PSIP1

Last updated
PSIP1
Protein PSIP1 PDB 1z9e.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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
View/Edit Human View/Edit Mouse

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]

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]

Related Research Articles

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<span class="mw-page-title-main">PCAF</span> Protein-coding gene in humans

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<span class="mw-page-title-main">TAF4</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">HIV integration</span>

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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164985 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028484 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: PSIP1 PC4 and SFRS1 interacting protein 1".
  6. Singh DP, Kimura A, Chylack LT, Shinohara T (January 2000). "Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing". Gene. 242 (1–2): 265–73. doi:10.1016/S0378-1119(99)00506-5. PMID   10721720.
  7. Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, Engelborghs Y, De Clercq E, Debyser Z (January 2003). "HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells". J. Biol. Chem. 278 (1): 372–81. doi: 10.1074/jbc.M209278200 . PMID   12407101.
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  13. Pradeepa, Madapura M.; Sutherland, Heidi G.; Ule, Jernej; Grimes, Graeme R.; Bickmore, Wendy A. (2012-05-17). "Psip1/Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing". PLOS Genetics. 8 (5): e1002717. doi: 10.1371/journal.pgen.1002717 . ISSN   1553-7404. PMC   3355077 . PMID   22615581.
  14. Pradeepa, Madapura M.; McKenna, Fionnuala; Taylor, Gillian C. A.; Bengani, Hemant; Grimes, Graeme R.; Wood, Andrew J.; Bhatia, Shipra; Bickmore, Wendy A. (2017-04-06). "Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip". PLOS Genetics. 13 (4): e1006677. doi: 10.1371/journal.pgen.1006677 . ISSN   1553-7404. PMC   5383017 . PMID   28384324.
  15. Llano M, Morrison J, Poeschla EM (2009). "Virological and Cellular Roles of the Transcriptional Coactivator LEDGF/P75". HIV Interactions with Host Cell Proteins. Current Topics in Microbiology and Immunology. Vol. 339. pp. 125–46. doi:10.1007/978-3-642-02175-6_7. ISBN   978-3-642-02174-9. PMC   3093762 . PMID   20012527.{{cite book}}: |journal= ignored (help)
  16. Cherepanov P, Sun ZY, Rahman S, Maertens G, Wagner G, Engelman A (June 2005). "Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75". Nat. Struct. Mol. Biol. 12 (6): 526–32. doi:10.1038/nsmb937. PMID   15895093. S2CID   20898124.
  17. Ge H, Si Y, Wolffe AP (December 1998). "A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2". Mol. Cell. 2 (6): 751–9. doi: 10.1016/S1097-2765(00)80290-7 . PMID   9885563.
  18. Hughes S, Jenkins V, Dar MJ, Engelman A, Cherepanov P (January 2010). "Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase kinase (ASK) and stimulates its enzymatic activity". J. Biol. Chem. 285 (1): 541–54. doi: 10.1074/jbc.M109.036491 . PMC   2804203 . PMID   19864417.

Further reading