PSIP1

PC4 and SFRS1 interacting protein 1, also known as lens epithelium-derived growth factor (LEDGF/p75), dense fine speckles 70kD protein (DFS 70) or transcriptional coactivator p75/p52, is a is_associated_with::protein that in humans is encoded by the PSIP1 is_associated_with::gene.

Function
PSIP1 has not been clearly linked to a specific cellular mechanism. The term LEDGF/p75 (Lens epithelium-derived growth factor) has entered common usage based on the initial characterization of PSIP1, however this is a misnomer, as the protein is present in most tissues and has no direct role in the development of lens epithelium. LEDGF/p75, a transcription coactivator, gained prominence as a host factor that assists HIV integration and is probably the only integrase interactor whose knock-down severely affects the HIV integration levels. The interaction between HIV is_associated_with::integrase and human LEDGF/p75 is a promising target for anti-HIV drug discovery.

Structure
LEDGF/p75 is a 60kDa, 530-amino-acid-long protein. The N-terminal portion of the protein consists of a PWWP domain, a nuclear localization sequence, and two copies of the is_associated_with::AT-hook DNA binding motif. The C-terminal portion of LEDGF/p75 contains a structure termed the integrase-binding domain, which interacts with lentiviral integrase proteins as well as numerous cellular proteins. The N-terminal portion interacts strongly with is_associated_with::chromatin, making LEDGF/p75 a constitutively nuclear protein. An isoform of the protein, LEDGF/p52, is produced by is_associated_with::alternative splicing. LEDGF/p52 shares the N-terminal 325 amino acids of LEDGF/p75 but lacks the integrase-binding domain.

Interactions
PSIP1 has been shown to interact with the proteins is_associated_with::ASF/SF2, JPO2, Cdc7-Dbf4, and is_associated_with::POGZ as well as the menin/MLL protein complex.