Q9QXV8 · SPY2_MOUSE
- ProteinProtein sprouty homolog 2
- GeneSpry2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids315 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2 (PubMed:29501879).
Thereby acts as an antagonist of FGF-induced retinal lens fiber differentiation, may inhibit limb bud outgrowth and may negatively modulate respiratory organogenesis (PubMed:10074434, PubMed:10498682, PubMed:29501879).
Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (PubMed:25576668).
Inhibits CBL/C-CBL-mediated EGFR ubiquitination (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 (PubMed:10074434, PubMed:10498682, PubMed:29501879).
Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (PubMed:25576668).
Inhibits CBL/C-CBL-mediated EGFR ubiquitination (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 143-144 | Cleavage; by FAP | ||||
Sequence: PA |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein sprouty homolog 2
- Short namesSpry-2
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9QXV8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Associated with microtubules in unstimulated cells but is translocated to the membrane ruffles in cells stimulated with EGF (epidermal growth factor).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 55 | Abolishes FGF2-induced lens fiber differentiation via inhibition of FGF-mediated ERK1/2 phosphorylation. | ||||
Sequence: Y → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 13 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000076902 | 1-315 | Protein sprouty homolog 2 | |||
Sequence: MEARAQSGNGSQPLLQTAHDSGRQRGEPDPRDALTQQVHVLSLDQIRAIRNTNEYTEGPTVVPRPGLKPAPRPSTQHKHERLHGLPEHRQPPRLQPSQVHSSRAPLSRSISTVSSGSRSSTRTSTSSSSSEQRLLGPSFSHGPAAADGIIRVQPKSELKPGDVKPLSKDDLGLHAYRCEDCGKCKCKECTYPRPLPSDWICDKQCLCSAQNVIDYGTCVCCVKGLFYHCSNDDEDNCADNPCSCSQSHCCTRWSAMGVMSLFLPCLWCYLPAKGCLKLCQGCYDRVNRPGCRCKNSNTVCCKVPTVPPRNFEKPT |
Post-translational modification
Cleaved at Pro-143 by the prolyl endopeptidase FAP (seprase) activity (in vitro).
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the testes and brain (at protein level) (PubMed:10074434, PubMed:17974561).
In adult, highly expressed in the lung, heart and at lower levels in skeletal muscle and kidney (PubMed:10074434).
In adult, highly expressed in the lung, heart and at lower levels in skeletal muscle and kidney (PubMed:10074434).
Developmental stage
At 8.5 dpc, expressed in the primitive streak, rostral forebrain, cells lateral to the posterior hindbrain, anterior hindbrain and developing midbrain. At 9.5 dpc, continues to be expressed in the rostral forebrain and primitive streak, and is also detected in the branchial arches and the forelimb bud. At 10.5 dpc, expressed in the somites, frontonasal processes, tailbud, and hindlimb bud (PubMed:10498682).
Highly expressed in lung epithelial cells, primarily in the distal airways at 12 dpc (PubMed:10074434).
Highly expressed in lung epithelial cells, primarily in the distal airways at 12 dpc (PubMed:10074434).
Gene expression databases
Interaction
Subunit
Forms heterodimers with SPRY1 (PubMed:16877379).
Forms a tripartite complex containing GAB1, METTL13 and SPRY2 (By similarity).
Within the complex interacts with METTL13 (By similarity).
Interacts with RAF1 (By similarity).
Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction disrupts SPRY2 interaction with GRB2, potentially via disruption of SPRY2 serine dephosphorylation (PubMed:17974561).
Interacts with PPP2R1A/PP2A-A and PPP2CA/PP2A-C; the interaction with PPP2CA/PP2A-C is inhibited by interaction with TESK1, possibly by vesicular sequestration of SPRY2 (By similarity).
Inhibition of the interaction with the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme results in loss of PP2A-mediated dephosphorylation, resulting in the loss of SPRY2 interaction with GRB2 (By similarity).
Interacts with GRB2 (By similarity).
Interacts with CBL/C-CBL; the interaction inhibits CBL-mediated ubiquitination of EGFR (By similarity).
Interacts (via C-terminus) with CAV1 (via C-terminus) (PubMed:16877379).
Forms a tripartite complex containing GAB1, METTL13 and SPRY2 (By similarity).
Within the complex interacts with METTL13 (By similarity).
Interacts with RAF1 (By similarity).
Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction disrupts SPRY2 interaction with GRB2, potentially via disruption of SPRY2 serine dephosphorylation (PubMed:17974561).
Interacts with PPP2R1A/PP2A-A and PPP2CA/PP2A-C; the interaction with PPP2CA/PP2A-C is inhibited by interaction with TESK1, possibly by vesicular sequestration of SPRY2 (By similarity).
Inhibition of the interaction with the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme results in loss of PP2A-mediated dephosphorylation, resulting in the loss of SPRY2 interaction with GRB2 (By similarity).
Interacts with GRB2 (By similarity).
Interacts with CBL/C-CBL; the interaction inhibits CBL-mediated ubiquitination of EGFR (By similarity).
Interacts (via C-terminus) with CAV1 (via C-terminus) (PubMed:16877379).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-19 | Polar residues | ||||
Sequence: MEARAQSGNGSQPLLQTAH | ||||||
Region | 1-39 | Disordered | ||||
Sequence: MEARAQSGNGSQPLLQTAHDSGRQRGEPDPRDALTQQVH | ||||||
Region | 51-141 | Disordered | ||||
Sequence: NTNEYTEGPTVVPRPGLKPAPRPSTQHKHERLHGLPEHRQPPRLQPSQVHSSRAPLSRSISTVSSGSRSSTRTSTSSSSSEQRLLGPSFSH | ||||||
Compositional bias | 73-88 | Basic and acidic residues | ||||
Sequence: PSTQHKHERLHGLPEH | ||||||
Compositional bias | 94-136 | Polar residues | ||||
Sequence: LQPSQVHSSRAPLSRSISTVSSGSRSSTRTSTSSSSSEQRLLG | ||||||
Region | 117-315 | Required for interaction with CAV1 | ||||
Sequence: SRSSTRTSTSSSSSEQRLLGPSFSHGPAAADGIIRVQPKSELKPGDVKPLSKDDLGLHAYRCEDCGKCKCKECTYPRPLPSDWICDKQCLCSAQNVIDYGTCVCCVKGLFYHCSNDDEDNCADNPCSCSQSHCCTRWSAMGVMSLFLPCLWCYLPAKGCLKLCQGCYDRVNRPGCRCKNSNTVCCKVPTVPPRNFEKPT | ||||||
Domain | 177-291 | SPR | ||||
Sequence: RCEDCGKCKCKECTYPRPLPSDWICDKQCLCSAQNVIDYGTCVCCVKGLFYHCSNDDEDNCADNPCSCSQSHCCTRWSAMGVMSLFLPCLWCYLPAKGCLKLCQGCYDRVNRPGC | ||||||
Region | 178-315 | Required for interaction with TESK1 | ||||
Sequence: CEDCGKCKCKECTYPRPLPSDWICDKQCLCSAQNVIDYGTCVCCVKGLFYHCSNDDEDNCADNPCSCSQSHCCTRWSAMGVMSLFLPCLWCYLPAKGCLKLCQGCYDRVNRPGCRCKNSNTVCCKVPTVPPRNFEKPT |
Domain
The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.
Sequence similarities
Belongs to the sprouty family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length315
- Mass (Da)34,623
- Last updated2000-05-01 v1
- Checksum81514698EAD809A7
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-19 | Polar residues | ||||
Sequence: MEARAQSGNGSQPLLQTAH | ||||||
Compositional bias | 73-88 | Basic and acidic residues | ||||
Sequence: PSTQHKHERLHGLPEH | ||||||
Compositional bias | 94-136 | Polar residues | ||||
Sequence: LQPSQVHSSRAPLSRSISTVSSGSRSSTRTSTSSSSSEQRLLG | ||||||
Sequence conflict | 163 | in Ref. 2; AAD34167 | ||||
Sequence: V → I |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF176905 EMBL· GenBank· DDBJ | AAD56006.1 EMBL· GenBank· DDBJ | mRNA | ||
AF153084 EMBL· GenBank· DDBJ | AAD34167.1 EMBL· GenBank· DDBJ | mRNA |