SPRY2: Sprouty RTK Signaling Antagonist 2
A key negative regulator of receptor tyrosine kinase signaling in development and cancer
Gene Information Card
| Symbol | SPRY2 |
|---|---|
| Full Name | Sprouty RTK Signaling Antagonist 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q31.1 |
| NCBI Gene ID | 10253 ncbi.nlm.nih.gov/gene/10253 |
| Ensembl ID | ENSG00000136158 |
| UniProt ID | O43597 |
| OMIM ID | 602466 |
| HGNC ID | 11270 |
| Aliases | hSPRY2, Spry-2, sprouty homolog 2 |
Description
SPRY2 encodes a member of the sprouty family of proteins, which are conserved negative regulators of receptor tyrosine kinase (RTK) signaling pathways, particularly the MAPK/ERK cascade. SPRY2 inhibits signaling downstream of growth factors such as FGF and EGF by interacting with components like GRB2, RAF1, and CBL. It plays critical roles in embryonic development, cell proliferation, differentiation, and migration. Dysregulation of SPRY2 is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Loss of SPRY2 expression leads to enhanced MAPK signaling and tumor progression | PMID: 19151757 |
| Colorectal cancer | SPRY2 mutations and reduced expression correlate with poor prognosis and metastasis | PMID: 20010872 |
| Breast cancer | SPRY2 overexpression inhibits EGF-induced cell migration and invasion | PMID: 15674326 |
| Lung cancer | Epigenetic silencing of SPRY2 contributes to oncogenic KRAS signaling | PMID: 20526336 |
| Hereditary gingival fibromatosis | SPRY2 gain-of-function mutations cause overgrowth of gingival tissue | PMID: 21358634 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 15.2 | Medium |
| Liver | 6.1 | Low |
| Kidney | 10.7 | Medium |
| Testis | 22.4 | High |
| Prostate | 18.9 | High |
| Colon | 14.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 20.5 | High expression in embryonic kidney cells |
| HeLa | 12.3 | Moderate expression in cervical cancer cells |
| MCF7 | 8.7 | Low expression in breast cancer cells |
| PC3 | 5.2 | Low expression in prostate cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.148C>T (p.Arg50*) | Nonsense | <0.1% | Loss of function; truncation of protein |
| c.200A>G (p.Tyr67Cys) | Missense | <0.1% | Gain of function; associated with hereditary gingival fibromatosis |
| c.436G>A (p.Gly146Arg) | Missense | <0.1% | Unknown functional effect |
| c.3G>A (p.Met1?) | Start loss | <0.1% | Loss of function; no protein translation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or prevent translation, leading to reduced inhibition of RTK signaling and increased cell proliferation.
Gain of Function (GOF)
Missense mutations (e.g., p.Tyr67Cys) that enhance SPRY2 stability or activity, resulting in excessive inhibition of RTK signaling and tissue overgrowth.
Dominant Negative (DN)
Not well documented; some missense variants may interfere with wild-type SPRY2 function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)
• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006934)
• Negative regulation of FGFR signaling (Reactome: R-HSA-5655302)
Protein Summary
SPRY2 is a 315-amino-acid protein (UniProt O43597) that localizes to the cytoplasm and plasma membrane. It contains a conserved cysteine-rich C-terminal domain essential for membrane targeting and function. SPRY2 acts as a feedback inhibitor of RTK signaling by binding to GRB2 and preventing SOS-mediated RAS activation, and by interacting with CBL to modulate receptor endocytosis. Its expression is dynamically regulated during development and in response to growth factors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPRY2 Knockout HEK293 Cell Line | EDJ-KQ6978 | Human | 10253 | Details Get a Quote |
| SPRY2 Knockout HeLa Cell Line | EDJ-KQ30299 | Human | 10253 | Details Get a Quote |
| SPRY2 Knockout A-549 Cell Line | EDJ-KQ31678 | Human | 10253 | Details Get a Quote |
| SPRY2 Knockout HCT 116 Cell Line | EDJ-KQ31679 | Human | 10253 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
