Atlas of Genetics and Cytogenetics in Oncology and Haematology


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PTPN1 (protein tyrosine phosphatase, non-receptor type 1)

Identity

Other namesPTP1B
HGNC (Hugo) PTPN1
LocusID (NCBI) 5770
Location 20q13.13
Location_base_pair Starts at 49126858 and ends at 49201300 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order According to NCBI Map Viewer, PTPN1 gene is located between: LOC284751, COX6CP2 (cytochrome c oxidase subunit VIc pseudogene 2) (in centromeric position), MIR645 (microRNA 645) and FAM65c (family with sequence similarity 65, member c) (in telomeric position).

DNA/RNA

Note PTPN1 is located at 49126891-49201299 bp; chromosome 20, strand +, Unigene cluster Hs.417549, Entrez gene Id 57570.
The gene is located in a genomic region that has been identified in multiple linkage studies as a QTL for obesity and diabetes (Ghosh et al., 1999; Soro et al., 2002).
Description In humans, PTPN1, the gene coding for PTP-1B, is located on human chromosome 20q13. The 10 exons of the gene span more than 74 kb of genomic DNA, in the centromere-to-telomere orientation. The promoter region of PTPN1 gene contains no TATA box, but multiple GC rich sequences in which a number of consensus SP-1 binding sites are present (Forsell et al., 2000).
Transcription The open reading frame includes 1305 bp and codes for a protein of 435 amino acids (Olivier et al., 2004).
According to Ensembl, PTPN1 gene has two alternative transcripts:
- PTPN1-001: 10 exons, 3529 bp mRNA, 435 amino acids;
- PTPN1-201: 9 exons, 1634 bp mRNA, 362 amino acids.
(Ensembl database: Ensembl Reference Sequence: ENST00000371621 (PTPN1-001), ENST00000541713 (PTPN1-201)).
Pseudogene No human pseudogene for PTPN1 has been identified.

Protein

Description Size: 435 amino acids; 49967 Da.
Expression PTP1B is expressed abundantly.
Localisation Endoplasmic reticulum membrane; peripheral membrane protein; cytoplasmic side.
Function Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily; IUBMB enzyme nomenclature: EC 3.1.3.48.
PTP1B (P18031 in UniProtKB) has an N-terminal catalytic phosphatase domain (residues 1-300) followed by a regulatory region of about 80-100 residues and a membrane localization domain (residues 400-435) that tethers the enzyme to the cytoplasmic face of the endoplasmic reticulum (ER). The enzymatic activity is tightly controlled by means of four described mechanisms: oxidation, phosphorylation, SUMOylation, and proteolysis. PTP1B activity is regulated in vivo by reversible oxidation involving Cys 215 at its active site and SUMOylation at two lysines (i.e., 335 and 347). Serine or tyrosine phosphorylation can affect protein interactions (Yip et al., 2010).

Mutations

Note The 1484insG variation (OMIM variation (176885.0001)) (Meshkani et al., 2007), the single-nucleotide polymorphism (SNP) 981CT (Mok et al., 2002), VS6+G82A polymorphism, G82G, Pro387Leu variant (Ukkola et al., 2005).

Implicated in

Entity Various diseases and cancers
Note PTP1B is involved in direct/enzymatic or indirect interactions with several proteins. In the figure, the PTPN1/PTP1B human interactome is drawn. Each protein is depicted as circle whose color refers to the human pathology where the interaction with PTP1B is found misregulated. The numbers refer to the PMID of the articles supporting the interaction data.
 
The PTP1B human interactome. Interactions are categorized according to OLS (The Ontology Lookup Service) and according to evidence collected in the major PPI databases (Protein-Protein Interaction Databases). Interactions indicated with dashed lines are enzymatic reaction. Interactions indicated with continuous lines are interactions related to methodologies like: two hybrid, protein complementation assay, affinity chromatography technology and similar methodologies that imply a physical interaction. According to Mentha - the Interactome browser.
Oncogenesis PTP1B as a putative tumor suppressor.
Several evidences support the notion that PTP1B is a negative regulator of cell growth, although loss of function mutations and gene silencing have not been found in human cancer. PTP1B dephosphorylates and inactivates a number of receptor protein tyrosine kinases, including the EGF (epidermal growth factor) and PDGF (platelet-derived growth factor) receptors and therefore can exert a suppressive action on growth factor cell signaling (Haj et al., 2002). Ferrari et al. have used HEK293 human embryonic kidney cell line, stimulated with a high EGF concentration and observed that overexpression of PTP1B reduces EGF-dependent ERK activation, by dephosphorylating phospho-tyrosines of the scaffold protein GAB1. These phospho-tyrosines are the docking sites of the ERK activator SHP2 phosphatase. On the contrary, inhibition of the PTP1B enzymatic activity has an opposite effect, allowing SHP2 to localize on GAB1 and exert its positive role on RAS/ERK signaling (Ferrari et al., 2010).
In 2006, Akasaki et al. proposed a molecular mechanism to explain the involvement of PTP1B in the proapoptotic effect caused by troglitazone, an anti-diabetic drug, now withdrawn by Food and Drug Administration that could represent a promising drug for adjuvant therapy of glioma and other highly migratory tumors. The troglitazone is a pharmacological agonist of the peroxisome proliferator-activated receptor-gamma (PPARgamma), that acts, in synergy with apoptosis inducing agents, to facilitate caspase signaling, in human glioma cells. Troglitazone activates PTP1B, which subsequently reduces phosphotyrosine 705 in the prosurvival protein STAT3. Reduction of pY705-STAT3 in glioma cells causes down-regulation of anti-apoptotic proteins FLIP (FLICE-inhibitory protein) and Bcl-2 (Akasaki et al., 2006; Coras et al., 2007; Lund et al., 2005).
PTP1B can also contribute to cell-cell association since it is bound to the cytoplasmic domain of N-cadherin and it is responsible for dephosphorylating phospho-tyrosine residues belonging to beta-catenin, thus maintaining the cadherin-actin connection and cell adhesion (Balsamo et al., 1998). Moreover, PTP1B is required for the trafficking of the N-cadherin precursor from the endoplasmic reticulum to the Golgi apparatus, because, by dephosphorylating the p120 catenin, it promotes the binding between N-cadherin precursor and p120 catenin, an interaction required for a correct anterograde movement (Hernández et al., 2010).
  
Entity Autoimmunity and B-cell lymphomas
Note Lu et al. have reported a novel negative feedback loop involving the anti-tumor IL-4/Jak/STAT6 signaling and the phosphatase PTP1B, in a type of aggressive non-Hodgkin lymphoma, the activated B-cell-like diffuse large B-cell lymphomas (ABC-DLBCL). In this lymphoma, STAT6 is dephosphorylated in the nucleus and in the cytoplasm and the authors have demonstrated, by immunohistochemical analysis of 371 cases of hematolymphoid malignancies, that PTP1B is more commonly expressed in the ABC-like DLBCL. Since ABC-like DLBCL express also higher levels of TCPTP (an ubiquitous tyrosine-specific phosphatase in which the catalytic domain has 72% identity to that of PTP1B), compared with other lymphomas (GCB-like DLBCL), the authors suggested that both the phosphatases PTP1B and TCPTP regulate STAT6 signaling, by dephosphorylating STAT6 in the cytoplasm and in the nucleus, respectively. This result identifies an important regulatory loop in neoplasia, where IL-4 induces PTP1B, which suppresses IL-4 induced STAT6 signaling, and suggests that augmentation of PTP1B expression may render tumor cells insensitive to the anti-tumor effect of the IL-4/Jak/STAT6 pathway (Lu et al., 2008).
  
Entity Breast cancer
Note PTP1b as a tumor promoter.
In clinical samples, it has been long noted that PTP1B expression increases in several human breast and ovarian cancers (Wiener et al., 1994b).
Recently, several studies have pointed out a positive role of PTP1B in oncogenic properties of breast cancer cells as well as in the sensitization or resistance of cancer cells to apoptosis induced by cytotoxic compounds. PTP1B positively regulates ErbB2-induced tumorigenesis at the level of the Ras/MAP Kinase, probably by dephosphorylating p62Dok on Tyr398, thus blocking its association with the Ras GTPase-activating protein p120 RasGAP, the Ras inhibitor (Dubé et al., 2004; Mertins et al., 2008).
PTP1B is also described as a positive regulator of human breast adenocarcinoma (MCF-7) cell line proliferation. Also in this case, PTP1B exerts a positive effect on ERK phosphorylation by a mechanism independent of the regulation of RasGAP, of the phosphorylation state of p62Dok Tyr398 or of the phosphorylation of STAT3 on Tyr705. In fact, in MCF-7 cells resistant to tamoxifen, PTP1B and the highly similar TC-PTP phosphatase are overexpressed, while ERK and STAT3 are hyperphosphorylated. This result indicates PTP1B as a new target for the treatment of tamoxifen-resistant breast cancers (Blanquart et al., 2009).
PTP1B is shown to be required for ErbB2-mediated transformation of MCF-10A human breast epithelial cells and its overexpression alters acinar morphogenesis via activation of Src. MCF-10A cells are immortalized, nontransformed cells derived from a reduction mammoplasty, which form organized acini when grown within three-dimensional matrices such as reconstituted basement membrane. In this model, transformation causes characteristic changes in acinar morphogenesis, proliferation, and luminal apoptosis, that resemble those seen in human ductal carcinoma of the breast. In MCF-10A, PTP1B expression is increased by ErbB2 and PTP1B activates the tyrosine kinase Src by dephosphorylation of its repressing tyrosine 527 (Arias-Romero et al., 2009). This result is in accordance with previous studies that analyzed frozen sections from 29 human mammary tumors and demonstrated a significant association between PTP1B overexpression and breast cancer (P < 0,038) and between the overexpression of PTP1B and the overexpression of ErbB-2 (P < 0,006) (Wiener et al., 1994b). An analogous study found a correlation between increased PTP1B overexpression, statistically associated with human ovarian carcinoma, and the expression of ErbB-2, EGFR, and CSFR growth factor receptor protein tyrosine kinases (Wiener et al., 1994a).
  
Entity Susceptibility to insulin resistance and metabolic syndrome
Note Protein tyrosine phosphatase PTP1B negatively regulates insulin and leptin signaling. Therefore, it is considered a promising drug target for enhancing insulin sensitivity in type 2 diabetes and controlling body mass in obesity. PTP1B, in fact, dephosphorylates activating phospho-tyrosines present on the Insulin receptor molecule (INSR; OMIM 147670) in hepatocytes and myocytes, thus inhibiting insulin signaling (Ng, 2011). The activation segment within the insulin receptor contains three sites of autophosphorylation, pTyr-1158, pTyr-1162, and pTyr-1163. PTP1B exhibited a striking affinity preference for the bis- and the tris-phosphorylated peptides, with KMs of 14 and 8 μM, respectively, compared to the mono-phosphorylated peptides, where the KMs were above 100 μM, but PTP1B preferentially dephosphorylates pTyr-1162 within the tris-phosphorylated segment (Salmeen et al., 2000). When PTP1B is overexpressed, it plays a role in insulin resistance (Ahmad et al., 1997; Salmeen et al., 2000). Di Paola et al. have identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that is associated with several features of insulin resistance and metabolic syndrome. The 1484insG allele causes PTP1B overexpression, probably by increasing PTP1B mRNA stability (Di Paola et al., 2002).
Mok et al. identified a single-nucleotide polymorphism in exon 8, designated 981CT, that could be associated with a reduced risk of diabetes since subjects with the PTP1B 981T/981C were 40% less likely to present an impaired glucose tolerance or type II diabetes (Mok et al., 2002). The PTPN1 Pro387Leu missense variant was associated with lower glucose tolerance and with a 3.7-fold increased risk of type 2 diabetes (Ukkola et al., 2005). PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. The G82A heterozygotes are potentially at higher risk for type 2 diabetes (Ukkola et al., 2005).
Obesity research is aiming at understanding and targeting the neural signaling pathways that control energy balance. The adipocyte-secreted hormone leptin acts in the brain to decrease appetite and increase energy expenditure via the simultaneous suppression of hypothalamic neurones that synthesize agouti-related protein (AgRP) and the stimulation of neurone producing proopiomelanocortin (POMC). Unfortunately, leptin cannot be used to control obesity due to the development of a resistance to leptin. PTP1B has thus became an interesting target because of its negative regulatory role on leptin signaling, mediated through a direct and selective dephosphorylation of the two main signaling molecules downstream of the activated leptin receptor, JAK2 and STAT3 (Lund et al., 2005). Moreover, interactions between the gene variants of PTPN1 and leptin receptor have been shown to contribute to the phenotypic variability of insulin sensitivity (Ukkola et al., 2005).
A recent study conducted on a sample of families with two or more members with type 2 diabetes, has revealed an association of common PTPN1 SNPs and haplotypes with coronary artery calcification (CorCP), which is a surrogate measure of atherosclerosis and subclinical cardiovascular disease. The authors observed that PTPN1 haplotype GACTTCAGO, associated with type 2 diabetes, was also significantly associated with increased CorCP (Burdon et al., 2006). The Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort study has investigated the possible role of common genetic variations in PTPN1 on the development of hypertension, hyperlipidemia and obesity. The study has analyzed common (> 2%) sequence variation of PTPN1 in Japanese and Chinese descent, in order to study the association of individual SNPs and resulting haplotypes with quantitative phenotypes characteristic of the metabolic syndrome (Olivier et al., 2004). Because of the regulating properties of PTP1B, efforts are made to produce small molecules able to target the active site of the phosphatase in order to treat diabetes. Recently Haque et al. have isolated a single chain variable fragment antibody that stabilizes the inactive form of PTP1B thereby inhibiting its catalytic activity. This small molecule could inspire development of inhibitors that stabilize the inactive conformation of PTP1B (Haque et al., 2011).
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615

External links

Nomenclature
HGNC (Hugo)PTPN1   9642
Cards
AtlasPTPN1ID41909ch20q13
Entrez_Gene (NCBI)PTPN1  5770  protein tyrosine phosphatase, non-receptor type 1
GeneCards (Weizmann)PTPN1
Ensembl (Hinxton)ENSG00000196396 [Gene_View]  chr20:49126858-49201300 [Contig_View]  PTPN1 [Vega]
ICGC DataPortalENSG00000196396
cBioPortalPTPN1
AceView (NCBI)PTPN1
Genatlas (Paris)PTPN1
WikiGenes5770
SOURCE (Princeton)NM_001278618 NM_002827
Genomic and cartography
GoldenPath (UCSC)PTPN1  -  20q13.13   chr20:49126858-49201300 +  20q13.1-q13.2   [Description]    (hg19-Feb_2009)
EnsemblPTPN1 - 20q13.1-q13.2 [CytoView]
Mapping of homologs : NCBIPTPN1 [Mapview]
OMIM125853   176885   
Gene and transcription
Genbank (Entrez)AI474453 AK290638 AK299830 AK316563 AU117677
RefSeq transcript (Entrez)NM_001278618 NM_002827
RefSeq genomic (Entrez)AC_000152 NC_000020 NC_018931 NG_012119 NT_011362 NW_001838666 NW_004929418
Consensus coding sequences : CCDS (NCBI)PTPN1
Cluster EST : UnigeneHs.417549 [ NCBI ]
CGAP (NCI)Hs.417549
Alternative Splicing : Fast-db (Paris)GSHG0018831
Alternative Splicing GalleryENSG00000196396
Gene ExpressionPTPN1 [ NCBI-GEO ]     PTPN1 [ SEEK ]   PTPN1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP18031 (Uniprot)
NextProtP18031  [Medical]
With graphics : InterProP18031
Splice isoforms : SwissVarP18031 (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 ]   
Domaine pattern : Prosite (Expaxy)TYR_PHOSPHATASE_1 (PS00383)    TYR_PHOSPHATASE_2 (PS50056)    TYR_PHOSPHATASE_PTP (PS50055)   
Domains : Interpro (EBI)Prot-tyrosine_phosphatase-like [organisation]   Ptpn1/Ptpn2 [organisation]   Tyr/Dual-sp_Pase [organisation]   Tyr_Pase_AS [organisation]   Tyr_Pase_rcpt/non-rcpt [organisation]  
Related proteins : CluSTrP18031
Domain families : Pfam (Sanger)Y_phosphatase (PF00102)   
Domain families : Pfam (NCBI)pfam00102   
Domain families : Smart (EMBL)PTPc (SM00194)  
DMDM Disease mutations5770
Blocks (Seattle)P18031
PDB (SRS)1A5Y    1AAX    1BZC    1BZH    1BZJ    1C83    1C84    1C85    1C86    1C87    1C88    1ECV    1EEN    1EEO    1G1F    1G1G    1G1H    1G7F    1G7G    1GFY    1I57    1JF7    1KAK    1KAV    1L8G    1LQF    1NL9    1NNY    1NO6    1NWE    1NWL    1NZ7    1OEM    1OEO    1OES    1OET    1OEU    1OEV    1ONY    1ONZ    1PA1    1PH0    1PTT    1PTU    1PTV    1PTY    1PXH    1PYN    1Q1M    1Q6J    1Q6M    1Q6N    1Q6P    1Q6S    1Q6T    1QXK    1SUG    1T48    1T49    1T4J    1WAX    1XBO    2AZR    2B07    2B4S    2BGD    2BGE    2CM2    2CM3    2CM7    2CM8    2CMA    2CMB    2CMC    2CNE    2CNF    2CNG    2CNH    2CNI    2F6F    2F6T    2F6V    2F6W    2F6Y    2F6Z    2F70    2F71    2FJM    2FJN    2H4G    2H4K    2HB1    2HNP    2HNQ    2NT7    2NTA    2QBP    2QBQ    2QBR    2QBS    2VEU    2VEV    2VEW    2VEX    2VEY    2ZMM    2ZN7    3A5J    3A5K    3CWE    3D9C    3EAX    3EB1    3EU0    3I7Z    3I80    3QKP    3QKQ    3SME    3ZMP    3ZMQ    3ZV2    4BJO    4I8N   
PDB (PDBSum)1A5Y    1AAX    1BZC    1BZH    1BZJ    1C83    1C84    1C85    1C86    1C87    1C88    1ECV    1EEN    1EEO    1G1F    1G1G    1G1H    1G7F    1G7G    1GFY    1I57    1JF7    1KAK    1KAV    1L8G    1LQF    1NL9    1NNY    1NO6    1NWE    1NWL    1NZ7    1OEM    1OEO    1OES    1OET    1OEU    1OEV    1ONY    1ONZ    1PA1    1PH0    1PTT    1PTU    1PTV    1PTY    1PXH    1PYN    1Q1M    1Q6J    1Q6M    1Q6N    1Q6P    1Q6S    1Q6T    1QXK    1SUG    1T48    1T49    1T4J    1WAX    1XBO    2AZR    2B07    2B4S    2BGD    2BGE    2CM2    2CM3    2CM7    2CM8    2CMA    2CMB    2CMC    2CNE    2CNF    2CNG    2CNH    2CNI    2F6F    2F6T    2F6V    2F6W    2F6Y    2F6Z    2F70    2F71    2FJM    2FJN    2H4G    2H4K    2HB1    2HNP    2HNQ    2NT7    2NTA    2QBP    2QBQ    2QBR    2QBS    2VEU    2VEV    2VEW    2VEX    2VEY    2ZMM    2ZN7    3A5J    3A5K    3CWE    3D9C    3EAX    3EB1    3EU0    3I7Z    3I80    3QKP    3QKQ    3SME    3ZMP    3ZMQ    3ZV2    4BJO    4I8N   
PDB (IMB)1A5Y    1AAX    1BZC    1BZH    1BZJ    1C83    1C84    1C85    1C86    1C87    1C88    1ECV    1EEN    1EEO    1G1F    1G1G    1G1H    1G7F    1G7G    1GFY    1I57    1JF7    1KAK    1KAV    1L8G    1LQF    1NL9    1NNY    1NO6    1NWE    1NWL    1NZ7    1OEM    1OEO    1OES    1OET    1OEU    1OEV    1ONY    1ONZ    1PA1    1PH0    1PTT    1PTU    1PTV    1PTY    1PXH    1PYN    1Q1M    1Q6J    1Q6M    1Q6N    1Q6P    1Q6S    1Q6T    1QXK    1SUG    1T48    1T49    1T4J    1WAX    1XBO    2AZR    2B07    2B4S    2BGD    2BGE    2CM2    2CM3    2CM7    2CM8    2CMA    2CMB    2CMC    2CNE    2CNF    2CNG    2CNH    2CNI    2F6F    2F6T    2F6V    2F6W    2F6Y    2F6Z    2F70    2F71    2FJM    2FJN    2H4G    2H4K    2HB1    2HNP    2HNQ    2NT7    2NTA    2QBP    2QBQ    2QBR    2QBS    2VEU    2VEV    2VEW    2VEX    2VEY    2ZMM    2ZN7    3A5J    3A5K    3CWE    3D9C    3EAX    3EB1    3EU0    3I7Z    3I80    3QKP    3QKQ    3SME    3ZMP    3ZMQ    3ZV2    4BJO    4I8N   
PDB (RSDB)1A5Y    1AAX    1BZC    1BZH    1BZJ    1C83    1C84    1C85    1C86    1C87    1C88    1ECV    1EEN    1EEO    1G1F    1G1G    1G1H    1G7F    1G7G    1GFY    1I57    1JF7    1KAK    1KAV    1L8G    1LQF    1NL9    1NNY    1NO6    1NWE    1NWL    1NZ7    1OEM    1OEO    1OES    1OET    1OEU    1OEV    1ONY    1ONZ    1PA1    1PH0    1PTT    1PTU    1PTV    1PTY    1PXH    1PYN    1Q1M    1Q6J    1Q6M    1Q6N    1Q6P    1Q6S    1Q6T    1QXK    1SUG    1T48    1T49    1T4J    1WAX    1XBO    2AZR    2B07    2B4S    2BGD    2BGE    2CM2    2CM3    2CM7    2CM8    2CMA    2CMB    2CMC    2CNE    2CNF    2CNG    2CNH    2CNI    2F6F    2F6T    2F6V    2F6W    2F6Y    2F6Z    2F70    2F71    2FJM    2FJN    2H4G    2H4K    2HB1    2HNP    2HNQ    2NT7    2NTA    2QBP    2QBQ    2QBR    2QBS    2VEU    2VEV    2VEW    2VEX    2VEY    2ZMM    2ZN7    3A5J    3A5K    3CWE    3D9C    3EAX    3EB1    3EU0    3I7Z    3I80    3QKP    3QKQ    3SME    3ZMP    3ZMQ    3ZV2    4BJO    4I8N   
Human Protein AtlasENSG00000196396 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP18031
HPRD01477
IPIIPI00297261   IPI01014223   IPI00816802   
Protein Interaction databases
DIP (DOE-UCLA)P18031
IntAct (EBI)P18031
FunCoupENSG00000196396
BioGRIDPTPN1
InParanoidP18031
Interologous Interaction database P18031
IntegromeDBPTPN1
STRING (EMBL)PTPN1
Ontologies - Pathways
Ontology : AmiGOprotein tyrosine phosphatase activity  protein tyrosine phosphatase activity  insulin receptor binding  protein binding  early endosome  endoplasmic reticulum  endoplasmic reticulum membrane  cytosol  plasma membrane  blood coagulation  zinc ion binding  insulin receptor signaling pathway  regulation of signal transduction  cytokine-mediated signaling pathway  enzyme binding  protein kinase binding  regulation of endocytosis  platelet activation  negative regulation of vascular endothelial growth factor receptor signaling pathway  endoplasmic reticulum unfolded protein response  receptor tyrosine kinase binding  cytoplasmic vesicle  actin cytoskeleton reorganization  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  platelet-derived growth factor receptor-beta signaling pathway  poly(A) RNA binding  negative regulation of insulin receptor signaling pathway  ephrin receptor binding  interferon-gamma-mediated signaling pathway  regulation of interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  regulation of type I interferon-mediated signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  negative regulation of ERK1 and ERK2 cascade  sorting endosome  regulation of hepatocyte growth factor receptor signaling pathway  peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity  
Ontology : EGO-EBIprotein tyrosine phosphatase activity  protein tyrosine phosphatase activity  insulin receptor binding  protein binding  early endosome  endoplasmic reticulum  endoplasmic reticulum membrane  cytosol  plasma membrane  blood coagulation  zinc ion binding  insulin receptor signaling pathway  regulation of signal transduction  cytokine-mediated signaling pathway  enzyme binding  protein kinase binding  regulation of endocytosis  platelet activation  negative regulation of vascular endothelial growth factor receptor signaling pathway  endoplasmic reticulum unfolded protein response  receptor tyrosine kinase binding  cytoplasmic vesicle  actin cytoskeleton reorganization  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  platelet-derived growth factor receptor-beta signaling pathway  poly(A) RNA binding  negative regulation of insulin receptor signaling pathway  ephrin receptor binding  interferon-gamma-mediated signaling pathway  regulation of interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  regulation of type I interferon-mediated signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  negative regulation of ERK1 and ERK2 cascade  sorting endosome  regulation of hepatocyte growth factor receptor signaling pathway  peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity  
Pathways : KEGGAdherens junction    Insulin signaling pathway   
Protein Interaction DatabasePTPN1
Wikipedia pathwaysPTPN1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)PTPN1
snp3D : Map Gene to Disease5770
SNP (GeneSNP Utah)PTPN1
SNP : HGBasePTPN1
Genetic variants : HAPMAPPTPN1
Exome VariantPTPN1
1000_GenomesPTPN1 
ICGC programENSG00000196396 
Somatic Mutations in Cancer : COSMICPTPN1 
CONAN: Copy Number AnalysisPTPN1 
Mutations and Diseases : HGMDPTPN1
Mutations and Diseases : intOGenPTPN1
Genomic VariantsPTPN1  PTPN1 [DGVbeta]
dbVarPTPN1
ClinVarPTPN1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM125853    176885   
MedgenPTPN1
GENETestsPTPN1
Disease Genetic AssociationPTPN1
Huge Navigator PTPN1 [HugePedia]  PTPN1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGenePTPN1
Homology/Alignments : Family Browser (UCSC)PTPN1
Phylogenetic Trees/Animal Genes : TreeFamPTPN1
Chemical/Protein Interactions : CTD5770
Chemical/Pharm GKB GenePA33985
Clinical trialPTPN1
Cancer Resource (Charite)ENSG00000196396
Other databases
Probes
Litterature
PubMed229 Pubmed reference(s) in Entrez
CoreMinePTPN1
iHOPPTPN1
OncoSearchPTPN1

Bibliography

Overexpression of the tyrosine phosphatase PTP1B is associated with human ovarian carcinomas.
Wiener JR, Hurteau JA, Kerns BJ, Whitaker RS, Conaway MR, Berchuck A, Bast RC Jr.
Am J Obstet Gynecol. 1994a Apr;170(4):1177-83.
PMID 8166206
 
Overexpression of the protein tyrosine phosphatase PTP1B in human breast cancer: association with p185c-erbB-2 protein expression.
Wiener JR, Kerns BJ, Harvey EL, Conaway MR, Iglehart JD, Berchuck A, Bast RC Jr.
J Natl Cancer Inst. 1994b Mar 2;86(5):372-8.
PMID 7905928
 
Improved sensitivity to insulin in obese subjects following weight loss is accompanied by reduced protein-tyrosine phosphatases in adipose tissue.
Ahmad F, Considine RV, Bauer TL, Ohannesian JP, Marco CC, Goldstein BJ.
Metabolism. 1997 Oct;46(10):1140-5.
PMID 9322796
 
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Written01-2012Giuseppe Leuzzi, Alberto Calderone, Luisa Castagnoli
Department of Biology, University of Rome Tor Vergata, Rome, Italy

Citation

This paper should be referenced as such :
Leuzzi G, Calderone A, Castagnoli L
PTPN1 (protein tyrosine phosphatase, non-receptor type 1);
Atlas Genet Cytogenet Oncol Haematol. January 2012
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/PTPN1ID41909ch20q13.html

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