PSIP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | PSIP1 , DFS70, LEDGF, PAIP, PSIP2, p52, p75, PC4 and SFRS1 interacting protein 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 603620; MGI: 2142116; HomoloGene: 13242; GeneCards: PSIP1; OMA:PSIP1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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 protein that in humans is encoded by the PSIP1 gene. [5] [6]
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 [7] and is probably the only integrase interactor whose knock-down severely affects the HIV integration levels. [8] [9] [10] The interaction between HIV integrase and human LEDGF/p75 is a promising target for anti-HIV drug discovery. [11] LEDGF/p75 recruits MLL complexes to HOX genes to regulate their expression. [12] LEDGF/p52 is shown to recruit splicing factors to H3K36 trimethylated chromatin to modulate alternative splicing, [13] also regulates HOTTIP lncRNA, which is shown to regulate HOX genes in cis. [14]
LEDGF/p75 is a 60kDa, 530-amino-acid-long protein. [15] The N-terminal portion of the protein consists of a PWWP domain, a nuclear localization sequence, and two copies of the AT-hook DNA binding motif. The C-terminal portion of LEDGF/p75 contains a structure termed the integrase-binding domain, [16] which interacts with lentiviral integrase proteins as well as numerous cellular proteins. The N-terminal portion interacts strongly with chromatin, making LEDGF/p75 a constitutively nuclear protein. An isoform of the protein, LEDGF/p52, is produced by alternative splicing. LEDGF/p52 shares the N-terminal 325 amino acids of LEDGF/p75 but lacks the integrase-binding domain.
PSIP1 has been shown to interact with the proteins ASF/SF2, JPO2, Cdc7-Dbf4, and POGZ as well as the menin/MLL protein complex. [17] [18]
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