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  6. Tyrosine-protein phosphatase non-receptor type 12

Tchem Tyrosine-protein phosphatase non-receptor type 12

Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades (PubMed:18559503). Dephosphorylates cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby regulates signaling via ERBB2 and PTK2B/PYK2 (PubMed:17329398, PubMed:27134172). Selectively dephosphorylates ERBB2 phosphorylated at 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248' (PubMed:27134172).

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a protein-protein interaction domain, and may regulate protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of the oncogene c-ABL and thus may play a role in oncogenesis. This PTP was also shown to interact with, and dephosphorylate, various products related to cytoskeletal structure and cell adhesion, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin. This suggests it has a regulatory role in controlling cell shape and mobility. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

 Comments

Property Summary

NCBI Gene PubMed Count 78
PubMed Score 65.86
PubTator Score 66.77

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (5)

Disease Target Count
Colon Carcinoma 25
Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Pyoderma gangrenosum 9 3.455 1.7
Disease Target Count
Carcinoma of colon 32

Expression

  Differential Expression (19)

Disease log2 FC p
chronic lymphocytic leukemia 2.021 3.7e-05
ependymoma 1.100 2.2e-02
oligodendroglioma 1.300 8.9e-03
psoriasis -1.200 3.3e-04
glioblastoma 2.000 5.6e-03
osteosarcoma 1.567 2.7e-03
medulloblastoma 1.600 3.3e-03
atypical teratoid / rhabdoid tumor 1.700 2.4e-04
medulloblastoma, large-cell 1.200 1.1e-02
primitive neuroectodermal tumor 1.500 6.4e-05
adrenocortical carcinoma 1.027 2.8e-02
primary pancreatic ductal adenocarcinoma 1.352 5.7e-03
lung cancer -1.500 1.3e-02
pancreatic cancer 1.400 2.8e-03
pediatric high grade glioma 1.500 5.6e-03
primary Sjogren syndrome 1.200 3.1e-03
ulcerative colitis 1.100 1.9e-07
ovarian cancer 1.500 1.1e-03
Gaucher disease type 1 -2.100 1.4e-02

Synonym

Accession Q05209 A4D1C5 B4DKY2 E9PBR5 E9PEH9 Q16130 Q59FD6 Q75MN8 Q86XU4
Symbols PTPG1
PTP-PEST

Gene

PTPN12

PANTHER Protein Class (3)

PDB

5J8R  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (14)

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 GO Function (3)

 GO Component (6)

 GO Process (5)

 Compartment GO Term (31)

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 IMPC Phenotype (9)

 MGI Phenotype (8)

 HCA RNA Cell Line (56)

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Pathway (12)

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Protein-protein Interaction (7)

PDGFA   SHC1   NRG1   ERBB4   AIFM1   PSTPIP2   PXN  

Ligand (1)

Structure of CHEMBL2396718

CHEMBL2396718
pIC50 6.10

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
488884 confirmatory 66 / 0 / 17 SAR Selectivity Analysis of small molecule inhibitors of PEST using pCAP in a fluorescence assay

Gene RIF (22)

PMID Text
26537073 PTPN12 expression decreases in human renal cell carcinoma
25868976 Study suggests that PTPN12 expression is a valuable prognostic biomarker for non-small cell lung cancer.
25663493 The decrease expression of PTPN12 might be important in conferring a more aggressive behavior in NPC. Thus, PTPN12 expression may be used as a novel independent prognostic biomarker for patients with NPC.
24475046 Decreased expression of PTPN12 correlates with tumor recurrence and poor survival of patients with hepatocellular carcinoma.
24285539 the activity of SHP-2, PTP-1beta, and PTP-PEST was enhanced by LKB1-expressing cells.
24284071 these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity.
23957009 MRNAs of PTPN12, MSH6, and ZEB1 orthologous genes from different animal species have binding sites for hsa-miR-1279 which consist of homologous oligonucleotides encoding similar human oligopeptides
23733313 Overexpression of PTPN12 inhibited proliferation and migration in OSCC cells.
23435421 The involvement of PTPN12 in the antioxidant response of breast cancer cells suggests that PTPN12 may represent a novel therapeutic target for this disease
23044628 PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.
22644489 This report identifies two additional PTPs, SHP-2 and PTP-PEST, that are also directly activated by the Rb-E2F pathway and which can contribute to signal transduction during p53-independent apoptosis
22458809 Studies indicate that CD45, nonreceptor SH2 domain-containing PTP-1 (SHP-1) and PEST domain-enriched tyrosine phosphatase (PEP) are expressed at elevated levels in immune cells and play essential roles in T cell homeostasis.
22429674 High expression of PTPN12 is associated with favorable disease free survival in esophageal squamous cell carcinoma patients.
21876001 activated Ras induces extracellular signal-regulated kinase 1 and 2-dependent phosphorylation of PTP-PEST at S571, which recruits PIN1 to bind to PTP-PEST
21483099 Suggest PTPN12 and ERK5 mediate HER2-driven cell motility in ovarian cancer cells, through FAK targeting.
21376233 Using a genetic screen, study identifies the PTPN12 tyrosine phosphatase as a tumor suppressor in
20519451 PTP-PEST functions as a suppressor of epithelial cell motility by controlling Rho GTPase activity and the assembly of adherens junctions.
19919952 conclusion: protein phosphatase 1alpha associates with the non-catalytic domain of protein tyrosine phosphatase-PEST (PTP-PEST)and regulates PTP activity via dephosphorylation of phospho-Ser39
17608818 No association was detected between individual PTPN12 tag SNPs and GD but preliminary evidence suggests PTPN12 confers an increased risk of mild/moderate ophthalmopathy (NOSPECS classes 2-4) and that PTPN12 interacts with the TSHR.
17608818 Observational study of gene-disease association. (HuGE Navigator)
17329398 These data demonstrate that LPXN forms a signaling complex with Pyk2, c-Src, and PTP-PEST to regulate migration of prostate cancer cells.
17130234 PTP-PEST actively contributes to the cellular apoptotic response and reveal the importance of caspases as regulators of PTPs in apoptosis.

AA Sequence 

MEQVEILRKFIQRVQAMKSPDHNGEDNFARDFMRLRRLSTKYRTEKIYPTATGEKEENVKKNRYKDILPF      1 - 70
DHSRVKLTLKTPSQDSDYINANFIKGVYGPKAYVATQGPLANTVIDFWRMIWEYNVVIIVMACREFEMGR     71 - 140
KKCERYWPLYGEDPITFAPFKISCEDEQARTDYFIRTLLLEFQNESRRLYQFHYVNWPDHDVPSSFDSIL    141 - 210
DMISLMRKYQEHEDVPICIHCSAGCGRTGAICAIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTK    211 - 280
EQYELVHRAIAQLFEKQLQLYEIHGAQKIADGVNEINTENMVSSIEPEKQDSPPPKPPRTRSCLVEGDAK    281 - 350
EEILQPPEPHPVPPILTPSPPSAFPTVTTVWQDNDRYHPKPVLHMVSSEQHSADLNRNYSKSTELPGKNE    351 - 420
STIEQIDKKLERNLSFEIKKVPLQEGPKSFDGNTLLNRGHAIKIKSASPCIADKISKPQELSSDLNVGDT    421 - 490
SQNSCVDCSVTQSNKVSVTPPEESQNSDTPPRPDRLPLDEKGHVTWSFHGPENAIPIPDLSEGNSSDINY    491 - 560
QTRKTVSLTPSPTTQVETPDLVDHDNTSPLFRTPLSFTNPLHSDDSDSDERNSDGAVTQNKTNISTASAT    561 - 630
VSAATSTESISTRKVLPMSIARHNIAGTTHSGAEKDVDVSEDSPPPLPERTPESFVLASEHNTPVRSEWS    631 - 700
ELQSQERSEQKKSEGLITSENEKCDHPAGGIHYEMCIECPPTFSDKREQISENPTEATDIGFGNRCGKPK    701 - 770
GPRDPPSEWT                                                                771 - 780
//

Text Mined References (91)

PMID Year Title
27134172 2016 Crystal Structure and Substrate Specificity of PTPN12.
26537073 Protein tyrosine phosphatase nonreceptor type 12 suppresses the proliferation of renal cell carcinoma by inhibiting the activity of the PI3K/mTOR pathway.
25868976 2015 Tyrosine-protein phosphatase non-receptor type 12 expression is a good prognostic factor in resectable non-small cell lung cancer.
25663493 2015 The prognostic significance of tyrosine-protein phosphatase nonreceptor type 12 expression in nasopharyngeal carcinoma.
24658140 2014 The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
24475046 2014 Decreased expression of PTPN12 correlates with tumor recurrence and poor survival of patients with hepatocellular carcinoma.
24412244 2014 Charting the molecular links between driver and susceptibility genes in colorectal cancer.
24285539 2014 Liver kinase B1 expression promotes phosphatase activity and abrogation of receptor tyrosine kinase phosphorylation in human cancer cells.
24284071 2014 PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24189400 2013 Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.
23957009 2013 miR-1279, miR-548j, miR-548m, and miR-548d-5p binding sites in CDSs of paralogous and orthologous PTPN12, MSH6, and ZEB1 Genes.
23733313 2013 PTPN12 inhibits oral squamous epithelial carcinoma cell proliferation and invasion and can be used as a prognostic marker.
23435421 2014 PTPN12 promotes resistance to oxidative stress and supports tumorigenesis by regulating FOXO signaling.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23044628 2012 Clinicopathological significance of PTPN12 expression in human breast cancer.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22644489 2012 SHP-2 and PTP-pest induction during Rb-E2F associated apoptosis.
22458809 2013 Regulating naïve and memory CD8 T cell homeostasis--a role for protein tyrosine phosphatases.
22429674 2012 Tyrosine-protein phosphatase nonreceptor type 12 is a novel prognostic biomarker for esophageal squamous cell carcinoma.
22223895 2012 Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-?-acetylation features.
21876001 2011 Ras-induced and extracellular signal-regulated kinase 1 and 2 phosphorylation-dependent isomerization of protein tyrosine phosphatase (PTP)-PEST by PIN1 promotes FAK dephosphorylation by PTP-PEST.
21483099 2011 Tyrosine phosphatases in the HER2-directed motility of ovarian cancer cells: Involvement of PTPN12, ERK5 and FAK.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21376233 2011 Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase.
21269460 2011 Initial characterization of the human central proteome.
20519451 2010 PTP-PEST controls motility, adherens junction assembly, and Rho GTPase activity in colon cancer cells.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20029029 2009 Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6.
19919952 2010 Protein phosphatase 1alpha associates with protein tyrosine phosphatase-PEST inducing dephosphorylation of phospho-serine 39.
19380743 2009 Charting the molecular network of the drug target Bcr-Abl.
19167335 2009 Large-scale structural analysis of the classical human protein tyrosine phosphatome.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18559503 2008 ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity.
18220336 2008 Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.
18088087 2008 Phosphoproteome of resting human platelets.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17608818 2007 Preliminary evidence for interaction of PTPN12 polymorphism with TSHR genotype and association with Graves' ophthalmopathy.
17329398 2007 Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells.
17130234 2007 Caspase-3 regulates catalytic activity and scaffolding functions of the protein tyrosine phosphatase PEST, a novel modulator of the apoptotic response.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
17046825 2006 Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
15831474 2005 Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases.
15588985 2005 Substrate-trapping techniques in the identification of cellular PTP targets.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15231748 2004 Functional proteomics mapping of a human signaling pathway.
15146197 2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.
15122254 2004 Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy.
14707117 2004 Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12853948 2003 The DNA sequence of human chromosome 7.
12714323 2003 Nitric oxide-induced inhibition of aortic smooth muscle cell motility: role of PTP-PEST and adaptor proteins p130cas and Crk.
12690205 2003 Human chromosome 7: DNA sequence and biology.
12674328 2003 Leupaxin is a critical adaptor protein in the adhesion zone of the osteoclast.
12665801 2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.
12614164 2003 Identification of protein tyrosine phosphatases associating with the PDGF receptor.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12052829 2002 Serine/threonine phosphorylation of ShcA. Regulation of protein-tyrosine phosphatase-pest binding and involvement in insulin signaling.
11971877 2002 Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder.
11950600 2002 Roles for the tubulin- and PTP-PEST-binding paxillin LIM domains in cell adhesion and motility.
11731619 2001 The protein tyrosine phosphatase-PEST is implicated in the negative regulation of epidermal growth factor on PRL signaling in mammary epithelial cells.
11711533 2002 PSTPIP is a substrate of PTP-PEST and serves as a scaffold guiding PTP-PEST toward a specific dephosphorylation of WASP.
11432829 2001 PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates.
11337490 2001 Inhibition of the catalytic activity of cell adhesion kinase beta by protein-tyrosine phosphatase-PEST-mediated dephosphorylation.
11314030 2001 Activation of the focal adhesion kinase signaling pathway by structural alterations in the carboxyl-terminal region of c-Crk II.
11163214 2000 Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation.
11158295 2001 SH2 domain-mediated interaction of inhibitory protein tyrosine kinase Csk with protein tyrosine phosphatase-HSCF.
10940933 2000 Subcellular localization of intracellular protein tyrosine phosphatases in T cells.
10625692 2000 The noncatalytic domain of protein-tyrosine phosphatase-PEST targets paxillin for dephosphorylation in vivo.
10400685 1999 Intact LIM 3 and LIM 4 domains of paxillin are required for the association to a novel polyproline region (Pro 2) of protein-tyrosine phosphatase-PEST.
10092676 1999 Hic-5, a paxillin homologue, binds to the protein-tyrosine phosphatase PEST (PTP-PEST) through its LIM 3 domain.
10085298 1999 Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts.
9920935 1999 Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST.
9857189 1998 A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion.
9847074 1998 Toward a complete human genome sequence.
9804817 1998 PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase.
9748319 1998 Combination of gene targeting and substrate trapping to identify substrates of protein tyrosine phosphatases using PTP-PEST as a model.
9497381 1998 Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin.
9422760 1998 Identification of a novel polyproline recognition site in the cytoskeletal associated protein, proline serine threonine phosphatase interacting protein.
9285683 1997 Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition.
9135065 1997 Coupling of the murine protein tyrosine phosphatase PEST to the epidermal growth factor (EGF) receptor through a Src homology 3 (SH3) domain-mediated association with Grb2.
8887669 1996 Identification of p130(cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST.
8626541 1996 Phosphotyrosine-independent binding of SHC to the NPLH sequence of murine protein-tyrosine phosphatase-PEST. Evidence for extended phosphotyrosine binding/phosphotyrosine interaction domain recognition specificity.
8454633 1993 Cloning and expression of PTP-PEST. A novel, human, nontransmembrane protein tyrosine phosphatase.
8349645 1993 Cloning and expression of PTP-PEST. A novel, human, nontransmembrane protein tyrosine phosphatase.
7929214 1994 Activators of protein kinase C stimulate association of Shc and the PEST tyrosine phosphatase.
7520867 1994 PTP-PEST: a protein tyrosine phosphatase regulated by serine phosphorylation.
7509295 1994 Chromosomal localization of the protein tyrosine phosphatase G1 gene and characterization of the aberrant transcripts in human colon cancer cells.
1932742 1991 Identification of novel protein tyrosine phosphatases of hematopoietic cells by polymerase chain reaction amplification.
1472029 1992 Cloning and characterization of a human cDNA encoding a novel putative cytoplasmic protein-tyrosine-phosphatase.