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Coactivator-Associated Methyltransferase 1 Pleckstrin homology (PH) domain CARM1 (also known as protein arginine methyltransferase 4/PRMT4) is a protein arginine methyltransferase recruited by several transcription factors. It methylates a variety of proteins and plays a role in gene expression. The N-terminal domain of CARM1 contains a N-terminal PH domain, a catalytic core module composed of two parts (a Rossmann fold topology (RF) and a beta-barrel), and a C-terminal domain. The N-terminal and the C-terminal end of CARM1 catalytic module contain molecular switches that may explain how CARM1 regulates its biological activities by protein-protein interactions. 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.",