PTPN11 encodes SHP2, a widely expressed soluble non-receptor protein tyrosine phosphatase. Its tandem N-terminal SH2 domains both autoinhibit the catalytic PTP domain and recruit SHP2 to phosphotyrosine-containing receptors and adaptors, where ligand binding activates tyrosine dephosphorylation. SHP2 also has phosphotyrosine-dependent molecular-adaptor and scaffolding activities. These coupled functions commonly promote RAS-ERK output downstream of receptor tyrosine kinases, while producing inhibitory effects in selected immune-receptor pathways. PTPN11 is required in many developmental and homeostatic contexts, and altered catalytic regulation causes RASopathy syndromes and contributes to malignancy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm is a principal compartment for soluble SHP2 signaling. Reason: SHP2 is a non-receptor phosphatase recruited from the cytoplasm to phosphotyrosine-containing receptor and adaptor complexes. |
| GO:0038127 ERBB signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SHP2 participates in ERBB-family receptor signaling in appropriate cellular contexts. Reason: ERBB signaling is one receptor-specific use of SHP2's general phosphotyrosine-binding, phosphatase, and adaptor activities rather than a distinct core activity. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0030971 receptor tyrosine kinase binding | IBA GO_REF:0000033 | ACCEPT | Summary: Receptor tyrosine kinase binding reflects core SH2-guided recruitment of SHP2 to activated signaling complexes. Reason: Binding activated phosphotyrosine-containing receptors is central to SHP2 localization, activation, and access to receptor-proximal substrates. |
| GO:0050839 cell adhesion molecule binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: SHP2 binds phosphorylated cell-adhesion receptors in specific signaling contexts. Reason: This is a supported recruitment context, but it is narrower than SHP2's defining phosphotyrosine-binding and catalytic activities. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of ERK1/2 output is a recurrent, central consequence of SHP2 activity downstream of receptor tyrosine kinases. Reason: SHP2 commonly promotes RAS-ERK signaling, including by dephosphorylating inhibitory substrates such as Sprouty proteins. Supporting Evidence: PMID:28074573 Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling. PMID:24431450 Ptpn11 interacts with Fgf8 and is essential for ERK activation in RG and nascent BG. |
| GO:0004725 protein tyrosine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization is experimentally reported for SHP2. Reason: Nuclear access is supported but is secondary to the predominant cytosolic and receptor-proximal signaling mechanism. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm is a principal compartment for soluble SHP2 signaling. Reason: SHP2 is a non-receptor phosphatase recruited from the cytoplasm to phosphotyrosine-containing receptor and adaptor complexes. |
| GO:0031295 T cell costimulation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SHP2 participates in T-cell costimulatory and coinhibitory receptor networks. Reason: T-cell costimulation is an immune-context output of SHP2 recruitment and catalysis, not its project-independent core function. |
| GO:0050858 negative regulation of antigen receptor-mediated signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SHP2 can attenuate antigen-receptor signaling after recruitment by inhibitory receptors. Reason: The annotation is a context-specific immune outcome of the core phosphatase/recruitment mechanism. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SHP2 can promote PI3K-AKT signaling in receptor and mechanotransduction contexts. Reason: PI3K-AKT regulation is a pathway-specific downstream outcome rather than a distinct SHP2 molecular activity. |
| GO:0060338 regulation of type I interferon-mediated signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SHP2 regulates type-I-interferon signaling in innate-immune contexts. Reason: This immune pathway is a context-specific deployment of SHP2 catalytic and scaffolding functions. |
| GO:1902564 negative regulation of neutrophil activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SHP2 contributes to inhibitory control of neutrophil activation. Reason: Neutrophil activation is a cell-type-specific downstream outcome and is retained as non-core. |
| GO:0005515 protein binding | IPI PMID:10206955 The myeloid-specific sialic acid-binding receptor, CD33, ass... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P20138, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:10206955 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P29317, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:10655584 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:10660596 Tyrosine dephosphorylation and deactivation of insulin recep... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P35570, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:10660596 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:10681522 Dissecting the interaction of SHP-2 with PZR, an immunoglobu... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:O95297, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:10681522 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:10704309 Identification of natural ligands for SH2 domains from a pha... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P16284, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:10704309 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:11323411 Phosphotyrosines 627 and 659 of Gab1 constitute a bisphospho... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:11323411 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:11453982 Co-clustering of Fcgamma and B cell receptors induces dephos... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:11453982 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:12577067 A proteomics strategy to elucidate functional protein-protei... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P62993, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:12577067 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:12614164 Identification of protein tyrosine phosphatases associating ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P09619, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:12614164 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:12855672 Activation of gp130 transduces hypertrophic signal through i... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:12855672 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:14652006 Characterization of phosphotyrosine binding motifs in the cy... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q7Z6A9, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:14652006 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:14665621 Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylatio... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P49023, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:14665621 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:14701753 Distinct domains in the SHP-2 phosphatase differentially reg... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:14701753 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:15170389 Interaction of the tyrosine phosphatase SHP-2 with Gab2 regu... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9UQC2, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:15170389 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:15240681 SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q15116, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:15240681 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:15574420 A novel role for Gab1 and SHP2 in epidermal growth factor-in... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:15574420 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:16253990 Increased proliferation and altered growth factor dependence... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9UQC2, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:16253990 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P00533, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:16273093 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:16337946 Pinpointing phosphotyrosine-dependent interactions downstrea... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q08345, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:16337946 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:16354697 Focal adhesion kinase is a substrate and downstream effector... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q05397, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:16354697 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:16963136 An ITIM-like motif within the CCK2 receptor sequence require... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P32239, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:16963136 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:17936057 A2 isoform of mammalian translation factor eEF1A displays in... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P68105, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:17936057 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:17947393 ITIM-dependent endocytosis of CD33-related Siglecs: role of ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P20138, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:17947393 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:18579758 Association of protein tyrosine phosphatases (PTPs)-1B with ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P08581, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:18579758 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:19172738 Phosphorylation-dependent binding of 14-3-3 terminates signa... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9UQC2, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:19172738 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P62993, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:19380743 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:20308328 Functional effects of PTPN11 (SHP2) mutations causing LEOPAR... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:20308328 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:20473329 SIRPalpha1 receptors interfere with the EGFRvIII signalosome... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P00533, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:20473329 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P49247, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:21516116 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:21706016 Selected reaction monitoring mass spectrometry reveals the d... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P62993, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:21706016 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:23397142 Analysis of protein-protein interactions in cross-talk pathw... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P09619, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:23397142 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:24642916 Fine specificity and molecular competition in SLAM family re... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9BZW8, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:24642916 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P08581, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:24728074 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P49247, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:25416956 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:27229929 Systematic interactome mapping of acute lymphoblastic leukem... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13049, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:27229929 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:28046066 HTLV-1 bZIP Factor Enhances T-Cell Proliferation by Impeding... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q15116, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:28046066 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:28065597 A Global Analysis of the Receptor Tyrosine Kinase-Protein Ph... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P00533, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:28065597 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q8WU20, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:29997244 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13049, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:31515488 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:31585087 Oncogenic Mutations Rewire Signaling Pathways by Switching P... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P62993, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:31585087 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P62993, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:31980649 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:O95297, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:33961781 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P00533, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:35384245 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P00533, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:35512704 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P62993, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:40205054 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:7493946 Adapter function of protein-tyrosine phosphatase 1D in insul... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P06213, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:7493946 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:7504175 Pleiotropic insulin signals are engaged by multisite phospho... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P35570, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:7504175 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:7513703 Activation of the SH2-containing protein tyrosine phosphatas... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P35568, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:7513703 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:7523381 The ubiquitously expressed Syp phosphatase interacts with c-... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P62993, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:7523381 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:7530043 Direct determination of the sequence recognition requirement... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P09619, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:7530043 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:7642582 Localization of the insulin-like growth factor I receptor bi... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P08069, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:7642582 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:7688466 The 64-kDa protein that associates with the platelet-derived... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P09619, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:7688466 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:8119896 Characterization of protein tyrosine phosphatase SH-PTP2. St... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P09619, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:8119896 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:8183548 Receptor-binding, tyrosine phosphorylation and chromosome lo... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P09619, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:8183548 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:8538796 Spatial constraints on the recognition of phosphoproteins by... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P09619, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:8538796 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:8648092 Human and mouse killer-cell inhibitory receptors recruit PTP... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P43628, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:8648092 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:8810330 Activation of protein-tyrosine phosphatase SH-PTP2 by a tyro... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P97710, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:8810330 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:8895367 Interaction of SH2-containing protein tyrosine phosphatase 2... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P08069, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:8895367 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:9312087 Characterization of phosphotyrosine binding motifs in the cy... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P16284, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:9312087 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:9535915 Roles of the complex formation of SHPS-1 with SHP-2 in insul... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P97710, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:9535915 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:9593725 Association of the insulin receptor with phospholipase C-gam... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P06213, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:9593725 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:9632781 Binding of Shp2 tyrosine phosphatase to FRS2 is essential fo... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q8WU20, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:9632781 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:9658397 Determination of Gab1 (Grb2-associated binder-1) interaction... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:9658397 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:9774457 Recruitment and activation of SHP-1 protein-tyrosine phospha... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P16284, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:9774457 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:9792637 Purification and cloning of PZR, a binding protein and putat... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:O95297, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:9792637 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | MODIFY | Summary: Protein-kinase binding is directionally correct but unnecessarily broad for a phosphotyrosine-directed SH2 phosphatase. Reason: The reviewed biology supports the more informative protein tyrosine kinase binding term. Proposed replacements: protein tyrosine kinase binding |
| GO:0030971 receptor tyrosine kinase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Receptor tyrosine kinase binding reflects core SH2-guided recruitment of SHP2 to activated signaling complexes. Reason: Binding activated phosphotyrosine-containing receptors is central to SHP2 localization, activation, and access to receptor-proximal substrates. |
| GO:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SHP2 can promote lipopolysaccharide-responsive signaling in innate-immune cells. Reason: This is a stimulus- and cell-type-specific consequence of SHP2 signaling and is not a core molecular activity. |
| GO:0032331 negative regulation of chondrocyte differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SHP2-dependent signaling can inhibit chondrocyte differentiation. Reason: Chondrocyte differentiation is a pleiotropic developmental output downstream of SHP2 and is retained as non-core. |
| GO:0032728 positive regulation of interferon-beta production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SHP2 has reported context-dependent effects on interferon-beta production. Reason: This innate-immune output is retained as non-core and should not be generalized to all SHP2 signaling contexts. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SHP2 has reported context-dependent effects on tumor-necrosis-factor production. Reason: This cytokine output is an immune-context consequence rather than a defining SHP2 function. |
| GO:0045778 positive regulation of ossification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SHP2 promotes ossification in developmental signaling contexts. Reason: Ossification is a downstream developmental outcome, not the phosphatase's core molecular activity. |
| GO:0050839 cell adhesion molecule binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SHP2 binds phosphorylated cell-adhesion receptors in specific signaling contexts. Reason: This is a supported recruitment context, but it is narrower than SHP2's defining phosphotyrosine-binding and catalytic activities. |
| GO:0007173 epidermal growth factor receptor signaling pathway | TAS Reactome:R-HSA-177929 | KEEP AS NON CORE | Summary: SHP2 participates in epidermal-growth-factor-receptor signaling. Reason: EGFR signaling is one receptor-specific deployment of SHP2's general receptor-proximal functions. |
| GO:0019221 cytokine-mediated signaling pathway | TAS Reactome:R-HSA-512988 | KEEP AS NON CORE | Summary: SHP2 participates in multiple cytokine-receptor signaling pathways. Reason: The broad cytokine pathway term summarizes context-specific deployments of SHP2 and is retained as non-core. |
| GO:0019221 cytokine-mediated signaling pathway | TAS Reactome:R-HSA-9674555 | KEEP AS NON CORE | Summary: SHP2 participates in multiple cytokine-receptor signaling pathways. Reason: The broad cytokine pathway term summarizes context-specific deployments of SHP2 and is retained as non-core. |
| GO:0031295 T cell costimulation | TAS Reactome:R-HSA-388841 | KEEP AS NON CORE | Summary: SHP2 participates in T-cell costimulatory and coinhibitory receptor networks. Reason: T-cell costimulation is an immune-context output of SHP2 recruitment and catalysis, not its project-independent core function. |
| GO:0060338 regulation of type I interferon-mediated signaling pathway | TAS Reactome:R-HSA-912694 | KEEP AS NON CORE | Summary: SHP2 regulates type-I-interferon signaling in innate-immune contexts. Reason: This immune pathway is a context-specific deployment of SHP2 catalytic and scaffolding functions. |
| GO:0004725 protein tyrosine phosphatase activity | EXP PMID:22759635 A Src family kinase-Shp2 axis controls RUNX1 activity in meg... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004725 protein tyrosine phosphatase activity | EXP PMID:26617336 Inhibition of SHP2-mediated dephosphorylation of Ras suppres... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004725 protein tyrosine phosphatase activity | TAS Reactome:R-HSA-1549564 | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004725 protein tyrosine phosphatase activity | TAS Reactome:R-HSA-389758 | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004725 protein tyrosine phosphatase activity | TAS Reactome:R-HSA-914036 | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004725 protein tyrosine phosphatase activity | TAS Reactome:R-HSA-997309 | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleoplasmic localization is reported in nuclear signaling and transcriptional contexts. Reason: Nucleoplasmic access is plausible and curated, but it is secondary to SHP2's core cytosolic/receptor-proximal role. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | UNDECIDED | Summary: A nucleolar high-content localization signal is present, but its functional significance is unclear. Reason: The available evidence does not establish a nucleolar SHP2 activity; the annotation is not removed because the experimental curator may have additional context. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol is the principal soluble compartment for SHP2 signaling. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | IDA PMID:20170098 Salicylic acid based small molecule inhibitor for the oncoge... | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0019221 cytokine-mediated signaling pathway | IDA PMID:11294841 Signaling pathways recruited by the cardiotrophin-like cytok... | KEEP AS NON CORE | Summary: SHP2 participates in multiple cytokine-receptor signaling pathways. Reason: The broad cytokine pathway term summarizes context-specific deployments of SHP2 and is retained as non-core. |
| GO:0005925 focal adhesion | IDA PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | KEEP AS NON CORE | Summary: SHP2 is active at focal adhesions during EphA2-integrin signaling. Reason: Focal-adhesion recruitment is a specific signaling context rather than a universal SHP2 location. |
| GO:0033629 negative regulation of cell adhesion mediated by integrin | IMP PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | KEEP AS NON CORE | Summary: SHP2 contributes to EphA2-dependent inhibition of integrin-mediated adhesion. Reason: This adhesion phenotype is a pathway-specific downstream consequence and is retained as non-core. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | IDA PMID:32184441 Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1... | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0050860 negative regulation of T cell receptor signaling pathway | IDA PMID:32184441 Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1... | KEEP AS NON CORE | Summary: PD-1-recruited SHP2 can inhibit T-cell-receptor signaling. Reason: This is a well-defined immune-checkpoint deployment of SHP2's core phosphotyrosine binding and phosphatase activities. |
| GO:0050868 negative regulation of T cell activation | IDA PMID:32184441 Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1... | KEEP AS NON CORE | Summary: PD-1-recruited SHP2 can inhibit T-cell activation. Reason: T-cell activation is a context-specific physiological output rather than SHP2's core molecular function. |
| GO:0042311 vasodilation | IMP PMID:26706435 PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation... | KEEP AS NON CORE | Summary: Endothelial SHP2 signaling contributes to flow-mediated vasodilation. Reason: Vasodilation is a tissue-level mechanotransduction outcome and is retained as non-core. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:26706435 PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation... | KEEP AS NON CORE | Summary: SHP2 can promote PI3K-AKT signaling in receptor and mechanotransduction contexts. Reason: PI3K-AKT regulation is a pathway-specific downstream outcome rather than a distinct SHP2 molecular activity. |
| GO:0071260 cellular response to mechanical stimulus | IMP PMID:26706435 PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation... | KEEP AS NON CORE | Summary: SHP2 participates in endothelial responses to mechanical flow. Reason: Mechanical-stimulus response is a context-specific upstream input to SHP2 signaling. |
| GO:1902533 positive regulation of intracellular signal transduction | IMP PMID:26706435 PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation... | MARK AS OVER ANNOTATED | Summary: SHP2 can promote intracellular signaling, but this term is too broad to convey the mechanism. Reason: The generic term adds little beyond more specific ERK and PI3K-AKT annotations and risks causal over-propagation. |
| GO:0042130 negative regulation of T cell proliferation | IDA PMID:15568026 B and T lymphocyte attenuator regulates T cell activation th... | KEEP AS NON CORE | Summary: Inhibitory-receptor recruitment of SHP2 can reduce T-cell proliferation. Reason: This is a downstream immune-cell outcome rather than a core molecular activity. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | TAS Reactome:R-HSA-177923 | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | TAS Reactome:R-HSA-177924 | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | TAS Reactome:R-HSA-177926 | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | TAS Reactome:R-HSA-177935 | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SHP2 can promote lipopolysaccharide-responsive signaling in innate-immune cells. Reason: This is a stimulus- and cell-type-specific consequence of SHP2 signaling and is not a core molecular activity. |
| GO:1902564 negative regulation of neutrophil activation | IDA PMID:34234773 The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling... | KEEP AS NON CORE | Summary: SHP2 contributes to inhibitory control of neutrophil activation. Reason: Neutrophil activation is a cell-type-specific downstream outcome and is retained as non-core. |
| GO:0005515 protein binding | IPI PMID:12051764 SPAP2, an Ig family receptor containing both ITIMs and ITAMs... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q96P31, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:12051764 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | UNDECIDED | Summary: A high-throughput mitochondrial-localization signal is reported. Reason: A single HTP localization does not establish a functional mitochondrial pool of SHP2; retain undecided rather than overruling the experimental source. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8937744 | KEEP AS NON CORE | Summary: Reactome event Reactome:R-HSA-8937744 places SHP2 in the nucleoplasm in a specific nuclear signaling context. Reason: Nucleoplasmic access is plausible and curated, but it is secondary to SHP2's core cytosolic/receptor-proximal role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8937767 | KEEP AS NON CORE | Summary: Reactome event Reactome:R-HSA-8937767 places SHP2 in the nucleoplasm in a specific nuclear signaling context. Reason: Nucleoplasmic access is plausible and curated, but it is secondary to SHP2's core cytosolic/receptor-proximal role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9008894 | KEEP AS NON CORE | Summary: Reactome event Reactome:R-HSA-9008894 places SHP2 in the nucleoplasm in a specific nuclear signaling context. Reason: Nucleoplasmic access is plausible and curated, but it is secondary to SHP2's core cytosolic/receptor-proximal role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698016 | KEEP AS NON CORE | Summary: Reactome event Reactome:R-HSA-9698016 places SHP2 in the nucleoplasm in a specific nuclear signaling context. Reason: Nucleoplasmic access is plausible and curated, but it is secondary to SHP2's core cytosolic/receptor-proximal role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698021 | KEEP AS NON CORE | Summary: Reactome event Reactome:R-HSA-9698021 places SHP2 in the nucleoplasm in a specific nuclear signaling context. Reason: Nucleoplasmic access is plausible and curated, but it is secondary to SHP2's core cytosolic/receptor-proximal role. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109699 | ACCEPT | Summary: Reactome event Reactome:R-HSA-109699 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1112690 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1112690 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1112703 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1112703 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1112708 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1112708 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433428 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1433428 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433454 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1433454 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433488 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1433488 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433514 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1433514 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1549564 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1549564 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1562641 | ACCEPT | Summary: Reactome event Reactome:R-HSA-1562641 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177923 | ACCEPT | Summary: Reactome event Reactome:R-HSA-177923 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177924 | ACCEPT | Summary: Reactome event Reactome:R-HSA-177924 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177926 | ACCEPT | Summary: Reactome event Reactome:R-HSA-177926 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177935 | ACCEPT | Summary: Reactome event Reactome:R-HSA-177935 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-177944 | ACCEPT | Summary: Reactome event Reactome:R-HSA-177944 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-186778 | ACCEPT | Summary: Reactome event Reactome:R-HSA-186778 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-204873 | ACCEPT | Summary: Reactome event Reactome:R-HSA-204873 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205234 | ACCEPT | Summary: Reactome event Reactome:R-HSA-205234 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205238 | ACCEPT | Summary: Reactome event Reactome:R-HSA-205238 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-210294 | ACCEPT | Summary: Reactome event Reactome:R-HSA-210294 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: Reactome event Reactome:R-HSA-2316434 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: Reactome event Reactome:R-HSA-2400009 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-388829 | ACCEPT | Summary: Reactome event Reactome:R-HSA-388829 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389758 | ACCEPT | Summary: Reactome event Reactome:R-HSA-389758 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389759 | ACCEPT | Summary: Reactome event Reactome:R-HSA-389759 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389941 | ACCEPT | Summary: Reactome event Reactome:R-HSA-389941 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654584 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654584 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654587 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654587 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654594 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654594 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654596 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654596 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654607 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654607 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654608 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654608 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654620 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654620 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654622 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654622 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654631 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654631 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654633 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654633 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654641 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654641 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654643 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654643 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654655 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654655 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654658 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654658 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654667 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654667 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654669 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654669 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654672 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654672 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654673 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654673 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654677 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654677 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654679 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654679 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654684 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654684 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654692 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654692 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654697 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654697 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654709 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654709 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654714 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654714 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654729 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654729 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654730 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654730 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654734 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5654734 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5684169 | ACCEPT | Summary: Reactome event Reactome:R-HSA-5684169 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8855508 | ACCEPT | Summary: Reactome event Reactome:R-HSA-8855508 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8865994 | ACCEPT | Summary: Reactome event Reactome:R-HSA-8865994 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987014 | ACCEPT | Summary: Reactome event Reactome:R-HSA-8987014 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987070 | ACCEPT | Summary: Reactome event Reactome:R-HSA-8987070 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987132 | ACCEPT | Summary: Reactome event Reactome:R-HSA-8987132 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8987236 | ACCEPT | Summary: Reactome event Reactome:R-HSA-8987236 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-909738 | ACCEPT | Summary: Reactome event Reactome:R-HSA-909738 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-914036 | ACCEPT | Summary: Reactome event Reactome:R-HSA-914036 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9674816 | ACCEPT | Summary: Reactome event Reactome:R-HSA-9674816 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698005 | ACCEPT | Summary: Reactome event Reactome:R-HSA-9698005 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698007 | ACCEPT | Summary: Reactome event Reactome:R-HSA-9698007 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698008 | ACCEPT | Summary: Reactome event Reactome:R-HSA-9698008 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698013 | ACCEPT | Summary: Reactome event Reactome:R-HSA-9698013 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698016 | ACCEPT | Summary: Reactome event Reactome:R-HSA-9698016 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698029 | ACCEPT | Summary: Reactome event Reactome:R-HSA-9698029 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-997309 | ACCEPT | Summary: Reactome event Reactome:R-HSA-997309 places SHP2 in the cytosol, consistent with its soluble receptor-proximal role. Reason: The many pathway-event and localization annotations consistently place soluble SHP2 in the cytosol before or during recruitment to signaling complexes. |
| GO:0005737 cytoplasm | IC PMID:26358190 Siglec1 suppresses antiviral innate immune response by induc... | ACCEPT | Summary: Cytoplasm is a principal compartment for soluble SHP2 signaling. Reason: SHP2 is a non-receptor phosphatase recruited from the cytoplasm to phosphotyrosine-containing receptor and adaptor complexes. |
| GO:0032480 negative regulation of type I interferon production | IDA PMID:26358190 Siglec1 suppresses antiviral innate immune response by induc... | KEEP AS NON CORE | Summary: Scaffolded SHP2 suppresses type-I-interferon production in a Siglec1-DAP12-TRIM27 pathway. Reason: This is a supported innate-immune deployment of SHP2's adaptor activity rather than its universal core process. |
| GO:0060090 molecular adaptor activity | IDA PMID:26358190 Siglec1 suppresses antiviral innate immune response by induc... | ACCEPT | Summary: Molecular-adaptor activity is a genuine non-catalytic core activity of SHP2. Reason: SHP2 can bridge receptors to downstream proteins without serving as substrate or enzyme in that interaction and can recruit effectors through scaffolding. Supporting Evidence: PMID:7493946 While the receptor and the phosphatase do not serve as substrates for each other, their interaction promotes IRS-1 binding to the receptor, indicating that PTP1D functions as an adapter for insulin receptor and IRS-1. |
| GO:0005515 protein binding | IPI PMID:19275884 SHP-2 inhibits tyrosine phosphorylation of Cas-L and regulat... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q14511, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:19275884 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:34310951 CLEC12B Decreases Melanoma Proliferation by Repressing Signa... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q2HXU8, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:34310951 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0032331 negative regulation of chondrocyte differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SHP2-dependent signaling can inhibit chondrocyte differentiation. Reason: Chondrocyte differentiation is a pleiotropic developmental output downstream of SHP2 and is retained as non-core. |
| GO:0045778 positive regulation of ossification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SHP2 promotes ossification in developmental signaling contexts. Reason: Ossification is a downstream developmental outcome, not the phosphatase's core molecular activity. |
| GO:0030159 signaling receptor complex adaptor activity | IPI PMID:7493946 Adapter function of protein-tyrosine phosphatase 1D in insul... | ACCEPT | Summary: Signaling-receptor-complex adaptor activity captures SHP2-mediated assembly of receptor-proximal signaling complexes. Reason: Direct receptor and IRS1 recruitment experiments establish a core adaptor role in addition to phosphatase catalysis. Supporting Evidence: PMID:7493946 While the receptor and the phosphatase do not serve as substrates for each other, their interaction promotes IRS-1 binding to the receptor, indicating that PTP1D functions as an adapter for insulin receptor and IRS-1. |
| GO:0005515 protein binding | IPI PMID:15133037 The major vault protein is a novel substrate for the tyrosin... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q14764, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:15133037 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IMP PMID:16481357 Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyro... | KEEP AS NON CORE | Summary: SHP2 positively transduces fibroblast-growth-factor-receptor signals. Reason: FGFR signaling is a major developmental context of the general SHP2 phosphatase/adaptor mechanism; it is retained as non-core rather than treated as a separate molecular activity. Supporting Evidence: PMID:24431450 Ptpn11 interacts with Fgf8 and is essential for ERK activation in RG and nascent BG. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | IDA PMID:16481357 Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyro... | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005515 protein binding | IPI PMID:15985432 Flow activates ERK1/2 and endothelial nitric oxide synthase ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q13480, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:15985432 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0045296 cadherin binding | IPI PMID:15985432 Flow activates ERK1/2 and endothelial nitric oxide synthase ... | KEEP AS NON CORE | Summary: A direct cadherin interaction is reported in endothelial mechanotransduction. Reason: Cadherin binding is a specific adhesion-context interaction and is not the general core binding mode of SHP2. |
| GO:0050839 cell adhesion molecule binding | IPI PMID:15985432 Flow activates ERK1/2 and endothelial nitric oxide synthase ... | KEEP AS NON CORE | Summary: SHP2 binds phosphorylated cell-adhesion receptors in specific signaling contexts. Reason: This is a supported recruitment context, but it is narrower than SHP2's defining phosphotyrosine-binding and catalytic activities. |
| GO:1990782 protein tyrosine kinase binding | IPI PMID:15985432 Flow activates ERK1/2 and endothelial nitric oxide synthase ... | ACCEPT | Summary: Protein tyrosine kinase binding is a core recruitment activity of SHP2 in receptor-proximal signaling. Reason: Tandem SH2 domains bind phosphorylated kinase/receptor complexes, controlling localization and catalytic activation. |
| GO:0004725 protein tyrosine phosphatase activity | IMP PMID:10206955 The myeloid-specific sialic acid-binding receptor, CD33, ass... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005515 protein binding | IPI PMID:10887109 Myeloid specific human CD33 is an inhibitory receptor with d... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P20138, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:10887109 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0046326 positive regulation of D-glucose import across plasma membrane | IDA PMID:7493946 Adapter function of protein-tyrosine phosphatase 1D in insul... | KEEP AS NON CORE | Summary: SHP2 adaptor function can promote insulin-stimulated glucose import. Reason: Glucose import is a physiological output of one receptor context, not a core activity of SHP2. |
| GO:0046628 positive regulation of insulin receptor signaling pathway | IDA PMID:7493946 Adapter function of protein-tyrosine phosphatase 1D in insul... | KEEP AS NON CORE | Summary: SHP2 positively regulates insulin-receptor signaling in an adaptor context. Reason: Insulin signaling is a receptor-specific deployment of the core adaptor and phosphotyrosine-binding functions. |
| GO:0019901 protein kinase binding | ISS GO_REF:0000024 | MODIFY | Summary: Protein-kinase binding is directionally correct but unnecessarily broad for a phosphotyrosine-directed SH2 phosphatase. Reason: The reviewed biology supports the more informative protein tyrosine kinase binding term. Proposed replacements: protein tyrosine kinase binding |
| GO:0032728 positive regulation of interferon-beta production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SHP2 has reported context-dependent effects on interferon-beta production. Reason: This innate-immune output is retained as non-core and should not be generalized to all SHP2 signaling contexts. |
| GO:0032760 positive regulation of tumor necrosis factor production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SHP2 has reported context-dependent effects on tumor-necrosis-factor production. Reason: This cytokine output is an immune-context consequence rather than a defining SHP2 function. |
| GO:0001784 phosphotyrosine residue binding | IPI PMID:11986327 Cloning and characterization of human Siglec-11. A recently ... | ACCEPT | Summary: Phosphotyrosine-residue binding by tandem SH2 domains is a core recruitment and activation mechanism of SHP2. Reason: Binding phosphorylated motifs relieves N-SH2-mediated autoinhibition and positions the catalytic domain near substrates. Supporting Evidence: PMID:32184441 SHP-2 interaction with two ITSM-pY248 phosphopeptides induced robust enzymatic activation. |
| GO:0005515 protein binding | IPI PMID:19843936 FCRL3, an autoimmune susceptibility gene, has inhibitory pot... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q96P31, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:19843936 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:20933011 FCRL6 receptor: expression and associated proteins. | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q6DN72, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:20933011 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:26755705 Identification of CD112R as a novel checkpoint for human T c... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q6DKI7, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:26755705 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0004725 protein tyrosine phosphatase activity | IMP PMID:17562706 Identification of CLEC12B, an inhibitory receptor on myeloid... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005515 protein binding | IPI PMID:17562706 Identification of CLEC12B, an inhibitory receptor on myeloid... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q2HXU8, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:17562706 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0032991 protein-containing complex | IMP PMID:17562706 Identification of CLEC12B, an inhibitory receptor on myeloid... | MARK AS OVER ANNOTATED | Summary: SHP2 forms signaling complexes, but the generic protein-containing-complex term identifies no specific complex. Reason: Without a named stable complex, GO:0032991 adds little biological information and should not be elevated to a core location. |
| GO:0035335 peptidyl-tyrosine dephosphorylation | IMP PMID:17562706 Identification of CLEC12B, an inhibitory receptor on myeloid... | ACCEPT | Summary: Peptidyl-tyrosine dephosphorylation is the direct biological process executed by SHP2 catalysis. Reason: SHP2 removes phosphate from tyrosine residues on physiological protein substrates. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005515 protein binding | IPI PMID:23112346 Mice lacking the ITIM-containing receptor G6b-B exhibit macr... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:O95866, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:23112346 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0004725 protein tyrosine phosphatase activity | IDA PMID:28074573 Structural, Functional, and Clinical Characterization of a N... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IMP PMID:28074573 Structural, Functional, and Clinical Characterization of a N... | ACCEPT | Summary: Positive regulation of ERK1/2 output is a recurrent, central consequence of SHP2 activity downstream of receptor tyrosine kinases. Reason: SHP2 commonly promotes RAS-ERK signaling, including by dephosphorylating inhibitory substrates such as Sprouty proteins. Supporting Evidence: PMID:28074573 Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling. PMID:24431450 Ptpn11 interacts with Fgf8 and is essential for ERK activation in RG and nascent BG. |
| GO:0071364 cellular response to epidermal growth factor stimulus | IMP PMID:28074573 Structural, Functional, and Clinical Characterization of a N... | KEEP AS NON CORE | Summary: SHP2 participates in cellular responses to EGF. Reason: EGF response is an input-specific signaling context of SHP2's general receptor-proximal functions. |
| GO:0004725 protein tyrosine phosphatase activity | IDA PMID:26742426 Determination of the catalytic activity of LEOPARD syndrome-... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005515 protein binding | IPI PMID:26742426 Determination of the catalytic activity of LEOPARD syndrome-... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q6P1J9, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:26742426 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005634 nucleus | IDA PMID:26742426 Determination of the catalytic activity of LEOPARD syndrome-... | KEEP AS NON CORE | Summary: Nuclear localization is experimentally reported for SHP2. Reason: Nuclear access is supported but is secondary to the predominant cytosolic and receptor-proximal signaling mechanism. |
| GO:0005737 cytoplasm | IDA PMID:26742426 Determination of the catalytic activity of LEOPARD syndrome-... | ACCEPT | Summary: Cytoplasm is a principal compartment for soluble SHP2 signaling. Reason: SHP2 is a non-receptor phosphatase recruited from the cytoplasm to phosphotyrosine-containing receptor and adaptor complexes. |
| GO:0043254 regulation of protein-containing complex assembly | IDA PMID:7493946 Adapter function of protein-tyrosine phosphatase 1D in insul... | KEEP AS NON CORE | Summary: SHP2 can regulate assembly of receptor-associated signaling complexes. Reason: Complex assembly is a context-specific consequence of its adaptor function and is retained as non-core. |
| GO:0005515 protein binding | IPI PMID:16254138 The inhibitory receptor IRp60 (CD300a) suppresses the effect... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9UGN4, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:16254138 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005515 protein binding | IPI PMID:16339535 The inhibitory receptor IRp60 (CD300a) is expressed and func... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9UGN4, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:16339535 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0035335 peptidyl-tyrosine dephosphorylation | IDA PMID:15133037 The major vault protein is a novel substrate for the tyrosin... | ACCEPT | Summary: Peptidyl-tyrosine dephosphorylation is the direct biological process executed by SHP2 catalysis. Reason: SHP2 removes phosphate from tyrosine residues on physiological protein substrates. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005515 protein binding | IPI PMID:10540326 Molecular and functional characterization of IRp60, a member... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9UGN4, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:10540326 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005634 nucleus | IDA PMID:15133037 The major vault protein is a novel substrate for the tyrosin... | KEEP AS NON CORE | Summary: Nuclear localization is experimentally reported for SHP2. Reason: Nuclear access is supported but is secondary to the predominant cytosolic and receptor-proximal signaling mechanism. |
| GO:0005737 cytoplasm | IDA PMID:15133037 The major vault protein is a novel substrate for the tyrosin... | ACCEPT | Summary: Cytoplasm is a principal compartment for soluble SHP2 signaling. Reason: SHP2 is a non-receptor phosphatase recruited from the cytoplasm to phosphotyrosine-containing receptor and adaptor complexes. |
| GO:0038127 ERBB signaling pathway | IDA PMID:15133037 The major vault protein is a novel substrate for the tyrosin... | KEEP AS NON CORE | Summary: SHP2 participates in ERBB-family receptor signaling in appropriate cellular contexts. Reason: ERBB signaling is one receptor-specific use of SHP2's general phosphotyrosine-binding, phosphatase, and adaptor activities rather than a distinct core activity. |
| GO:0007420 brain development | IMP PMID:11704759 Mutations in PTPN11, encoding the protein tyrosine phosphata... | KEEP AS NON CORE | Summary: Human variant evidence and conditional mouse genetics support roles for PTPN11 in brain development. Reason: Brain development is a broad pleiotropic output; cell-type-specific mechanisms such as Bergmann-glia specification are more informative than treating it as a core molecular function. Supporting Evidence: PMID:24431450 Deleting Ptpn11 in the entire cerebellum by En1-cre blocks transformation of RG into BG but preserves other major cerebellar cell types. |
| GO:0007507 heart development | IMP PMID:12058348 Grouping of multiple-lentigines/LEOPARD and Noonan syndromes... | KEEP AS NON CORE | Summary: Human PTPN11 variants support a role in heart development. Reason: Cardiac development is a pleiotropic RASopathy outcome downstream of SHP2 signaling and is retained as non-core. |
| GO:0036302 atrioventricular canal development | IMP PMID:12058348 Grouping of multiple-lentigines/LEOPARD and Noonan syndromes... | KEEP AS NON CORE | Summary: Human PTPN11 variant phenotypes support involvement in atrioventricular-canal development. Reason: This specific developmental phenotype is downstream of SHP2's general signaling activities and is retained as non-core. |
| GO:0048806 genitalia development | IMP PMID:12058348 Grouping of multiple-lentigines/LEOPARD and Noonan syndromes... | KEEP AS NON CORE | Summary: Human PTPN11 variant phenotypes support involvement in genital development. Reason: This is a pleiotropic developmental outcome rather than a defining molecular activity. |
| GO:0048839 inner ear development | IMP PMID:12058348 Grouping of multiple-lentigines/LEOPARD and Noonan syndromes... | KEEP AS NON CORE | Summary: Human PTPN11 variant phenotypes support involvement in inner-ear development. Reason: This is a pleiotropic developmental outcome rather than a defining molecular activity. |
| GO:0060325 face morphogenesis | IMP PMID:11704759 Mutations in PTPN11, encoding the protein tyrosine phosphata... | KEEP AS NON CORE | Summary: Human PTPN11 variant phenotypes support involvement in facial morphogenesis. Reason: Craniofacial morphology is a pleiotropic RASopathy outcome downstream of altered SHP2 signaling. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:15133037 The major vault protein is a novel substrate for the tyrosin... | MODIFY | Summary: Phosphoprotein-phosphatase activity is correct but less informative than SHP2's tyrosine-specific soluble phosphatase activity. Reason: Replace the generic parent term with non-membrane-spanning protein tyrosine phosphatase activity. Proposed replacements: non-membrane spanning protein tyrosine phosphatase activity Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004725 protein tyrosine phosphatase activity | IDA PMID:15133037 The major vault protein is a novel substrate for the tyrosin... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0004725 protein tyrosine phosphatase activity | IDA PMID:23029125 Src homology-2 domain-containing protein tyrosine phosphatas... | ACCEPT | Summary: Protein tyrosine phosphatase activity is the established catalytic activity of SHP2. Reason: The broader protein-tyrosine-phosphatase term accurately captures the same core catalysis represented more specifically by GO:0004726. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0005515 protein binding | IPI PMID:19509291 GAREM, a novel adaptor protein for growth factor receptor-bo... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:Q9H706, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:19509291 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0005158 insulin receptor binding | IPI PMID:7493946 Adapter function of protein-tyrosine phosphatase 1D in insul... | KEEP AS NON CORE | Summary: SHP2 directly binds activated insulin receptor through phosphotyrosine-dependent SH2 interactions. Reason: Insulin-receptor binding is a supported receptor-specific instance of SHP2's broader phosphotyrosine/receptor-kinase binding activity. |
| GO:0005515 protein binding | IPI PMID:18604210 An essential function for beta-arrestin 2 in the inhibitory ... | MARK AS OVER ANNOTATED | Summary: IPI evidence reports an interaction with UniProtKB:P43626, but generic protein binding is not an informative SHP2 activity. Reason: The interaction from PMID:18604210 is preserved; however, GO:0005515 does not distinguish phosphotyrosine-dependent recruitment, substrate recognition, receptor binding, or a context-specific association. |
| GO:0004726 non-membrane spanning protein tyrosine phosphatase activity | IMP PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | ACCEPT | Summary: Non-membrane-spanning protein tyrosine phosphatase activity is SHP2's defining catalytic function. Reason: Biochemical and substrate-trapping studies establish dephosphorylation of phosphotyrosine residues on protein substrates by soluble SHP2. Supporting Evidence: PMID:16481357 a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. |
| GO:0048013 ephrin receptor signaling pathway | IDA PMID:10655584 Activation of EphA2 kinase suppresses integrin function and ... | KEEP AS NON CORE | Summary: SHP2 participates in EphA2/ephrin-receptor signaling. Reason: Ephrin-receptor signaling is one receptor-specific deployment of SHP2's core phosphatase and recruitment functions. |
| GO:0005737 cytoplasm | IDA PMID:10940933 Subcellular localization of intracellular protein tyrosine p... | ACCEPT | Summary: Cytoplasm is a principal compartment for soluble SHP2 signaling. Reason: SHP2 is a non-receptor phosphatase recruited from the cytoplasm to phosphotyrosine-containing receptor and adaptor complexes. |
Loading supporting content…
Download this section (compressed HTML)Q: Which direct SHP2 substrates are necessary and sufficient for positive RAS-ERK signaling downstream of each major receptor family?
Q: Which SHP2 outputs in human developmental tissues require catalytic activity, tandem-SH2 recruitment, or the C-terminal adaptor function?
Q: Does the FGF8-SHP2-ERK requirement for Bergmann-glia specification observed in mouse operate equivalently in human cerebellar development?
Experiment: Perform domain-resolved rescue of endogenous PTPN11 loss with wild-type, catalytic-dead, tandem-SH2-binding-defective, and C-terminal phosphosite-mutant SHP2, coupled to quantitative phosphoproteomics and ERK reporters.
Hypothesis: Catalytic and phosphotyrosine-recruitment functions are jointly required for robust ERK output, whereas a subset of receptor-complex assembly is retained by catalytically inactive SHP2.
Type: genetic rescue and phosphoproteomics
Experiment: Use human iPSC-derived cerebellar radial-glia/Bergmann-glia differentiation with temporally controlled PTPN11 perturbation, FGF8 stimulation, single-cell transcriptomics, and live ERK reporters.
Hypothesis: PTPN11 acts cell-autonomously downstream of FGF signaling during human Bergmann-glia specification, matching the mouse radial-glia phenotype.
Type: human cerebellar differentiation and signaling assay
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)