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UniProtKB - Q06124 (PTN11_HUMAN)
Protein
Tyrosine-protein phosphatase non-receptor type 11
Gene
PTPN11
Organism
Homo sapiens (Human)
Status
Functioni
Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573).
Positively regulates MAPK signal transduction pathway (PubMed:28074573).
Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573).
Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (PubMed:18559669).
Dephosphorylates CDC73 (PubMed:26742426).
Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity).
By similarity5 PublicationsCatalytic activityi
- H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphatePROSITE-ProRule annotation3 PublicationsEC:3.1.3.48PROSITE-ProRule annotation3 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 425 | SubstrateBy similarity | 1 | |
| Active sitei | 459 | Phosphocysteine intermediate | 1 | |
| Binding sitei | 506 | SubstrateBy similarity | 1 |
GO - Molecular functioni
- cadherin binding Source: ARUK-UCL
- cell adhesion molecule binding Source: ARUK-UCL
- insulin receptor binding Source: BHF-UCL
- non-membrane spanning protein tyrosine phosphatase activity Source: FlyBase
- peptide hormone receptor binding Source: Ensembl
- phosphoprotein phosphatase activity Source: UniProtKB
- phosphotyrosine residue binding Source: UniProtKB
- protein kinase binding Source: ARUK-UCL
- protein tyrosine kinase binding Source: ARUK-UCL
- protein tyrosine phosphatase activity Source: UniProtKB
- receptor tyrosine kinase binding Source: Ensembl
- signaling receptor complex adaptor activity Source: BHF-UCL
GO - Biological processi
- abortive mitotic cell cycle Source: Ensembl
- atrioventricular canal development Source: BHF-UCL
- axonogenesis Source: Ensembl
- Bergmann glial cell differentiation Source: Ensembl
- brain development Source: BHF-UCL
- cellular response to epidermal growth factor stimulus Source: UniProtKB
- cerebellar cortex formation Source: Ensembl
- cytokine-mediated signaling pathway Source: Reactome
- DNA damage checkpoint signaling Source: Ensembl
- ephrin receptor signaling pathway Source: UniProtKB
- epidermal growth factor receptor signaling pathway Source: Reactome
- ERBB signaling pathway Source: UniProtKB
- face morphogenesis Source: BHF-UCL
- fibroblast growth factor receptor signaling pathway Source: FlyBase
- genitalia development Source: BHF-UCL
- glucose homeostasis Source: Ensembl
- heart development Source: BHF-UCL
- homeostasis of number of cells within a tissue Source: Ensembl
- hormone-mediated signaling pathway Source: Ensembl
- hormone metabolic process Source: Ensembl
- inner ear development Source: BHF-UCL
- integrin-mediated signaling pathway Source: Ensembl
- intestinal epithelial cell migration Source: Ensembl
- megakaryocyte development Source: Ensembl
- microvillus organization Source: Ensembl
- multicellular organismal reproductive process Source: Ensembl
- multicellular organism growth Source: Ensembl
- negative regulation of cell adhesion mediated by integrin Source: Ensembl
- negative regulation of chondrocyte differentiation Source: UniProtKB
- negative regulation of cortisol secretion Source: Ensembl
- negative regulation of growth hormone secretion Source: Ensembl
- negative regulation of insulin secretion Source: Ensembl
- neurotrophin TRK receptor signaling pathway Source: Ensembl
- organ growth Source: Ensembl
- peptidyl-tyrosine dephosphorylation Source: UniProtKB
- platelet-derived growth factor receptor signaling pathway Source: Ensembl
- platelet formation Source: Ensembl
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of glucose import Source: BHF-UCL
- positive regulation of hormone secretion Source: Ensembl
- positive regulation of insulin receptor signaling pathway Source: BHF-UCL
- positive regulation of interferon-beta production Source: ARUK-UCL
- positive regulation of interleukin-6 production Source: ARUK-UCL
- positive regulation of mitotic cell cycle Source: Ensembl
- positive regulation of ossification Source: UniProtKB
- positive regulation of peptidyl-tyrosine phosphorylation Source: ARUK-UCL
- positive regulation of tumor necrosis factor production Source: ARUK-UCL
- regulation of cell adhesion mediated by integrin Source: UniProtKB
- regulation of protein-containing complex assembly Source: BHF-UCL
- regulation of protein export from nucleus Source: Ensembl
- regulation of type I interferon-mediated signaling pathway Source: Reactome
- T cell costimulation Source: Reactome
- triglyceride metabolic process Source: Ensembl
Keywordsi
| Molecular function | Hydrolase, Protein phosphatase |
Enzyme and pathway databases
| BRENDAi | 3.1.3.48, 2681 |
| PathwayCommonsi | Q06124 |
| Reactomei | R-HSA-1059683, Interleukin-6 signaling R-HSA-109704, PI3K Cascade R-HSA-110056, MAPK3 (ERK1) activation R-HSA-112411, MAPK1 (ERK2) activation R-HSA-114604, GPVI-mediated activation cascade R-HSA-1170546, Prolactin receptor signaling R-HSA-1257604, PIP3 activates AKT signaling R-HSA-1295596, Spry regulation of FGF signaling R-HSA-1433557, Signaling by SCF-KIT R-HSA-180292, GAB1 signalosome R-HSA-186763, Downstream signal transduction R-HSA-210990, PECAM1 interactions R-HSA-210993, Tie2 Signaling R-HSA-2219530, Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-2586552, Signaling by Leptin R-HSA-388841, Costimulation by the CD28 family R-HSA-389513, CTLA4 inhibitory signaling R-HSA-389948, PD-1 signaling R-HSA-391160, Signal regulatory protein family interactions R-HSA-418886, Netrin mediated repulsion signals R-HSA-432142, Platelet sensitization by LDL R-HSA-512988, Interleukin-3, Interleukin-5 and GM-CSF signaling R-HSA-5654689, PI-3K cascade:FGFR1 R-HSA-5654693, FRS-mediated FGFR1 signaling R-HSA-5654695, PI-3K cascade:FGFR2 R-HSA-5654700, FRS-mediated FGFR2 signaling R-HSA-5654706, FRS-mediated FGFR3 signaling R-HSA-5654710, PI-3K cascade:FGFR3 R-HSA-5654712, FRS-mediated FGFR4 signaling R-HSA-5654720, PI-3K cascade:FGFR4 R-HSA-5654726, Negative regulation of FGFR1 signaling R-HSA-5654727, Negative regulation of FGFR2 signaling R-HSA-5654732, Negative regulation of FGFR3 signaling R-HSA-5654733, Negative regulation of FGFR4 signaling R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-877312, Regulation of IFNG signaling R-HSA-8853659, RET signaling R-HSA-8854691, Interleukin-20 family signaling R-HSA-8865999, MET activates PTPN11 R-HSA-8934593, Regulation of RUNX1 Expression and Activity R-HSA-9008059, Interleukin-37 signaling R-HSA-9028731, Activated NTRK2 signals through FRS2 and FRS3 R-HSA-909733, Interferon alpha/beta signaling R-HSA-912694, Regulation of IFNA signaling R-HSA-936964, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon R-HSA-9607240, FLT3 Signaling R-HSA-9645135, STAT5 Activation R-HSA-9674555, Signaling by CSF3 (G-CSF) R-HSA-9702518, STAT5 activation downstream of FLT3 ITD mutants R-HSA-9703648, Signaling by FLT3 ITD and TKD mutants |
| SABIO-RKi | Q06124 |
| SignaLinki | Q06124 |
| SIGNORi | Q06124 |
Protein family/group databases
| MoonDBi | Q06124, Predicted |
Names & Taxonomyi
| Protein namesi | Recommended name: Tyrosine-protein phosphatase non-receptor type 11 (EC:3.1.3.482 Publications)Alternative name(s): Protein-tyrosine phosphatase 1D Short name: PTP-1D Protein-tyrosine phosphatase 2C Short name: PTP-2C SH-PTP2 Short name: SHP-2 Short name: Shp2 SH-PTP3 |
| Gene namesi | Name:PTPN11 Synonyms:PTP2C, SHPTP2 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:9644, PTPN11 |
| MIMi | 176876, gene |
| neXtProti | NX_Q06124 |
| VEuPathDBi | HostDB:ENSG00000179295 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
LEOPARD syndrome 1 (LPRD1)10 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_015614 | 279 | Y → C in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 7 PublicationsCorresponds to variant dbSNP:rs121918456EnsemblClinVar. | 1 | |
| Natural variantiVAR_027188 | 279 | Y → S in LPRD1. 2 PublicationsCorresponds to variant dbSNP:rs121918456EnsemblClinVar. | 1 | |
| Natural variantiVAR_027190 | 461 | A → T in LPRD1. 1 PublicationCorresponds to variant dbSNP:rs121918468EnsemblClinVar. | 1 | |
| Natural variantiVAR_027191 | 464 | G → A in LPRD1. 2 PublicationsCorresponds to variant dbSNP:rs121918469EnsemblClinVar. | 1 | |
| Natural variantiVAR_015621 | 468 | T → M in LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 5 PublicationsCorresponds to variant dbSNP:rs121918457EnsemblClinVar. | 1 | |
| Natural variantiVAR_027192 | 498 | R → L in LPRD1. 1 PublicationCorresponds to variant dbSNP:rs397507542EnsemblClinVar. | 1 | |
| Natural variantiVAR_027193 | 498 | R → W in LPRD1; reduced phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs397507541EnsemblClinVar. | 1 | |
| Natural variantiVAR_027194 | 506 | Q → P in LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 4 PublicationsCorresponds to variant dbSNP:rs397509345EnsemblClinVar. | 1 | |
| Natural variantiVAR_076499 | 510 | Q → E in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 3 PublicationsCorresponds to variant dbSNP:rs397507549EnsemblClinVar. | 1 | |
| Natural variantiVAR_027196 | 510 | Q → P in LPRD1. 1 PublicationCorresponds to variant dbSNP:rs121918470EnsemblClinVar. | 1 |
Noonan syndrome 1 (NS1)15 Publications
The disease is caused by variants affecting the gene represented in this entry. Mutations in PTPN11 account for more than 50% of the cases.
Disease descriptionA form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_027183 | 2 | T → I in NS1. 1 PublicationCorresponds to variant dbSNP:rs267606990EnsemblClinVar. | 1 | |
| Natural variantiVAR_015601 | 42 | T → A in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507501EnsemblClinVar. | 1 | |
| Natural variantiVAR_027184 | 58 | N → K in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507506EnsemblClinVar. | 1 | |
| Natural variantiVAR_066060 | 59 | T → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs886043790EnsemblClinVar. | 1 | |
| Natural variantiVAR_015602 | 60 | G → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507509EnsemblClinVar. | 1 | |
| Natural variantiVAR_015603 | 61 | D → G in NS1. 4 PublicationsCorresponds to variant dbSNP:rs121918461EnsemblClinVar. | 1 | |
| Natural variantiVAR_015604 | 61 | D → N in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507510EnsemblClinVar. | 1 | |
| Natural variantiVAR_015605 | 62 | Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918460EnsemblClinVar. | 1 | |
| Natural variantiVAR_015606 | 63 | Y → C in NS1. 6 PublicationsCorresponds to variant dbSNP:rs121918459EnsemblClinVar. | 1 | |
| Natural variantiVAR_027185 | 69 | E → Q in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar. | 1 | |
| Natural variantiVAR_015995 | 71 | F → L in NS1; also found in myelodysplastic syndrome. 2 PublicationsCorresponds to variant dbSNP:rs397507512EnsemblClinVar. | 1 | |
| Natural variantiVAR_015607 | 72 | A → G in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918454EnsemblClinVar. | 1 | |
| Natural variantiVAR_015608 | 72 | A → S in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918453EnsemblClinVar. | 1 | |
| Natural variantiVAR_015609 | 73 | T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918462EnsemblClinVar. | 1 | |
| Natural variantiVAR_015610 | 76 | E → D in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507514EnsemblClinVar. | 1 | |
| Natural variantiVAR_027186 | 79 | Q → P in NS1. 1 Publication | 1 | |
| Natural variantiVAR_015611 | 79 | Q → R in NS1. 4 PublicationsCorresponds to variant dbSNP:rs121918466EnsemblClinVar. | 1 | |
| Natural variantiVAR_015612 | 106 | D → A in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507517EnsemblClinVar. | 1 | |
| Natural variantiVAR_015613 | 139 | E → D in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507520EnsemblClinVar. | 1 | |
| Natural variantiVAR_027187 | 256 | Q → R in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507523EnsemblClinVar. | 1 | |
| Natural variantiVAR_078101 | 261 | L → F in NS1; increases MAPK signaling; increases protein tyrosine phosphatase activity; changed substrate selectivity for GAB1. 1 PublicationCorresponds to variant dbSNP:rs397507525EnsemblClinVar. | 1 | |
| Natural variantiVAR_078102 | 261 | L → H in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs765642157EnsemblClinVar. | 1 | |
| Natural variantiVAR_078103 | 262 | L → F in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 Publication | 1 | |
| Natural variantiVAR_078104 | 262 | L → R in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs397507526EnsemblClinVar. | 1 | |
| Natural variantiVAR_078105 | 265 | R → Q in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs376607329EnsemblClinVar. | 1 | |
| Natural variantiVAR_015614 | 279 | Y → C in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 7 PublicationsCorresponds to variant dbSNP:rs121918456EnsemblClinVar. | 1 | |
| Natural variantiVAR_015615 | 282 | I → V in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507529EnsemblClinVar. | 1 | |
| Natural variantiVAR_015617 | 285 | F → L in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507531EnsemblClinVar. | 1 | |
| Natural variantiVAR_015616 | 285 | F → S in NS1. 2 PublicationsCorresponds to variant dbSNP:rs121918463EnsemblClinVar. | 1 | |
| Natural variantiVAR_015619 | 308 | N → D in NS1; common mutation. 5 PublicationsCorresponds to variant dbSNP:rs28933386EnsemblClinVar. | 1 | |
| Natural variantiVAR_015618 | 308 | N → S in NS1; some patients also manifest giant cell lesions of bone and soft tissue. 2 PublicationsCorresponds to variant dbSNP:rs121918455EnsemblClinVar. | 1 | |
| Natural variantiVAR_015620 | 309 | I → V in NS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201787206EnsemblClinVar. | 1 | |
| Natural variantiVAR_027189 | 411 | T → M in NS1. 1 PublicationCorresponds to variant dbSNP:rs121918467EnsemblClinVar. | 1 | |
| Natural variantiVAR_071706 | 491 | P → S in NS1; increased phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs397507539EnsemblClinVar. | 1 | |
| Natural variantiVAR_015622 | 501 | R → K in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507543EnsemblClinVar. | 1 | |
| Natural variantiVAR_015623 | 502 | S → T in NS1. 2 PublicationsCorresponds to variant dbSNP:rs121918458EnsemblClinVar. | 1 | |
| Natural variantiVAR_016003 | 503 | G → R in NS1 and JMML; JMML patient also shows growth retardation and pulmonic stenosis. 2 PublicationsCorresponds to variant dbSNP:rs397507545EnsemblClinVar. | 1 | |
| Natural variantiVAR_015624 | 504 | M → V in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507547EnsemblClinVar. | 1 | |
| Natural variantiVAR_027195 | 506 | Q → R in NS1. 1 Publication | 1 | |
| Natural variantiVAR_076499 | 510 | Q → E in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 3 PublicationsCorresponds to variant dbSNP:rs397507549EnsemblClinVar. | 1 | |
| Natural variantiVAR_027197 | 560 | L → F in NS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs397516797EnsemblClinVar. | 1 |
Leukemia, juvenile myelomonocytic (JMML)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_015991 | 61 | D → V in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918461EnsemblClinVar. | 1 | |
| Natural variantiVAR_015992 | 61 | D → Y in JMML. 1 PublicationCorresponds to variant dbSNP:rs397507510EnsemblClinVar. | 1 | |
| Natural variantiVAR_015993 | 69 | E → K in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar. | 1 | |
| Natural variantiVAR_015996 | 72 | A → T in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918453EnsemblClinVar. | 1 | |
| Natural variantiVAR_015997 | 72 | A → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918454EnsemblClinVar. | 1 | |
| Natural variantiVAR_015998 | 76 | E → A in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar. | 1 | |
| Natural variantiVAR_015999 | 76 | E → G in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar. | 1 | |
| Natural variantiVAR_016000 | 76 | E → K in JMML; increases protein tyrosine phosphatase activity against CDC73. 2 PublicationsCorresponds to variant dbSNP:rs121918464EnsemblClinVar. | 1 | |
| Natural variantiVAR_016001 | 76 | E → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar. | 1 | |
| Natural variantiVAR_016002 | 503 | G → A in JMML. 1 PublicationCorresponds to variant dbSNP:rs397507546EnsemblClinVar. | 1 | |
| Natural variantiVAR_016003 | 503 | G → R in NS1 and JMML; JMML patient also shows growth retardation and pulmonic stenosis. 2 PublicationsCorresponds to variant dbSNP:rs397507545EnsemblClinVar. | 1 |
Metachondromatosis (MC)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA skeletal disorder with radiologic features of both multiple exostoses and Ollier disease, characterized by the presence of exostoses, commonly of the bones of the hands and feet, and enchondromas of the metaphyses of long bones and iliac crest.
Related information in OMIMMutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 459 | C → S: Abolishes phosphatase activity. 1 Publication | 1 |
Keywords - Diseasei
Deafness, Disease variantOrganism-specific databases
| DisGeNETi | 5781 |
| GeneReviewsi | PTPN11 |
| MalaCardsi | PTPN11 |
| MIMi | 151100, phenotype 156250, phenotype 163950, phenotype 607785, phenotype |
| OpenTargetsi | ENSG00000179295 |
| Orphaneti | 86834, Juvenile myelomonocytic leukemia 2499, Metachondromatosis 648, Noonan syndrome 500, Noonan syndrome with multiple lentigines |
| PharmGKBi | PA33986 |
Miscellaneous databases
| Pharosi | Q06124, Tchem |
Chemistry databases
| ChEMBLi | CHEMBL3864 |
| DrugBanki | DB02779, Dodecyltrimethylammonium |
| DrugCentrali | Q06124 |
Genetic variation databases
| BioMutai | PTPN11 |
| DMDMi | 84028248 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Initiator methioninei | RemovedCombined sources | |||
| ChainiPRO_0000094767 | 2 – 593 | Tyrosine-protein phosphatase non-receptor type 11Add BLAST | 592 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 2 | N-acetylthreonineCombined sources | 1 | |
| Modified residuei | 62 | PhosphotyrosineCombined sources | 1 | |
| Modified residuei | 66 | PhosphotyrosineBy similarity | 1 | |
| Modified residuei | 542 | Phosphotyrosine; by PDGFR1 Publication | 1 | |
| Modified residuei | 580 | Phosphotyrosine; by PDGFRCombined sources | 1 |
Post-translational modificationi
Phosphorylated on Tyr-542 and Tyr-580 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. Phosphorylated upon activation of the receptor-type kinase FLT3. Phosphorylated upon activation of the receptor-type kinase PDGFRA (By similarity). Phosphorylated by activated PDGFRB.By similarity5 Publications
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
| CPTACi | CPTAC-1556 |
| EPDi | Q06124 |
| jPOSTi | Q06124 |
| MassIVEi | Q06124 |
| MaxQBi | Q06124 |
| PaxDbi | Q06124 |
| PeptideAtlasi | Q06124 |
| PRIDEi | Q06124 |
| ProteomicsDBi | 58414 [Q06124-1] 58415 [Q06124-2] 58416 [Q06124-3] |
| TopDownProteomicsi | Q06124-2 [Q06124-2] |
PTM databases
| DEPODi | PTPN11 |
| GlyGeni | Q06124, 1 site, 1 O-linked glycan (1 site) |
| iPTMneti | Q06124 |
| MetOSitei | Q06124 |
| PhosphoSitePlusi | Q06124 |
Expressioni
Tissue specificityi
Widely expressed, with highest levels in heart, brain, and skeletal muscle.3 Publications
Gene expression databases
| Bgeei | ENSG00000179295, Expressed in substantia nigra and 255 other tissues |
| ExpressionAtlasi | Q06124, baseline and differential |
| Genevisiblei | Q06124, HS |
Organism-specific databases
| HPAi | ENSG00000179295, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with phosphorylated LIME1 and BCAR3.
Interacts with SHB and INPP5D/SHIP1 (By similarity).
Interacts with MILR1 (tyrosine-phosphorylated).
Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2.
Interacts with PDGFRA (tyrosine phosphorylated).
Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).
Interacts with PTPNS1 and CD84.
Interacts with phosphorylated SIT1 and MPZL1.
Interacts with FCRL4, FCRL6 and ANKHD1.
Interacts with KIR2DL1; the interaction is enhanced by ARRB2.
Interacts with GAB2.
Interacts with TERT; the interaction retains TERT in the nucleus.
Interacts with PECAM1 and FER.
Interacts with EPHA2 (activated); participates in PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling.
Interacts with ROS1; mediates PTPN11 phosphorylation.
Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity.
Interacts with GAREM1 isoform 1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation.
Interacts with CDC73 (PubMed:26742426).
Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (By similarity).
Interacts with MPIG6B (via ITIM motif) (PubMed:23112346).
Interacts with SIGLEC10 (By similarity).
Interacts with FCRL3 (via phosphorylated ITIM motifs) (PubMed:11162587, PubMed:19843936).
Interacts with CLEC12B (via ITIM motif); this interaction triggers dephosphorylation and activation of PTPN11.
By similarity29 PublicationsBinary interactionsi
Q06124
Isoform 1 [Q06124-2]
| With | #Exp. | IntAct |
|---|---|---|
| CDC73 [Q6P1J9] | 2 | EBI-17635971,EBI-930143 |
| GAB1 [Q13480] | 2 | EBI-17635971,EBI-517684 |
| GMNN [O75496] | 3 | EBI-17635971,EBI-371669 |
| TLK1 [Q9UKI8] | 3 | EBI-17635971,EBI-740492 |
GO - Molecular functioni
- cadherin binding Source: ARUK-UCL
- cell adhesion molecule binding Source: ARUK-UCL
- insulin receptor binding Source: BHF-UCL
- peptide hormone receptor binding Source: Ensembl
- phosphotyrosine residue binding Source: UniProtKB
- protein kinase binding Source: ARUK-UCL
- protein tyrosine kinase binding Source: ARUK-UCL
- receptor tyrosine kinase binding Source: Ensembl
Protein-protein interaction databases
| BioGRIDi | 111745, 261 interactors |
| CORUMi | Q06124 |
| DIPi | DIP-516N |
| ELMi | Q06124 |
| IntActi | Q06124, 203 interactors |
| MINTi | Q06124 |
| STRINGi | 9606.ENSP00000340944 |
Chemistry databases
| BindingDBi | Q06124 |
Miscellaneous databases
| RNActi | Q06124, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| AlphaFoldDBi | Q06124 |
| SASBDBi | Q06124 |
| SMRi | Q06124 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | Q06124 |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 6 – 102 | SH2 1PROSITE-ProRule annotationAdd BLAST | 97 | |
| Domaini | 112 – 216 | SH2 2PROSITE-ProRule annotationAdd BLAST | 105 | |
| Domaini | 247 – 517 | Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST | 271 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 459 – 465 | Substrate bindingBy similarity | 7 | |
| Regioni | 548 – 571 | DisorderedSequence analysisAdd BLAST | 24 |
Domaini
The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme.
Sequence similaritiesi
Keywords - Domaini
Repeat, SH2 domainPhylogenomic databases
| eggNOGi | KOG0790, Eukaryota |
| GeneTreei | ENSGT00940000153876 |
| HOGENOMi | CLU_001645_9_10_1 |
| InParanoidi | Q06124 |
| OMAi | KYYIATQ |
| OrthoDBi | 411281at2759 |
| PhylomeDBi | Q06124 |
| TreeFami | TF351632 |
Family and domain databases
| Gene3Di | 3.30.505.10, 2 hits 3.90.190.10, 1 hit |
| InterProi | View protein in InterPro IPR029021, Prot-tyrosine_phosphatase-like IPR000242, PTP_cat IPR000980, SH2 IPR036860, SH2_dom_sf IPR016130, Tyr_Pase_AS IPR003595, Tyr_Pase_cat IPR000387, Tyr_Pase_dom IPR012152, Tyr_Pase_non-rcpt_typ-6/11 |
| Pfami | View protein in Pfam PF00017, SH2, 2 hits PF00102, Y_phosphatase, 1 hit |
| PIRSFi | PIRSF000929, Tyr-Ptase_nr_6, 1 hit |
| PRINTSi | PR00700, PRTYPHPHTASE PR00401, SH2DOMAIN |
| SMARTi | View protein in SMART SM00194, PTPc, 1 hit SM00404, PTPc_motif, 1 hit SM00252, SH2, 2 hits |
| SUPFAMi | SSF52799, SSF52799, 1 hit SSF55550, SSF55550, 2 hits |
| PROSITEi | View protein in PROSITE PS50001, SH2, 2 hits PS00383, TYR_PHOSPHATASE_1, 1 hit PS50056, TYR_PHOSPHATASE_2, 1 hit PS50055, TYR_PHOSPHATASE_PTP, 1 hit |
Sequences (3+)i
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q06124-2) [UniParc]FASTAAdd to basket
Also known as: PTP2C
This isoform has been chosen as the canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA
60 70 80 90 100
VTHIKIQNTG DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY
110 120 130 140 150
PLNCADPTSE RWFHGHLSGK EAEKLLTEKG KHGSFLVRES QSHPGDFVLS
160 170 180 190 200
VRTGDDKGES NDGKSKVTHV MIRCQELKYD VGGGERFDSL TDLVEHYKKN
210 220 230 240 250
PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT DKVKQGFWEE
260 270 280 290 300
FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP
310 320 330 340 350
VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS
360 370 380 390 400
RVIVMTTKEV ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE
410 420 430 440 450
LKLSKVGQGN TERTVWQYHF RTWPDHGVPS DPGGVLDFLE EVHHKQESIM
460 470 480 490 500
DAGPVVVHCS AGIGRTGTFI VIDILIDIIR EKGVDCDIDV PKTIQMVRSQ
510 520 530 540 550
RSGMVQTEAQ YRFIYMAVQH YIETLQRRIE EEQKSKRKGH EYTNIKYSLA
560 570 580 590
DQTSGDQSPL PPCTPTPPCA EMREDSARVY ENVGLMQQQK SFR
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| A0A0U1RRI0 | A0A0U1RRI0_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 196 | Annotation score: | ||
| H0YF12 | H0YF12_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 108 | Annotation score: | ||
| A0A1W2PPU4 | A0A1W2PPU4_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 578 | Annotation score: | ||
| A0A8I5KRZ3 | A0A8I5KRZ3_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 555 | Annotation score: | ||
| A0A8I5KVS6 | A0A8I5KVS6_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 461 | Annotation score: | ||
| A0A8I5KW48 | A0A8I5KW48_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 671 | Annotation score: | ||
| A0A8I5QJ58 | A0A8I5QJ58_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 536 | Annotation score: | ||
| A0A8I5QL30 | A0A8I5QL30_HUMAN | Tyrosine-protein phosphatase non-re... | PTPN11 | 468 | Annotation score: |
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 535 | S → R in BAA02740 (PubMed:8216283).Curated | 1 | |
| Sequence conflicti | 548 | S → P in BAA02740 (PubMed:8216283).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_027183 | 2 | T → I in NS1. 1 PublicationCorresponds to variant dbSNP:rs267606990EnsemblClinVar. | 1 | |
| Natural variantiVAR_015601 | 42 | T → A in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507501EnsemblClinVar. | 1 | |
| Natural variantiVAR_027184 | 58 | N → K in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507506EnsemblClinVar. | 1 | |
| Natural variantiVAR_066060 | 59 | T → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs886043790EnsemblClinVar. | 1 | |
| Natural variantiVAR_015602 | 60 | G → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507509EnsemblClinVar. | 1 | |
| Natural variantiVAR_015990 | 60 | G → V in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs397507509EnsemblClinVar. | 1 | |
| Natural variantiVAR_015603 | 61 | D → G in NS1. 4 PublicationsCorresponds to variant dbSNP:rs121918461EnsemblClinVar. | 1 | |
| Natural variantiVAR_015604 | 61 | D → N in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507510EnsemblClinVar. | 1 | |
| Natural variantiVAR_015991 | 61 | D → V in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918461EnsemblClinVar. | 1 | |
| Natural variantiVAR_015992 | 61 | D → Y in JMML. 1 PublicationCorresponds to variant dbSNP:rs397507510EnsemblClinVar. | 1 | |
| Natural variantiVAR_015605 | 62 | Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918460EnsemblClinVar. | 1 | |
| Natural variantiVAR_015606 | 63 | Y → C in NS1. 6 PublicationsCorresponds to variant dbSNP:rs121918459EnsemblClinVar. | 1 | |
| Natural variantiVAR_015993 | 69 | E → K in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar. | 1 | |
| Natural variantiVAR_027185 | 69 | E → Q in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar. | 1 | |
| Natural variantiVAR_015994 | 71 | F → K in acute myeloid leukemia; requires 2 nucleotide substitutions. 1 Publication | 1 | |
| Natural variantiVAR_015995 | 71 | F → L in NS1; also found in myelodysplastic syndrome. 2 PublicationsCorresponds to variant dbSNP:rs397507512EnsemblClinVar. | 1 | |
| Natural variantiVAR_015607 | 72 | A → G in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918454EnsemblClinVar. | 1 | |
| Natural variantiVAR_015608 | 72 | A → S in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918453EnsemblClinVar. | 1 | |
| Natural variantiVAR_015996 | 72 | A → T in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918453EnsemblClinVar. | 1 | |
| Natural variantiVAR_015997 | 72 | A → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918454EnsemblClinVar. | 1 | |
| Natural variantiVAR_015609 | 73 | T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918462EnsemblClinVar. | 1 | |
| Natural variantiVAR_015998 | 76 | E → A in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar. | 1 | |
| Natural variantiVAR_015610 | 76 | E → D in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507514EnsemblClinVar. | 1 | |
| Natural variantiVAR_015999 | 76 | E → G in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar. | 1 | |
| Natural variantiVAR_016000 | 76 | E → K in JMML; increases protein tyrosine phosphatase activity against CDC73. 2 PublicationsCorresponds to variant dbSNP:rs121918464EnsemblClinVar. | 1 | |
| Natural variantiVAR_016001 | 76 | E → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar. | 1 | |
| Natural variantiVAR_027186 | 79 | Q → P in NS1. 1 Publication | 1 | |
| Natural variantiVAR_015611 | 79 | Q → R in NS1. 4 Publications |