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

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

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

PTPN7

LOCATION

1q32.1

LOCUSID

5778

ALIAS

BPTP-4,HEPTP,LC-PTP,LPTP,PTPNI

FUSION GENES

Show Gene Fusions

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

Acute leukemia

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.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
8084610	1994	Structure of the human LC-PTP (HePTP) gene: similarity in genomic organization within protein-tyrosine phosphatase genes.	Adachi M et al
18728972	2008	Immunohistochemical 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
10940933	2000	Subcellular localization of intracellular protein tyrosine phosphatases in T cells.	Gjörloff-Wingren A et al
16226275	2005	Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site.	Mustelin T et al
10415025	1999	Direct suppression of TCR-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine-specific phosphatase.	Oh-hora M et al
10702794	2000	The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP.	Pettiford SM et al
10206983	1999	Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP).	Saxena M et al
7557444	1995	Cloning and expression of PCPTP1 encoding protein tyrosine phosphatase.	Shiozuka K et al
8309248	1994	A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1.	Zanke B et al
1530918	1992	Cloning 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 ID	Transcript ID	Uniprot
ENSG00000143851	ENST00000309017	P35236
ENSG00000143851	ENST00000367279	P35236
ENSG00000143851	ENST00000367279	A0A024R9A7
ENSG00000143851	ENST00000435759	C9JAW7
ENSG00000143851	ENST00000462815	F8WF66
ENSG00000143851	ENST00000464870	E7EUM0
ENSG00000143851	ENST00000467283	C9IYI6
ENSG00000143851	ENST00000476061	H7C5I3
ENSG00000143851	ENST00000477554	J3KR55
ENSG00000143851	ENST00000477625	H7C4T8
ENSG00000143851	ENST00000480836	F8WEY3
ENSG00000143851	ENST00000486116	E9PE54
ENSG00000143851	ENST00000492451	C9JBA9
ENSG00000143851	ENST00000495688	P35236
ENSG00000143851	ENST00000495688	A0A024R963
ENSG00000143851	ENST00000496197	F8WF08
ENSG00000143851	ENST00000629151	F8WF66

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
MAPK signaling pathway	KEGG	ko04010
MAPK signaling pathway	KEGG	hsa04010

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
31266805	2019	The protein tyrosine phosphatase PTPN7 is a negative regulator of ERK activation and thromboxane generation in platelets.	8
31266805	2019	The protein tyrosine phosphatase PTPN7 is a negative regulator of ERK activation and thromboxane generation in platelets.	8
20668459	2010	Genetic variants that affect length/height in infancy/early childhood in Vietnamese-Korean families.	5
20668459	2010	Genetic variants that affect length/height in infancy/early childhood in Vietnamese-Korean families.	5
19053285	2008	Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.	18
19053285	2008	Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.	18
16441242	2006	Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases.	27
16441242	2006	Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases.	27
16226275	2005	Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site.	19
16226275	2005	Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site.	19

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/css/lib/cancer-prone-explorer/