PSIP1 (PC4 and SFRS1 interacting protein 1)

Identity

Other names	LEDGF (lens epithelium-derived growth factor)
	p75
	p52
Hugo	PSIP1
Location	9p22.3

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
Hugo	PSIP1
GDB	PSIP1
Entrez_Gene	PSIP1  11168  PC4 and SFRS1 interacting protein 1
	Cards
Atlas	PSIP1ID405ch9q22
GeneCards	PSIP1
Ensembl	PSIP1 [Search_View]   ENSG00000164985 [Gene_View]
Genatlas	PSIP1
GeneLynx	PSIP1
eGenome	PSIP1
euGene	11168
	Genomic and cartography
GoldenPath	PSIP1  -  9p22.3   chr9:15454066-15500982 -  9p22.3   [Description]    (hg18-Mar_2006)
Ensembl	PSIP1 - 9p22.3 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	PSIP1
	Gene and transcription
Genbank	AF063020 [ ENTREZ ]
Genbank	AF098482 [ ENTREZ ]
Genbank	AF098483 [ ENTREZ ]
Genbank	AF432220 [ ENTREZ ]
Genbank	BC013160 [ ENTREZ ]
RefSeq	NM_021144 [ SRS ]    NM_021144 [ ENTREZ ]
RefSeq	NM_033222 [ SRS ]    NM_033222 [ ENTREZ ]
RefSeq	AC_000052 [ SRS ]    AC_000052 [ ENTREZ ]
RefSeq	NC_000009 [ SRS ]    NC_000009 [ ENTREZ ]
RefSeq	NT_008413 [ SRS ]    NT_008413 [ ENTREZ ]
RefSeq	NW_924062 [ SRS ]    NW_924062 [ ENTREZ ]
AceView	PSIP1 AceView - NCBI
Unigene	Hs.658434 [ SRS ]    Hs.658434 [ NCBI ]     HS658434 [ spliceNest ]
Fast-db	18022 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O75475 [ SRS]    O75475 [ EXPASY ]     O75475 [ INTERPRO ]
Prosite	PS50812 PWWP [ SRS ]    PS50812 PWWP [ Expasy ]
Interpro	IPR000637 AT_hook_DNA_bd [ SRS ]    IPR000637 AT_hook_DNA_bd [ EBI ]
Interpro	IPR000313 PWWP [ SRS ]    IPR000313 PWWP [ EBI ]
CluSTr	O75475
Pfam	PF00855 PWWP [ SRS ]    PF00855 PWWP [ Sanger ]    pfam00855 [ NCBI-CDD ]
Smart	SM00293 PWWP [EMBL]
Blocks	O75475
PDB	1Z9E [ SRS ]    1Z9E [ PdbSum ],   1Z9E [ IMB ]   1Z9E [ RSDB ]
PDB	2B4J [ SRS ]    2B4J [ PdbSum ],   2B4J [ IMB ]   2B4J [ RSDB ]
HPRD	04688
	Protein Interaction databases
DIP	O75475
IntAct	O75475
	Polymorphism : SNP, mutations, diseases
OMIM	603620    [ map ]
GENECLINICS	603620
SNP	PSIP1 [dbSNP-NCBI]
SNP	NM_021144 [SNP-NCI]
SNP	NM_033222 [SNP-NCI]
SNP	PSIP1 [GeneSNPs - Utah]  PSIP1] [HGBASE - SRS]
HAPMAP	PSIP1 [HAPMAP]
COSMIC	PSIP1 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	PSIP1 [Translocation breakpoints In Cancer]
HGMD	PSIP1
	General knowledge
Family Browser	PSIP1 [UCSC Family Browser]
SOURCE	NM_021144
SOURCE	NM_033222
SMD	Hs.658434
SAGE	Hs.658434
GO	DNA binding [Amigo]  DNA binding
GO	nucleus [Amigo]  nucleus
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
PubGene	PSIP1
TreeFam	PSIP1
CTD	11168 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PSIP1 Related clones (RZPD - Berlin)
	PubMed
PubMed	48 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	03-2007	Cristina 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:26:19 2008