrane ruffles
  • three potential Src homology-3 (SH3)-binding proline-rich regions
  • a PEST sequence
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Spry4
    ortholog to murine, chimpanze, rat Spry4
    Homologene
    FAMILY
  • sprouty family
  • CATEGORY transcription factor , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text peri- and paranuclear cytoplasmic puncta
    basic FUNCTION
  • palmitoylated phosphoprotein that can attenuate or potentiate numerous growth factor-induced signaling pathways inhibitor of the receptor-transduced mitogen-activated protein kinase (MAPK) signaling pathway
  • inhibitor for receptor tyrosine kinase signaling cascades, such as those of FGF receptor family members and EGF receptor family members
  • both redundant and non-redundant functions for SPRY2 and SPRY4 on embryonic development and FGF signaling
  • suppressing cell spreading by inhibiting the kinase activity of TESK1
  • having a cellular function to regulate the actin cytoskeleton, independent of its inhibitory activity on the Ras/MAP kinase signalling
  • selectively suppresses Ras-independent angiogenic factor signals and is an important negative regulator of pathophysiological angiogenesis
  • inhibites the PKC pathway, suppressing various signals downstream of PKC, such as phosphorylation of MARCKS and PKD
  • also supressing upstream signals of PKC such as Ca2+ mobilization, PIP2 breakdown and IP3 production in response to VEGF-A
  • might be involved in the timely restriction of MAPK signals under hypoxic conditions, similar to its role in mitogen-regulated processes
  • SPRY1, SPRY2, SPRY3, SPRY4, are central and complex regulators of the receptor tyrosine kinase (RTK) signalling pathway
  • regulates angiogenesis in part by regulating endothelial cell migration
  • unanticipated role for SPRY4 in regulating SRC activity and ITGB3 protein levels, which contributes to the regulation of migration and adhesion of endothelial cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with TESK1 (inhibits the kinase activity of TESK1 by binding to it through the C-terminal cysteine-rich region)
  • FGF signaling inhibitor
  • conserved target of WNT/beta-catenin signaling pathway based on the conservation of double TCF/LEF-binding sites within 5'-promoter region of mammalian SPRY4 orthologs
  • 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)
  • downstream target of WNT7A/FZD9 signaling
  • SPRY4 overexpression resulted in decreased ITGB3 protein levels in a post-transcriptional manner in part by modulating its tyrosine phosphorylation by SRC
  • KHSRP promotes the down-regulation of SPRY4 by a post-transcriptional mRNA regulation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    epigenetic silencing and loss-of-function mutations in progenitor cells could lead to carcinogenesis
    tumoral     --low  
    in prostate cancer by DNA methylation and this decreased expression may contribute to increased cell migration
    Susceptibility
  • to testicular germ cell tumors (TGCT)
  • to congenital Hypogonadotropic Hypogonadism
  • Variant & Polymorphism other rs4324715 and rs6897876 increasing the risk of testicular germ cell tumors (TGCT)
    Candidate gene
    Marker
    Therapy target pharmacogenomics target in the fields of oncology and regenerative medicine
    SystemTypeDisorderPubmed
    cancerlung 
    may have efficacy in the treatment of non-small cell lung cancer
    miscelleaneousvascular 
    targeting SPRY4 may be exploited as a target in anti-angiogenesis therapies
    ANIMAL & CELL MODELS