PAXIP1

Description

The PAXIP1 (PAX interacting protein 1) is a protein-coding gene located on chromosome 7.

PAX-interacting protein 1 is a protein that in humans is encoded by the PAXIP1 gene. This gene is a member of the paired box (PAX) gene family and encodes a nuclear protein with six BRCT (breast cancer carboxy-terminal) domains. This protein plays a critical role in maintaining genome stability, condensation of chromatin and progression through mitosis. Protein-affecting variants have also been implicated in Alzheimer's disease. PAXIP1 has been shown to interact with PAX2 and TP53BP1.

PAXIP1 is involved in both DNA damage response and transcriptional regulation through histone methyltransferase (HMT) complexes. It plays a critical role in early development and is essential for cell survival after ionizing radiation by participating in the homologous recombination mechanism for repairing double-strand breaks (DSBs). PAXIP1's localization to DNA damage foci is dependent on RNF8 and UBE2N, and it recruits TP53BP1 to these foci. Effective DNA damage response often requires the association of PAXIP1 with TP53BP1 phosphorylated by ATM at 'Ser-25'. PAXIP1, in collaboration with TP53BP1, regulates ATM association. It's proposed that PAXIP1 recruits PAGR1 to sites of DNA damage, and the PAGR1:PAXIP1 complex is crucial for cell survival in response to DNA damage, potentially independent of MLL-containing HMT complexes. PAXIP1 promotes ubiquitination of PCNA following UV irradiation, possibly regulating the recruitment of polymerase eta and RAD51 to chromatin after DNA damage. PAXIP1 contributes to transcriptional regulation by linking MLL-containing HMT complexes to gene promoters, interacting with promoter-bound transcription factors like PAX2. It associates with gene promoters regulated by KMT2D/MLL2. During immunoglobulin class switching in activated B-cells, PAXIP1 participates in trimethylation of histone H3 at 'Lys-4' and in transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus. This function seems to involve the recruitment of MLL-containing HMT complexes. However, conflicting reports suggest that its role in transcriptional regulation during immunoglobulin class switching might be independent of the MLL2/MLL3 complex.

PAXIP1 is also known as CAGF28, CAGF29, PACIP1, PAXIP1L, PTIP, TNRC2.

Associated Diseases

WES Whole Exome Sequencing