PTPN21 (protein tyrosine phosphatase, non-receptor type 21)
2008-02-01 Antonio Feliciello AffiliationDipartimento di Biologia e Patologia Molecolare e Cellulare, Instituto di Endocrinologia ed Oncologia Sperimentale, 80131 Napoli, Italia
Identity
HGNC
LOCATION
14q31.3
LOCUSID
ALIAS
PTPD1,PTPRL10
FUSION GENES
DNA/RNA
Transcription
cDNA approximately 6.2 kb; at nucleotide 333-335 ATG of transcription initiation sites.
Pseudogene
No
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.
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
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
Implicated in
Entity name
Sporadic colorectal cancer.
Note
PTPD1 is overexpressed in MIN (microsatellite instability pathway) colorectal cancer cells lines.
Article 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
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38785187 | 2024 | Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways. | 0 |
| 38785187 | 2024 | Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways. | 0 |
| 33431714 | 2021 | Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18. | 5 |
| 33431714 | 2021 | Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18. | 5 |
| 31898344 | 2020 | PTPN21-CDS(long) isoform inhibits the response of acute lymphoblastic leukemia cells to NK-mediated lysis via the KIR/HLA-I axis. | 2 |
| 31898344 | 2020 | PTPN21-CDS(long) isoform inhibits the response of acute lymphoblastic leukemia cells to NK-mediated lysis via the KIR/HLA-I axis. | 2 |
| 31217419 | 2019 | PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport. | 34 |
| 31217419 | 2019 | PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport. | 34 |
| 25062045 | 2014 | Dynamic recruitment of protein tyrosine phosphatase PTPD1 to EGF stimulation sites potentiates EGFR activation. | 10 |
| 25062045 | 2014 | Dynamic recruitment of protein tyrosine phosphatase PTPD1 to EGF stimulation sites potentiates EGFR activation. | 10 |
| 21752600 | 2011 | Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia. | 10 |
| 21752600 | 2011 | Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia. | 10 |
| 20923765 | 2010 | PTPD1 supports receptor stability and mitogenic signaling in bladder cancer cells. | 23 |
| 20923765 | 2010 | PTPD1 supports receptor stability and mitogenic signaling in bladder cancer cells. | 23 |
| 18223254 | 2008 | Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration. | 29 |
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
