PTPRH

Gene Summary

Gene:PTPRH; protein tyrosine phosphatase, receptor type H
Aliases: SAP1, R-PTP-H
Location:19q13.42
Summary:The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. The extracellular region contains eight fibronectin type III-like repeats and multiple N-glycosylation sites. The gene was shown to be expressed primarily in brain and liver, and at a lower level in heart and stomach. It was also found to be expressed in several cancer cell lines, but not in the corresponding normal tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:receptor-type tyrosine-protein phosphatase H
Source:NCBIAccessed: 11 March, 2017

Ontology:

What does this gene/protein do?
Show (10)

Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 11 March 2017 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 11 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (7)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: PTPRH (cancer-related)

Sato T, Soejima K, Arai E, et al.
Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer.
Oncol Rep. 2015; 34(3):1137-45 [PubMed] Free Access to Full Article Related Publications
PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of the present study was to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LADC). PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with LADC, a major NSCLC subtype. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. PTPRH mRNA expression was significantly upregulated in NSCLC. PTPRH DNA methylation was reduced in LADC samples and inversely correlated with mRNA expression. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P=1.64x10(-4)) and overall survival (P=5.54x10(-5)). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P=6.88x10(-3)). It was confirmed that PTPRH is overexpressed in NSCLC. Furthermore, we determined that PTPRH is epigenetically regulated by DNA hypomethylation, with prognostic implications for LADC.

Jönsson JM, Bartuma K, Dominguez-Valentin M, et al.
Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.
Fam Cancer. 2014; 13(4):537-45 [PubMed] Free Access to Full Article Related Publications
Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.

Lee M, Lee Y, Cho HJ, et al.
Copy number variations of chromosome 17p13.1 might be linked to high risk of lung cancer in heavy smokers.
Mol Biol Rep. 2011; 38(8):5211-7 [PubMed] Related Publications
Lung cancer is the most common cause of cancer death worldwide. Smoking is known as the strongest single factor in the development of lung cancer. However, there are inherited genetic factors that cause different responses to cigarette smoking exposure among individuals. We tried to identify these differences in heavy smokers by examining copy number variations (CNVs) between lung cancer patients and healthy controls. Analysis by array comparative genomic hybridization which was tested with 20-person training set (10 lung cancer patients, 10 healthy controls) showed 26 significant (adjusted P < 0.05) clones with either copy number gains or losses. Three genes, KCTD11, FGF11, and PTPRH on chromosomal regions 17p13.1 (KCTD11 and FGF11) and 19q13.42 (PTPRH), were selected (adjusted P < 0.001) and tested by real-time quantitative PCR with 34 healthy controls and 54 lung cancer patients. KCTD11 on the chromosomal region 17p13.1 showed significant high odds ratio (OR = 16.0) in heavy smokers, implying that this is a susceptibility region for lung cancer in this group. Therefore, CNVs of 17p13.1 is a promising candidate to identify individuals with a high genetic risk for the development of lung cancer.

Nagy N, Klein G, Klein E
To the genesis of Burkitt lymphoma: regulation of apoptosis by EBNA-1 and SAP may determine the fate of Ig-myc translocation carrying B lymphocytes.
Semin Cancer Biol. 2009; 19(6):407-10 [PubMed] Related Publications
Chromosomal translocations that juxtapose one of the three immunoglobulin loci to the c-myc protooncogene are the hallmark of Burkitt lymphomas (BLs), whether they carry the Epstein Barr Virus (EBV) or not. Ig/myc translocations occur as accidents of normal B lymphocyte differentiation. Unless protected, the translocation carrying cells are apoptosis prone. However, the high B cell stimulatory cytokine level found in the two BL prone conditions, in chronic hyperendemic malaria and HIV infection, may rescue them. X-linked lymphoproliferative disease (XLP) is due to the lack of functional SAP protein, a consequence of mutation or deletion of the SAP gene. We and others have shown that SAP is pro-apoptotic. Here we summarize our finding that 8 of 10 EBV carrying, but none of 9 EBV negative BL lines express SAP. We suggest that the apoptosis prone Ig/myc translocation carrying EBV negative precursors of BL can only grow into lymphomas if they do not express SAP. However, their EBV positive counterparts are permissive for SAP expression, due to the anti-apoptotic function of EBNA-1.

Hearle N, Lucassen A, Wang R, et al.
Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11-negative PJS cases.
Genes Chromosomes Cancer. 2004; 41(2):163-9 [PubMed] Related Publications
Germ-line mutations in the serine-threonine kinase gene STK11 (LKB1) cause Peutz-Jeghers syndrome (PJS), a rare autosomal dominantly inherited disease, characterized by hamartomatous polyposis and mucocutaneous pigmentation. STK11 mutations only account for about half of PJS cases, and a second disease locus has been proposed at chromosome segment 19q13.4 on the basis of genetic linkage analysis in one family. We identified a t(11;19)(q13;q13.4) in a PJS polyp arising from the small bowel in a female infant age 6 days. Because the breakpoint in 19q13.4 may disrupt the putative PJS disease gene mapping to this region, we mapped the breakpoint and analyzed DNA from the case and a series of STK11-negative PJS cases. Using two-color interphase fluorescence in situ hybridization, the breakpoint region was refined to a 0.5-Mb region within 19q13.4. Eight candidate genes mapping to the breakpoint region--U2AF2, EPN1, NALP4, NALP11, NALP5, ZNF444, PTPRH, and KIAA1811--were screened for mutations in germ-line and polyp DNA from the case and from 15 PJS cases that did not harbor germ-line STK11 mutations. No pathogenic mutations in the candidate genes were identified. This report provides further evidence of the existence of a second PJS disease locus at 19q13.4 and excludes involvement of eight candidate genes.

Marneros AG, Mehenni H, Reichenberger E, et al.
Gene for the human transmembrane-type protein tyrosine phosphatase H (PTPRH): genomic structure, fine-mapping and its exclusion as a candidate for Peutz-Jeghers syndrome.
Cytogenet Cell Genet. 2001; 92(3-4):213-6 [PubMed] Related Publications
Mutations in the serine/threonine kinase STK11 lead to Peutz-Jeghers syndrome (PJS) in a subset of affected individuals. Significant evidence for linkage to a second potential PJS disease locus on 19q13.4 has previously been described in one PJS family (PJS07). In the current study, we investigated this second locus for PJS gene candidates. We mapped the main candidate gene in this region, the gene for the transmembrane-type protein tyrosine phosphatase H (PTPRH), within 15 kb telomeric to the marker D19S880. We determined its genomic structure, and performed mutation analysis of all exons and the exon-intron junctions of the PTPRH gene in the PJS07 family. No disease causing mutation was identified in PTPRH in affected individuals, suggesting the existence of an as yet not identified gene on 19q13.4 as a second PJS gene.

Chai Y, Chipitsyna G, Cui J, et al.
c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells.
Oncogene. 2001; 20(11):1357-67 [PubMed] Related Publications
Elk-1, a c-Fos protooncogene regulator, which belongs to the ETS-domain family of transcriptional factors, plays an important role in the induction of immediate early gene expression in response to a variety of extracellular signals. In this study, we demonstrate for the first time the in vitro and in vivo interaction of Elk-1 with BRCA1 splice variants BRCA1a and BRCA1b using GST-pull down assays, co-imunoprecipitations/Western blot analysis of cell extracts from breast cancer cells and mammalian two-hybrid assays. We have localized the BRCA1 interaction domain of Elk-1 protein to the conserved ETS domain, a motif involved in DNA binding and protein-protein interactions. We also observed binding of BRCA1 proteins to other ETS-domain transcription factors SAP1, ETS-1, ERG-2 and Fli-1 but not to Elk-1 splice variant DeltaElk-1 and c-Fos protooncogene. Both BRCA1a and BRCA1b splice variants function as growth suppressors of human breast cancer cells. Interestingly, our studies reveal that although both Elk-1 and SAP-1 are highly homologous members of a subfamily of ETS domain proteins called ternary complex factors, it is only Elk-1 but not SAP-1 that can augment the growth suppressive function of BRCA1a/1b proteins in breast cancer cells. Thus Elk-1 could be a potential downstream target of BRCA1 in its growth control pathway. Furthermore, we have observed inhibition of c-Fos promoter activity in BRCA1a transfected stable breast cancer cells and over expression of BRCA1a/1b attenuates MEK-induced SRE activation in vivo. These results demonstrate for the first time a link between the growth suppressive function of BRCA1a/1b proteins and signal transduction pathway involving Elk-1 protein. All these results taken together suggest that one of the mechanisms by which BRCA1a/1b proteins function as growth/tumor suppressors is through inhibition of the expression of Elk-1 target genes like c-Fos.

Reichard U, Margraf S, Hube B, Rüchel R
A method for recovery of Candida albicans DNA from larger blood samples and its detection by polymerase chain reaction on proteinase genes.
Mycoses. 1997; 40(7-8):249-53 [PubMed] Related Publications
A method for the detection of Candida albicans from up to 15 ml of blood by polymerase chain reaction (PCR), based on the differential resistance of mammalian and fungal cells towards detergent was developed. The procedure essentially involved removal of the blood cells by sodium dodecyl sulfate (SDS) induced lysis, followed by DNA extraction after degradation of fungal cell walls by a recombinant beta-1,3-glucanase. The genes of two different aspartic proteinases from C. albicans, SAP1 and SAP2, with an overall homology of 77% in their nucleotide sequences, were chosen as targets for PCR. The oligonucleotide primers used were directed to strictly conserved regions similar in both genes. As the number of base pairs between the primers are different in the two genes, amplification products of 220 bp and 238 bp in length were obtained. This led to a characteristic double band in subsequent agarose gel electrophoresis. The detection limit for a nested PCR was less than 10 C. albicans cells ml-1 of seeded blood. The detection limit of conventional PCR from a blood volume in the 10 ml range was less than 100 yeasts ml-1. Preliminary trials with clinical blood specimens suggested, that conventional PCR from large blood samples, being less laborious and prone to contamination than nested PCR, could be suited for the detection of deepseated C. albicans mycosis.

Seo Y, Matozaki T, Tsuda M, et al.
Overexpression of SAP-1, a transmembrane-type protein tyrosine phosphatase, in human colorectal cancers.
Biochem Biophys Res Commun. 1997; 231(3):705-11 [PubMed] Related Publications
SAP-1 is a human transmembrane-type protein tyrosine phosphatase that is abundant in colon and pancreatic cancer cell lines. The expression of SAP-1 in surgically excised human colorectal cancer specimens has now been investigated by immunohistochemical staining and in situ hybridization. Normal colon tissue or adenomas with mild dysplasia showed no detectable expression of SAP-1. In contrast, 2 of 17 adenomas with moderate or severe dysplasia and 19 of 48 (40%) adenocarcinomas expressed SAP-1, SAP-1 was localized predominantly to the apical surface of colonic cells in adenoma tissue showing moderate dysplasia, but it was also observed in the cytoplasm and at the basal surface of both adenoma cells showing severe dysplasia and adenocarcinoma cells. In situ hybridization with a SAP-1 antisense RNA probe detected SAP-1 mRNA in 6 of 9 colorectal cancers, but not in the surrounding mesenchymal tissue or normal mucosa. Sequencing of the K-RAS gene revealed that 10 of 15 (67%) SAP-1-positive cancers contained a mutation in codon 12. The serum concentration of carcinoembryonic antigen was normal in approximately half of the patients with SAP-1-positive colorectal cancers. These results suggest that SAP-1 is frequently overexpressed in human colorectal cancers and that such overexpression may occur relatively late in the adenoma-carcinoma sequence.

Matozaki T, Suzuki T, Uchida T, et al.
Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and its expression in gastrointestinal cancers.
J Biol Chem. 1994; 269(3):2075-81 [PubMed] Related Publications
To determine the expression of various protein-tyrosine phosphatases (PTPs) in human gastric cancers, cDNAs encoding conserved PTP domains were amplified by reverse transcriptase polymerase chain reaction from KATO-III cell mRNA and sequenced. Among 72 polymerase chain reaction clones, one of the cDNA sequences encoded a novel potential PTP (stomach cancer-associated PTP, SAP-1). The full length (3.9 kilobases) of the SAP-1 cDNA was further isolated from the KATO-III cell cDNA library and the WiDr cell cDNA library. The predicted amino acid sequence of the SAP-1 cDNA showed that mature SAP-1 consisted of 1093 amino acids and a transmembrane-type PTP, which possessed a single PTP-conserved domain in the cytoplasmic region. The extracellular region of SAP-1 consisted of eight fibronectin type III-like structure repeats and contained multiple N-glycosylation sites. These data suggest that SAP-1 is structurally similar to HPTP beta and that SAP-1 and HPTP beta represent a subfamily of transmembrane-type PTPs. SAP-1 was mainly expressed in brain and liver and at a lower level in heart and stomach as a 4.2-kilobase mRNA, but it was not detected in pancreas or colon. In contrast, among cancer cell lines tested, SAP-1 was highly expressed in pancreatic and colorectal cancer cells. The bacterially expressed SAP-1 fusion protein had tyrosine-specific phosphatase activity. Immunoblotting with anti-SAP-1 antibody showed that SAP-1 is a 200-kDa protein. In addition, transient transfection of SAP-1 cDNA to COS cells resulted in the predominant expression of a 200-kDa protein recognized by anti-SAP-1 antibody. SAP-1 is mapped to chromosome 19 region q13.4 and might be related to carcinoembryonic antigen mapped to 19q13.2.

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Cite this page: Cotterill SJ. PTPRH, Cancer Genetics Web: http://www.cancer-genetics.org/PTPRH.htm Accessed:

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