DUSP18 Human, Active

Dual Specificity Phosphatase 18 (DUSP18) is a member of the dual-specificity phosphatase (DSP) family, which is part of the larger type I cysteine-based protein-tyrosine phosphatase superfamily. These enzymes are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues, playing a crucial role in modulating various signaling pathways .

The DUSP18 gene is located on chromosome 22 and encodes a protein consisting of 212 amino acids with a molecular mass of approximately 23.6 kDa . The protein contains a consensus DUSP C-terminal catalytic domain but lacks the N-terminal CH2 domain found in the mitogen-activated protein kinase phosphatase (MKP) class of DUSPs .

DUSP18 exhibits a preferential enzymatic activity for phosphorylated tyrosine residues over threonine residues. It can dephosphorylate single and diphosphorylated synthetic MAPK peptides, with a preference for the phosphotyrosine and diphosphorylated forms . Additionally, DUSP18 dephosphorylates p-nitrophenyl phosphate (pNPP) in vitro and is inhibited by iodoacetic acid while being activated by manganese ions .

DUSP18 is extensively expressed in various tissues, with the highest levels observed in the liver, brain, ovary, and testis . The recombinant form of DUSP18 is produced in E. coli as a single, non-glycosylated polypeptide chain and is purified using proprietary chromatographic techniques .

As a dual-specificity phosphatase, DUSP18 plays a significant role in regulating critical signaling pathways by dephosphorylating key proteins involved in these pathways. This regulation is essential for maintaining cellular homeostasis and responding to various physiological stimuli .

Mutations or dysregulation of DUSP18 have been associated with certain diseases, including spastic paraplegia 26, an autosomal recessive disorder . Understanding the function and regulation of DUSP18 can provide insights into the pathogenesis of such diseases and potentially lead to the development of targeted therapies.