This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregula... See more...

Aliases for SPRY2 Gene

Aliases for SPRY2 Gene

  • Sprouty RTK Signaling Antagonist 2 2 3 5
  • Protein Sprouty Homolog 2 3 4
  • HSPRY2 2 3
  • Sprouty (Drosophila) Homolog 2 2
  • Sprouty Homolog 2 (Drosophila) 2
  • Spry-2 4
  • IGAN3 3
  • SPRY2 5

External Ids for SPRY2 Gene

Previous GeneCards Identifiers for SPRY2 Gene

  • GC13M078877
  • GC13M074905
  • GC13M079846
  • GC13M078708
  • GC13M079808
  • GC13M080910
  • GC13M061613

Summaries for SPRY2 Gene

Entrez Gene Summary for SPRY2 Gene

  • This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregulated in response to fibroblast growth factor two. This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. The protein interacts with Cas-Br-M (murine) ectropic retroviral transforming sequence, and can function as a bimodal regulator of epidermal growth factor receptor/mitogen-activated protein kinase signaling. This protein may play a role in alveoli branching during lung development as shown by a similar mouse protein. [provided by RefSeq, Jul 2008]

CIViC Summary for SPRY2 Gene

GeneCards Summary for SPRY2 Gene

SPRY2 (Sprouty RTK Signaling Antagonist 2) is a Protein Coding gene. Diseases associated with SPRY2 include Iga Nephropathy 3 and Adrenal Cortical Adenocarcinoma. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein kinase binding and protein serine/threonine kinase inhibitor activity. An important paralog of this gene is SPRY1.

UniProtKB/Swiss-Prot Summary for SPRY2 Gene

  • Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2 (By similarity). Thereby acts as an antagonist of FGF-induced retinal lens fiber differentiation, may inhibit limb bud outgrowth and may negatively modulate respiratory organogenesis (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (By similarity).

Gene Wiki entry for SPRY2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SPRY2 Gene

Genomics for SPRY2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SPRY2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH13J080334 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 600.7 +1.9 1905 9.2 HNRNPL GATAD2A CTCF ATF7 PRDM10 ZNF629 TFE3 ZNF692 BACH1 JUND SPRY2 lnc-NDFIP2-31 RBM26 RNU6-61P lnc-NDFIP2-32 RF00017-1463 NDFIP2
GH13J080361 Enhancer 1 FANTOM5 ENCODE 12 -21.0 -21022 1.6 GATAD2A CTCF IKZF1 RCOR2 LARP7 ZIC2 PKNOX1 RXRB SMAD5 IKZF2 SPRY2 LOC105370276 RNU6-61P RF00026-298 lnc-NDFIP2-8
GH13J080234 Enhancer 1.1 FANTOM5 Ensembl ENCODE 11.1 +105.3 105325 2.4 PRDM10 SCRT2 ZBTB44 TCF7L2 BCL11A NBN IKZF1 SPI1 BATF TBP HSALNG0098178 SPRY2 piR-47628-050 NDFIP2
GH13J080444 Enhancer 1 FANTOM5 Ensembl ENCODE 10.2 -102.8 -102775 4.2 IKZF2 SP1 PKNOX1 YBX1 RELB FOXA2 ZBTB40 YY1 IKZF1 JUNB RNU6-61P SPRY2 LINC00377 piR-46381-024 HSALNG0098195
GH13J079775 Enhancer 0.8 Ensembl ENCODE 11.4 +564.4 564429 2.2 CTCF PRDM10 RAD21 TRIM22 ZNF561 SCRT2 SP1 CEBPB BCLAF1 ZNF592 SPRY2 lnc-NDFIP2-4 HSALNG0098157 NDFIP2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SPRY2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SPRY2

Top Transcription factor binding sites by QIAGEN in the SPRY2 gene promoter:
  • MZF-1
  • Nkx2-5
  • Oct-B1
  • oct-B2
  • oct-B3
  • POU2F1
  • POU2F1a
  • POU2F2
  • POU2F2 (Oct-2.1)
  • SREBP-1b

Genomic Locations for SPRY2 Gene

Genomic Locations for SPRY2 Gene
chr13:80,335,976-80,341,126
(GRCh38/hg38)
Size:
5,151 bases
Orientation:
Minus strand
chr13:80,910,111-80,915,086
(GRCh37/hg19)
Size:
4,976 bases
Orientation:
Minus strand

Genomic View for SPRY2 Gene

Genes around SPRY2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPRY2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPRY2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPRY2 Gene

Proteins for SPRY2 Gene

  • Protein details for SPRY2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43597-SPY2_HUMAN
    Recommended name:
    Protein sprouty homolog 2
    Protein Accession:
    O43597
    Secondary Accessions:
    • B2R9J9
    • Q5T6Z7

    Protein attributes for SPRY2 Gene

    Size:
    315 amino acids
    Molecular mass:
    34688 Da
    Quaternary structure:
    • Interacts with RAF1 (PubMed:12717443). Part of a tripartite complex containing GAB1, METTL13 and SPRY2 (PubMed:29408807). Interacts with METTL13 (PubMed:29408807).

    Three dimensional structures from OCA and Proteopedia for SPRY2 Gene

neXtProt entry for SPRY2 Gene

Post-translational modifications for SPRY2 Gene

  • Cleaved at Pro-144 by the prolyl endopeptidase FAP (seprase) activity (in vitro).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SPRY2 Gene

No data available for DME Specific Peptides for SPRY2 Gene

Domains & Families for SPRY2 Gene

Gene Families for SPRY2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for SPRY2 Gene

InterPro:
Blocks:
  • Sprouty
ProtoNet:

Suggested Antigen Peptide Sequences for SPRY2 Gene

GenScript: Design optimal peptide antigens:
  • Protein sprouty homolog 2 (SPY2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43597

UniProtKB/Swiss-Prot:

SPY2_HUMAN :
  • The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.
  • Belongs to the sprouty family.
Domain:
  • The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.
Family:
  • Belongs to the sprouty family.
genes like me logo Genes that share domains with SPRY2: view

Function for SPRY2 Gene

Molecular function for SPRY2 Gene

UniProtKB/Swiss-Prot Function:
Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2 (By similarity). Thereby acts as an antagonist of FGF-induced retinal lens fiber differentiation, may inhibit limb bud outgrowth and may negatively modulate respiratory organogenesis (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (By similarity).

Phenotypes From GWAS Catalog for SPRY2 Gene

Gene Ontology (GO) - Molecular Function for SPRY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12815057
GO:0019901 protein kinase binding IPI 20736167
GO:0030291 protein serine/threonine kinase inhibitor activity IC 20736167
GO:0043539 protein serine/threonine kinase activator activity IMP 18070883
genes like me logo Genes that share ontologies with SPRY2: view
genes like me logo Genes that share phenotypes with SPRY2: view

Human Phenotype Ontology for SPRY2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SPRY2 Gene

MGI Knock Outs for SPRY2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPRY2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SPRY2 Gene

Localization for SPRY2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPRY2 Gene

Cytoplasm, cytoskeleton. Cell projection, ruffle membrane. Note=Associated with microtubules in unstimulated cells but is translocated to the membrane ruffles in cells stimulated ith EGF (epidermal growth factor). {ECO:0000269 PubMed:10887178}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SPRY2 gene
Compartment Confidence
cytoskeleton 5
plasma membrane 4
nucleus 4
cytosol 4
extracellular 2
endoplasmic reticulum 2
mitochondrion 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Actin filaments (3)
  • Microtubules (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SPRY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol ISS,TAS --
GO:0005856 cytoskeleton ISS --
genes like me logo Genes that share ontologies with SPRY2: view

Pathways & Interactions for SPRY2 Gene

genes like me logo Genes that share pathways with SPRY2: view

SIGNOR curated interactions for SPRY2 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for SPRY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000132 establishment of mitotic spindle orientation IEA --
GO:0007275 multicellular organism development IEA --
GO:0007605 sensory perception of sound IEA --
GO:0008285 negative regulation of cell proliferation IEA --
GO:0009966 regulation of signal transduction IEA --
genes like me logo Genes that share ontologies with SPRY2: view

Drugs & Compounds for SPRY2 Gene

(1) Drugs for SPRY2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with SPRY2: view

Transcripts for SPRY2 Gene

mRNA/cDNA for SPRY2 Gene

4 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPRY2

Alternative Splicing Database (ASD) splice patterns (SP) for SPRY2 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4a · 4b · 4c
SP1: - - - -
SP2: - - -
SP3: -
SP4:

Relevant External Links for SPRY2 Gene

GeneLoc Exon Structure for
SPRY2

Expression for SPRY2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SPRY2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SPRY2 Gene

This gene is overexpressed in Pancreas (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SPRY2 Gene



Protein tissue co-expression partners for SPRY2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SPRY2

SOURCE GeneReport for Unigene cluster for SPRY2 Gene:

Hs.18676

Evidence on tissue expression from TISSUES for SPRY2 Gene

  • Nervous system(4.7)
  • Skin(4.5)
  • Muscle(2.6)
  • Lung(2.5)
  • Heart(2.5)
  • Liver(2.3)
  • Intestine(2.3)
  • Kidney(2.3)
  • Pancreas(2.2)
  • Thyroid gland(2.2)
  • Eye(2)
  • Bone marrow(2)
genes like me logo Genes that share expression patterns with SPRY2: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for SPRY2 Gene

Orthologs for SPRY2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SPRY2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SPRY2 30 31
  • 99.89 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SPRY2 30 31
  • 93.97 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Spry2 30
  • 92.14 (n)
Mouse
(Mus musculus)
Mammalia Spry2 30 17 31
  • 91.93 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SPRY2 30 31
  • 88.36 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SPRY2 31
  • 80 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SPRY2 31
  • 75 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SPRY2 30 31
  • 80.62 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SPRY2 31
  • 81 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia spry2 30
  • 72.31 (n)
Str.92 30
African clawed frog
(Xenopus laevis)
Amphibia LOC398313 30
Zebrafish
(Danio rerio)
Actinopterygii spry2 30 31
  • 62.86 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta sty 31 32
  • 15 (a)
OneToMany
Species where no ortholog for SPRY2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for SPRY2 Gene

ENSEMBL:
Gene Tree for SPRY2 (if available)
TreeFam:
Gene Tree for SPRY2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SPRY2: view image

Paralogs for SPRY2 Gene

Paralogs for SPRY2 Gene

(3) SIMAP similar genes for SPRY2 Gene using alignment to 1 proteins:

  • SPY2_HUMAN
genes like me logo Genes that share paralogs with SPRY2: view

Variants for SPRY2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SPRY2 Gene

SNP ID Clinical significance and condition Chr 13 pos Variation AA Info Type
rs869025336 Risk Factor: IgA nephropathy, susceptibility to, 3. IgA nephropathy 3 (IGAN3) [MIM:616818] 80,337,351(-) G/Ap.Arg119Trp MISSENSE_VARIANT
rs504122 - p.Pro106Ser

Additional dbSNP identifiers (rs#s) for SPRY2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SPRY2 Gene

Variant ID Type Subtype PubMed ID
esv2747714 CNV deletion 23290073
esv3632829 CNV gain 21293372
nsv819288 CNV loss 19587683
nsv832660 CNV gain 17160897

Variation tolerance for SPRY2 Gene

Residual Variation Intolerance Score: 21.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.12; 80.57% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPRY2 Gene

Human Gene Mutation Database (HGMD)
SPRY2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPRY2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPRY2 Gene

Disorders for SPRY2 Gene

MalaCards: The human disease database

(9) MalaCards diseases for SPRY2 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
iga nephropathy 3
  • iga nephropathy, susceptibility to, 3
adrenal cortical adenocarcinoma
  • adrenocortical carcinoma
thanatophoric dysplasia, type ii
  • td2
achondroplasia
  • ach
legius syndrome
  • lgss
- elite association - COSMIC cancer census association via MalaCards
Search SPRY2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SPY2_HUMAN
  • IgA nephropathy 3 (IGAN3) [MIM:616818]: A form of IgA nephropathy, a common primary glomerulonephritis characterized by glomerular sclerosis, interstitial fibrosis, and mesangial glomerular deposits of immunoglobulin A and immunoglobulin G visible on renal biopsies. IgA nephropathy is associated with renal insufficiency that can progress to end-stage renal disease. Proteinuria and hematuria are characteristic clinical presentations. {ECO:0000269 PubMed:25782674}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for SPRY2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with SPRY2: view

No data available for Genatlas for SPRY2 Gene

Publications for SPRY2 Gene

  1. Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. (PMID: 10887178) Lim J … Guy GR (The Journal of biological chemistry 2000) 3 4 23
  2. sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. (PMID: 9458049) Hacohen N … Krasnow MA (Cell 1998) 2 3 4
  3. Modifier variant of METTL13 suppresses human GAB1-associated profound deafness. (PMID: 29408807) Yousaf R … Riazuddin S (The Journal of clinical investigation 2018) 3 4
  4. A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy. (PMID: 25782674) Milillo A … Sangiorgi E (European journal of human genetics : EJHG 2015) 3 4
  5. Cleavage-site specificity of prolyl endopeptidase FAP investigated with a full-length protein substrate. (PMID: 21288888) Huang CH … Chen X (Journal of biochemistry 2011) 3 4

Products for SPRY2 Gene

Sources for SPRY2 Gene