Pleckstrin homology-like domain of Ubiquitin carboxyl-terminal hydrolase 37
Members here include USP37, USP29, and USP26. All of these contain a single PH-like domain. USP37 (also called ubiquitin carboxyl-terminal hydrolase 37, ubiquitin thiolesterase 37, deubiquitinating enzyme 37, and tmp_locus_50) is a deubiquitinase that antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), resulting in promoting S phase entry. USP37 mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex and 'Lys-48'-linked polyubiquitin chains in vitro. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2). USP29 (also called ubiquitin carboxyl-terminal hydrolase 29, ubiquitin thiolesterase 29, deubiquitinating enzyme 29, and HOM-TES-84/86) plays a role in apoptosis and oxidative stress. In response to oxidative stress, JTV1 dissociates from the ARS complex, translocates to the nucleus, associates with far upstream element binding protein (FBP) and co-activates the transcription of USP29 which binds to, cleaves poly-ubiquitin chains from, and stabilizes p53 leading to apoptosis. The X-linked deubiquitination enzyme USP26 (also called ubiquitin carboxyl-terminal hydrolase 26, ubiquitin thiolesterase 26, and deubiquitinating enzyme 26) is a regulator of androgen receptor (AR) signaling. It binds to AR using three nuclear receptor interaction motifs (LXXLL, FXXLF and FXXFF) and modulates AR ubiquitination. Polymorphism of Usp26 correlates with idiopathic male infertility. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
Jiyao W et al.(2023). "The conserved domain database in 2023.",