EBV Nuclear Antigen/EBNA1

The N-terminus contains the region UR1 that binds zinc and is essential for EBNA1 to activate transcription (PubMed:19521517, PubMed:36037477). This domain dimerizes upon coordinating (PubMed:19521517). The Gly-Gly-Ala repeat region (GAr) inhibits the mRNA translation of EBNA1 in cis and thus prevents MHC-I restricted presentation of EBNA1 epitopes to the host cytotoxic T cells (PubMed:12958359). The chromosome-tethering regions contain Gly-Arg (GR) repeats that function as AT hooks and are involved in EBNA1 stable replication and partition of episomes (PubMed:11172042, PubMed:15479791, PubMed:24067969). The C-terminus DNA binding and dimerization domain (DBD/DD) is required for the viral latent DNA replication (PubMed:36037477).

Responsible for the origin of replication (oriP) dependent replication and maintenance of viral episomes during latent infection (PubMed:15479791, PubMed:2996781). EBNA1 dimer interacts with the DS (dyad symmetry) element within the origin of replication oriP and with a host mitotic chromosome to initiate viral DNA replication during latency (PubMed:24067969, PubMed:2996781, PubMed:31142669, PubMed:8551585). EBNA1 binding to DS recruits the host origin recognition complex (ORC) (PubMed:12953058). Governs the faithful mitotic segregation of the viral episomes by binding both the FR (family of repeats) element within oriP and the host mitotic chromosomes (PubMed:11172042, PubMed:15479791, PubMed:24067969). Forms a cell cycle-dependent tyrosine-dependent DNA cross-link and single-strand cleavage at oriP required for terminating replication and maintaining viral episomes (PubMed:33482082). Counteracts the stabilization of host p53/TP53 by host USP7, thereby decreasing apoptosis and increasing host cell survival (PubMed:15808506). Induces degradation of host PML through the ubiquitin-proteasome system, which promotes lytic reactivation and may impair the host cell DNA repair (PubMed:18833293). Increases the association of CK2 with PML proteins which increases the phosphorylation of PML proteins by CK2, triggering the polyubiquitylation and degradation of PML (PubMed:20719947). Displays inhibitory effects on a SUMO2-modified complex that includes STUB1, KAP1 and USP7 (PubMed:32176739). This inhibitory effect possibly participates to the maintenance of latency linked to PML silencing (PubMed:32176739).

Phosphorylation at Ser-385 increases the nuclear import efficiency of EBNA1.

Phosphorylation at Ser-393 is required for interaction with CSNK2B.

Belongs to the herpesviridae EBNA1 family.

• Host nucleus

BKRF1, EBNA1, Epstein-Barr nuclear antigen 1, EBNA-1, EBV nuclear antigen 1

• swissprot:P03211

Proteins

56427Da