PSIP1 (PC4 and SFRS1 interacting protein 1)

2007-03-01 Cristina Morerio , Claudio Panarello Affiliation

Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy

Identity

HGNC

PSIP1

LOCATION

9p22.3

LOCUSID

11168

ALIAS

DFS70,LEDGF,PAIP,PSIP2,p52,p75

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

The gene contains at least 15 exons and 14 introns.

Transcription

Two alternative splice variants: p75 and p52.

Proteins

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 name

t(9;11)(p22;p15) NUP98-PSIP1

Note

acute non lymphoblastic leukemia (AML), one case of transformed .

Hybrid gene

5NUP98 - 3PSIP1.

Fusion protein

fuses the GLFG repeat domains of NUP98 to the COOH-terminus of PSIP1.

Bibliography

Pubmed ID	Last Year	Title	Authors
11103774	2000	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 et al
12407101	2003	HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells.	Cherepanov P et al
15389814	2005	Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis.	Daniels T et al
17363574	2007	Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer.	Daugaard M et al
15982735	2005	NUP98-LEDGF fusion and t(9;11) in transformed chronic myeloid leukemia.	Grand FH et al
11737860	2001	Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation.	Hussey DJ et al
15725483	2005	t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia.	Morerio C et al
10721720	2000	Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing.	Singh DP et al
16318853	2006	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 et al
16980622	2006	Disruption of Ledgf/Psip1 results in perinatal mortality and homeotic skeletal transformations.	Sutherland HG et al
12181742	2002	Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders.	Wu X et al

Other Information

Locus ID:

NCBI: 11168
MIM: 603620
HGNC: 9527
Ensembl: ENSG00000164985

Variants:

dbSNP: 11168
ClinVar: 11168
TCGA: ENSG00000164985
COSMIC: PSIP1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000164985	ENST00000380715	O75475
ENSG00000164985	ENST00000380716	O75475
ENSG00000164985	ENST00000380733	O75475
ENSG00000164985	ENST00000380738	O75475
ENSG00000164985	ENST00000397519	O75475
ENSG00000164985	ENST00000481862	V9GYT7

Expression (GTEx)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Disease	REACTOME	R-HSA-1643685
Infectious disease	REACTOME	R-HSA-5663205
HIV Infection	REACTOME	R-HSA-162906
HIV Life Cycle	REACTOME	R-HSA-162587
Early Phase of HIV Life Cycle	REACTOME	R-HSA-162594
Integration of provirus	REACTOME	R-HSA-162592
Integration of viral DNA into host genomic DNA	REACTOME	R-HSA-175567
2-LTR circle formation	REACTOME	R-HSA-164843
Autointegration results in viral DNA circles	REACTOME	R-HSA-177539
Host Interactions of HIV factors	REACTOME	R-HSA-162909
Interactions of Vpr with host cellular proteins	REACTOME	R-HSA-176033
Vpr-mediated nuclear import of PICs	REACTOME	R-HSA-180910
APOBEC3G mediated resistance to HIV-1 infection	REACTOME	R-HSA-180689

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
12407101	2003	HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells.	293
16311605	2005	A role for LEDGF/p75 in targeting HIV DNA integration.	284
16959972	2006	An essential role for LEDGF/p75 in HIV integration.	248
12796494	2003	LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells.	203
18598942	2008	Menin critically links MLL proteins with LEDGF on cancer-associated target genes.	198
15308744	2004	LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes.	156
22615581	2012	Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing.	140
15371438	2004	Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase.	128
15855167	2005	Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication.	109
16439544	2006	Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus.	101

Citation

Cristina Morerio ; Claudio Panarello

PSIP1 (PC4 and SFRS1 interacting protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2007-03-01

Online version: http://atlasgeneticsoncology.org/gene/405/psip1