PTPN4 protein tyrosine phosphatase non-receptor type 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PTPN4provided by HGNC
Official Full Name: protein tyrosine phosphatase non-receptor type 4provided by HGNC
Primary source: HGNC:HGNC:9656
See related: Ensembl:ENSG00000088179 MIM:176878; AllianceGenome:HGNC:9656
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MEG; PTPMEG; PTPMEG1
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 protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in thyroid (RPKM 7.2), brain (RPKM 5.8) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q14.2

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (119759922..119984899)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (120193967..120419641)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (120517498..120742475)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.
Title: E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.
MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis.
Title: MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis.
Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein.
Title: Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein.
Study identified a nonsense mutation of PTPN4 with mutation ratio of 90.90% from 1 case of rectal cancer. Overexpression of PTPN4 suppressed the growth of colorectal cancer cells. PTPN4 dephosphorylates pSTAT3 at the Tyr705 residue with a direct interaction and depresses the transcriptional activity of STAT3.
Title: Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer.
Data show that mutations affect the regulation of the protein tyrosine phosphatase non-receptor type 4 (PTPN4) bidomain and indicate that the PDZ-PDZ ligand regulation of PTPN4 is a linker-mediated mechanism.
Title: Regulation of the Human Phosphatase PTPN4 by the inter-domain linker connecting the PDZ and the phosphatase domains.
Binding assays confirmed that three (Cyto8-mtxd-1, Cyto8-mtxk-4 and Cyto8-mtxd-1k-4) out of the five designed peptides exhibit moderately or considerably increased affinity as compared to the native peptide Cyto8-RETEV
Title: Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma.
the p38gamma.PTPN4 interaction promotes cellular signaling, preventing cell death induction.
Title: Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ.
Deletion of PTPN4 has been reported in monozygotic twins with a Rett syndrome-like phenotype.
Title: Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype.
The physiologically active PTPN4 two-domain (the PDZ and the phosphatase domains) adopts a predominant compact conformation in solution. PDZ ligand binding restores the catalytic competence of PTPN4 disrupting the transient interdomain communication.
Title: Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain.
These findings suggest that PTPN4 negatively regulates cell proliferation and motility through dephosphorylation of CrkI.
Title: PTPN4 negatively regulates CrkI in human cell lines.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH91837 (e-PCR)
- UniSTS:88833

RH65502 (e-PCR)
- UniSTS:84747

RH68765 (e-PCR)
- UniSTS:43026

SHGC-35144 (e-PCR)
- UniSTS:49260

RH120908 (e-PCR)
- UniSTS:133763

PTPN4_3121 (e-PCR)
- UniSTS:462474

SHGC-33019 (e-PCR)
- UniSTS:64750

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytoskeletal protein binding	IEA Inferred from Electronic Annotation more info
enables glutamate receptor binding	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in protein dephosphorylation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasmic side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tyrosine-protein phosphatase non-receptor type 4

Names: PTPase-MEG1; megakaryocyte phosphatase; megakaryocyte protein-tyrosine phosphatase; protein tyrosine phosphatase MEG1; protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte)

NP_002821.1

EC 3.1.3.48

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002830.4 → NP_002821.1 tyrosine-protein phosphatase non-receptor type 4

See identical proteins and their annotated locations for NP_002821.1

Status: REVIEWED

Source sequence(s)

AC016691, BC010674, M68941

Consensus CDS

CCDS2129.1

UniProtKB/Swiss-Prot

B2RBV8, P29074, Q9UDA7

Related

ENSP00000263708.2, ENST00000263708.7

Conserved Domains (5) summary

smart00295
Location:30 → 222

B41; Band 4.1 homologues

cd00047
Location:682 → 909

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

cd00992
Location:515 → 602

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13189
Location:216 → 310

FERM_C_PTPN4_PTPN3_like; FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 3 and 4 (PTPN4 and PTPN3)

pfam08736
Location:325 → 365

FA; FERM adjacent (FA)