Recombinant Epstein-Barr virus Epstein-Barr nuclear antigen 1 (EBNA1), partial, Biotinylated

Function

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)

Subcellular Location

Host nucleus

Subunit

Homodimer (PubMed:19521517, PubMed:9878348). Dimers can assemble into higher-order oligomers like a homohexamer (PubMed:28701406). Binding to the DS element involves 2 dimers of EBNA1 (PubMed:14506283, PubMed:15808506, PubMed:18833293, PubMed:31142669). Interacts with human USP7; this interaction is independent and simultaneous to EBNA1 interaction with CSNK2B as well as necessary for PML nuclear bodies disruption by EBNA1 (PubMed:14506283, PubMed:15808506, PubMed:18833293, PubMed:20719947, PubMed:24216761). Interacts with host CSNK2B (via KSSR motif); the interaction requires phosphorylation of EBNA1, is independent and simultaneous to EBNA1 interaction with USP7 as well as necessary for PML nuclear bodies disruption by EBNA1. EBNA1, USP7 and CSNK2B form a ternary complex. EBNA1, USP7 and CSNK2B form a ternary complex (PubMed:20719947, PubMed:24216761). Interacts with human EBP2; it is not clear if this interaction is linked with the ability of EBNA1 to associate with host mitotic chromosomes (PubMed:10074103, PubMed:15479791). Interacts with BGLF4; this interaction facilitates the switch from latent to lytic DNA replication by down-regulating EBNA1 replication function (PubMed:19244323). Interacts with human PAX5; this interaction promotes EBNA1-dependent transcription (PubMed:31941781). Interacts with host KPNA1/Importin subunit alpha-5; this interaction allows the nuclear import of EBNA1 (PubMed:10612665). Interacts with host KPNA2/Importin subunit alpha-1; this interaction allows the nuclear import of EBNA1 (PubMed:10612665, PubMed:28104399, PubMed:9020106). Interacts with host C1QBP/P32 (PubMed:9299613). Interacts with host BIRC5/Survivin; this interaction is probably important for EBV episome maintenance in Burkitt's lymphoma host cells (PubMed:28077791)

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