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SPRY1
Localization (UniProt annotation) Cytoplasm Membrane; Peripheral membraneprotein Note=Found in the cytoplasm in unstimulated cells but istranslocated to the membrane ruffles in cells stimulated with EGF(epidermal growth factor) Function (UniProt annotation) May function as an antagonist of fibroblast growthfactor (FGF) pathways and may negatively modulate respiratoryorganogenesis Catalytic Activity (UniProt annotation) N/A Protein Sequence MDPQNQHGSGSSLVVIQQPSLDSRQRLDYEREIQPTAILSLDQIKAIRGSNEYTEGPSVVKRPAPRTAPRQEKHERTHEI
IPINVNNNYEHRHTSHLGHAVLPSNARGPILSRSTSTGSAASSGSNSSASSEQGLLGRSPPTRPVPGHRSERAIRTQPKQ
LIVDDLKGSLKEDLTQHKFICEQCGKCKCGECTAPRTLPSCLACNRQCLCSAESMVEYGTCMCLVKGIFYHCSNDDEGDS
YSDNPCSCSQSHCCSRYLCMGAMSLFLPCLLCYPPAKGCLKLCRRCYDWIHRPGCRCKNSNTVYCKLESCPSRGQGKPS
ELM Motif Motif Instance Description Motif Regex NA NA NA NA
GO:0000132 P:establishment of mitotic spindle orientation GO:0001656 P:metanephros development GO:0001657 P:ureteric bud development GO:0001759 P:organ induction GO:0005654 C:nucleoplasm GO:0005794 C:Golgi apparatus GO:0005829 C:cytosol GO:0005886 C:plasma membrane GO:0008285 P:negative regulation of cell proliferation GO:0034260 P:negative regulation of GTPase activity GO:0040037 P:negative regulation of fibroblast growth factor receptor signaling pathway GO:0042059 P:negative regulation of epidermal growth factor receptor signaling pathway GO:0043407 P:negative regulation of MAP kinase activity GO:0046580 P:negative regulation of Ras protein signal transduction GO:0051387 P:negative regulation of neurotrophin TRK receptor signaling pathway GO:0060449 P:bud elongation involved in lung branching GO:0060940 P:epithelial to mesenchymal transition involved in cardiac fibroblast development GO:0070373 P:negative regulation of ERK1 and ERK2 cascade
Pathway ID Pathway Name Pathway Description (KEGG) R-HSA-182971 EGFR downregulation. Regulation of receptor tyrosine kinase (RTK) activity is implicated in the control of almost all cellular functions. One of the best understood RTKs is epidermal growth factor receptor (EGFR). Growth factors can bind to EGFR and activate it to initiate signalling cascades within the cell. EGFRs can also be recruited to clathrin-coated pits which can be internalised into endocytic vesicles. From here, EGFRs can either be recycled back to the plasma membrane or directed to lysosomes for destruction.This provides a mechanism by which EGFR signalling is negatively regulated and controls the strength and duration of EGFR-induced signals. It also prevents EGFR hyperactivation as commonly seen in tumorigenesis.The proto-oncogene Cbl can negatively regulate EGFR signalling. The Cbl family of RING-type ubiquitin ligases are able to poly-ubiquitinate EGFR, an essential step in EGFR degradation. All Cbl proteins have a unique domain that recognises phosphorylated tyrosine residues on activated EGFRs. They also direct the ubiquitination and degradation of activated EGFRs by recruiting ubiquitin-conjugation enzymes. Cbl proteins function by specifically targeting activated EGFRs and mediating their down-regulation, thus providing a means by which signaling processes can be negatively regulated.Cbl also promotes receptor internalization via it's interaction with an adaptor protein, CIN85 (Cbl-interacting protein of 85kDa). CIN85 binds to Cbl via it's SH3 domain and is enhanced by the EGFR-induced tyrosine phosphorylation of Cbl. The proline-rich region of CIN85 interacts with endophilins which are regulatory components of clathrin-coated vesicles (CCVs). Endophilins bind to membranes and induce membrane curvature, in conjunction with other proteins involved in CCV formation. The rapid recruitment of endophilin to the activated receptor complex by CIN85 is the mechanism which controls receptor internalization
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source BAG3 Affinity Capture-Luminescence physical 23824909 , (Europe PMC )NA BioGRID CACNA1A Two-hybrid, two hybrid physical, physical association 21078624 , (Europe PMC )0.37 BioGRID, IntAct CBL Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 15004239 , 16893902 , 19915061 , (Europe PMC )0.40 BioGRID, IntAct, MINT CBLB Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID CREB5 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct ELAVL1 Affinity Capture-RNA physical 19322201 , (Europe PMC )NA BioGRID GEMIN4 Two-hybrid, two hybrid, two hybrid array, two hybrid prey pooling approach physical, physical association 21988832 , (Europe PMC )0.62 BioGRID, IntAct GRB2 Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 16893902 , (Europe PMC )0.40 BioGRID, IntAct, MINT HEXIM2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct HOXA1 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 21516116 , 25416956 , (Europe PMC )0.70 BioGRID, IntAct HRG Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct KPNA2 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct KRTAP10-1 Two-hybrid physical 25416956 , (Europe PMC )NA BioGRID KRTAP10-3 Two-hybrid physical 25416956 , (Europe PMC )NA BioGRID KRTAP10-5 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct KRTAP10-7 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.49, 0.56 BioGRID, IntAct KRTAP10-8 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct KRTAP10-9 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct KRTAP4-2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct LAT Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID LCE1B Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct LCE2D Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct MAP4K1 Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID MDFI Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct MEOX2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct NEDD4 Affinity Capture-Western physical 19864419 , (Europe PMC )NA BioGRID NOTCH2NLA Two-hybrid physical 25416956 , (Europe PMC )NA BioGRID OTX1 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct PLCG1 Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID R3HDM2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct SH3KBP1 Affinity Capture-Western physical 15962011 , (Europe PMC )NA BioGRID SOCS4 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct SPRY2 Affinity Capture-Western, Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 15004239 , 25416956 , (Europe PMC )0.56 BioGRID, IntAct STAT3 Two-hybrid physical 21988832 , (Europe PMC )NA BioGRID TESK1 Affinity Capture-Western physical 17974561 , (Europe PMC )NA BioGRID YY1 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source CACNA1A Two-hybrid, two hybrid physical, physical association 21078624 , (Europe PMC )0.37 BioGRID, IntAct CBL Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 15004239 , 16893902 , 19915061 , (Europe PMC )0.40 BioGRID, IntAct, MINT CREB5 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct EBI-10171679 two hybrid array, two hybrid prey pooling approach, validated two hybrid physical association 25416956 , (Europe PMC )0.56 IntAct EBI-10173330 two hybrid array, two hybrid prey pooling approach, validated two hybrid physical association 25416956 , (Europe PMC )0.56 IntAct GEMIN4 Two-hybrid, two hybrid, two hybrid array, two hybrid prey pooling approach physical, physical association 21988832 , (Europe PMC )0.62 BioGRID, IntAct GRB2 Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 16893902 , (Europe PMC )0.40 BioGRID, IntAct, MINT HEXIM2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct HOXA1 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 21516116 , 25416956 , (Europe PMC )0.70 BioGRID, IntAct HRG Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct KPNA2 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct KRTAP10-5 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct KRTAP10-7 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.49, 0.56 BioGRID, IntAct KRTAP10-8 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct KRTAP10-9 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct KRTAP4-2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct LCE1B Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct LCE2D Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct MDFI Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct MEOX2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct NOTCH2NL two hybrid array, two hybrid prey pooling approach, validated two hybrid physical association 25416956 , (Europe PMC )0.70 IntAct OTX1 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct R3HDM2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct SOCS4 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct SPRY2 Affinity Capture-Western, Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 15004239 , 25416956 , (Europe PMC )0.56 BioGRID, IntAct STAT3 two hybrid physical association 21988832 , (Europe PMC )0.37 IntAct TGOLN2 proximity-dependent biotin identification association 29568061 , (Europe PMC )0.35 IntAct YY1 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source BAG3 Affinity Capture-Luminescence physical 23824909 , (Europe PMC )NA BioGRID CACNA1A Two-hybrid, two hybrid physical, physical association 21078624 , (Europe PMC )0.37 BioGRID, IntAct CBL Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 15004239 , 16893902 , 19915061 , (Europe PMC )0.40 BioGRID, IntAct, MINT CBLB Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID CREB5 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct EBI-10171679 two hybrid array, two hybrid prey pooling approach, validated two hybrid physical association 25416956 , (Europe PMC )0.56 IntAct EBI-10173330 two hybrid array, two hybrid prey pooling approach, validated two hybrid physical association 25416956 , (Europe PMC )0.56 IntAct ELAVL1 Affinity Capture-RNA physical 19322201 , (Europe PMC )NA BioGRID GEMIN4 Two-hybrid, two hybrid, two hybrid array, two hybrid prey pooling approach physical, physical association 21988832 , (Europe PMC )0.62 BioGRID, IntAct GRB2 Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 16893902 , (Europe PMC )0.40 BioGRID, IntAct, MINT HEXIM2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct HOXA1 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 21516116 , 25416956 , (Europe PMC )0.70 BioGRID, IntAct HRG Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct KPNA2 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct KRTAP10-1 Two-hybrid physical 25416956 , (Europe PMC )NA BioGRID KRTAP10-3 Two-hybrid physical 25416956 , (Europe PMC )NA BioGRID KRTAP10-5 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct KRTAP10-7 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.49, 0.56 BioGRID, IntAct KRTAP10-8 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct KRTAP10-9 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct KRTAP4-2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct LAT Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID LCE1B Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct LCE2D Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct MAP4K1 Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID MDFI Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.70 BioGRID, IntAct MEOX2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct NEDD4 Affinity Capture-Western physical 19864419 , (Europe PMC )NA BioGRID NOTCH2NL two hybrid array, two hybrid prey pooling approach, validated two hybrid physical association 25416956 , (Europe PMC )0.70 IntAct NOTCH2NLA Two-hybrid physical 25416956 , (Europe PMC )NA BioGRID OTX1 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct PLCG1 Affinity Capture-Western physical 19915061 , (Europe PMC )NA BioGRID R3HDM2 Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 25416956 , (Europe PMC )0.56 BioGRID, IntAct SH3KBP1 Affinity Capture-Western physical 15962011 , (Europe PMC )NA BioGRID SOCS4 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct SPRY2 Affinity Capture-Western, Two-hybrid, two hybrid array, two hybrid prey pooling approach, validated two hybrid physical, physical association 15004239 , 25416956 , (Europe PMC )0.56 BioGRID, IntAct STAT3 Two-hybrid physical 21988832 , (Europe PMC )NA BioGRID STAT3 two hybrid physical association 21988832 , (Europe PMC )0.37 IntAct TESK1 Affinity Capture-Western physical 17974561 , (Europe PMC )NA BioGRID TGOLN2 proximity-dependent biotin identification association 29568061 , (Europe PMC )0.35 IntAct YY1 Two-hybrid, two hybrid physical, physical association 21988832 , (Europe PMC )0.37 BioGRID, IntAct