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

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which in humans is encoded by the PSIP1 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

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

Coactivator (genetics)

A coactivator is a protein that increases gene expression by binding to an activator which contains a DNA binding domain. The coactivator is unable to bind DNA by itself....

, gained prominence as a host factor which assists HIV integration and is probably the only protein whose knock down severely affects the HIV integration levels (~ 9 fold). The interaction between HIV integrase

Integrase

Retroviral integrase is an enzyme produced by a retrovirus that enables its genetic material to be integrated into the DNA of the infected cell...

 and human LEDGF/p75 is a promising target for anti-HIV drug discovery.

Structure

LEDGF/p75 is a 60kDa, 530 amino acid long protein. The N-terminal portion of the protein consists of a PWWP domain, a nuclear localization sequence, and two copies of the AT-hook

AT-hook

right|thumb|The second AT-hook of [[HMGA1]] bound to the minor-groove of AT-rich DNA. The amino-acid side chains and nucleotides have been hidden....

 DNA binding motif. The C-terminal portion of LEDGF/p75 contains a structure termed the integrase binding domain, which interacts with lentiviral

Lentivirus

Lentivirus is a genus of slow viruses of the Retroviridae family, characterized by a long incubation period...

 integrase proteins as well as numerous cellular proteins. The N-terminal portion interacts strongly with chromatin

Chromatin

Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

, making LEDGF/p75 a constitutively nuclear protein. An isoform of the protein, LEDGF/p52, is produced by alternative splicing

Alternative splicing

Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA 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

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with the proteins ASF/SF2

ASF/SF2

ASF/SF2 also known as splicing factor, arginine/serine-rich 1 or SFRS1, is a protein which in humans is encoded by the SFRS1 gene. ASF/SF2 is an essential sequence specific splicing factor involved in pre-mRNA splicing. SFRS1 is the gene that codes for ASF/SF2 and is found on chromosome 17...

, JPO2, ASK, and POGZ

POGZ

Pogo transposable element with ZNF domain is a protein that in humans is encoded by the POGZ gene.-Further reading:...

 as well as the menin

Menin

Menin may refer to:*Menin , office in Ancien Régime France*Umberto Menin, Italian artist*The French name for the Belgian town of Menen *Menin, a tumor suppressor associated with multiple endocrine neoplasia type 1....

/MLL

MLL (gene)

Histone-lysine N-methyltransferase HRX is an enzyme that in humans is encoded by the MLL gene.MLL is a histone methyltransferase deemed a positive global regulator of gene transcription...

protein complex.