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PTPN6 (protein tyrosine phosphatase, non-receptor type 6)

Written2012-11Alessandro Beghini, Francesca Lazzaroni
Department of Medical Biotechnology, Translational Medicine, Universita degli Studi di Milano, Milano, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)HCP
HCPH
PTP-1C
SHP-1
SHP1
Other aliasHPTP1C
SH-PTP1
SHP-1L
HGNC (Hugo) PTPN6
LocusID (NCBI) 5777
Atlas_Id 41920
Location_base_pair Starts at 6951271 and ends at 6961316 bp from pter ( according to hg19-Feb_2009)  [Mapping PTPN6.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AK8 (9q34.13) / PTPN6 (12p13.31)PTPN6 (12p13.31) / CIDEC (3p25.3)PTPN6 (12p13.31) / P3H3 (12p13.31)
PTPN6 (12p13.31) / PTPN6 (12p13.31)
Note Orientation: plus strand.

DNA/RNA

 
  Schematic representation of the human PTPN6 gene. Adapted from Wu et al., 2003.
Description The human PTPN6 gene is divided in 17 exons spanning a length of 14740 bp. A notable feature of the PTPN6 gene is that it has two promoter regions. Whereas the distal promoter, P1, located upstream of the very short exon 1 (also known as exon 1a) is active in epithelial cells, the proximal promoter P2 that initiates gene transcription from exon 2 (known as exon 1b), is utilized by the hematopoietic cells. The function of P1 promoter has been partially elucidated, while the structure and regulatory mechanism of the P2 promoter remain essentially unknown.
Recent findings, characterized the hematopoietic cell-specific P2 promoter of PTPN6 gene as well as identified the PU.1 transcription factor as the activator of the P2 promoter.
Transcription There are three transcript variants:
The variant 1 represents the predominant variant and encodes the shortest isoform.
The variant 2 originates by an alternate 5' terminal exon compared to transcript variant 1, resulting in an isoform (2) with a distinct and longer (by 2 aa) N-terminus, compared to isoform 1.
The variant 3 uses an alternate 5' terminal exon, and an alternate acceptor splice site at the penultimate exon, compared to transcript variant 1, resulting in a longer isoform (3, also known as 70 kDa SHP-1L protein) with distinct N and C termini, compared to isoform 1.

Protein

Description PTPN6 contain two adjacent NH2 - terminal SH2 domains, two tandem Src homology (SH2) domains, a catalytic domain, and a -COOH terminal tail of 100 amino-acid residues.
Expression PTPN6 tyrosine phosphatase is encoded by the PTPN6 gene and expressed primarily in the hematopoietic and epithelial cells.
 
  Crystal structure of human protein tyrosine phosphatase SHP-1. The blue region represents the N-terminal of protein, while the red region represents the C-terminal of protein.
Function PTPN6 plays a peculiar role in the maturation and functional differentiation of lymphoid and myeloid cells as underlined by the aberrant proliferation and impaired hematopoiesis in the "motheaten" (me) mice that display defects in the Shp-1 gene expression. The role of PTPN6 in hematopoiesis has been shown in motheaten and viable motheaten (meν) mice, characterized by mutations at the Shp-1 locus. The Shp-1 mRNA from me bone marrow cells have a 101 bp frameshift deletion in the coding region of the N-terminal SH2 domain, while meν bone marrow cells have an in-frame 15 bp deletion or a 69 bp in-frame insertion within the PTPase catalytic domain. Shp-1 acts in the immune and other hematopoietic cells by inhibiting signaling through receptors for cytokines, growth factors and chemokines as well as receptors involved in the immune responses and programmed cell death. Moreover, PTPN6 acts as tumor suppressor and loss of its expression has been identified in the whole spectrum of myeloid and lymphoid malignancies.
According to Gilfillan, PTPN6 is found to be constitutively associated with FcεRI, with an opponing roles in FcεRI-mediated mast cell signaling. The study demonstrated that PTPN6 caused the decreased phosphorylation of FcεRI and Syk, but, also, an enhanced phosphorylation of JNK and an increased of the TNF production is observed. This study, suggests that PTPN6 may play a negative role proximal to FcεRI.
It was also demonstrated that the PTPN6 protein tyrosine phosphatase negatively modulates the glucose homeostasis and insulin activity, through a dephosphorylation of transmembrane glycoprotein Carcinoembryonic Antigen-related Cell Adhesion Molecule-1 (CEACAM-1).
The data obtained from in vitro studies, suggested that the deficiency of PTPN6 was associated with the increase in insulin-evoked tyrosin phosphorylation of the insulin receptor, IRS-1 and IRS-2, as well as enhanced activation of PI3K and Akt in liver and skeletal muscle.
Moreover, the activation of PTPN6, through a PKC-δ and p38α MAPK actions on PDGFRβ is involved in hyperglycemia and causes an increase vascular cell apoptosis and diabetic vascular complications.

Mutations

Note The absence or impaired function of PTPN6 in the homozygous state causes the development of the motheaten phenotype in mice, an autosomal recessive condition with focal skin inflammation and the absence of hair. Failure of neutrophils to undergo apoptosis results in the accumulation of these cells in the peripheral blood, skin, lung and spleen of affected mice.
Somatic A pathologically similar extensive skin infiltration by neutrophils is present in Pyoderma gangrenosum (PG) and Sweet's syndrome (SW), two uncommon neutrophilic dermatoses of unknown origin. Isoforms resulting from deletions of exons 2, 5, 11, and 15 and retention of intron 1 or 5 were identified in a patients with a familial case of SW, who had a neonatal onset of an inflammatory disorder with skin lesions and a biopsy specimen consistent with SW. These isoforms were associated with a heterozygous E441G mutation and a heterozygous 1,7-kbp deletion in the promoter region of the PTPN6 gene. The E441G mutation changes the hydrophilic, negatively charged amino acid glutamate to the hydrophobic nonpolar, aliphatic amino acid glycine, thereby potentially affecting the tertiary structure of PTPN6. SW an acute febrile neutrophilic dermatoses appears in several clinical forms as idiopathic, tumor associated, postinfectious and drug induced (for example after an administration of granulocyte macrophage colony stimulating factor). SW and PG have strong associations with hematological tumors. Recent studies have shown that patient with leukemia and lymphoma had methylated a P2 promoter in the PTPN6 gene, causing the absence of PTPN6 protein.
PTPN6 is expressed at low level in non-hematopoietic cells while higher levels of this protein are found in hematopoietic precursors. PTPN6 promoter methylation causes loss of expression in leukemias, which results in the activation of the JAK/STAT pathway. PTPN6 plays a role in chronic myelogenous leukemia transformation and progression: it seems to be physically associated with BCR-ABL being able both to block BCR-ABL-dependent transformation and to mediate PP2A induced BCR-ABL proteosome-degradation. The tyrosine phosphatase PTPN6 plays a prominent role as resistance determinant of Imatinib (IMA) treatment response in Chronic Myelogenous Leukemia cell lines (sensitive/KCL22-S and resistant/KCL22-R).
The lack of PTPN6 expression is frequent in malignant T cells and results from methylation of the PTPN6 gene promoter. Loss of PTPN6 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK + anaplastic large-cell lymphoma.
According to Wu's research, in most human Burkitt's lymphoma cell lines, the expression of SHP-1 is decreased suggesting a role of SHP-1 in a developing of Burkitt's lymphoma, a non-Hodgkin's lymphoma, associated with EBV infection.
Moreover the activity of PTPN6, is also implicated in a breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer.

Implicated in

Note
  
Entity T-cell lymphomas
Disease Cutaneous T-cell lymphoma (CTCL) is generally classified as a type of non-Hodgkin's lymphoma, and it represents a spectrum of diseases composed of malignant clonal helper T lymphocytes of the CD4 phenotype. Widely known variants include Sezary syndrome, Woringer-Kolopp disease (Pagetoid Reticulosis), CD8+ T-cell lymphoma, granulomatous slack skin, peripheral T-cell lymphoma, angiocentric lymphoma, adult T-cell leukemia/lymphoma, large-cell or anaplastic lymphoma, and lymphomatoid granulomatosis. Poikiloderma atrophicans vasculare, small and large plaque parapsoriasis, alopecia mucinosa, and lymphomatoid papulosis likely represent early forms of CTCL, but there is a problem to whether these represent CTCL or separate premalignant entities. Accurate diagnosis of early CTCL is difficult because of the varied clinical and histologic expressions of the disease and because of a lack of uniformity regarding diagnosis and treatment.
Prognosis Treatment regimens in CTCL include skin-directed therapies with UVA irradiation, topical chemotherapy with mechlorethamine (nitrogen mustard) and carmustine, and electron beam radiation, as well as systemic therapies such as chemotherapy and interferons.
  
  
Entity Acute myeloid leukemia
Note The first hint that A-to-I RNA editing has fundamental implications in leukemic disorders derives from Beghini and co-authors, who detected altered editing events in the protein tyrosine phosphatase (PTPN6/SHP-1) transcript of patients affected by AML (Galeano et al., 2012).
The analysis of PTPN6 mRNA revealed a multiple A-I editing conversion of A7866, a branch site in IVS3 of PTPN6 mRNA causing the retention of IVS1.
Disease Adult acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets. Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of acute leukemia in adults. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia. Most AML subtypes are based on how mature (developed) the cancer cells are at the time of diagnosis and how different they are from normal cells. Acute promyelocytic leukemia (APL) is a subtype of AML that occurs when parts of two genes stick together. APL usually occurs in middle-aged adults. Symptoms of APL may include both bleeding and forming blood clots.
Prognosis Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Intrathecal chemotherapy may be used to treat adult AML that has spread, or may spread to the brain and spinal cord. Combination chemotherapy is treatment using more than one anticancer drug.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells that are abnormal or destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
  
  
Entity Pyoderma gangrenosum (PG)
Disease Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis first described in 1930. Clinically it begins with sterile pustules that rapidly progress and turn into painful ulcers of variable depth and size with undermined violaceous borders. The legs are most commonly affected but other parts of the skin and mucous membranes may also be involved. Extracutaneous manifestations include involvement of upper airway mucosa, eye, sterile pulmonary neutrophilic infiltrates, and neutrophilic myositis. The ulcer starts as a follicular pustule with rapid growth, tissue necrosis and enlargement of the area. The surrounding skin is erythematous with infiltration end edema.
Ulcerative colitis is found in 10-15% of cases. Another associated disease is Crohn's regional enteritis with a frequency close to that of ulcerative colitis. Hepatitis C, seronegative polyarticular arthritis, spondylitis, and a broad spectrum of lymphoproliferative disorders including monoclonal gammopathies, leukemia, lymphoma, and myelodysplastic syndrome have been described in association with PG. Two main variants of PG exist: classic and atypical.
Classic PG: characterized by a deep ulceration with a violaceous border that overhangs the ulcer bed. May occur anywhere on the body; but most commonly found on the legs.
Atypical PG: has a vesciculopustular component only at the border, is erosive or superficially ulcerated, and most often occurs on the dorsal surface of the hands, the extensor parts of the forearms, or the face.
Prognosis Local care: debridement, intralesional injection of steroids or cyclosporin, topical agents to alter immune response (nitrogen mustard, steroids, acetic acid, 5-aminosalicylic acid) or inhibit infection. Systemic care: glucocorticoids (prednisone). These agents have anti-inflammatory properties and cause metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. Immunosuppressives agents (Cyclosporine, Azathioprine, Mycophenolate, Cyclophosphamide, Tacrolimus, Chlorambucil) have immunomodulatory effects. These agents are used to improve the clinical and immunologic aspects of the disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes. Immunomodulators (Thalidomide, Clofazimine).
  
  
Entity Sweet's syndrome (SW)
Disease Sweet's syndrome (acute febrile neutrophilic dermatosis) is characterized by physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions (papules, nodules, and plaques), and a diffuse infiltrate consisting predominantly of mature neutrophils that are typically located in the upper dermis. Sweet's syndrome presents in three clinical settings:
Classical Sweet's syndrome (CSS) usually presents in women between the age of 30 to 50 years, it is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy.
The malignancy-associated Sweet's syndrome (MASS) can occur as a paraneoplastic syndrome in patients with an established cancer or individuals whose Sweet's syndrome-related hematologic dyscrasia or solid tumor was previously undiscovered; MASS is most commonly related to acute myelogenous leukemia. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer.
Drug-induced Sweet's syndrome (DISS) most commonly occurs in patients who have been treated with granulocyte-colony stimulating factor, however, other medications may also be associated with DISS.
Prognosis The pathogenesis of Sweet's syndrome may be multifactorial and still remains to be definitively established. Systemic corticosteroids are the therapeutic gold standard for Sweet's syndrome. Horio et al. originally described the dramatic improvement in patients with Sweet's syndrome who were treated with potassium iodide in 1980. He confirmed his earlier observations with a larger study in 1983. Subsequently, several other investigators have also observed similar improvement when using potassium iodide to treat patients with Sweet's syndrome. Vasculitis and hypothyroidism are potential drug-induced side effects of potassium iodide. Other agents are: colchicine, indomethacin, clofazimine, cyclosporin, dapsone.
  

Bibliography

Decreased expression level of SH2 domain-containing protein tyrosine phosphatase-1 (Shp1) is associated with progression of chronic myeloid leukaemia.
Amin HM, Hoshino K, Yang H, Lin Q, Lai R, Garcia-Manero G.
J Pathol. 2007 Aug;212(4):402-10.
PMID 17503411
 
Human protein tyrosine phosphatase 1C (PTPN6) gene structure: alternate promoter usage and exon skipping generate multiple transcripts.
Banville D, Stocco R, Shen SH.
Genomics. 1995 May 1;27(1):165-73.
PMID 7665165
 
RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia.
Beghini A, Ripamonti CB, Peterlongo P, Roversi G, Cairoli R, Morra E, Larizza L.
Hum Mol Genet. 2000 Sep 22;9(15):2297-304.
PMID 11001933
 
Sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis.
Cohen PR.
Orphanet J Rare Dis. 2007 Jul 26;2:34. (REVIEW)
PMID 17655751
 
Neutrophils require SHP1 to regulate IL-1b production and prevent inflammatory skin disease.
Croker BA, Lewis RS, Babon JJ, Mintern JD, Jenne DE, Metcalf D, Zhang JG, Cengia LH, O'Donnell JA, Roberts AW.
J Immunol. 2011 Jan 15;186(2):1131-9. doi: 10.4049/jimmunol.1002702. Epub 2010 Dec 15.
PMID 21160041
 
A-to-I RNA editing: the "ADAR" side of human cancer.
Galeano F, Tomaselli S, Locatelli F, Gallo A.
Semin Cell Dev Biol. 2012 May;23(3):244-50. doi: 10.1016/j.semcdb.2011.09.003. Epub 2011 Sep 13. (REVIEW)
PMID 21930228
 
A-to-I RNA editing and cancer: from pathology to basic science.
Gallo A, Galardi S.
RNA Biol. 2008 Jul-Sep;5(3):135-9. Epub 2008 Jul 5. (REVIEW)
PMID 18758244
 
The tyrosine kinase network regulating mast cell activation.
Gilfillan AM, Rivera J.
Immunol Rev. 2009 Mar;228(1):149-69. doi: 10.1111/j.1600-065X.2008.00742.x. (REVIEW)
PMID 19290926
 
Treatment of acute febrile neutrophilic dermatosis (Sweet's Syndrome) with potassium iodide.
Horio T, Imamura S, Danno K, Furukawa F, Ofuji S.
Dermatologica. 1980;160(5):341-7.
PMID 7364144
 
The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells.
Iype T, Sankarshanan M, Mauldin IS, Mullins DW, Lorenz U.
J Immunol. 2010 Nov 15;185(10):6115-27. doi: 10.4049/jimmunol.1000622. Epub 2010 Oct 15.
PMID 20952680
 
The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system.
Lodeiro M, Alen BO, Mosteiro CS, Beiroa D, Nogueiras R, Theodoropoulou M, Pardo M, Gallego R, Pazos Y, Casanueva FF, Camina JP.
Mol Biol Cell. 2011 Nov;22(21):4182-91. doi: 10.1091/mbc.E11-04-0373. Epub 2011 Sep 7.
PMID 21900501
 
SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms.
Nagaishi T, Pao L, Lin SH, Iijima H, Kaser A, Qiao SW, Chen Z, Glickman J, Najjar SM, Nakajima A, Neel BG, Blumberg RS.
Immunity. 2006 Nov;25(5):769-81. Epub 2006 Nov 2.
PMID 17081782
 
Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses.
Nesterovitch AB, Gyorfy Z, Hoffman MD, Moore EC, Elbuluk N, Tryniszewska B, Rauch TA, Simon M, Kang S, Fisher GJ, Mikecz K, Tharp MD, Glant TT.
Am J Pathol. 2011 Apr;178(4):1434-41. doi: 10.1016/j.ajpath.2010.12.035. Epub 2011 Mar 4.
PMID 21406173
 
CEACAM1: a key regulator of vascular permeability.
Nouvion AL, Oubaha M, Leblanc S, Davis EC, Jastrow H, Kammerer R, Breton V, Turbide C, Ergun S, Gratton JP, Beauchemin N.
J Cell Sci. 2010 Dec 15;123(Pt 24):4221-30. doi: 10.1242/jcs.073635. Epub 2010 Nov 16.
PMID 21081647
 
Treatment of pyoderma gangrenosum with infliximab in Crohn's disease.
Sapienza MS, Cohen S, Dimarino AJ.
Dig Dis Sci. 2004 Sep;49(9):1454-7.
PMID 15481318
 
Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene.
Tsui HW, Siminovitch KA, de Souza L, Tsui FW.
Nat Genet. 1993 Jun;4(2):124-9.
PMID 8348149
 
PU.1 activates transcription of SHP-1 gene in hematopoietic cells.
Wlodarski P, Zhang Q, Liu X, Kasprzycka M, Marzec M, Wasik MA.
J Biol Chem. 2007 Mar 2;282(9):6316-23. Epub 2007 Jan 11.
PMID 17218319
 
The function of the protein tyrosine phosphatase SHP-1 in cancer.
Wu C, Sun M, Liu L, Zhou GW.
Gene. 2003 Mar 13;306:1-12. (REVIEW)
PMID 12657462
 
Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease.
Xiao W, Ando T, Wang HY, Kawakami Y, Kawakami T.
Blood. 2010 Dec 23;116(26):6003-13. doi: 10.1182/blood-2010-05-283937. Epub 2010 Sep 21.
PMID 20858858
 
Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1.
Yang J, Liang X, Niu T, Meng W, Zhao Z, Zhou GW.
J Biol Chem. 1998 Oct 23;273(43):28199-207.
PMID 9774441
 
Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13.
Yi TL, Cleveland JL, Ihle JN.
Mol Cell Biol. 1992 Feb;12(2):836-46.
PMID 1732748
 
Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signalling.
Zhang J, Somani AK, Siminovitch KA.
Semin Immunol. 2000 Aug;12(4):361-78. (REVIEW)
PMID 10995583
 

Citation

This paper should be referenced as such :
Beghini, A ; Lazzaroni, F
PTPN6 (protein tyrosine phosphatase, non-receptor type 6)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(5):327-332.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PTPN6ID41920ch12p13.html


External links

Nomenclature
HGNC (Hugo)PTPN6   9658
Cards
AtlasPTPN6ID41920ch12p13
Entrez_Gene (NCBI)PTPN6  5777  protein tyrosine phosphatase, non-receptor type 6
AliasesHCP; HCPH; HPTP1C; PTP-1C; 
SH-PTP1; SHP-1; SHP-1L; SHP1
GeneCards (Weizmann)PTPN6
Ensembl hg19 (Hinxton)ENSG00000111679 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000111679 [Gene_View]  chr12:6951271-6961316 [Contig_View]  PTPN6 [Vega]
ICGC DataPortalENSG00000111679
TCGA cBioPortalPTPN6
AceView (NCBI)PTPN6
Genatlas (Paris)PTPN6
WikiGenes5777
SOURCE (Princeton)PTPN6
Genetics Home Reference (NIH)PTPN6
Genomic and cartography
GoldenPath hg38 (UCSC)PTPN6  -     chr12:6951271-6961316 +  12p13.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PTPN6  -     12p13.31   [Description]    (hg19-Feb_2009)
EnsemblPTPN6 - 12p13.31 [CytoView hg19]  PTPN6 - 12p13.31 [CytoView hg38]
Mapping of homologs : NCBIPTPN6 [Mapview hg19]  PTPN6 [Mapview hg38]
OMIM176883   
Gene and transcription
Genbank (Entrez)AF178946 AK223629 AK290421 AK298470 AK300167
RefSeq transcript (Entrez)NM_002831 NM_080548 NM_080549
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PTPN6
Cluster EST : UnigeneHs.63489 [ NCBI ]
CGAP (NCI)Hs.63489
Alternative Splicing GalleryENSG00000111679
Gene ExpressionPTPN6 [ NCBI-GEO ]   PTPN6 [ EBI - ARRAY_EXPRESS ]   PTPN6 [ SEEK ]   PTPN6 [ MEM ]
Gene Expression Viewer (FireBrowse)PTPN6 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5777
GTEX Portal (Tissue expression)PTPN6
Human Protein AtlasENSG00000111679-PTPN6 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP29350   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP29350  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP29350
Splice isoforms : SwissVarP29350
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 ]   
PhosPhoSitePlusP29350
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_cat    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)  PTPc_motif (SM00404)  SH2 (SM00252)  
Conserved Domain (NCBI)PTPN6
DMDM Disease mutations5777
Blocks (Seattle)PTPN6
PDB (SRS)1FPR    1GWZ    1X6C    2B3O    2RMX    2YU7    3PS5    4GRY    4GRZ    4GS0    4HJP    4HJQ   
PDB (PDBSum)1FPR    1GWZ    1X6C    2B3O    2RMX    2YU7    3PS5    4GRY    4GRZ    4GS0    4HJP    4HJQ   
PDB (IMB)1FPR    1GWZ    1X6C    2B3O    2RMX    2YU7    3PS5    4GRY    4GRZ    4GS0    4HJP    4HJQ   
PDB (RSDB)1FPR    1GWZ    1X6C    2B3O    2RMX    2YU7    3PS5    4GRY    4GRZ    4GS0    4HJP    4HJQ   
Structural Biology KnowledgeBase1FPR    1GWZ    1X6C    2B3O    2RMX    2YU7    3PS5    4GRY    4GRZ    4GS0    4HJP    4HJQ   
SCOP (Structural Classification of Proteins)1FPR    1GWZ    1X6C    2B3O    2RMX    2YU7    3PS5    4GRY    4GRZ    4GS0    4HJP    4HJQ   
CATH (Classification of proteins structures)1FPR    1GWZ    1X6C    2B3O    2RMX    2YU7    3PS5    4GRY    4GRZ    4GS0    4HJP    4HJQ   
SuperfamilyP29350
Human Protein Atlas [tissue]ENSG00000111679-PTPN6 [tissue]
Peptide AtlasP29350
HPRD01475
IPIIPI00218604   IPI00396552   IPI00183046   IPI00941721   IPI01010823   IPI01010249   IPI01009534   IPI01009928   IPI01014929   IPI01014461   IPI01013987   IPI01013529   
Protein Interaction databases
DIP (DOE-UCLA)P29350
IntAct (EBI)P29350
FunCoupENSG00000111679
BioGRIDPTPN6
STRING (EMBL)PTPN6
ZODIACPTPN6
Ontologies - Pathways
QuickGOP29350
Ontology : AmiGOphosphotyrosine binding  hematopoietic progenitor cell differentiation  negative regulation of humoral immune response mediated by circulating immunoglobulin  protein tyrosine phosphatase activity  transmembrane receptor protein tyrosine phosphatase activity  protein binding  extracellular region  nucleus  nucleolus  cytoplasm  cytosol  cell-cell junction  protein dephosphorylation  apoptotic process  G-protein coupled receptor signaling pathway  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  positive regulation of phosphatidylinositol 3-kinase signaling  membrane  SH3 domain binding  peptidyl-tyrosine phosphorylation  protein kinase binding  cell differentiation  platelet activation  platelet formation  T cell costimulation  abortive mitotic cell cycle  positive regulation of cell adhesion mediated by integrin  peptidyl-tyrosine dephosphorylation  intracellular signal transduction  specific granule lumen  megakaryocyte development  alpha-beta T cell receptor complex  negative regulation of T cell proliferation  SH2 domain binding  natural killer cell mediated cytotoxicity  neutrophil degranulation  negative regulation of MAP kinase activity  regulation of B cell differentiation  negative regulation of peptidyl-tyrosine phosphorylation  cell adhesion molecule binding  B cell receptor signaling pathway  negative regulation of B cell receptor signaling pathway  negative regulation of T cell receptor signaling pathway  leukocyte migration  regulation of release of sequestered calcium ion into cytosol  regulation of type I interferon-mediated signaling pathway  extracellular exosome  regulation of ERK1 and ERK2 cascade  platelet aggregation  tertiary granule lumen  regulation of G1/S transition of mitotic cell cycle  
Ontology : EGO-EBIphosphotyrosine binding  hematopoietic progenitor cell differentiation  negative regulation of humoral immune response mediated by circulating immunoglobulin  protein tyrosine phosphatase activity  transmembrane receptor protein tyrosine phosphatase activity  protein binding  extracellular region  nucleus  nucleolus  cytoplasm  cytosol  cell-cell junction  protein dephosphorylation  apoptotic process  G-protein coupled receptor signaling pathway  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  positive regulation of phosphatidylinositol 3-kinase signaling  membrane  SH3 domain binding  peptidyl-tyrosine phosphorylation  protein kinase binding  cell differentiation  platelet activation  platelet formation  T cell costimulation  abortive mitotic cell cycle  positive regulation of cell adhesion mediated by integrin  peptidyl-tyrosine dephosphorylation  intracellular signal transduction  specific granule lumen  megakaryocyte development  alpha-beta T cell receptor complex  negative regulation of T cell proliferation  SH2 domain binding  natural killer cell mediated cytotoxicity  neutrophil degranulation  negative regulation of MAP kinase activity  regulation of B cell differentiation  negative regulation of peptidyl-tyrosine phosphorylation  cell adhesion molecule binding  B cell receptor signaling pathway  negative regulation of B cell receptor signaling pathway  negative regulation of T cell receptor signaling pathway  leukocyte migration  regulation of release of sequestered calcium ion into cytosol  regulation of type I interferon-mediated signaling pathway  extracellular exosome  regulation of ERK1 and ERK2 cascade  platelet aggregation  tertiary granule lumen  regulation of G1/S transition of mitotic cell cycle  
Pathways : BIOCARTAEPO Signaling Pathway [Genes]    Growth Hormone Signaling Pathway [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    IL 3 signaling pathway [Genes]    Ras-Independent pathway in NK cell-mediated cytotoxicity [Genes]   
Pathways : KEGGAdherens junction    Jak-STAT signaling pathway    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    B cell receptor signaling pathway    Leishmaniasis    Proteoglycans in cancer   
REACTOMEP29350 [protein]
REACTOME PathwaysR-HSA-983695 [pathway]   
NDEx NetworkPTPN6
Atlas of Cancer Signalling NetworkPTPN6
Wikipedia pathwaysPTPN6
Orthology - Evolution
OrthoDB5777
GeneTree (enSembl)ENSG00000111679
Phylogenetic Trees/Animal Genes : TreeFamPTPN6
HOVERGENP29350
HOGENOMP29350
Homologs : HomoloGenePTPN6
Homology/Alignments : Family Browser (UCSC)PTPN6
Gene fusions - Rearrangements
Fusion : MitelmanPTPN6/P3H3 [12p13.31/12p13.31]  
Fusion: TCGAPTPN6 12p13.31 LEPREL2 BLCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPTPN6 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PTPN6
dbVarPTPN6
ClinVarPTPN6
1000_GenomesPTPN6 
Exome Variant ServerPTPN6
ExAC (Exome Aggregation Consortium)ENSG00000111679
GNOMAD BrowserENSG00000111679
Genetic variants : HAPMAP5777
Genomic Variants (DGV)PTPN6 [DGVbeta]
DECIPHERPTPN6 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPTPN6 
Mutations
ICGC Data PortalPTPN6 
TCGA Data PortalPTPN6 
Broad Tumor PortalPTPN6
OASIS PortalPTPN6 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPTPN6  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPTPN6
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 PTPN6
DgiDB (Drug Gene Interaction Database)PTPN6
DoCM (Curated mutations)PTPN6 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PTPN6 (select a term)
intoGenPTPN6
NCG5 (London)PTPN6
Cancer3DPTPN6(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM176883   
Orphanet
MedgenPTPN6
Genetic Testing Registry PTPN6
NextProtP29350 [Medical]
TSGene5777
GENETestsPTPN6
Target ValidationPTPN6
Huge Navigator PTPN6 [HugePedia]
snp3D : Map Gene to Disease5777
BioCentury BCIQPTPN6
ClinGenPTPN6
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5777
Chemical/Pharm GKB GenePA34002
Clinical trialPTPN6
Miscellaneous
canSAR (ICR)PTPN6 (select the gene name)
Probes
Litterature
PubMed338 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePTPN6
EVEXPTPN6
GoPubMedPTPN6
iHOPPTPN6
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:31:34 CEST 2017

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