dual specificity protein phosphatases 14, 18, 21, 28 and similar proteins
This family is composed of dual specificity protein phosphatase 14 (DUSP14, also known as MKP-6), 18 (DUSP18), 21 (DUSP21), 28 (DUSP28), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP14 directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses. DUSP18 has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane. DUSP28 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells.
Feature 1: catalytic site [active site], 2 residue positions
Conserved feature residue pattern:C R
Evidence:
Comment:the catalytic cysteine initiates a nucleophilic attack on the phosphate group of the substrate, forming a transient phosphoenzyme intermediate and releasing the substrate dephosphorylated; the transition state is stabilized by the arginine present in the catalytic pocket
Jiyao W et al.(2023). "The conserved domain database in 2023.",