protein NPAT (nuclear protein of the ataxia telangiectasia mutated locus, nuclear protein of the ATM locus, p220, NPAT, CAND3, E14)

Function

• required for progression through G1 & S phases of the cell cycle & for S phase entry
• activates transcription of the histone H2A, histone H2B, histone H3 & histone H4 genes in conjunction with MIZF
• also positively regulates the ATM, MIZF & PRKDC promoters
• transcriptional activation may be accomplished at least in part by recruitment of NuA4 histone acetyltransferase complex to target gene promoters
• interacts with the cylin/CDK complexes CCNE1/CDK2 & CCNA1/CDK2
• interacts with BZW1, CASP8AP2, CREBBP, MIZF & YY1
• interacts with the RUVBL1, RUVBL2 & TRRAP subunits of the NuA4 complex
• may also interact with GAPDH, NME1, NME2 & STIP1
• phosphorylated upon DNA damage, probably by ATM or ATR
• phosphorylated by CCNE1/CDK2, which promotes association with histone gene clusters & stimulates activation of histone transcription
• phosphorylated by CCNA1/CDK2 in vitro

Structure

• the LisH domain is required for the activation of histone gene transcription
• belongs to the NPAT family
• contains 1 LisH domain

Compartment

• nucleus
• concentrates in two Cajal bodies tethered to histone gene clusters at chromosome 6p21 during G1, S & G2 phases
• also concentrates in two additional Cajal bodies tethered to histone gene clusters at chromosome 1q21, specifically during S & G2 phases

Expression

• ubiquitously expressed
• expressed throughout the cell cycle
• expression peaks at the G1/S phase boundary & declines during S phase
• induced by expression of E2F1, E2F2, E2F3 & E2F4
• expression is reduced in response to radiation-induced DNA damage

More general terms

• transcription factor (TF)
• phosphoprotein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4863
• OMIM: https://mirror.omim.org/entry/601448
• UniProt: http://www.uniprot.org/uniprot/Q14207.html