PTPN7 (protein tyrosine phosphatase, non-receptor type 7)

2010-01-01   Marie Fridberg , Helena Tassidis , Anette Gjörloff Wingren 

Department of Tumor Biology, Lund University, Malmo University Hospital, Malmo, Sweden (MF, HT); Department of Laboratory Science, Health, Society, Malmo University, Malmo University Hospital, Malmo, Sweden (AGW)

Identity

HGNC
LOCATION
1q32.1
LOCUSID
ALIAS
BPTP-4,HEPTP,LC-PTP,LPTP,PTPNI
FUSION GENES

DNA/RNA

Description

The premessenger has 10 exons and covers 14.59 kb on the genome.

Transcription

The complete mRNA is 3784 bp long. 2 alternatively spliced transcript variants encoding different isoforms have been found, but it has also been reported that transcription produces 16 different mRNAs, 15 alternatively spliced variants and 1 unspliced form. Of the 2 described variants, variant 1 (2,805 bp linear mRNA) contains a different 5 region, which includes a part of the coding sequence when compared to variant 2. Variant 2 (3,263 bp linear mRNA) contains an alternate 5 region, which includes an additional in-frame translation start codon, as compared to variant 1. It thus encodes a protein that is 39 aa longer at the N-terminus.

Pseudogene

No pseudogenes have been found.

Proteins

Description

The hematopoietic protein tyrosine phosphatase (HePTP) protein is a 40,5 kDa protein of 360 amino acids. It is a class I non-receptor PTP that is strongly expressed in T cells. It is composed of a C-terminal classical PTP domain (residues 44-339) and a short N-terminal extension (residues 1-43) that functions to direct HePTP to its physiological substrates.

Expression

Thymus, spleen, leukocytes.

Localisation

Cytoplasmic.

Function

Protein tyrosine phosphatase activity, hydrolase activity, phosphoric monoester hydrolase activity, receptor activity- participation in MAPK signaling pathways, T cell receptor signaling pathway and protein amino acid dephosphorylation.
The protein can interact with tyrosine-phosphorylated MAPK1, MAPK3 and several other MAP kinases and suppress the MAP kinase activities. Plays a role in the regulation of T and B-lymphocyte development and signal transduction.

Homology

HePTP has high homologies with striatal-enriched phosphatase (STEP) and PCPTP (PC12 protein Tyr phosphatase).

Mutations

Germinal

No germline mutations are described.

Somatic

Mutations have not been observed.

Implicated in

Entity name
Disease
Myelodysplastic syndrome and myelogenous leukemia; HePTP often is dysregulated in the preleukemic disorder myelodysplastic syndrome and myelogenous leukemia (elevated expression of HePTP). The first indication of a role of HePTP in cell proliferation or differentiation came from the finding that the HePTP gene is located on the long arm of chromosome 1, which is often found in extra copies (trisomy) in bone marrow cells from patients with myelodysplastic syndrome, which is characterized by reduced hematopoiesis and increased risk of acute leukemia.
Entity name
Non-Hodgkin Lymphoma
Disease
Pediatric lymphoma; HePTP is down-regulated in pediatric lymphoma compared to control lymphoid cells. Loss of HePTP might indicate increased cell proliferation and/or survival of lymphoma cells.

Bibliography

Pubmed IDLast YearTitleAuthors
80846101994Structure of the human LC-PTP (HePTP) gene: similarity in genomic organization within protein-tyrosine phosphatase genes.Adachi M et al
187289722008Immunohistochemical analyses of phosphatases in childhood B-cell lymphoma: lower expression of PTEN and HePTP and higher number of positive cells for nuclear SHP2 in B-cell lymphoma cases compared to controls.Fridberg M et al
109409332000Subcellular localization of intracellular protein tyrosine phosphatases in T cells.Gjörloff-Wingren A et al
162262752005Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site.Mustelin T et al
104150251999Direct suppression of TCR-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine-specific phosphatase.Oh-hora M et al
107027942000The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP.Pettiford SM et al
102069831999Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP).Saxena M et al
75574441995Cloning and expression of PCPTP1 encoding protein tyrosine phosphatase.Shiozuka K et al
83092481994A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1.Zanke B et al
15309181992Cloning and expression of an inducible lymphoid-specific, protein tyrosine phosphatase (HePTPase).Zanke B et al

Other Information

Locus ID:

NCBI: 5778
MIM: 176889
HGNC: 9659
Ensembl: ENSG00000143851

Variants:

dbSNP: 5778
ClinVar: 5778
TCGA: ENSG00000143851
COSMIC: PTPN7

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000143851ENST00000309017P35236
ENSG00000143851ENST00000367279P35236
ENSG00000143851ENST00000367279A0A024R9A7
ENSG00000143851ENST00000435759C9JAW7
ENSG00000143851ENST00000462815F8WF66
ENSG00000143851ENST00000464870E7EUM0
ENSG00000143851ENST00000467283C9IYI6
ENSG00000143851ENST00000476061H7C5I3
ENSG00000143851ENST00000477554J3KR55
ENSG00000143851ENST00000477625H7C4T8
ENSG00000143851ENST00000480836F8WEY3
ENSG00000143851ENST00000486116E9PE54
ENSG00000143851ENST00000492451C9JBA9
ENSG00000143851ENST00000495688P35236
ENSG00000143851ENST00000495688A0A024R963
ENSG00000143851ENST00000496197F8WF08
ENSG00000143851ENST00000629151F8WF66

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
MAPK signaling pathwayKEGGhsa04010

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
164412422006Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases.18
162262752005Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site.16
190532852008Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.15
206684592010Genetic variants that affect length/height in infancy/early childhood in Vietnamese-Korean families.2
312668052019The protein tyrosine phosphatase PTPN7 is a negative regulator of ERK activation and thromboxane generation in platelets.0

Citation

Marie Fridberg ; Helena Tassidis ; Anette Gjörloff Wingren

PTPN7 (protein tyrosine phosphatase, non-receptor type 7)

Atlas Genet Cytogenet Oncol Haematol. 2010-01-01

Online version: http://atlasgeneticsoncology.org/gene/41921/ptpn7id41921ch1q32