PAXIP1

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. [provided by RefSeq]

Full Name

PAXIP1

Function

Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. Plays a role in early development. In DNA damage response is required for cell survival after ionizing radiation. In vitro shown to be involved in the homologous recombination mechanism for the repair of double-strand breaks (DSBs). Its localization to DNA damage foci requires RNF8 and UBE2N. Recruits TP53BP1 to DNA damage foci and, at least in particular repair processes, effective DNA damage response appears to require the association with TP53BP1 phosphorylated by ATM at 'Ser-25'. Together with TP53BP1 regulates ATM association. Proposed to recruit PAGR1 to sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage; the function is probably independent of MLL-containing histone methyltransferase (HMT) complexes. However, this function has been questioned (By similarity).
Promotes ubiquitination of PCNA following UV irradiation and may regulate recruitment of polymerase eta and RAD51 to chromatin after DNA damage. Proposed to be involved in transcriptional regulation by linking MLL-containing histone methyltransferase (HMT) complexes to gene promoters by interacting with promoter-bound transcription factors such as PAX2. Associates with gene promoters that are known to be regulated by KMT2D/MLL2. During immunoglobulin class switching in activated B-cells is involved 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 appears to involve the recruitment of MLL-containing HMT complexes. Conflictingly, its function in transcriptional regulation during immunoglobulin class switching is reported to be independent of the MLL2/MLL3 complex (By similarity).

Biological Process

Adipose tissue developmentIEA:Ensembl
Chorion developmentIEA:Ensembl
DNA damage response, signal transduction by p53 class mediatorManual Assertion Based On ExperimentIMP:UniProtKB
DNA recombinationIEA:UniProtKB-KW
DNA repairIEA:UniProtKB-KW
Endothelial cell migrationIEA:Ensembl
Histone H3-K4 methylationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of histone acetylationISS:UniProtKB
Positive regulation of histone H3-K36 methylationISS:UniProtKB
Positive regulation of histone H3-K4 methylationISS:UniProtKB
Positive regulation of isotype switchingISS:UniProtKB
Positive regulation of isotype switching to IgG isotypesIEA:Ensembl
Positive regulation of protein ubiquitinationISS:UniProtKB
Positive regulation of response to DNA damage stimulusIEA:Ensembl
Positive regulation of transcription initiation from RNA polymerase II promoterManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cell cycle G2/M phase transitionIEA:Ensembl
Response to ionizing radiationManual Assertion Based On ExperimentIDA:UniProtKB
VasculogenesisIEA:Ensembl

Cellular Location

Nucleus matrix
Chromosome
Localizes to DNA damage foci upon ionizing radiation.