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PSIP1 (PC4 and SFRS1 interacting protein 1)

Identity

Other namesLEDGF (lens epithelium-derived growth factor)
p75
p52
HGNC (Hugo) PSIP1
Location 9p22.3
Location_base_pair Starts at 15454065 and ends at 15501003 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Description The gene contains at least 15 exons and 14 introns.
Transcription Two alternative splice variants: p75 and p52.

Protein

Description 530 amino acids (p75), 333 amino acids (p52); N-term - PWWP (proline-tryptophan-tryptophan-proline) domain ­ NLS (nuclear localization signal) ­ AT-hook-like ­ Coiled coil ­ IBD (integrase binding domain) ­ HTH1 (helix-turn-helix DNA binding motif) ­ HTH2 ­ C-term.
Expression Expression of PSIP1 has been reported to be increased in human breast and bladder cancer, prostate tumorsand benign prostate hyperplasia.
Localisation nuclear.
Function Transcriptional regulation of stress-associated genes, mRNA splicing and cell survival. The involvement of PSIP1 (LEDGF) has been reported in human immunodeficiency virus type-1 (HIV-1) integration, autoimmune disorders, and neurogenesis. Recent data reveal LEDGF as an oncogenic protein that controls a caspase-independent lysosomal cell death pathway.
Homology PSIP1 belongs to the hepatoma-derived growth factor (HDGF) family of proteins that contain a well conserved N-terminal amino acid sequence known as the HATH (homologous to amino terminus of HDGF) region.

Implicated in

Entity t(9;11)(p22;p15) NUP98-PSIP1
Note acute non lymphoblastic leukemia (ANLL), one case of transformed .
Hybrid/Mutated Gene 5'NUP98 - 3'PSIP1.
Abnormal Protein fuses the GLFG repeat domains of NUP98 to the COOH-terminus of PSIP1.
  

External links

Nomenclature
HGNC (Hugo)PSIP1   9527
Entrez_Gene (NCBI)PSIP1  11168  PC4 and SFRS1 interacting protein 1
Cards
AtlasPSIP1ID405ch9q22
GeneCards (Weizmann)PSIP1
Ensembl (Hinxton)ENSG00000164985 [Gene_View]  PSIP1 [Vega]
AceView (NCBI)PSIP1
Genatlas (Paris)PSIP1
euGene (Indiana)11168
SOURCE (Stanford)NM_001128217 NM_021144 NM_033222
Genomic and cartography
GoldenPath (UCSC)PSIP1  -  9p22.3   chr9:15454065-15501003 -  9p22.2   [Description]    (hg18-Mar_2006)
EnsemblPSIP1 - 9p22.2 [CytoView]
Mapping of homologs : NCBIPSIP1 [Mapview]
OMIM603620   
Gene and transcription
Gene : Genbank (Entrez)AF063020 AF098482 AF098483 AF432220 BC013160
Reference sequence (RefSeq transcript) :SRSNM_001128217 NM_021144 NM_033222
Reference transcript : EntrezNM_001128217 NM_021144 NM_033222
RefSeq genomic : SRSAC_000052 AC_000141 NC_000009 NT_008413 NW_001839149 NW_924062
RefSeq genomic : EntrezAC_000052 AC_000141 NC_000009 NT_008413 NW_001839149 NW_924062
Consensus coding sequences : CCDS NCBIPSIP1
Cluster EST : UnigeneHs.658434 [ SRS ] Hs.658434 [ NCBI ]
Alternative Splicing : Fast-db (Paris)18022
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtO75475 (SRS) O75475 (Expasy) O75475 (Uniprot)
With graphics : InterProO75475
Splice isoforms : VarSplice FASTAO75475(VarSplice FASTA)
Domaine pattern : Prosite (SRS)PWWP (PS50812)   
Domain pattern : Prosite (Expaxy)PWWP (PS50812)   
Domains : Interpro (SRS)AT_hook_DNA_bd    PWWP   
Domains : Interpro (EBI)AT_hook_DNA_bd    PWWP   
Related proteins : CluSTrO75475
Domain families : Pfam SRSPWWP (PF00855)   
Domain families : Pfam SangerPWWP (PF00855)   
Domain families : Pfam NCBIpfam00855   
Domain families : Smart EMBLPWWP (SM00293)
Blocks (Seattle)O75475
Crystal structure of protein : PDB SRS1Z9E    2B4J   
Crystal structure of protein : PDBSum1Z9E    2B4J   
Crystal structure of protein : IMB1Z9E    2B4J   
Crystal structure of protein : PDB RSDB1Z9E    2B4J   
HPRD04688
Protein Interaction databases
DIP (DOE-UCLA)O75475
IntAct (EBI)O75475
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIPSIP1
SNP : GeneSNP UtahPSIP1
SNP : HGBasePSIP1
Genetic variants : HAPMAPPSIP1
Somatic Mutations in Cancer : COSMICPSIP1 
Translocation Breakpoints in Cancer : TICdbPSIP1 
Mutations and Diseases : HGMDPSIP1
Hereditary diseases : OMIM603620   
Hereditary diseases : GENETests603620   
Diseases : Genetic AssociationPSIP1
General knowledge
Homologs : HomoloGenePSIP1
Homology/Alignments : Family Browser UCSCPSIP1
Phylogenetic Trees/Animal Genes : TreeFamPSIP1
Chemical/Protein Interactions : CTD11168
Keywords Ontology : AmiGODNA binding  nucleus  cytosol  transcription  regulation of transcription, DNA-dependent  provirus integration  initiation of viral infection  interspecies interaction between organisms  
Keywords Ontology : EGO-EBIDNA binding  nucleus  cytosol  transcription  regulation of transcription, DNA-dependent  provirus integration  initiation of viral infection  interspecies interaction between organisms  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesPSIP1 Related clones (RZPD - Berlin)
Literature
PubMed59 Pubmed reference(s) in Entrez
PubGenePSIP1

Bibliography

t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF).
Ahuja HG, Hong J, Aplan PD, Tcheurekdjian L, Forman SJ, Slovak ML
Cancer research. 2000 ; 60 (22) : 6227-6229.
PMID 11103774
 
Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing.
Singh DP, Kimura A, Chylack LT Jr, Shinohara T
Gene. 2000 ; 242 (1-2) : 265-273.
PMID 10721720
 
Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation.
Hussey DJ, Moore S, Nicola M, Dobrovic A
BMC genetics. 2001 ; 2 : page 20.
PMID 11737860
 
Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders.
Wu X, Daniels T, Molinaro C, Lilly MB, Casiano CA
Cell death and differentiation. 2002 ; 9 (9) : 915-925.
PMID 12181742
 
HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells.
Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, Engelborghs Y, De Clercq E, Debyser Z
The Journal of biological chemistry. 2003 ; 278 (1) : 372-381.
PMID 12407101
 
Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis.
Daniels T, Zhang J, Gutierrez I, Elliot ML, Yamada B, Heeb MJ, Sheets SM, Wu X, Casiano CA
The Prostate. 2005 ; 62 (1) : 14-26.
PMID 15389814
 
NUP98-LEDGF fusion and t(9;11) in transformed chronic myeloid leukemia.
Grand FH, Koduru P, Cross NC, Allen SL
Leukemia research. 2005 ; 29 (12) : 1469-1472.
PMID 15982735
 
t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia.
Morerio C, Acquila M, Rosanda C, Rapella A, Tassano E, Micalizzi C, Panarello C
Leukemia research. 2005 ; 29 (4) : 467-470.
PMID 15725483
 
DNA binding domains and nuclear localization signal of LEDGF: contribution of two helix-turn-helix (HTH)-like domains and a stretch of 58 amino acids of the N-terminal to the trans-activation potential of LEDGF.
Singh DP, Kubo E, Takamura Y, Shinohara T, Kumar A, Chylack LT Jr, Fatma N
Journal of molecular biology. 2006 ; 355 (3) : 379-394.
PMID 16318853
 
Disruption of Ledgf/Psip1 results in perinatal mortality and homeotic skeletal transformations.
Sutherland HG, Newton K, Brownstein DG, Holmes MC, Kress C, Semple CA, Bickmore WA
Molecular and cellular biology. 2006 ; 26 (19) : 7201-7210.
PMID 16980622
 
Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer.
Daugaard M, Kirkegaard-Sˆ½rensen T, Ostenfeld MS, Aaboe M, Hˆ½yer-Hansen M, Orntoft TF, Rohde M, Jˆ§ˆ§ttelˆ§ M
Cancer research. 2007 ; 67 (6) : 2559-2567.
PMID 17363574
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2007Cristina Morerio, Claudio Panarello
Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy.

Citation

This paper should be referenced as such :
Morerio C, Panarello C . PSIP1 (PC4 and SFRS1 interacting protein 1). Atlas Genet Cytogenet Oncol Haematol. March 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/PSIP1ID405ch9q22.html

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indexed on : Sat Jun 27 16:39:01 CEST 2009
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