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PTPRJ (protein tyrosine phosphatase, receptor type, J)

Written2011-03Francesca Sacco, Savatore Corallino, Luisa Castagnoli
Department of Biology, University of Rome Tor Vergata, via ricerca scientifica, 00133 Rome, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)DEP1
HPTPeta
CD148
Other aliasR-PTP-ETA
SCC1
HGNC (Hugo) PTPRJ
LocusID (NCBI) 5795
Atlas_Id 41932
Location 11p11.2  [Link to chromosome band 11p11]
Location_base_pair Starts at 47980558 and ends at 48132714 bp from pter ( according to hg19-Feb_2009)  [Mapping PTPRJ.png]
Fusion genes
(updated 2016)
PTPRJ (11p11.2) / C2CD2L (11q23.3)PTPRJ (11p11.2) / FCER1G (1q23.3)PTPRJ (11p11.2) / LPXN (11q12.1)
PTPRJ (11p11.2) / MED26 (19p13.11)PTPRJ (11p11.2) / PTPRJ (11p11.2)SOX6 (11p15.2) / PTPRJ (11p11.2)
Note This gene is a member of the Human CCDS set: CCDS44596, CCDS7945.

DNA/RNA

Description Gene ENSG00000149177 has 24 alternate exons.
Transcription Multiple transcript variants encoding different isoforms have been found for this gene. Three transcripts are described in Ensembl (ID: ENSG00000149177).
The first (ENST00000418331) represents the longer isoform and encodes a protein that consists of an extracellular fibronectin type 3 domain and a cytosolic catalytic domain. The second isoform (ENST00000440289) has multiple differences in the presence and absence of exons at its 3' end, compared to the first isoform. These differences produce a unique 3' UTR and the encoded protein is shorter and consists of the extracellular fibronectin type 3 domain without the cytosolic catalytic region. The third transcript (ENST00000278456) has the same length as the first, but it encodes a truncated protein, that consists of fibronectin type 3 domains. Only the first two isoforms are members of the human CCDS set and have been described in NCBI (IDs: NM_001098503.1, NM_001098503.1).
The cDNA encoding PTPRJ/DEP-1 was isolated from a HeLa cell library (Ostman et al., 1994). The expression level and the activity of DEP-1 increase with cell density. This increase occurs gradually with increasing cell contact and is initiated before saturation cell density is reached. These observations suggest that DEP-1 may contribute to the mechanism of contact inhibition of cell growth.

Protein

 
  DEP-1: location of SNPs and mutations reported in human cancer. DEP-1 sequence is according to UniProtKB/Swiss-Prot: PTPRJ_HUMAN, Q12913. FNIII: Fibronectin domain, TM: Trans-membrane, KIM: Kinase Interaction Motif, PTP: Protein Tyrosine Phosphatase.
Description DEP-1 corresponds to a single-pass, type I membrane receptor-type protein tyrosine phosphatase; it is a 200-250 kDa transmembrane molecule with a 35 residue signal peptide, 940 residue extracellular portion, 21 residues in helical transmembrane region and 341 aminoacids in the intracytoplasmic tail, with a single catalytic domain at the carbossi-terminus.
The protein N-terminus has nine fibronectin type III (FNIII) repeats, contains 34 potential N-linked glycosylation sites and it was found glycosylated in seven asparagine residues by mass spectrometry (Liu et al., 2005; Chen et al., 2009). DEP-1 can dimerize (binding site 972-996) through the transmembrane domain (Chin et al., 2005) but it is unclear whether it can exist as dimers, physiologically. Sedimentation velocity measurements show that DEP1, along with other single-domain receptor phosphatases (e.g., IA2, IA2beta, GLEPP1 and STEP) is monomeric in solution (Barr et al., 2009).
The regulation of receptor-like protein tyrosine phosphatases is generally poorly understood. Sorby et al. have identified MatrigelTM (a preparation of extracellular matrix proteins) as a source of DEP-1 ligand(s) and agonist(s) (Sorby et al., 2001).
Expression DEP-1 is expressed in several cell types, including endothelial, epithelial, and in all haematopoietic lineages. It was found to be present on many epithelial cell types with glandular and endocrine differentiation as well as on fibrocytes, melanocytes and Schwann cells (Autschbach et al., 1999). It is widely expressed on B and T cells, granulocytes, macrophages, certain dendritic cells as well as mature thymocytes and it was shown to negatively regulate T cell receptor and terminating its response to stimulation. DEP-1 is thought to play a role in the down regulation of T cell activation and signalling, by interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells (LAT) and by reducing TCR-induced transcription factor (nuclear factor of activated T cells) (Lin and Weiss, 2003; Lin et al., 2004; Zhu et al., 2008; Tangye et al., 1998; Baker et al., 2001). DEP-1 expression is regulated during T cell activation and is constitutive in autoimmune murine T cells. These expression data suggest that DEP-1 plays a regulatory role to control an immune response and the proposed model of action describes DEP-1 as excluded from the immunologic synapse (i.e., the site of APC and T cell contact) during early T cell-APC (Antigen Presenting Cell) interactions. After T cell-APC disengagement, DEP-1 is no longer excluded by the synapse and can access and dephosphorylate substrates to down-regulate prolongation of the response (Lin et al., 2004).
It is interesting to note that the expression patterns of DEP-1 are different between humans and mice, where the expression in the T cell lineage is more restricted (Lin et al., 2004). Recently, DEP-1 is indicated as the phosphatase that can compensate for the absence of CD45, the prototypical receptor-like PTP expressed on immune cells (Zhu et al., 2008).
Function DEP-1 is a member of the protein tyrosine phosphatase (PTP) family. Since its expression is increased with increasing cell density, it is strongly suggested that DEP-1 may contribute to the mechanism of contact inhibition of cell growth (Ostman et al., 1994). It seems to be involved in protein tyrosine kinase signaling, cell-cell signaling, vasculogenesis and heart development (Takahashi et al., 2003).

Implicated in

Note
  
Entity Thyroid cancer
Note Allelic loss of this gene is involved in thyroid carcinogenesis: the loss of heterozygosity (LOH) of PTPRJ is detected in 11/76 (14,5%) thyroid tumors (adenomas and carcinomas). DEP-1 overexpression in a malignant rat thyroid cell line was reported to specifically induce dephosphorylation of the Src-inhibitory Y529 and thus to increase Src activity. In addition, there are data suggesting that PTPRJ polymorphisms can affect susceptibility to thyroid carcinomas: DEP-1 homozygous for the Gln276Pro, Arg326Gln and the Glu872Asp allele were more frequent in thyroid carcinoma patients than in healthy individuals. Moreover, PTPRJ LOH was more frequent in thyroid carcinomas of heterozygotes for Gln276Pro and Arg326Gln compared with homozygotes, suggesting that the presence of hemizygosity for these polymorphisms in the tumor facilitates tumor progression (Iuliano et al., 2004). It was recently reported that the homozygous genotype PTPRJ/DEP-1 for Glu872Asp is associated with an increased risk to develop papillary thyroid carcinoma (Iuliano et al., 2010).
DEP-1 can dephosphorylate the single-pass transmembrane tyrosine kinase receptor RET, impairing its signaling. Iervolino et al. show that Tyr1062 is critical for the binding of RET to DEP-1 and that DEP-1 can dephosphorylate the Tyr905 and Tyr1062 of the mutant RET bearing a germ-line Cys634Arg point mutation, responsible for the inheritance of multiple endocrine neoplasia types 2A (RET-MEN2A) and of the RET/PTC (papillary thyroid carcinoma) chimeric oncoprotein (Iervolino et al., 2006). The authors also show a DEP-1 dose dependent reduction of the transforming activity of RET-MEN2A. Furthermore, Iervolino et al. verified that the conformationally altered RET, bearing the mutation Met918Threo, responsible for MEN2B, does not bind or is dephosphorylated by DEP-1. This resistance to DEP-1 may account for the high oncogenic activity of the MEN2B RET alleles.
The rat protein tyrosine phosphatase eta, homologue of DEP-1, suppresses the neoplastic phenotype of retrovirally transformed thyroid cell, causing G1 growth arrest, by increasing the cyclin-dependent kinase inhibitor p27Kip1 protein level, through reduction of its proteasome-dependent degradation rate (Trapasso et al., 2000).
  
  
Entity Colon rectal cancer
Note DEP-1 is a candidate human homologue of the mouse colon cancer susceptibility locus SCC1.
Germline allele-specific epigenetic silencing of the gene PTPRJ, encoding DEP-1, is described in early-onset familial colorectal cancer, due to a 170-kb intragenic duplication affecting the 5' end of the phosphatase gene PTPRJ the tandem duplication in a head-to-tail orientation (Venkatachalam et al., 2010; Ruivenkamp et al., 2002; Ruivenkamp et al., 2003a; Ruivenkamp et al., 2003b). PTPRJ is frequently deleted in human colon, lung and breast carcinomas or it shows allelic imbalance in loss of heterozygosity (LOH) and missense mutations. LOH of PTPRJ occurs early in progressed colorectal adenoma. Ruivenkamp et al. (2002) identified 5 somatic missense mutations in the PTPRJ gene, in colon cancer. All are localized in the extracellular fibronectin domains, two, Arg214Cys and Arg326Gln, result in loss of a positive charge. Mita et al. show, in their association study, that the Arg326Gln SNP demonstrates a close association with colon rectal cancer risk (Mita et al., 2010).
Nutrients, which are considered to be chemoprotective with respect to colon cancer development, including butyrate, green tea and apple polyphenols, seem to elevate transcription of endogenous DEP-1 mRNA and expression of DEP-1 protein. Upregulation of DEP-1 expression with a consequent inhibition of cell growth and migration may present a mechanism of chemoprevention by nutrients (Balavenkatraman et al., 2006).
  
  
Entity Meningiomas
Note Suppressor of epithelial tumor.
LOH of the PTPRJ gene are observed in average 38% of human meningiomas of all grades (Petermann et al., 2010). Also, RNAi-mediated suppression of DEP-1, in DEP-1 positive meningioma cell lines (i.e., KT21, SF3061), causes enhanced motility and colony formation in semi-solid media (Petermann et al., 2010). It is therefore suggested that DEP-1 acts as a negative regulator of PDGF signaling and as a positive regulator of adhesion signalling, cooperating in inhibition of cell motility and tumor invasiveness and behaving as a positive regulator of paxillin tyrosine phosphorylation in epithelial cells. DEP-1 negatively affects PDGF stimulated activation of inositol trisphosphate formation, Erk1/Erk2, p21Ras, and Src. Activation of receptor-associated PI3K activity and of Akt/PKB are weakly attenuated at early time points of PDGF stimulation (Jandt et al., 2003). PDGFR and DEP-1 physically interact and there is a site-specific reduction in tyrosine phosphorylation of the PDGF b-receptor after in vivo and in vitro exposure to DEP-1. In fact, DEP-1 dephosphorylates the PDGFb-receptor P-Tyr751 and P-Tyr1009/1021, which are required for activation of PI3-K and PLCgamma, respectively, while the PDGFR regulatory P-Tyr857 is less affected (Kovalenko et al., 2000). Moreover, DEP-1 interacts with and dephosphorylates the p85 subunit of PI3K, bound to PDGFR (Tsuboi et al., 2008).
  
  
Entity Various cancers
Note EGFR and DEP-1
EGFR and DEP-1 physically associate, and EGFR phosphorylates a substrate-trapping mutant of DEP-1. Sacco et al. suggest that DEP-1 could act on EGFR phospho-Tyr998 (Sacco et al., 2009). Tarcic et al. suggest a mechanism by which DEP-1 affects EGFR trafficking and signaling. They show that DEP-1 dephosphorylates EGFR at the cell surface and affects the major phosphorylation site on CBL (at Tyr731), thus hampering EGFR ability to associate with the dedicated ubiquitin ligase complex (i.e., CBL-GRB2). This blocks EGFR ubiquitinylation, translocation to endosomes and, consequently, downstream signalling. DEP-1 silencing, on the contrary, enhances tyrosine phosphorylation of endosomal EGFRs, accelerates degradation of EGFR and increases cell proliferation (Tarcic et al., 2009). Consistent with this observation and with the induction of DEP-1 expression in contact-inhibited cells, the gene encoding DEP-1 is often deleted or mutated in carcinomas (Ruivenkamp et al., 2003a).
A genomic analysis of four different DNA samples (peripheral blood, primary tumor, brain metastasis and an early passage xenograft) from a patient with basal-like breast cancer (i.e., ERBB2 and ER negative), identify a missense mutation (K1017N) in DEP1/PTPRJ that is highly enriched during disease progression, since it is found enriched in metastasis and in the human-in-mouse xenograft, compared to primary tumor (Ding et al., 2010). The mutation site is in the juxtamembrane domain (a basic residue motif) and is in close proximity to the tyrosine-protein phosphatase domain (aa 1041-1298). Sacco et al. reported that the DEP-1 charged peptide 1013-IKPKKSKLIRVE-1024 is responsible for interaction with its substrates, such as ERK1/2 (Sacco et al., 2009). The K1017N mutation found in the basal tumor and the K1016A mutation described in Sacco's report, both describe a change of a basic residue into a neutral residue. The DEP-1 positively charged peptide has a loose resemblance to the KIM domains that is essential to bind the common docking domain of ERK1/2 proteins. Therefore, a mutation in the DEP-1 KIM domain affects ERK1/2 recruitment, thus impacting specifically on phospho-Tyr204 ERK1/2 dephosphorylation efficiency. DEP-1 can therefore suppress proliferation by sequestering ERK1/2, irrespective of ERK1/2 phosphorylation state and by dephosphorylating the ERK1/2 activation loop.
Loss of heterozygosity, and missense mutations in the DEP-1 gene have been identified in several human cancers including colon, lung, and breast, which have also been associated with aberrant Hepatocyte Growth Factor Receptor Tyrosine Kinase (Met) signaling. Palka et al. identify the hepatocyte growth factor/scatter factor receptor Met, the adapter protein GAB1 and the junctional component p120 catenin as potential DEP-1 substrates. Moreover, they show that DEP-1 preferentially dephosphorylates Met at sites involved in Met signaling: a GAB1 binding site (Tyr1349) and a COOH-terminal tyrosine implicated in morphogenesis (Tyr1365), while leaving unaltered the phosphorylation at the Met activation loop (Palka et al., 2003; Wang et al., 2010). A phosphatome RNAi (RNA interference) screen in A549 cells (lung adenocarcinoma) designed to identify phosphatases that behave as key negative regulators of oncogenic Ras signalling, characterized DEP-1 as a specific inhibitor of oncogenic K-Ras activation of Akt. The basis for this may be due to the role of DEP-1 in dephosphorylating residues within the p85 subunit of PI3K, resulting in attenuated PI3K/Akt activation (Omerovic et al., 2010).
DEP-1 and VEGFR
Whether or not DEP-1 plays a role in hematologic malignancies is not clear.
DEP1 targets VEGFR2 phospho-tyrosines: In contact-inhibited endothelial cells, the phosphatase DEP-1, by binding beta-catenin and p120, may associate with the cadherin-receptor complex and dephosphorylate VEGFR-2 that is in complex with VEC (vascular endothelial cadherin). Retention of VEGFR-2 at the membrane by VEC and its dephosphorylation by DEP-1 limits its internalization and signaling (Lampugnani et al., 2003; Holsinger et al., 2002; Lampugnani et al., 2006; Lampugnani and Dejana, 2007a; Lampugnani and Dejana, 2007b; Dejana et al., 2008).
Despite its negative role on global VEGFR2 phosphorylation, DEP-1 is a positive regulator of VEGF mediated Src and Akt activation and endothelial cell survival.
In fact, when DEP-1 is depleted, inhibitory Src Y529 phosphorylation is increased and consequently, Src activation is impaired. Reduced Src activity correlates with decreased phosphorylation of GAB1 that cannot associate with PI3K (phosphatidylinositol 3-kinase), thus impairing AKT activation (Chabot et al., 2009).
  
  
Entity Cogan's syndrome
Note DEP-1 has been implicated in an autoimmune disease, the Cogan's syndrome, which is a chronic inflammatory disease characterized by sensorineural hearing loss, keratitis, and vasculitis. A screen for autoantigens in this disease revealed antibodies to DEP-1, which is expressed on the sensory epithelia of the inner ear and on endothelial cells (Lunardi et al., 2002). These autoantibodies inhibit proliferation of DEP-1 expressing cells and can replicate the hearing loss feature of Cogan's disease, when infused into mice. It is not determined whether these antibodies are causative for this autoimmune disease and/or others (e.g., pseudo-Pendred syndrome) (Davis et al., 2006).
  

Bibliography

Expression of the membrane protein tyrosine phosphatase CD148 in human tissues.
Autschbach F, Palou E, Mechtersheimer G, Rohr C, Pirotto F, Gassler N, Otto HF, Schraven B, Gaya A.
Tissue Antigens. 1999 Nov;54(5):485-98.
PMID 10599888
 
Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation.
Baker JE, Majeti R, Tangye SG, Weiss A.
Mol Cell Biol. 2001 Apr;21(7):2393-403.
PMID 11259588
 
DEP-1 protein tyrosine phosphatase inhibits proliferation and migration of colon carcinoma cells and is upregulated by protective nutrients.
Balavenkatraman KK, Jandt E, Friedrich K, Kautenburger T, Pool-Zobel BL, Ostman A, Bohmer FD.
Oncogene. 2006 Oct 12;25(47):6319-24. Epub 2006 May 8.
PMID 16682945
 
Large-scale structural analysis of the classical human protein tyrosine phosphatome.
Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Muller S, Knapp S.
Cell. 2009 Jan 23;136(2):352-63.
PMID 19167335
 
New role for the protein tyrosine phosphatase DEP-1 in Akt activation and endothelial cell survival.
Chabot C, Spring K, Gratton JP, Elchebly M, Royal I.
Mol Cell Biol. 2009 Jan;29(1):241-53. Epub 2008 Oct 20.
PMID 18936167
 
Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H.
J Proteome Res. 2009 Feb;8(2):651-61.
PMID 19159218
 
Transmembrane homodimerization of receptor-like protein tyrosine phosphatases.
Chin CN, Sachs JN, Engelman DM.
FEBS Lett. 2005 Jul 4;579(17):3855-8.
PMID 15978577
 
Sensori-neural deafness and hypothyroidism: autoimmunity causing 'pseudo-Pendred syndrome'.
Davis N, Lunardi C, Shield JP.
Horm Res. 2006;65(6):267-8. Epub 2006 Mar 21.
PMID 16582570
 
The role of adherens junctions and VE-cadherin in the control of vascular permeability.
Dejana E, Orsenigo F, Lampugnani MG.
J Cell Sci. 2008 Jul 1;121(Pt 13):2115-22. (REVIEW)
PMID 18565824
 
Genome remodelling in a basal-like breast cancer metastasis and xenograft.
Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Lin L, Crowder R, Tao Y, Snider JE, Smith SM, Dukes AF, Sanderson GE, Pohl CS, Delehaunty KD, Fronick CC, Pape KA, Reed JS, Robinson JS, Hodges JS, Schierding W, Dees ND, Shen D, Locke DP, Wiechert ME, Eldred JM, Peck JB, Oberkfell BJ, Lolofie JT, Du F, Hawkins AE, O'Laughlin MD, Bernard KE, Cunningham M, Elliott G, Mason MD, Thompson DM Jr, Ivanovich JL, Goodfellow PJ, Perou CM, Weinstock GM, Aft R, Watson M, Ley TJ, Wilson RK, Mardis ER.
Nature. 2010 Apr 15;464(7291):999-1005.
PMID 20393555
 
The transmembrane receptor protein tyrosine phosphatase DEP1 interacts with p120(ctn).
Holsinger LJ, Ward K, Duffield B, Zachwieja J, Jallal B.
Oncogene. 2002 Oct 10;21(46):7067-76.
PMID 12370829
 
Molecular cloning, characterization, and chromosomal localization of a novel protein-tyrosine phosphatase, HPTP eta.
Honda H, Inazawa J, Nishida J, Yazaki Y, Hirai H.
Blood. 1994 Dec 15;84(12):4186-94.
PMID 7994032
 
The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.
Iervolino A, Iuliano R, Trapasso F, Viglietto G, Melillo RM, Carlomagno F, Santoro M, Fusco A.
Cancer Res. 2006 Jun 15;66(12):6280-7.
PMID 16778204
 
The tyrosine phosphatase PTPRJ/DEP-1 genotype affects thyroid carcinogenesis.
Iuliano R, Le Pera I, Cristofaro C, Baudi F, Arturi F, Pallante P, Martelli ML, Trapasso F, Chiariotti L, Fusco A.
Oncogene. 2004 Nov 4;23(52):8432-8.
PMID 15378013
 
Role of PTPRJ genotype in papillary thyroid carcinoma risk.
Iuliano R, Palmieri D, He H, Iervolino A, Borbone E, Pallante P, Cianflone A, Nagy R, Alder H, Calin GA, Trapasso F, Giordano C, Croce CM, de la Chapelle A, Fusco A.
Endocr Relat Cancer. 2010 Oct 29;17(4):1001-6. Print 2010 Dec.
PMID 20823296
 
The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell-matrix adhesion.
Jandt E, Denner K, Kovalenko M, Ostman A, Bohmer FD.
Oncogene. 2003 Jul 3;22(27):4175-85.
PMID 12833140
 
Site-selective dephosphorylation of the platelet-derived growth factor beta-receptor by the receptor-like protein-tyrosine phosphatase DEP-1.
Kovalenko M, Denner K, Sandstrom J, Persson C, Gross S, Jandt E, Vilella R, Bohmer F, Ostman A.
J Biol Chem. 2000 May 26;275(21):16219-26.
PMID 10821867
 
Adherens junctions in endothelial cells regulate vessel maintenance and angiogenesis.
Lampugnani MG, Dejana E.
Thromb Res. 2007b;120 Suppl 2:S1-6.
PMID 18023702
 
The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling.
Lin J, Weiss A.
J Cell Biol. 2003 Aug 18;162(4):673-82. Epub 2003 Aug 11.
PMID 12913111
 
Regulated expression of the receptor-like tyrosine phosphatase CD148 on hemopoietic cells.
Lin J, Zhu JW, Baker JE, Weiss A.
J Immunol. 2004 Aug 15;173(4):2324-30.
PMID 15294945
 
Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.
Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD.
J Proteome Res. 2005 Nov-Dec;4(6):2070-80.
PMID 16335952
 
Autoantibodies to inner ear and endothelial antigens in Cogan's syndrome.
Lunardi C, Bason C, Leandri M, Navone R, Lestani M, Millo E, Benatti U, Cilli M, Beri R, Corrocher R, Puccetti A.
Lancet. 2002 Sep 21;360(9337):915-21.
PMID 12354474
 
Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers.
Mita Y, Yasuda Y, Sakai A, Yamamoto H, Toyooka S, Gunduz M, Tanabe S, Naomoto Y, Ouchida M, Shimizu K.
J Cancer Res Clin Oncol. 2010 Feb;136(2):249-59. Epub 2009 Aug 12.
PMID 19672627
 
Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras-mutated cancer cells.
Omerovic J, Clague MJ, Prior IA.
Biochem J. 2010 Jan 27;426(1):65-72.
PMID 19922411
 
Expression of DEP-1, a receptor-like protein-tyrosine-phosphatase, is enhanced with increasing cell density.
Ostman A, Yang Q, Tonks NK.
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9680-4.
PMID 7937872
 
Hepatocyte growth factor receptor tyrosine kinase met is a substrate of the receptor protein-tyrosine phosphatase DEP-1.
Palka HL, Park M, Tonks NK.
J Biol Chem. 2003 Feb 21;278(8):5728-35. Epub 2002 Dec 9.
PMID 12475979
 
Loss of the Protein-Tyrosine Phosphatase DEP-1/PTPRJ Drives Meningioma Cell Motility.
Petermann A, Haase D, Wetzel A, Balavenkatraman KK, Tenev T, Guhrs KH, Friedrich S, Nakamura M, Mawrin C, Bohmer FD.
Brain Pathol. 2010 Nov 22. doi: 10.1111/j.1750-3639.2010.00464.x.
PMID 21091576
 
Five new mouse susceptibility to colon cancer loci, Scc11-Scc15.
Ruivenkamp CA, Csikos T, Klous AM, van Wezel T, Demant P.
Oncogene. 2003b Oct 16;22(46):7258-60.
PMID 14562056
 
Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases.
Sacco F, Tinti M, Palma A, Ferrari E, Nardozza AP, Hooft van Huijsduijnen R, Takahashi T, Castagnoli L, Cesareni G.
J Biol Chem. 2009 Aug 14;284(33):22048-58. Epub 2009 Jun 3.
PMID 19494114
 
An extracellular ligand increases the specific activity of the receptor-like protein tyrosine phosphatase DEP-1.
Sorby M, Sandstrom J, Ostman A.
Oncogene. 2001 Aug 23;20(37):5219-24.
PMID 11526512
 
A mutant receptor tyrosine phosphatase, CD148, causes defects in vascular development.
Takahashi T, Takahashi K, St John PL, Fleming PA, Tomemori T, Watanabe T, Abrahamson DR, Drake CJ, Shirasawa T, Daniel TO.
Mol Cell Biol. 2003 Mar;23(5):1817-31.
PMID 12588999
 
Negative regulation of human T cell activation by the receptor-type protein tyrosine phosphatase CD148.
Tangye SG, Wu J, Aversa G, de Vries JE, Lanier LL, Phillips JH.
J Immunol. 1998 Oct 15;161(8):3803-7.
PMID 9780142
 
An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis.
Tarcic G, Boguslavsky SK, Wakim J, Kiuchi T, Liu A, Reinitz F, Nathanson D, Takahashi T, Mischel PS, Ng T, Yarden Y.
Curr Biol. 2009 Nov 17;19(21):1788-98.
PMID 19836242
 
Rat protein tyrosine phosphatase eta suppresses the neoplastic phenotype of retrovirally transformed thyroid cells through the stabilization of p27(Kip1).
Trapasso F, Iuliano R, Boccia A, Stella A, Visconti R, Bruni P, Baldassarre G, Santoro M, Viglietto G, Fusco A.
Mol Cell Biol. 2000 Dec;20(24):9236-46.
PMID 11094075
 
The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase.
Tsuboi N, Utsunomiya T, Roberts RL, Ito H, Takahashi K, Noda M, Takahashi T.
Biochem J. 2008 Jul 1;413(1):193-200.
PMID 18348712
 
Germline epigenetic silencing of the tumor suppressor gene PTPRJ in early-onset familial colorectal cancer.
Venkatachalam R, Ligtenberg MJ, Hoogerbrugge N, Schackert HK, Gorgens H, Hahn MM, Kamping EJ, Vreede L, Hoenselaar E, van der Looij E, Goossens M, Churchman M, Carvajal-Carmona L, Tomlinson IP, de Bruijn DR, Van Kessel AG, Kuiper RP.
Gastroenterology. 2010 Dec;139(6):2221-4. Epub 2010 Oct 29.
PMID 21036128
 
Involvement of receptor tyrosine phosphatase DEP-1 mediated PI3K-cofilin signaling pathway in sorafenib-induced cytoskeletal rearrangement in hepatoma cells.
Wang Z, Wang M, Carr BI.
J Cell Physiol. 2010 Aug;224(2):559-65.
PMID 20432459
 
Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling.
Zhu JW, Brdicka T, Katsumoto TR, Lin J, Weiss A.
Immunity. 2008 Feb;28(2):183-96. Epub 2008 Jan 31.
PMID 18249142
 

Citation

This paper should be referenced as such :
Sacco, F ; Corallino, S ; Castagnoli, L
PTPRJ (protein tyrosine phosphatase, receptor type, J)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(10):867-872.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PTPRJID41932ch11p11.html


External links

Nomenclature
HGNC (Hugo)PTPRJ   9673
Cards
AtlasPTPRJID41932ch11p11
Entrez_Gene (NCBI)PTPRJ  5795  protein tyrosine phosphatase, receptor type J
AliasesCD148; DEP1; HPTPeta; R-PTP-ETA; 
SCC1
GeneCards (Weizmann)PTPRJ
Ensembl hg19 (Hinxton)ENSG00000149177 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000149177 [Gene_View]  chr11:47980558-48132714 [Contig_View]  PTPRJ [Vega]
ICGC DataPortalENSG00000149177
TCGA cBioPortalPTPRJ
AceView (NCBI)PTPRJ
Genatlas (Paris)PTPRJ
WikiGenes5795
SOURCE (Princeton)PTPRJ
Genetics Home Reference (NIH)PTPRJ
Genomic and cartography
GoldenPath hg38 (UCSC)PTPRJ  -     chr11:47980558-48132714 +  11p11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PTPRJ  -     11p11.2   [Description]    (hg19-Feb_2009)
EnsemblPTPRJ - 11p11.2 [CytoView hg19]  PTPRJ - 11p11.2 [CytoView hg38]
Mapping of homologs : NCBIPTPRJ [Mapview hg19]  PTPRJ [Mapview hg38]
OMIM600925   
Gene and transcription
Genbank (Entrez)AI218139 AL359057 AL832403 BC019824 BC063417
RefSeq transcript (Entrez)NM_001098503 NM_002843
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PTPRJ
Cluster EST : UnigeneHs.318547 [ NCBI ]
CGAP (NCI)Hs.318547
Alternative Splicing GalleryENSG00000149177
Gene ExpressionPTPRJ [ NCBI-GEO ]   PTPRJ [ EBI - ARRAY_EXPRESS ]   PTPRJ [ SEEK ]   PTPRJ [ MEM ]
Gene Expression Viewer (FireBrowse)PTPRJ [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5795
GTEX Portal (Tissue expression)PTPRJ
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ12913   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ12913  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ12913
Splice isoforms : SwissVarQ12913
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 ]   
PhosPhoSitePlusQ12913
Domaine pattern : Prosite (Expaxy)FN3 (PS50853)    TYR_PHOSPHATASE_1 (PS00383)    TYR_PHOSPHATASE_2 (PS50056)    TYR_PHOSPHATASE_PTP (PS50055)   
Domains : Interpro (EBI)FN3_dom    Ig-like_fold    Prot-tyrosine_phosphatase-like    PTPase_domain    Tyr_Pase_AS    Tyr_Pase_cat    TYR_PHOSPHATASE_dom   
Domain families : Pfam (Sanger)fn3 (PF00041)    Y_phosphatase (PF00102)   
Domain families : Pfam (NCBI)pfam00041    pfam00102   
Domain families : Smart (EMBL)FN3 (SM00060)  PTPc (SM00194)  PTPc_motif (SM00404)  
Conserved Domain (NCBI)PTPRJ
DMDM Disease mutations5795
Blocks (Seattle)PTPRJ
PDB (SRS)2CFV    2DLE    2NZ6   
PDB (PDBSum)2CFV    2DLE    2NZ6   
PDB (IMB)2CFV    2DLE    2NZ6   
PDB (RSDB)2CFV    2DLE    2NZ6   
Structural Biology KnowledgeBase2CFV    2DLE    2NZ6   
SCOP (Structural Classification of Proteins)2CFV    2DLE    2NZ6   
CATH (Classification of proteins structures)2CFV    2DLE    2NZ6   
SuperfamilyQ12913
Human Protein AtlasENSG00000149177
Peptide AtlasQ12913
HPRD02955
IPIIPI00943343   IPI00290328   IPI00847732   IPI00982486   IPI00982293   
Protein Interaction databases
DIP (DOE-UCLA)Q12913
IntAct (EBI)Q12913
FunCoupENSG00000149177
BioGRIDPTPRJ
STRING (EMBL)PTPRJ
ZODIACPTPRJ
Ontologies - Pathways
QuickGOQ12913
Ontology : AmiGOimmunological synapse  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  platelet-derived growth factor receptor binding  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  cell-cell junction  beta-catenin binding  negative regulation of cell proliferation  cell surface  negative regulation of platelet-derived growth factor receptor signaling pathway  phosphatase activity  phosphatase activity  protein kinase binding  regulation of cell adhesion  negative regulation of cell growth  negative regulation of cell migration  ruffle membrane  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  specific granule membrane  negative regulation of epidermal growth factor receptor signaling pathway  negative regulation of vascular permeability  neutrophil degranulation  negative regulation of MAP kinase activity  gamma-catenin binding  positive regulation of cell adhesion  platelet-derived growth factor receptor signaling pathway  T cell receptor signaling pathway  negative regulation of T cell receptor signaling pathway  negative regulation of T cell receptor signaling pathway  positive chemotaxis  mitogen-activated protein kinase binding  positive regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  negative regulation of protein kinase B signaling  contact inhibition  extracellular exosome  delta-catenin binding  
Ontology : EGO-EBIimmunological synapse  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  platelet-derived growth factor receptor binding  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  cell-cell junction  beta-catenin binding  negative regulation of cell proliferation  cell surface  negative regulation of platelet-derived growth factor receptor signaling pathway  phosphatase activity  phosphatase activity  protein kinase binding  regulation of cell adhesion  negative regulation of cell growth  negative regulation of cell migration  ruffle membrane  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  specific granule membrane  negative regulation of epidermal growth factor receptor signaling pathway  negative regulation of vascular permeability  neutrophil degranulation  negative regulation of MAP kinase activity  gamma-catenin binding  positive regulation of cell adhesion  platelet-derived growth factor receptor signaling pathway  T cell receptor signaling pathway  negative regulation of T cell receptor signaling pathway  negative regulation of T cell receptor signaling pathway  positive chemotaxis  mitogen-activated protein kinase binding  positive regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  negative regulation of protein kinase B signaling  contact inhibition  extracellular exosome  delta-catenin binding  
Pathways : KEGGAdherens junction   
REACTOMEQ12913 [protein]
REACTOME PathwaysR-HSA-6807004 [pathway]   
NDEx NetworkPTPRJ
Atlas of Cancer Signalling NetworkPTPRJ
Wikipedia pathwaysPTPRJ
Orthology - Evolution
OrthoDB5795
GeneTree (enSembl)ENSG00000149177
Phylogenetic Trees/Animal Genes : TreeFamPTPRJ
HOVERGENQ12913
HOGENOMQ12913
Homologs : HomoloGenePTPRJ
Homology/Alignments : Family Browser (UCSC)PTPRJ
Gene fusions - Rearrangements
Fusion : MitelmanPTPRJ/C2CD2L [11p11.2/11q23.3]  
Fusion : MitelmanPTPRJ/FCER1G [11p11.2/1q23.3]  [t(1;11)(q23;p11)]  
Fusion : MitelmanSOX6/PTPRJ [11p15.2/11p11.2]  [t(11;11)(p11;p15)]  
Fusion: TCGAPTPRJ 11p11.2 C2CD2L 11q23.3 LAML
Fusion: TCGAPTPRJ 11p11.2 FCER1G 1q23.3 LUAD
Fusion: TCGASOX6 11p15.2 PTPRJ 11p11.2 LGG
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPTPRJ [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PTPRJ
dbVarPTPRJ
ClinVarPTPRJ
1000_GenomesPTPRJ 
Exome Variant ServerPTPRJ
ExAC (Exome Aggregation Consortium)PTPRJ (select the gene name)
Genetic variants : HAPMAP5795
Genomic Variants (DGV)PTPRJ [DGVbeta]
DECIPHERPTPRJ [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPTPRJ 
Mutations
ICGC Data PortalPTPRJ 
TCGA Data PortalPTPRJ 
Broad Tumor PortalPTPRJ
OASIS PortalPTPRJ [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPTPRJ  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPTPRJ
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 PTPRJ
DgiDB (Drug Gene Interaction Database)PTPRJ
DoCM (Curated mutations)PTPRJ (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PTPRJ (select a term)
intoGenPTPRJ
NCG5 (London)PTPRJ
Cancer3DPTPRJ(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600925   
Orphanet
MedgenPTPRJ
Genetic Testing Registry PTPRJ
NextProtQ12913 [Medical]
TSGene5795
GENETestsPTPRJ
Target ValidationPTPRJ
Huge Navigator PTPRJ [HugePedia]
snp3D : Map Gene to Disease5795
BioCentury BCIQPTPRJ
ClinGenPTPRJ
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5795
Chemical/Pharm GKB GenePA34018
Clinical trialPTPRJ
Miscellaneous
canSAR (ICR)PTPRJ (select the gene name)
Probes
Litterature
PubMed89 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePTPRJ
EVEXPTPRJ
GoPubMedPTPRJ
iHOPPTPRJ
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Aug 1 17:35:10 CEST 2017

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