Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
The myeloid-specific sialic acid-binding receptor, CD33, associates with the protein-tyrosine phosphatases, SHP-1 and SHP-2.
Molecular and functional characterization of IRp60, a member of the immunoglobulin superfamily that functions as an inhibitory receptor in human NK cells.
Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation.
Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein.
Dissecting the interaction of SHP-2 with PZR, an immunoglobulin family protein containing immunoreceptor tyrosine-based inhibitory motifs.
Identification of natural ligands for SH2 domains from a phage display cDNA library.
Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2.
Subcellular localization of intracellular protein tyrosine phosphatases in T cells.
Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component.
Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2.
Co-clustering of Fcgamma and B cell receptors induces dephosphorylation of the Grb2-associated binder 1 docking protein.
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.
Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia.
SPAP2, an Ig family receptor containing both ITIMs and ITAMs.
Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene.
A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling.
Identification of protein tyrosine phosphatases associating with the PDGF receptor.
Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes.
Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2.
Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor.
Distinct domains in the SHP-2 phosphatase differentially regulate epidermal growth factor receptor/NF-kappaB activation through Gab1 in glioblastoma cells.
The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal growth factor signaling.
Interaction of the tyrosine phosphatase SHP-2 with Gab2 regulates Rho-dependent activation of the c-fos serum response element by interleukin-2.
SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation.
B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator.
A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation.
Flow activates ERK1/2 and endothelial nitric oxide synthase via a pathway involving PECAM1, SHP2, and Tie2.
Increased proliferation and altered growth factor dependence of human mammary epithelial cells overexpressing the Gab2 docking protein.
The inhibitory receptor IRp60 (CD300a) suppresses the effects of IL-5, GM-CSF, and eotaxin on human peripheral blood eosinophils.
A quantitative protein interaction network for the ErbB receptors using protein microarrays.
Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1.
The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast cells.
Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA.
Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases.
An ITIM-like motif within the CCK2 receptor sequence required for interaction with SHP-2 and the activation of the AKT pathway.
Identification of CLEC12B, an inhibitory receptor on myeloid cells.
A2 isoform of mammalian translation factor eEF1A displays increased tyrosine phosphorylation and ability to interact with different signalling molecules.
ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2.
Association of protein tyrosine phosphatases (PTPs)-1B with c-Met receptor and modulation of corneal epithelial wound healing.
An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.
Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein.
SHP-2 inhibits tyrosine phosphorylation of Cas-L and regulates cell migration.
Charting the molecular network of the drug target Bcr-Abl.
GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling.
FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor-mediated signaling.
Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2).
Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling.
SIRPalpha1 receptors interfere with the EGFRvIII signalosome to inhibit glioblastoma cell transformation and migration.
FCRL6 receptor: expression and associated proteins.
Next-generation sequencing to generate interactome datasets.
Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor.
A Src family kinase-Shp2 axis controls RUNX1 activity in megakaryocyte and T-lymphocyte differentiation.
Src homology-2 domain-containing protein tyrosine phosphatase (SHP) 2 and p38 regulate the expression of chemokine CXCL8 in human astrocytes.
Mice lacking the ITIM-containing receptor G6b-B exhibit macrothrombocytopenia and aberrant platelet function.
Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma.
Fine specificity and molecular competition in SLAM family receptor signalling.
Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome.
A proteome-scale map of the human interactome network.
Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27.
Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis.
PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling.
Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling.
Identification of CD112R as a novel checkpoint for human T cells.
Systematic interactome mapping of acute lymphoblastic leukemia cancer gene products reveals EXT-1 tumor suppressor as a Notch1 and FBWX7 common interactor.
HTLV-1 bZIP Factor Enhances T-Cell Proliferation by Impeding the Suppressive Signaling of Co-inhibitory Receptors.
A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome.
Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome.
LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
Oncogenic Mutations Rewire Signaling Pathways by Switching Protein Recruitment to Phosphotyrosine Sites.
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release.
CLEC12B Decreases Melanoma Proliferation by Repressing Signal Transducer and Activator of Transcription 3.
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
Physical and functional interactome atlas of human receptor tyrosine kinases.
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
Multimodal cell maps as a foundation for structural and functional genomics.
Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction.
Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1.
Activation of the SH2-containing protein tyrosine phosphatase, SH-PTP2, by phosphotyrosine-containing peptides derived from insulin receptor substrate-1.
The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells.
Direct determination of the sequence recognition requirements of the SH2 domains of SH-PTP2.
Localization of the insulin-like growth factor I receptor binding sites for the SH2 domain proteins p85, Syp, and GTPase activating protein.
The 64-kDa protein that associates with the platelet-derived growth factor receptor beta subunit via Tyr-1009 is the SH2-containing phosphotyrosine phosphatase Syp.
Characterization of protein tyrosine phosphatase SH-PTP2. Study of phosphopeptide substrates and possible regulatory role of SH2 domains.
Receptor-binding, tyrosine phosphorylation and chromosome localization of the mouse SH2-containing phosphotyrosine phosphatase Syp.
Spatial constraints on the recognition of phosphoproteins by the tandem SH2 domains of the phosphatase SH-PTP2.
Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases.
Activation of protein-tyrosine phosphatase SH-PTP2 by a tyrosine-based activation motif of a novel brain molecule.
Interaction of SH2-containing protein tyrosine phosphatase 2 with the insulin receptor and the insulin-like growth factor-I receptor: studies of the domains involved using the yeast two-hybrid system.
Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of platelet/endothelial cell adhesion molecule-1 (PECAM-1) that are required for the cellular association and activation of the protein-tyrosine phosphatase, SHP-2.
Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation.
Association of the insulin receptor with phospholipase C-gamma (PLCgamma) in 3T3-L1 adipocytes suggests a role for PLCgamma in metabolic signaling by insulin.
Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation.
Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules.
Recruitment and activation of SHP-1 protein-tyrosine phosphatase by human platelet endothelial cell adhesion molecule-1 (PECAM-1). Identification of immunoreceptor tyrosine-based inhibitory motif-like binding motifs and substrates.
Purification and cloning of PZR, a binding protein and putative physiological substrate of tyrosine phosphatase SHP-2.
PI3K-containing complexes phosphorylate PIP2 to PIP3
PTPN11 binds p-Y759-IL6ST
GRB2 is indirectly recruited to p-KIT through SHP2
Phosphorylation of GAB2 by SFKs
Phosphorylation of SHP2 by SFKs
Synthesis of PIP3 from PIP2 by PI3K
PPTN11 dephosphorylates SPRY2
Indirect recruitment of PI3K to KIT via p(Y)-GAB2
Sustained activation of SRC kinase by SHP2
Dephosphorylation of Gab1 by SHP2
Dephosphorylation of PAG by SHP2
SHP2 dephosphorylates Tyr 992 on EGFR
Activation of SHP2 through the binding to phospho-Gab1
SHP2 binds to the active receptor
Interaction of Tie2 and Shp2
Indirect recruitment of GAB2 to p-KIT
SHP2 interacts with p-KIT
Interaction of PECAM-1 and SHP-2
PI3K phosphorylates PIP2 to PIP3
PI3K inhibitors block PI3K catalytic activity
SHP2 phosphatase binds CTLA-4
Regulation of T cell activation by CD28 family
Dephosphorylation of CD3-zeta by PD-1 bound phosphatases
Interaction of SHP-1 or SHP-2 with phospho PD-1
SHP-1 and SHP-2 bind pBTLA
Interleukin-3, Interleukin-5 and GM-CSF signaling
Activated FGFR1:p-FRS bind to PPTN11
Activated FGFR1:p-FRS phosphorylates PPTN11
Activated FGFR1:p-FRS2:p-PPTN11 binds GRB2:GAB1:PI3KR1
Activated FGFR1:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA
Activated FGFR2 phosphorylates PPTN11
Activated FGFR2:p-FRS bind to PPTN11
Activated FGFR2:p-FRS2:p-PPTN11 binds GRB2:GAB1:PI3KR1
Activated FGFR2:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA
Activated FGFR3 phosphorylates PPTN11
Activated FGFR3:p-FRS bind to PPTN11
Activated FGFR3:p-FRS2:p-PPTN11 binds GRB2:GAB1:PI3KR1
Activated FGFR3:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA
Activated FGFR4 phosphorylates PPTN11
Activated FGFR4:p-FRS bind to PPTN11
Activated FGFR4:p-FRS2:p-PPTN11 binds GRB2:GAB1:PI3KR1
Activated FGFR4:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1binds PIK3CA
CBL ubiquitinates FRS2 and FGFR1
p-CBL:GRB2 binds p-FRS2:activated FGFR1
CBL ubiquitinates FRS2 and FGFR2
CBL ubiquitinates FRS2 and FGFR3
CBL ubiquitinates FRS2 and FGFR4
FGFR1- and PTPN11- associated PI3K phosphorylates PIP2 to PIP3
FGFR2- and PTPN11- associated PI3K phosphorylates PIP2 to PIP3
FGFR3- and PTPN11-associated PI3K phosphorylates PIP2 to PIP3
FGFR4- and PTPN11-associated PI3K phosphorylates PIP2 to PIP3
p-CBL:GRB2 binds p-FRS2:activated FGFR2
p-CBL:GRB2 binds p-FRS2:activated FGFR3
p-CBL:GRB2 binds p-FRS2:activated FGFR4
p-5Y-GAB in RET-GRB2-GAB complexes binds PTPN11
PTPN11 dephosphorylates RUNX1
IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:PTPN11:IL10RB:p-TYK2 binds STAT3
IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:STAT3 phosphorylates STAT3
IL22:p‑Y251,p‑Y301‑IL22RA1:p‑JAK1:PTPN11:IL10RB:p‑TYK2 binds PTPN11
p-Y705-STAT3 dissociates from IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:p-Y705-STAT3
PTPNs gene transcription and translation
SHP1 and SHP2 bind the common beta chain
Regulation of IFNA/IFNB signaling
SHP1 and SHP2 dephosphorylate Y628 of IL3RB
Signaling by CSF3 (G-CSF)
p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS
FLT3 ITD mutants phosphorylate STAT5
FLT3 ITD mutants bind STAT5 through GAB2:PTPN11
FLT3 mutants:GRB2:p-Y-GAB2 binds PTPN11
PTPN11:p-STAT5 dissociates from mutant FLT3
PTPN11:p-STAT5 translocates to nucleus downstream of mutant FLT3
PTPN11:p-STAT5 binds BCL2L1 promoter
p-STAT5 dissociates from mutant FLT3
Dephosphorylation of STAT1 by SHP2
Shp2-dependent ERK signaling is essential for induction of Bergmann glia and foliation of the cerebellum.
PTPN11 / SHP2 manual review notes