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

General

phosphoprotein transcription factor (TF)

Properties

SIZE: entity length = 1427 aa MW = 154 kD COMPARTMENT: cell nucleus MOTIF: MIZF interaction {1-318} MOTIF: LisH {3-35} MIZF interaction {5-25} MIZF interaction {121-145} transcriptional activation {262-338} Ser phosphorylation site {S535} G1 phase acceleration {629-653} Ser phosphorylation site {S775} Ser phosphorylation site {S779} acceleration of G1 phase {828-853} G1 phase acceleration {1039-1054} Ser phosphorylation site {S1100} G1 phase acceleration {1228-1252} Thr phosphorylation site {T1270} G1 phase acceleration {1325-1349} Thr phosphorylation site {T1350}

Database Correlations

OMIM 601448 UniProt Q14207 Kegg hsa:4863

References

UniProt :accession Q14207