Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene. SHP1 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. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. SHP-1 gene has two promoters - P-1, active in epithelial cells, and P-2, active in hemopoietic cells. In addition the expression of SHP-1 is low in epithelial cells and high in hemopoetic cells. SHP-1 level in epithelial cells increases and in hematopoetic cells decreases in cancer.
Background References
1. "Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the apoptotic response to DNA damage." Yoshida K., Kharbanda S., Kufe D. J. Biol. Chem. 274:34663-34668(1999)
2. "Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization." Fiset A., Xu E., Bergeron S., Marette A., Pelletier G., Siminovitch K.A., Olivier M., Beauchemin N., Faure R.L. Cell. Signal. 23:911-919(2011)
3. "Crystal structure of human protein tyrosine phosphatase SHP-1 in the open conformation." Wang W., Liu L., Song X., Mo Y., Komma C., Bellamy H.D., Zhao Z.J., Zhou G.W.J. Cell. Biochem. 112:2062-2071(2011)
Sequence Similarity
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.
Post-translational Modification
Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation (By similarity). Phosphorylation at Tyr-564 enhances phosphatase activity.