VHR Dual Specificity Phosphatase (VHR) Active Protein

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1. [provided by RefSeq, Jul 2008]

DUSP3: a non-receptor, dual-specificity phosphoprotein phosphatase (DUSP). Different members of the DUSP family show distinct substrate specificities for MAPKs, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. DUSP3 inactivates the mitogen-activated kinases Erk2 and Jnk and is phosphorylated by ZAP-70. Phosphorylation by ZAP-70 is required for DUSP3 to inhibit the Erk2-Elk-1 pathway.

Protein type: EC 3.1.3.48; Motility/polarity/chemotaxis; Protein phosphatase, dual-specificity; EC 3.1.3.16

Chromosomal Location of Human Ortholog: 17q21

Cellular Component: nucleoplasm; cytoplasm; immunological synapse; cytosol; nucleus

Molecular Function: MAP kinase phosphatase activity; protein tyrosine/serine/threonine phosphatase activity; protein tyrosine phosphatase activity

Biological Process: negative regulation of JNK cascade; nerve growth factor receptor signaling pathway; in utero embryonic development; negative regulation of MAPKKK cascade; MyD88-independent toll-like receptor signaling pathway; stress-activated MAPK cascade; negative regulation of T cell receptor signaling pathway; toll-like receptor 3 signaling pathway; positive regulation of mitotic cell cycle; toll-like receptor 2 signaling pathway; toll-like receptor 10 signaling pathway; MyD88-dependent toll-like receptor signaling pathway; toll-like receptor 5 signaling pathway; toll-like receptor signaling pathway; innate immune response; toll-like receptor 9 signaling pathway; toll-like receptor 4 signaling pathway; negative regulation of T cell activation; inactivation of MAPK activity