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PTPN11 (Protein tyrosine phosphatase, non-receptor type, 11)

Written2005-02Marco Tartaglia, Bruce D Gelb
Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanitö, Rome, Italy

(Note : for Links provided by Atlas : click)

Identity

Other namesSHP-2
SH-PTP2 (Src homology 2 domain-containing protein tyrosine phosphatase, 2)
PTP2C (Protein tyrosine phosphatase 2C)
BPTP3
HGNC (Hugo) PTPN11
LocusID (NCBI) 5781
Atlas_Id 41910
Location 12q24.13  [Link to chromosome band 12q24]
Location_base_pair Starts at 112856536 and ends at 112947717 bp from pter ( according to hg19-Feb_2009)  [Mapping PTPN11.png]
Local_order centromere - FLJ34154 - RPL6 - PTPN11 - RPH3A - OAS1 - telomere
Fusion genes
(updated 2016)
ANP32B (9q22.33) / PTPN11 (12q24.13)CD4 (12p13.31) / PTPN11 (12q24.13)HDAC5 (17q21.31) / PTPN11 (12q24.13)
PAK2 (3q29) / PTPN11 (12q24.13)PTPN11 (12q24.13) / PTPN11 (12q24.13)RAC1 (7p22.1) / PTPN11 (12q24.13)

DNA/RNA

Description The PTPN11 gene is divided in 16 exons. Exon 1 contains the 5' untranslated region and the translation initiation ATG, and a few additional codons. Exon 15 contains the stop codon and exon 16 contains a major portion of the 3' untranslated region. Other features of the PTPN11 gene, such as the promoter region and enhancer elements have not been delineated.
Transcription A 7.0-kb transcript is detected in several tissues (heart, brain, lung, liver, skeletal muscle, kidney, and pancreas) with highest steady-state levels in heart and skeletal muscle. The predominant human PTPN11 mRNA contains an open reading frame of 1,779 bases, resulting in a predicted protein of 593 amino acid residues. A second mRNA containing 12 additional base pairs (exon 11) has been identified. Little additional information is available about this alternative transcript.
Pseudogene A number of PTPN11-related processed pseudogenes, i.e. with no apparent exon structure, have been documented in the human genome. All the pseudogenes share >92% nucleotide identity with the PTPN11 cDNA (including the 5'-UTR and 3'-UTR), but harbour frameshift mutations and multiple stop codons. Three of the five pseudogenes appear to be expressed with distinct tissue distributions and expression levels.

Protein

 
  PTPN11 genomic organization and SHP-2 domain structure:
Figure 1 : (A) The PTPN11 gene and SHP-2 domain characterization. The coding exons are shown as numbered filled boxes. The functional domains of the protein, comprising two tandemly arranged SH2 domains at the N terminus (N-SH2 and C-SH2) followed by a protein tyrosine phosphatase (PTP) domain, are shown below. Numbers below the domain structure indicate the amino-acid boundaries of those domains. (B) Three-dimensional structure of SHP-2 in its catalytically inactive conformation, as determined by Hof et al. (1998). Residues involved in catalysis are shown (space fill).
Figure 2 : Location of SHP-2 mutated residues in human disease. (A) Noonan syndrome and LEOPARD syndrome (germ-line origin; N=224); (B) Noonan syndrome with juvenile myelomonocytic leukemia (germ-line origin; N=11); (C) hematologic malignancies, including juvenile myelomonocytic leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia (somatic origin; N=97). The pictures show the C trace of SHP-2 in its catalytically inactive conformation. Affected residues are indicated with their side chains as black sticks.
Description SHP-2 is a member of a small subfamily of cytoplasmic Src homology 2 (SH2) domain-containing protein tyrosine phosphatases. Both the N-SH2 and C-SH2 domains selectively bind to short amino acid motifs containing a phosphotyrosyl residue and promote SHP-2 association with activated receptors and other signaling partners. Crystallographic data indicate that the N-SH2 domain also interacts with the PTP domain using a separate site. As these subdomains show negative cooperativity, the N-SH2 domain functions as an intramolecular switch controlling SHP-2 catalytic activation. Specifically, the N-SH2 domain interacts with the PTP domain basally, blocking the catalytic site. Binding of the N-SH2 phosphopeptide-binding site to the phosphotyrosyl ligand promotes a conformational change of the domain that weakens the auto-inhibiting intramolecular interaction, making the catalytic site available to substrate, thereby activating the phosphatase.
Expression Widely expressed in both embryonic and adult tissues.
Localisation Cytoplasmic. It binds to activated cell surface receptors, cell adhesion molecules and scaffolding adapters.
Function SHP-2 functions as an intracellular signal transducer. It positively modulates signal flow in most circumstances, but can also function as negative regulator depending upon its binding partner and interactions with downstream signaling networks. SHP-2 positively controls the activation of the RAS/MAPK cascade induced by several growth factors, and negatively regulates JAK/STAT signaling. In most cases, SHP-2's function in intracellular signaling appears to be immediately proximal to activated receptors and upstream to RAS. The mechanisms of SHP-2's action and its physiological substrates are still poorly defined. However, both membrane translocation and PTPase activity are required for SHP-2 function. SHP-2 is required during development. Embryos nullizygous for Shp-2 have defects in gastrulation and mesodermal patterning resulting in severe abnormalities in axial and paraxial mesodermal structures. Shp-2 function is also required for development of terminal and skeletal structures, semilunar valvulogenesis in the heart, and hematopoiesis.
Homology PTPN6 (protein tyrosine phosphatase, non-receptor type, 6) previously known as SHP1 or SHP-1 (Src homology 2 domain-containing protein tyrosine phosphatase, 1).

Mutations

Note At least two distinct classes of PTPN11 mutations have been identified in humans.
  • The first group, which has germ-line origin, causes Noonan syndrome and closely related developmental disorders.
  • The second group, acquired as a somatic event, has been documented in a heterogeneous group of hematologic malignancies and pre-leukemic disorders, and rarely in certain solid tumors.
    The vast majority of mutations affect residues residing at or close to the interface between the N-SH2 and PTP domains. Increasing evidence supports that both germ-line and somatic mutations promote SHP-2 gain-of-function by destabilizing the catalytically inactive conformation of the protein, and prolong signal flux through the RAS/MAPK pathway in a ligand-dependent manner.
    A mouse model bearing the NS-causative D61G mutation in the Ptpn11 gene has been recently generated and characterized. The Ptpn11D61G/D61G genotype is embryonic lethal. At day E13.5, these embryos are grossly edematous and hemorrhagic, have diffuse liver necrosis and severe cardiac defects. Heterozygous embryos exhibit cardiac defects, proportionate growth failure and perturbed craniofacial development. Hematologic anomalies include a mild myeloproliferative disease. Ptpn11D61G/+ embryonic fibroblasts exhibit a three-fold increased Shp-2 activity and increased association of Shp-2 with Gab1 after stimulation with EGF. Cell culture and whole embryo studies reveal that increased RAS/MAPK signaling is variably present, appearing to be cell-context specific.
  • Germinal Selection: 124A>G (T42A), 179-181delGTG (delGly60), 181-183delGAT (delAsp61), 182A>G (D61G), 184T>G (Y62D), 188A>G (Y63C), 214G>T (A72S), 215C>G (A72G), 218C>T (T73I), 228G>T,C (E76D), 236A>G (N79R), 317A>C (D106A), 836A>G (Y279C), 922A>G (N308D), 1403C>T (T468M), 1510A>G (M504V).
    Somatic Selection: 181G>T (D61Y), 182A>T (D61V), 205G>A (E69K), 211-213TTT>AAA (F71K), 214G>A (A72T), 215C>T (A72V), 226G>A (E76K), 226G>C (E76Q), 227A>T (E76V), 227A>G (E76G), 227A>C (E76A), 1471C>T (P491S), 1472C>T (P491L), 1504T>C (S502P), 1504T>G (S502A), 1520C>A (T507K), 1528C>A (Q510K).

    Implicated in

    Note
    Entity Noonan syndrome, Noonan-like/multiple giant cell lesion syndrome and LEOPARD syndrome.
    Note Germ-line origin. Gain-of-function mutations. Increased basal protein tyrosine phosphatase activity. Prolonged ligand-dependent activation of the RAS/MAPK cascade.
    Disease Noonan syndrome is a genetically heterogeneous and clinically variable developmental disorder defined by short stature, facial dysmorphism and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, down-slanting palpebral fissures, ptosis, high-arched palate and low-set, posteriorly rotated ears. Cardiovascular abnormalities, primarily pulmonic stenosis and hypertrophic cardiomyopathy, are present in up to 85% of affected individuals. Additional relatively frequent features are multiple skeletal defects, webbed neck, mental retardation, cryptorchidism and bleeding diathesis. Children with Noonan syndrome are predisposed to a spectrum of hematologic abnormalities, including transient monocytosis, thrombocytopenia and rarely juvenile myelomonocytic leukemia and acute leukemia.
      
    Entity Juvenile myelomonocytic leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, melanoma, neuroblastoma, lung adenocarcinoma, colon cancer.
    Note Somatic origin.
    Prognosis No data are currently available.
    Oncogenesis Gain-of-function mutations. Increased basal protein tyrosine phosphatase activity. Prolonged ligand-dependent activation of the RAS/MAPK cascade.
      

    Bibliography

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    Ahmad S, Banville D, Zhao Z, Fischer EH, Shen SH
    Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (6) : 2197-2201.
    PMID 7681589
     
    A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage.
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    The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2004 ; 18 (1) : 8-30.
    PMID 14718383
     
    Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation.
    Araki T, Mohi MG, Ismat FA, Bronson RT, Williams IR, Kutok JL, Yang W, Pao LI, Gilliland DG, Epstein JA, Neel BG
    Nature medicine. 2004 ; 10 (8) : 849-857.
    PMID 15273746
     
    Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia.
    Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR, Neel BG
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    PMID 15604238
     
    Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene.
    Digilio MC, Conti E, Sarkozy A, Mingarelli R, Dottorini T, Marino B, Pizzuti A, Dallapiccola B
    American journal of human genetics. 2002 ; 71 (2) : 389-394.
    PMID 12058348
     
    Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation.
    Fragale A, Tartaglia M, Wu J, Gelb BD
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    PMID 9491886
     
    PTPN11 mutations in LEOPARD syndrome.
    Legius E, Schrander-Stumpel C, Schollen E, Pulles-Heintzberger C, Gewillig M, Fryns JP
    Journal of medical genetics. 2002 ; 39 (8) : 571-574.
    PMID 12161596
     
    PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group.
    Loh ML, Reynolds MG, Vattikuti S, Gerbing RB, Alonzo TA, Carlson E, Cheng JW, Lee CM, Lange BJ, Children's Cancer Group, Meshinchi S
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 ; 18 (11) : 1831-1834.
    PMID 15385933
     
    Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis.
    Loh ML, Vattikuti S, Schubbert S, Reynolds MG, Carlson E, Lieuw KH, Cheng JW, Lee CM, Stokoe D, Bonifas JM, Curtiss NP, Gotlib J, Meshinchi S, Le Beau MM, Emanuel PD, Shannon KM
    Blood. 2004 ; 103 (6) : 2325-2331.
    PMID 14644997
     
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    Neel BG, Gu H, Pao L
    Trends in biochemical sciences. 2003 ; 28 (6) : 284-293.
    PMID 12826400
     
    Germ-line and somatic PTPN11 mutations in human disease.
    Tartaglia M, Gelb BD
    European journal of medical genetics. 2005 ; 48 (2) : 81-96.
    PMID 16053901
     
    Genotype-phenotype correlations in Noonan syndrome.
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    PMID 15001945
     

    Citation

    This paper should be referenced as such :
    Tartaglia, M ; Gelb, BD
    PTPN11 (protein tyrosine phosphatase, non-receptor type, 11)
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):123-126.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/PTPN11ID41910ch12q24.html


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
      t(5;16)(q32;p13) NDE1/PDGFRB

    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 3 ]
      Enchondromatosis LEOPARD syndrome Noonan syndrome

    External links

    Nomenclature
    HGNC (Hugo)PTPN11   9644
    Cards
    AtlasPTPN11ID41910ch12q24
    Entrez_Gene (NCBI)PTPN11  5781  protein tyrosine phosphatase, non-receptor type 11
    AliasesBPTP3; CFC; JMML; METCDS; 
    NS1; PTP-1D; PTP2C; SH-PTP2; SH-PTP3; SHP2
    GeneCards (Weizmann)PTPN11
    Ensembl hg19 (Hinxton)ENSG00000179295 [Gene_View]  chr12:112856536-112947717 [Contig_View]  PTPN11 [Vega]
    Ensembl hg38 (Hinxton)ENSG00000179295 [Gene_View]  chr12:112856536-112947717 [Contig_View]  PTPN11 [Vega]
    ICGC DataPortalENSG00000179295
    TCGA cBioPortalPTPN11
    AceView (NCBI)PTPN11
    Genatlas (Paris)PTPN11
    WikiGenes5781
    SOURCE (Princeton)PTPN11
    Genomic and cartography
    GoldenPath hg19 (UCSC)PTPN11  -     chr12:112856536-112947717 +  12q24.1   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)PTPN11  -     12q24.1   [Description]    (hg38-Dec_2013)
    EnsemblPTPN11 - 12q24.1 [CytoView hg19]  PTPN11 - 12q24.1 [CytoView hg38]
    Mapping of homologs : NCBIPTPN11 [Mapview hg19]  PTPN11 [Mapview hg38]
    OMIM151100   156250   163950   176876   607785   
    Gene and transcription
    Genbank (Entrez)AK289854 AK312147 AU123593 BC007869 BC008692
    RefSeq transcript (Entrez)NM_002834 NM_080601
    RefSeq genomic (Entrez)NC_000012 NC_018923 NG_007459 NT_029419 NW_004929385
    Consensus coding sequences : CCDS (NCBI)PTPN11
    Cluster EST : UnigeneHs.506852 [ NCBI ]
    CGAP (NCI)Hs.506852
    Alternative Splicing GalleryENSG00000179295
    Gene ExpressionPTPN11 [ NCBI-GEO ]   PTPN11 [ EBI - ARRAY_EXPRESS ]   PTPN11 [ SEEK ]   PTPN11 [ MEM ]
    Gene Expression Viewer (FireBrowse)PTPN11 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)5781
    GTEX Portal (Tissue expression)PTPN11
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ06124 (Uniprot)
    NextProtQ06124  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ06124
    Splice isoforms : SwissVarQ06124 (Swissvar)
    Catalytic activity : Enzyme3.1.3.48 [ Enzyme-Expasy ]   3.1.3.483.1.3.48 [ IntEnz-EBI ]   3.1.3.48 [ BRENDA ]   3.1.3.48 [ KEGG ]   
    PhosPhoSitePlusQ06124
    Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    TYR_PHOSPHATASE_1 (PS00383)    TYR_PHOSPHATASE_2 (PS50056)    TYR_PHOSPHATASE_PTP (PS50055)   
    Domains : Interpro (EBI)Prot-tyrosine_phosphatase-like    PTPase_domain    SH2    Tyr_Pase_AS    Tyr_Pase_non-rcpt_typ-6/11    TYR_PHOSPHATASE_dom   
    Domain families : Pfam (Sanger)SH2 (PF00017)    Y_phosphatase (PF00102)   
    Domain families : Pfam (NCBI)pfam00017    pfam00102   
    Domain families : Smart (EMBL)PTPc (SM00194)  SH2 (SM00252)  
    DMDM Disease mutations5781
    Blocks (Seattle)PTPN11
    PDB (SRS)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG    4NWF    4NWG    4OHD    4OHE    4OHH    4OHI    4OHL    4PVG    4QSY    4RDD    5DF6   
    PDB (PDBSum)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG    4NWF    4NWG    4OHD    4OHE    4OHH    4OHI    4OHL    4PVG    4QSY    4RDD    5DF6   
    PDB (IMB)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG    4NWF    4NWG    4OHD    4OHE    4OHH    4OHI    4OHL    4PVG    4QSY    4RDD    5DF6   
    PDB (RSDB)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG    4NWF    4NWG    4OHD    4OHE    4OHH    4OHI    4OHL    4PVG    4QSY    4RDD    5DF6   
    Structural Biology KnowledgeBase2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG    4NWF    4NWG    4OHD    4OHE    4OHH    4OHI    4OHL    4PVG    4QSY    4RDD    5DF6   
    SCOP (Structural Classification of Proteins)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG    4NWF    4NWG    4OHD    4OHE    4OHH    4OHI    4OHL    4PVG    4QSY    4RDD    5DF6   
    CATH (Classification of proteins structures)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG    4NWF    4NWG    4OHD    4OHE    4OHH    4OHI    4OHL    4PVG    4QSY    4RDD    5DF6   
    SuperfamilyQ06124
    Human Protein AtlasENSG00000179295
    Peptide AtlasQ06124
    HPRD01470
    IPIIPI00658023   IPI00298347   IPI00658002   IPI00063246   IPI00981283   
    Protein Interaction databases
    DIP (DOE-UCLA)Q06124
    IntAct (EBI)Q06124
    FunCoupENSG00000179295
    BioGRIDPTPN11
    STRING (EMBL)PTPN11
    ZODIACPTPN11
    Ontologies - Pathways
    QuickGOQ06124
    Ontology : AmiGODNA damage checkpoint  activation of MAPK activity  phosphoprotein phosphatase activity  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  SH3/SH2 adaptor activity  insulin receptor binding  protein binding  nucleus  cytoplasm  mitochondrion  cytosol  triglyceride metabolic process  epidermal growth factor receptor signaling pathway  integrin-mediated signaling pathway  axonogenesis  brain development  heart development  fibroblast growth factor receptor signaling pathway  hormone-mediated signaling pathway  regulation of phosphatidylinositol 3-kinase signaling  1-phosphatidylinositol-3-kinase activity  protein domain specific binding  cerebellar cortex formation  platelet activation  platelet formation  receptor tyrosine kinase binding  T cell costimulation  D1 dopamine receptor binding  microvillus organization  abortive mitotic cell cycle  regulation of cell adhesion mediated by integrin  negative regulation of cell adhesion mediated by integrin  multicellular organism growth  organ growth  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  megakaryocyte development  phosphatidylinositol-3-phosphate biosynthetic process  atrioventricular canal development  ERBB signaling pathway  regulation of multicellular organism growth  hormone metabolic process  glucose homeostasis  protein complex  regulation of protein complex assembly  phospholipase binding  insulin receptor substrate binding  positive regulation of mitotic cell cycle  negative regulation of insulin secretion  regulation of protein export from nucleus  phosphatidylinositol phosphorylation  positive regulation of hormone secretion  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  platelet-derived growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  ephrin receptor signaling pathway  phosphatidylinositol-mediated signaling  multicellular organismal reproductive process  genitalia development  inner ear development  homeostasis of number of cells within a tissue  leukocyte migration  peptide hormone receptor binding  negative regulation of cortisol secretion  Bergmann glial cell differentiation  negative regulation of growth hormone secretion  face morphogenesis  regulation of type I interferon-mediated signaling pathway  intestinal epithelial cell migration  positive regulation of ERK1 and ERK2 cascade  positive regulation of glucose import in response to insulin stimulus  
    Ontology : EGO-EBIDNA damage checkpoint  activation of MAPK activity  phosphoprotein phosphatase activity  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  SH3/SH2 adaptor activity  insulin receptor binding  protein binding  nucleus  cytoplasm  mitochondrion  cytosol  triglyceride metabolic process  epidermal growth factor receptor signaling pathway  integrin-mediated signaling pathway  axonogenesis  brain development  heart development  fibroblast growth factor receptor signaling pathway  hormone-mediated signaling pathway  regulation of phosphatidylinositol 3-kinase signaling  1-phosphatidylinositol-3-kinase activity  protein domain specific binding  cerebellar cortex formation  platelet activation  platelet formation  receptor tyrosine kinase binding  T cell costimulation  D1 dopamine receptor binding  microvillus organization  abortive mitotic cell cycle  regulation of cell adhesion mediated by integrin  negative regulation of cell adhesion mediated by integrin  multicellular organism growth  organ growth  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  megakaryocyte development  phosphatidylinositol-3-phosphate biosynthetic process  atrioventricular canal development  ERBB signaling pathway  regulation of multicellular organism growth  hormone metabolic process  glucose homeostasis  protein complex  regulation of protein complex assembly  phospholipase binding  insulin receptor substrate binding  positive regulation of mitotic cell cycle  negative regulation of insulin secretion  regulation of protein export from nucleus  phosphatidylinositol phosphorylation  positive regulation of hormone secretion  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  platelet-derived growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  ephrin receptor signaling pathway  phosphatidylinositol-mediated signaling  multicellular organismal reproductive process  genitalia development  inner ear development  homeostasis of number of cells within a tissue  leukocyte migration  peptide hormone receptor binding  negative regulation of cortisol secretion  Bergmann glial cell differentiation  negative regulation of growth hormone secretion  face morphogenesis  regulation of type I interferon-mediated signaling pathway  intestinal epithelial cell migration  positive regulation of ERK1 and ERK2 cascade  positive regulation of glucose import in response to insulin stimulus  
    Pathways : BIOCARTASignaling of Hepatocyte Growth Factor Receptor [Genes]    Insulin Signaling Pathway [Genes]    The Co-Stimulatory Signal During T-cell Activation [Genes]    IGF-1 Signaling Pathway [Genes]    IL 6 signaling pathway [Genes]   
    Pathways : KEGGRas signaling pathway    Jak-STAT signaling pathway    Natural killer cell mediated cytotoxicity    Leukocyte transendothelial migration    Neurotrophin signaling pathway    Adipocytokine signaling pathway    Epithelial cell signaling in Helicobacter pylori infection    Herpes simplex infection    Proteoglycans in cancer    Renal cell carcinoma    Chronic myeloid leukemia   
    REACTOMEQ06124 [protein]
    REACTOME PathwaysR-HSA-112411 MAPK1 (ERK2) activation [pathway]
    REACTOME PathwaysR-HSA-5654693 FRS-mediated FGFR1 signaling [pathway]
    REACTOME PathwaysR-HSA-388841 Costimulation by the CD28 family [pathway]
    REACTOME PathwaysR-HSA-5654695 PI-3K cascade:FGFR2 [pathway]
    REACTOME PathwaysR-HSA-1257604 PIP3 activates AKT signaling [pathway]
    REACTOME PathwaysR-HSA-1059683 Interleukin-6 signaling [pathway]
    REACTOME PathwaysR-HSA-5654699 SHC-mediated cascade:FGFR2 [pathway]
    REACTOME PathwaysR-HSA-418886 Netrin mediated repulsion signals [pathway]
    REACTOME PathwaysR-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon [pathway]
    REACTOME PathwaysR-HSA-1433557 Signaling by SCF-KIT [pathway]
    REACTOME PathwaysR-HSA-5654706 FRS-mediated FGFR3 signaling [pathway]
    REACTOME PathwaysR-HSA-110056 MAPK3 (ERK1) activation [pathway]
    REACTOME PathwaysR-HSA-5654700 FRS-mediated FGFR2 signaling [pathway]
    REACTOME PathwaysR-HSA-909733 Interferon alpha/beta signaling [pathway]
    REACTOME PathwaysR-HSA-1170546 Prolactin receptor signaling [pathway]
    REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
    REACTOME PathwaysR-HSA-109704 PI3K Cascade [pathway]
    REACTOME PathwaysR-HSA-5654720 PI-3K cascade:FGFR4 [pathway]
    REACTOME PathwaysR-HSA-5654726 Negative regulation of FGFR1 signaling [pathway]
    REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
    REACTOME PathwaysR-HSA-180292 GAB1 signalosome [pathway]
    REACTOME PathwaysR-HSA-912694 Regulation of IFNA signaling [pathway]
    REACTOME PathwaysR-HSA-5654727 Negative regulation of FGFR2 signaling [pathway]
    REACTOME PathwaysR-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer [pathway]
    REACTOME PathwaysR-HSA-389513 CTLA4 inhibitory signaling [pathway]
    REACTOME PathwaysR-HSA-5654689 PI-3K cascade:FGFR1 [pathway]
    REACTOME PathwaysR-HSA-391160 Signal regulatory protein (SIRP) family interactions [pathway]
    REACTOME PathwaysR-HSA-210993 Tie2 Signaling [pathway]
    REACTOME PathwaysR-HSA-210990 PECAM1 interactions [pathway]
    REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
    REACTOME PathwaysR-HSA-5654733 Negative regulation of FGFR4 signaling [pathway]
    REACTOME PathwaysR-HSA-432142 Platelet sensitization by LDL [pathway]
    REACTOME PathwaysR-HSA-186763 Downstream signal transduction [pathway]
    REACTOME PathwaysR-HSA-5654719 SHC-mediated cascade:FGFR4 [pathway]
    REACTOME PathwaysR-HSA-5654710 PI-3K cascade:FGFR3 [pathway]
    REACTOME PathwaysR-HSA-389948 PD-1 signaling [pathway]
    REACTOME PathwaysR-HSA-114604 GPVI-mediated activation cascade [pathway]
    REACTOME PathwaysR-HSA-5654732 Negative regulation of FGFR3 signaling [pathway]
    REACTOME PathwaysR-HSA-5654712 FRS-mediated FGFR4 signaling [pathway]
    REACTOME PathwaysR-HSA-512988 Interleukin-3, 5 and GM-CSF signaling [pathway]
    REACTOME PathwaysR-HSA-109704 PI3K Cascade [pathway]
    REACTOME PathwaysR-HSA-877312 Regulation of IFNG signaling [pathway]
    REACTOME PathwaysR-HSA-2586552 Signaling by Leptin [pathway]
    REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
    NDEx Network
    Atlas of Cancer Signalling NetworkPTPN11
    Wikipedia pathwaysPTPN11
    Orthology - Evolution
    OrthoDB5781
    GeneTree (enSembl)ENSG00000179295
    Phylogenetic Trees/Animal Genes : TreeFamPTPN11
    Homologs : HomoloGenePTPN11
    Homology/Alignments : Family Browser (UCSC)PTPN11
    Gene fusions - Rearrangements
    Polymorphisms : SNP, variants
    NCBI Variation ViewerPTPN11 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)PTPN11
    dbVarPTPN11
    ClinVarPTPN11
    1000_GenomesPTPN11 
    Exome Variant ServerPTPN11
    ExAC (Exome Aggregation Consortium)PTPN11 (select the gene name)
    Genetic variants : HAPMAP5781
    Genomic Variants (DGV)PTPN11 [DGVbeta]
    Mutations
    ICGC Data PortalPTPN11 
    TCGA Data PortalPTPN11 
    Broad Tumor PortalPTPN11
    OASIS PortalPTPN11 [ Somatic mutations - Copy number]
    Cancer Gene: CensusPTPN11 
    Somatic Mutations in Cancer : COSMICPTPN11 
    intOGen PortalPTPN11
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch PTPN11
    DgiDB (Drug Gene Interaction Database)PTPN11
    DoCM (Curated mutations)PTPN11 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)PTPN11 (select a term)
    intoGenPTPN11
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
    Diseases
    DECIPHER (Syndromes)12:112856536-112947717  ENSG00000179295
    CONAN: Copy Number AnalysisPTPN11 
    Mutations and Diseases : HGMDPTPN11
    OMIM151100    156250    163950    176876    607785   
    MedgenPTPN11
    Genetic Testing Registry PTPN11
    NextProtQ06124 [Medical]
    TSGene5781
    GENETestsPTPN11
    Huge Navigator PTPN11 [HugePedia]
    snp3D : Map Gene to Disease5781
    BioCentury BCIQPTPN11
    ClinGenPTPN11 (curated)
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD5781
    Chemical/Pharm GKB GenePA33986
    Clinical trialPTPN11
    Miscellaneous
    canSAR (ICR)PTPN11 (select the gene name)
    Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=PTPN11
    Probes
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMinePTPN11
    EVEXPTPN11
    GoPubMedPTPN11
    iHOPPTPN11
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Wed Aug 10 18:53:53 CEST 2016

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