PSIP1

PSIP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases PSIP1, DFS70, LEDGF, PAIP, PSIP2, p52, p75, PC4 and SFRS1 interacting protein 1
External IDs MGI: 2142116 HomoloGene: 13242 GeneCards: PSIP1
RNA expression pattern




More reference expression data
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

RefSeq (protein)

NP_001121689.1
NP_066967.3
NP_150091.2
NP_001304827.1
NP_001304829.1

NP_001277456.1
NP_598709.1

Location (UCSC) Chr 9: 15.46 – 15.51 Mb Chr 4: 83.46 – 83.49 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/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.[3][4]

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[5] and is probably the only integrase interactor whose knock-down severely affects the HIV integration levels.[6][7][8] The interaction between HIV integrase and human LEDGF/p75 is a promising target for anti-HIV drug discovery.[9]

Structure

LEDGF/p75 is a 60kDa, 530-amino-acid-long protein.[10] 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,[11] 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.[12][13]

References

  1. "Human PubMed Reference:".
  2. "Mouse PubMed Reference:".
  3. "Entrez Gene: PSIP1 PC4 and SFRS1 interacting protein 1".
  4. 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.
  5. 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.
  6. Vandekerckhove L, Christ F, Van Maele B, De Rijck J, Gijsbers R, Van den Haute C, Witvrouw M, Debyser Z (February 2006). "Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus". J. Virol. 80 (4): 1886–96. doi:10.1128/JVI.80.4.1886-1896.2006. PMC 1367129Freely accessible. PMID 16439544.
  7. Shun MC, Raghavendra NK, Vandegraaff N, Daigle JE, Hughes S, Kellam P, Cherepanov P, Engelman A (July 2007). "LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration". Genes Dev. 21 (14): 1767–78. doi:10.1101/gad.1565107. PMC 1920171Freely accessible. PMID 17639082.
  8. Llano M, Saenz DT, Meehan A, Wongthida P, Peretz M, Walker WH, Teo W, Poeschla EM (October 2006). "An essential role for LEDGF/p75 in HIV integration". Science. 314 (5798): 461–4. doi:10.1126/science.1132319. PMID 16959972.
  9. Christ F, Voet A, Marchand A, Nicolet S, Desimmie BA, Marchand D, Bardiot D, Van der Veken NJ, Van Remoortel B, Strelkov SV, De Maeyer M, Chaltin P, Debyser Z (June 2010). "Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication". Nat. Chem. Biol. 6 (6): 442–8. doi:10.1038/nchembio.370. PMID 20473303.
  10. Llano M, Morrison J, Poeschla EM (2009). "Virological and cellular roles of the transcriptional coactivator LEDGF/p75". Curr. Top. Microbiol. Immunol. 339: 125–46. doi:10.1007/978-3-642-02175-6_7. PMC 3093762Freely accessible. PMID 20012527.
  11. 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.
  12. 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.
  13. 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 2804203Freely accessible. PMID 19864417.

Further reading

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