PTPN21 (protein tyrosine phosphatase, non-receptor type 21)

2008-02-01 Antonio Feliciello Affiliation

Dipartimento di Biologia e Patologia Molecolare e Cellulare, Instituto di Endocrinologia ed Oncologia Sperimentale, 80131 Napoli, Italia

Identity

HGNC

PTPN21

LOCATION

14q31.3

LOCUSID

11099

ALIAS

PTPD1,PTPRL10

FUSION GENES

Show Gene Fusions

DNA/RNA

Transcription

cDNA approximately 6.2 kb; at nucleotide 333-335 ATG of transcription initiation sites.

Pseudogene

Proteins

Description

PTPD1 is a protein of 130 kDa composed 1174 amino acids.
It is constituted by an N-terminal sequence homologous to the Four-point-one Ezrin-Radixin-Moesin (FERM domain) protein family; a C-terminal catalytic domain (PTP) with the essential cysteine residue at position 1108; two putative SH3 domain binding domains (residues 565-574 and 334-343); an acidic region in the residues 712-722; two highly conserved SH2 binding motifs (Y158ESQ and Y217GEE) within the FERm domain that mediate interaction with src tyrosine kinase.

Expression

PTPD1 is widely expressed in a variety of tissues including placenta, lung, kidney, colon, skeletal muscle, and in most cell lines (HEK293, fibroblast, MCF-7; T82; B16).

Localisation

PTPD1 localizes at the outer mitochondrial membrane, the plasma membrane, Golgi apparatus, endoplasmic reticulum, actin filaments and adhesion plaques.

Function

PTPD1 is member of non-receptor tyrosine phosphatases that binds to- and activates src tyrosine kinase. PTPD1/src complex up-regulates epidermal growth factor receptor (EGFR) phosphorylation and increases ERK 1 / ERK 2 signaling in response to EGF. PTPD1 forms a stable complex with actin, src tyrosine kinase and FAK (Focal Adhesion Kinase). PTPD1 regulates FAK signalling and actin cytoskeleton remodelling, and promotes cell scattering and migration. Mitochondrial PTPD1 in complex with AKAP121 and src is required for efficient maintenance of mitochondrial membrane potential and oxidative ATP synthesis. PTPD1 has been also implicated in the regulation of the Tec family kinases and activation of Stat3 signaling pathway.
PTPD1 Interactors: KIF1C kinesin family member 1C, BMX non-receptor tyrosine kinase, Src v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian), TEC tyrosine kinase implicated in the signaling pathways of hematopoietic and antigen receptors, FAK tyrosine kinase of focal adhesion, Actin filaments

Homology

PTPD1 belongs to the same family of tyrosine phosphatase PTPH1 and PTPMEG1.

Implicated in

Entity name

Sporadic colorectal cancer.

Note

PTPD1 is overexpressed in MIN (microsatellite instability pathway) colorectal cancer cells lines.

Bibliography

Pubmed ID	Last Year	Title	Authors
15143158	2004	Mitochondrial AKAP121 binds and targets protein tyrosine phosphatase D1, a novel positive regulator of src signaling.	Cardone L et al
18223254	2008	Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration.	Carlucci A et al
9685376	1998	Characterization of KIF1C, a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum.	Dorner C et al
12082642	2002	Gene expression differences between the microsatellite instability (MIN) and chromosomal instability (CIN) phenotypes in colorectal cancer revealed by high-density cDNA array hybridization.	Dunican DS et al
11013262	2000	Protein-tyrosine phosphatase D1, a potential regulator and effector for Tec family kinases.	Jui HY et al
7805871	1994	Identification of a novel protein tyrosine phosphatase with sequence homology to the cytoskeletal proteins of the band 4.1 family.	L'Abbé D et al
16251349	2006	Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism.	Livigni A et al
7519780	1994	Src kinase associates with a member of a distinct subfamily of protein-tyrosine phosphatases containing an ezrin-like domain.	Møller NP et al

Other Information

Locus ID:

NCBI: 11099
MIM: 603271
HGNC: 9651
Ensembl: ENSG00000070778

Variants:

dbSNP: 11099
ClinVar: 11099
TCGA: ENSG00000070778
COSMIC: PTPN21

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000070778	ENST00000328736	Q16825
ENSG00000070778	ENST00000536337	G3V1Q9
ENSG00000070778	ENST00000553531	H0YJ59
ENSG00000070778	ENST00000555243	G3V3S6
ENSG00000070778	ENST00000556564	Q16825

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

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
18223254	2008	Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration.	18
20923765	2010	PTPD1 supports receptor stability and mitogenic signaling in bladder cancer cells.	12
19000305	2008	Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability.	10
19000305	2008	Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability.	10
21752600	2011	Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.	7
25062045	2014	Dynamic recruitment of protein tyrosine phosphatase PTPD1 to EGF stimulation sites potentiates EGFR activation.	5
31217419	2019	PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport.	4
16918960	2006	Use of Tag single nucleotide polymorphisms (SNPs) to screen PTPN21: no association with Graves' disease.	3

Citation

Antonio Feliciello

PTPN21 (protein tyrosine phosphatase, non-receptor type 21)

Atlas Genet Cytogenet Oncol Haematol. 2008-02-01

Online version: http://atlasgeneticsoncology.org/gene/41916/ptpn21