PSIP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.
The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).
Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor -like 1" which has an official symbol of NFE2L1.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a protein that in humans is encoded by the SMARCB1 gene.
COUP-TFII, also known as NR2F2 is a protein that in humans is encoded by the NR2F2 gene. The COUP acronym stands for chicken ovalbumin upstream promoter.
Histone acetyltransferase KAT2A is an enzyme that in humans is encoded by the KAT2A gene.
Probable ATP-dependent RNA helicase DDX5 also known as DEAD box protein 5 or RNA helicase p68 is an enzyme that in humans is encoded by the DDX5 gene.
General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.
Transcription initiation factor TFIID subunit 4 is a protein that in humans is encoded by the TAF4 gene.
Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.
Transcription initiation factor TFIID subunit 2 is a protein that in humans is encoded by the TAF2 gene.
Transcription initiation factor TFIID subunit 5 is a protein that in humans is encoded by the TAF5 gene.
Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the TRIM24 gene.
Polycomb protein EED is a protein that in humans is encoded by the EED gene.
Necdin is a protein that in humans is encoded by the NDN gene.
Endothelial differentiation-related factor 1 is a protein that in humans is encoded by the EDF1 gene.
Cell division cycle-associated 7-like protein is a protein that in humans is encoded by the CDCA7L gene.
Hepatoma-derived growth factor, related protein 3, also known as HDGFRP3, is a human gene.
AIDS is caused by the human immunodeficiency virus (HIV). Individuals with HIV have what is referred to as a "HIV infection". When infected semen, vaginal secretions, or blood come in contact with the mucous membranes or broken skin of an uninfected person, HIV may be transferred to the uninfected person, causing another infection. Additionally, HIV can also be passed from infected pregnant women to their uninfected baby during pregnancy and/or delivery, or via breastfeeding. As a result of HIV infection, a portion of these individuals will progress and go on to develop clinically significant AIDS.
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