SPRY2 (sprouty RTK signaling antagonist 2)

Gene

• Entrez ID: 10253
• Gene name: Sprouty RTK signaling antagonist 2
• Gene symbol: SPRY2
• Synonyms: IGAN3, hSPRY2
• Chromosome: 13
• Chromosome location: 13q31.1
• Summary: 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 stimu

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs869025336	G>A,T	Risk-factor	Coding sequence variant, missense variant, synonymous variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000672	hsa-miR-21-5p	Review	19935707
MIRT000672	hsa-miR-21-5p	Luciferase reporter assay	18508928
MIRT005511	hsa-miR-27a-3p	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	20638779
MIRT005511	hsa-miR-27a-3p	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	20638779
MIRT000672	hsa-miR-21-5p	Luciferase reporter assay, qRT-PCR	21278789
MIRT000672	hsa-miR-21-5p	Luciferase reporter assay, qRT-PCR	21278789
MIRT000672	hsa-miR-21-5p	Luciferase reporter assay	23239100
MIRT022159	hsa-miR-124-3p	Microarray	18668037
MIRT023487	hsa-miR-1-3p	Microarray	18668037
MIRT025117	hsa-miR-181a-5p	Sequencing	20371350
MIRT025980	hsa-miR-148a-3p	Sequencing	20371350
MIRT028756	hsa-miR-26b-5p	Microarray	19088304
MIRT005511	hsa-miR-27a-3p	qRT-PCR, Western blot	23650389
MIRT438903	hsa-miR-23a-3p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	23649631
MIRT438902	hsa-miR-24-2-5p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	23649631
MIRT005511	hsa-miR-27a-3p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	23649631
MIRT438903	hsa-miR-23a-3p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	23649631
MIRT438902	hsa-miR-24-2-5p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	23649631
MIRT005511	hsa-miR-27a-3p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	23649631
MIRT000672	hsa-miR-21-5p	qRT-PCR, Western blot	25728247
MIRT005511	hsa-miR-27a-3p	Luciferase reporter assay, Western blotting, Immunoprecipitaion (IP), Immunofluorescence, qRT-PCR	33638619
MIRT000672	hsa-miR-21-5p	Luciferase reporter assay, Western blotting, Immunofluorescence, qRT-PCR	33116513
MIRT755693	ebv-miR-BART1-5p	Luciferase reporter assay, Immunohistochemistry (IHC)	37097161
MIRT000672	hsa-miR-21-5p	Luciferase reporter assay, Western blotting, qRT-PCR, Immunoprecipitaion (IP)	34786052
MIRT1386032	hsa-miR-103a	CLIP-seq
MIRT1386033	hsa-miR-107	CLIP-seq
MIRT1386034	hsa-miR-1301	CLIP-seq
MIRT1386035	hsa-miR-3607-3p	CLIP-seq
MIRT1386036	hsa-miR-3686	CLIP-seq
MIRT1386037	hsa-miR-4520a-3p	CLIP-seq
MIRT1386038	hsa-miR-4520b-3p	CLIP-seq
MIRT1386039	hsa-miR-5047	CLIP-seq
MIRT1386040	hsa-miR-579	CLIP-seq
MIRT1386041	hsa-miR-586	CLIP-seq
MIRT2115513	hsa-miR-3148	CLIP-seq
MIRT1386036	hsa-miR-3686	CLIP-seq
MIRT2115514	hsa-miR-3688-3p	CLIP-seq
MIRT2115515	hsa-miR-4452	CLIP-seq
MIRT2115516	hsa-miR-4742-3p	CLIP-seq
MIRT2115517	hsa-miR-548m	CLIP-seq
MIRT2338162	hsa-miR-122	CLIP-seq
MIRT2338163	hsa-miR-21	CLIP-seq
MIRT2338164	hsa-miR-3135	CLIP-seq
MIRT2338165	hsa-miR-3152-5p	CLIP-seq
MIRT2338166	hsa-miR-4774-3p	CLIP-seq
MIRT2338167	hsa-miR-4802-3p	CLIP-seq
MIRT2338168	hsa-miR-491-3p	CLIP-seq
MIRT2338169	hsa-miR-590-5p	CLIP-seq
MIRT2395049	hsa-miR-338-5p	CLIP-seq
MIRT2631773	hsa-miR-128	CLIP-seq
MIRT2631774	hsa-miR-27a	CLIP-seq
MIRT2631775	hsa-miR-27b	CLIP-seq
MIRT2631776	hsa-miR-4684-3p	CLIP-seq
MIRT2631777	hsa-miR-5096	CLIP-seq
MIRT2631778	hsa-miR-513a-5p	CLIP-seq
MIRT2631779	hsa-miR-518a-5p	CLIP-seq
MIRT2631780	hsa-miR-527	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
CREB1	Unknown	14644509
ETS1	Unknown	14644509
SP1	Unknown	14644509
TFAP2A	Unknown	14644509

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000132	Process	Establishment of mitotic spindle orientation	IEA
GO:0005515	Function	Protein binding	IPI	12815057, 15962011, 16189514, 16877379, 16893902, 17974561, 18273061, 21516116, 21784977, 24722188, 25416956, 25910212, 29408807, 29892012, 31515488
GO:0005634	Component	Nucleus	ISS
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	ISS
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	ISS
GO:0005886	Component	Plasma membrane	TAS
GO:0007605	Process	Sensory perception of sound	IEA
GO:0008285	Process	Negative regulation of cell population proliferation	IEA
GO:0010628	Process	Positive regulation of gene expression	IMP	18070883
GO:0010719	Process	Negative regulation of epithelial to mesenchymal transition	ISS
GO:0010801	Process	Negative regulation of peptidyl-threonine phosphorylation	IDA	20736167
GO:0015629	Component	Actin cytoskeleton	IDA
GO:0015630	Component	Microtubule cytoskeleton	IDA
GO:0016020	Component	Membrane	ISS
GO:0016525	Process	Negative regulation of angiogenesis	IMP	24177325
GO:0019901	Function	Protein kinase binding	IPI	20736167
GO:0030291	Function	Protein serine/threonine kinase inhibitor activity	IC	20736167
GO:0030335	Process	Positive regulation of cell migration	IMP	20489163
GO:0030512	Process	Negative regulation of transforming growth factor beta receptor signaling pathway	ISS
GO:0031345	Process	Negative regulation of cell projection organization	ISS
GO:0031397	Process	Negative regulation of protein ubiquitination	IDA	17974561
GO:0032587	Component	Ruffle membrane	IEA
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	IMP	18070883
GO:0034260	Process	Negative regulation of GTPase activity	IEA
GO:0035924	Process	Cellular response to vascular endothelial growth factor stimulus	IDA	21536891
GO:0040037	Process	Negative regulation of fibroblast growth factor receptor signaling pathway	IBA	21873635
GO:0042059	Process	Negative regulation of epidermal growth factor receptor signaling pathway	TAS
GO:0042472	Process	Inner ear morphogenesis	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IMP	18070883
GO:0043407	Process	Negative regulation of MAP kinase activity	IBA	21873635
GO:0043539	Function	Protein serine/threonine kinase activator activity	IMP	18070883
GO:0045165	Process	Cell fate commitment	IEA
GO:0046580	Process	Negative regulation of Ras protein signal transduction	IBA	21873635
GO:0048513	Process	Animal organ development	IBA	21873635
GO:0051387	Process	Negative regulation of neurotrophin TRK receptor signaling pathway	IEA
GO:0051897	Process	Positive regulation of protein kinase B signaling	IMP	18070883
GO:0060437	Process	Lung growth	IEA
GO:0060449	Process	Bud elongation involved in lung branching	IEA
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	IDA	21536891
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	IMP	20489163
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	ISS
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IMP	18070883
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IEA
GO:1900747	Process	Negative regulation of vascular endothelial growth factor signaling pathway	IDA	21536891
GO:1902747	Process	Negative regulation of lens fiber cell differentiation	ISS
GO:1990752	Component	Microtubule end	IDA
GO:1990830	Process	Cellular response to leukemia inhibitory factor	IEA

Other IDs

• MIM: 602466
• HGNC: 11270
• e!Ensembl: ENSG00000136158

Protein

• UniProt ID: O43597
• Protein name: Protein sprouty homolog 2 (Spry-2)
• Protein 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 m
• PDB: 3BUM, 3OB1, 5HKY, 5HKZ, 5HL0
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF05210	Sprouty	183 → 294	Sprouty protein (Spry)	Family

• Sequence:

  MEARAQSGNGSQPLLQTPRDGGRQRGEPDPRDALTQQVHVLSLDQIRAIRNTNEYTEGPT
  VVPRPGLKPAPRPSTQHKHERLHGLPEHRQPPRLQHSQVHSSARAPLSRSISTVSSGSRS
  STRTSTSSSSSEQRLLGSSFSSGPVADGIIRVQPKSELKPGELKPLSKEDLGLHAYRCED
  CGKCKCKECTYPRPLPSDWICDKQCLCSAQNVIDYGTCVCCVKGLFYHCSNDDEDNCADN
  PCSCSQSHCCTRWSAMGVMSLFLPCLWCYLPAKGCLKLCQGCYDRVNRPGCRCKNSNTVC
  CKVPTVPPRNFEKPT

• Sequence length: 315

Pathways

KEGG:

MicroRNAs in cancer

Reactome:

Spry regulation of FGF signaling
EGFR downregulation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Glomerulonephritis	IGA Glomerulonephritis	rs778043831
Lung cancer	Malignant neoplasm of lung	rs121913530, rs121913529, rs878855122, rs1057519784, rs770315135	15136453

Unknown
Disease name	Disease term	dbSNP ID	References
Lung neoplasms	Lung Neoplasms		15136453
Lung diseases	Lung diseases		24210189