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 protein that in humans is encoded by the PSIP1 gene.^[5][6]

PSIP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Z9E, 2B4J, 2M16, 2MSR, 2MTN, 2N3A, 3F9K, 3HPG, 3HPH, 3U88, 3ZEH, 4FU6
Identifiers
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
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9p22.3 Start 15,464,066 bp[1] End 15,510,995 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 C3 Start 83,373,917 bp[2] End 83,404,696 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte ventricular zone ganglionic eminence cerebellar hemisphere right hemisphere of cerebellum Brodmann area 9 Achilles tendon optic nerve C1 segment nucleus accumbens Top expressed in tail of embryo ventricular zone genital tubercle spermatocyte zygote ganglionic eminence secondary oocyte lateral septal nucleus abdominal wall epiblast More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding transcription coactivator activity chromatin binding protein binding supercoiled DNA binding RNA binding Cellular component cytosol nuclear periphery nucleoplasm nucleolus nucleus Biological process regulation of transcription, DNA-templated response to heat response to oxidative stress transcription, DNA-templated establishment of integrated proviral latency mRNA 5'-splice site recognition positive regulation of transcription by RNA polymerase II viral process nuclear transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11168 101739 Ensembl ENSG00000164985 ENSMUSG00000028484 UniProt O75475 Q99JF8 RefSeq (mRNA) NM_001128217 NM_021144 NM_033222 NM_001317898 NM_001317900 NM_001290527 NM_133948 NM_001347143 NM_001355203 RefSeq (protein) NP_001121689 NP_001304827 NP_001304829 NP_066967 NP_150091 NP_001277456 NP_001334072 NP_598709 NP_001342132 Location (UCSC) Chr 9: 15.46 – 15.51 Mb Chr 4: 83.37 – 83.4 Mb PubMed search [3] [4]
Wikidata
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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^[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]

Structure

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.

Interactions

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]