Tyrosine-protein phosphatase non-receptor type 11

Function

Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity. Dephosphorylates CDC73. Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity). Dephosphorylates tyrosine-phosphorylated NEDD9/CAS-L. Acts as an effector of PDCD1-mediated inhibition of T-cell response: recruited by phosphorylated PDCD1, mediating dephosphorylation of key T-cell receptor (TCR) proximal signaling molecules, leading to TCR signaling inhibition.

Classification

Family (Pfam)

PF00017 SH2, PF00102 Y_phosphatase

InterPro

Prot-tyrosine_phosphatase-like, PTP_cat, SH2, SH2_dom_sf, Tyr_Pase_AS, Tyr_Pase_cat, Tyr_Pase_dom, Tyr_Pase_non-rcpt_typ-6/11

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 103

• 2SHP X-ray 2.00A
• 3B7O X-ray 1.60A
• 3MOW X-ray 2.30A
• 3O5X X-ray 2.00A
• 3TKZ X-ray 1.80A
• 3TL0 X-ray 2.05A
• 3ZM0 X-ray 1.50A
• 3ZM1 X-ray 1.40A
• 3ZM2 X-ray 1.50A
• 3ZM3 X-ray 1.50A
• 4DGP X-ray 2.30A
• 4DGX X-ray 2.30A
• … and 91 more

A predicted model is available from AlphaFold.

Gene Ontology · 55

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005925 focal adhesion
• GO:0005739 mitochondrion
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:0045296 cadherin binding
• GO:0050839 cell adhesion molecule binding
• GO:0005158 insulin receptor binding
• GO:0060090 molecular adaptor activity
• GO:0004726 non-membrane spanning protein tyrosine phosphatase activity
• GO:0051428 peptide hormone receptor binding
• GO:0004721 phosphoprotein phosphatase activity
• GO:0001784 phosphotyrosine residue binding
• GO:0019901 protein kinase binding
• GO:1990782 protein tyrosine kinase binding
• GO:0004725 protein tyrosine phosphatase activity
• GO:0030971 receptor tyrosine kinase binding
• GO:0030159 signaling receptor complex adaptor activity
• GO:0036302 atrioventricular canal development
• GO:0007420 brain development
• GO:0071364 cellular response to epidermal growth factor stimulus
• GO:0071260 cellular response to mechanical stimulus
• GO:0019221 cytokine-mediated signaling pathway
• GO:0048013 ephrin receptor signaling pathway
• GO:0007173 epidermal growth factor receptor signaling pathway
• GO:0038127 ERBB signaling pathway
• GO:0060325 face morphogenesis
• GO:0008543 fibroblast growth factor receptor signaling pathway
• GO:0048806 genitalia development
• GO:0007507 heart development
• GO:0048839 inner ear development
• GO:0033629 negative regulation of cell adhesion mediated by integrin
• GO:0032331 negative regulation of chondrocyte differentiation
• GO:1902564 negative regulation of neutrophil activation
• GO:0050868 negative regulation of T cell activation
• GO:0042130 negative regulation of T cell proliferation
• GO:0050860 negative regulation of T cell receptor signaling pathway
• GO:0032480 negative regulation of type I interferon production
• GO:0035335 peptidyl-tyrosine dephosphorylation
• GO:0046326 positive regulation of D-glucose import across plasma membrane
• GO:0070374 positive regulation of ERK1 and ERK2 cascade
• GO:0046628 positive regulation of insulin receptor signaling pathway
• GO:0032728 positive regulation of interferon-beta production
• GO:1902533 positive regulation of intracellular signal transduction
• GO:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway
• GO:0045778 positive regulation of ossification
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0032760 positive regulation of tumor necrosis factor production
• GO:0043254 regulation of protein-containing complex assembly
• GO:0060338 regulation of type I interferon-mediated signaling pathway
• GO:0031295 T cell costimulation
• GO:0042311 vasodilation

Disease associations

• LEOPARD syndrome 1 MONDO:0100082
• metachondromatosis MONDO:0007979
• Noonan syndrome 1 MONDO:0008104
• juvenile myelomonocytic leukemia MONDO:0011908

Drugs targeting this protein · 1

• BATOPROTAFIB inhibitor

Related proteins · sequence + function similarity

• Tyrosine-protein phosphatase non-receptor type 11 1.00
• Tyrosine-protein phosphatase non-receptor type 11 1.00
• Tyrosine-protein phosphatase non-receptor type 11 1.00
• Tyrosine-protein phosphatase non-receptor type 6 0.94
• Tyrosine-protein phosphatase non-receptor type 6 0.94
• Tyrosine-protein phosphatase non-receptor type 6 0.94
• Tyrosine-protein phosphatase non-receptor type ptp-2 0.80
• Receptor-type tyrosine-protein phosphatase alpha 0.79
• Receptor-type tyrosine-protein phosphatase alpha 0.79
• Receptor-type tyrosine-protein phosphatase alpha 0.78
• Receptor-type tyrosine-protein phosphatase epsilon 0.78
• Receptor-type tyrosine-protein phosphatase epsilon 0.78

Co-cited proteins · studied together in the literature

• C-type lectin domain family 12 member B 2 shared papers
• Myelin protein zero-like protein 1 1 shared papers
• Tyrosine-protein phosphatase non-receptor type 11 3 shared papers
• Ankyrin repeat and KH domain-containing protein 1 1 shared papers
• Tyrosine-protein phosphatase non-receptor type 6 9 shared papers
• Neurofibromin 1 shared papers
• Platelet endothelial cell adhesion molecule 1 shared papers
• Fc receptor-like protein 6 1 shared papers
• Signaling threshold-regulating transmembrane adapter 1 1 shared papers
• Signaling threshold-regulating transmembrane adapter 1 2 shared papers
• Tyrosine-protein phosphatase non-receptor type 11 6 shared papers
• Platelet endothelial cell adhesion molecule 1 shared papers

Literature · 75 cited papers

• CLEC12B Decreases Melanoma Proliferation by Repressing Signal Transducer and Activator of Transcription 3. J. Invest. Dermatol. · 2022
• Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Commun. Biol. · 2020
• Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome. Hum. Mutat. · 2017
• Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling. Biochem. Biophys. Res. Commun. · 2016
• A PTPN11 allele encoding a catalytically impaired SHP2 protein in a patient with a Noonan syndrome phenotype. Am. J. Med. Genet. A · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Mice lacking the ITIM-containing receptor G6b-B exhibit macrothrombocytopenia and aberrant platelet function. Sci. Signal. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. PLoS Genet. · 2010
• Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell proliferation but not migration. Cell. Signal. · 2010
• Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). J. Med. Chem. · 2010
• … and 63 more in the literature graph