PTPN6
GeneName
PTPN6
Summary
PTPN6, also known as HCP, SHP-1, or SHP1, is a 68kDa non-membrane spanning protein tyrosine phosphatase that is predominantly expressed in haematopoietic cells. It plays a crucial role in regulating various signalling pathways, including those involved in immune responses, by dephosphorylating tyrosine residues on target proteins. PTPN6 is localised in multiple cellular compartments such as the cytoplasm, nucleus, and plasma membrane, and is involved in processes like T cell activation, B cell receptor signalling, and negative regulation of inflammatory responses. Its function is mediated through interactions with cell adhesion molecules and other signalling proteins, contributing to cellular differentiation and proliferation.
Importance
PTPN6 is relevant to: - Immune regulation, particularly in T cell and B cell signalling, influencing the immune response and tolerance - Haematopoiesis and megakaryocyte development, which are essential for platelet formation - Pathological conditions such as autoimmune diseases and cancer, where its regulatory functions may impact disease progression and treatment responses - The modulation of cytokine signalling and inflammatory responses, making it a potential target for therapeutic interventions in inflammatory diseases
Top Products
For researchers investigating PTPN6, we highly recommend the top-selling recombinant monoclonal antibody, Anti-SHP1 antibody [Y476] (ab32559). This antibody has been validated in knockout models, ensuring its reliability in various applications, particularly in Western blotting (WB) and immunohistochemistry (IHC). With 29 citations, it is well-regarded in the research community, reflecting its effectiveness and trustworthiness for PTPN6 studies. This product offers the consistency and performance that researchers seek in their experiments.
Abcam Product Citation Summary
The data indicates that the PTPN6 antibody (ab124942) has been utilised in various studies involving human samples, particularly in the context of B-cell chronic lymphocytic leukaemia (B-CLL) and chronic obstructive pulmonary disease (COPD). The studies highlight its application in western blotting to investigate cellular mechanisms such as proliferation and apoptosis.
Abcam Product Citation Table
Domain
The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation.
Function
Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities (PubMed:21258366, PubMed:9733788). When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events (PubMed:11907092, PubMed:14739280, PubMed:37932456, PubMed:38166031). Modulates the signaling of several cytokine receptors including IL-4 receptor (PubMed:9065461). Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling (PubMed:34811497, PubMed:38532423). Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Acts also as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A (PubMed:37595871).
Post-translational modifications
Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation (By similarity). Phosphorylation at Tyr-564 by LYN enhances phosphatase activity. Phosphorylation at Thr-394 by TAOK3 leads to polyubiquitination and subsequent proteasomal degradation (PubMed:38166031).
Ubiquitinated after phosphorylation by TAOK3 (PubMed:38166031). Ubiquitinated by a cooperation between ITCH and WWP2 via 'Lys-27'-mediated polyubiquitin chains resulting in the reduction of its association with LCK (PubMed:29925997).
Sequence Similarities
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.
Tissue Specificity
Isoform 1 is expressed in hematopoietic cells. Isoform 2 is expressed in non-hematopoietic cells.
Cellular localization
- Cytoplasm
- Nucleus
- In neurons, translocates into the nucleus after treatment with angiotensin II (By similarity). Shuttles between the cytoplasm and nucleus via its association with PDPK1.
Alternative names
HCP, PTP1C, PTPN6, Tyrosine-protein phosphatase non-receptor type 6, Hematopoietic cell protein-tyrosine phosphatase, Protein-tyrosine phosphatase 1C, Protein-tyrosine phosphatase SHP-1, SH-PTP1, PTP-1C
Database links
swissprot:P29350 entrezGene:5777 omim:176883
Other research areas
- Immuno-oncology