Structural highlights
Function
[PTN6_HUMAN] Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
SHP-1 is a cytosolic protein-tyrosine phosphatase that behaves as a negative regulator in eukaryotic cellular signaling pathways. To understand its regulatory mechanism, we have determined the crystal structure of the C-terminal truncated human SHP-1 in the inactive conformation at 2.8-A resolution and refined the structure to a crystallographic R-factor of 24.0%. The three-dimensional structure shows that the ligand-free SHP-1 has an auto-inhibited conformation. Its N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, which supports that the phosphatase activity of SHP-1 is primarily regulated by the N-SH2 domain. In addition, the C-SH2 domain of SHP-1 has a different orientation from and is more flexible than that of SHP-2, which enables us to propose an enzymatic activation mechanism in which the C-SH2 domains of SHPs could be involved in searching for phosphotyrosine activators.
Crystal structure of human protein-tyrosine phosphatase SHP-1.,Yang J, Liu L, He D, Song X, Liang X, Zhao ZJ, Zhou GW J Biol Chem. 2003 Feb 21;278(8):6516-20. Epub 2002 Dec 13. PMID:12482860[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Keilhack H, Muller M, Bohmer SA, Frank C, Weidner KM, Birchmeier W, Ligensa T, Berndt A, Kosmehl H, Gunther B, Muller T, Birchmeier C, Bohmer FD. Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1. J Cell Biol. 2001 Jan 22;152(2):325-34. PMID:11266449
- ↑ Yang J, Liu L, He D, Song X, Liang X, Zhao ZJ, Zhou GW. Crystal structure of human protein-tyrosine phosphatase SHP-1. J Biol Chem. 2003 Feb 21;278(8):6516-20. Epub 2002 Dec 13. PMID:12482860 doi:10.1074/jbc.M210430200
