| Description | This entry represents the NS1-Nuc domain found mainly in the Parvovirinae subfamily of viruses in the family Parvoviridae.Adeno-associated virus (AAV) Replication (Rep) protein is essential for viral replication and integration. The catalytic domain has DNA binding and endonuclease activity.The family Parvoviridae is a group of small (18-26nm diameter), non-enveloped, and autonomously replicating icosahedral viruses containing a single-stranded linear DNA genome ranging from 4-6 kb in length, with terminal hairpins [E1]. The parvoviral single-stranded DNA genome contains two open reading frames (ORFs), one encoding nonstructural (NS) proteins, the other capsid proteins. All parvoviruses encode a nonstructural protein NS1 (termed Rep in adeno-associated virus [AAV]) that is essential for viral DNA replication and packaging of viral DNA into capsid. It may play other versatile roles, for example, in the transactivation of viral and cellular gene expression, DNA damage response, cell cycle arrest, apoptosis, and/or the modulation of innate immunity.The N terminus of the parvoviral NS1 protein contains an origin of replication binding (OBD) domain, also known as a DNA-specific binding domain or nuclease (NS1-Nuc) domain. Its central region contains a helicase domain, which includes an NTP-binding site, and its C terminus includes a transactivation domain (TAD). The PV NS1-Nuc domain plays an important role in the "rolling hairpin"replication of the single-stranded parvoviral DNA genome: after cellular enzymes have converted the viral genome into double-stranded DNA, it recognizes origin of replication sequences and cleaves (i.e., nicks) one strand DNA at a nearby site known as the terminal resolution site (trs). Since the DNA encountered by NS1 is double-stranded, it is assumed that binding of NS1 to its target sequences induces strand separation, allowing for the endonuclease activity of NS1 to cleave at the trs site [, , , , , , ]. A homologue of parvoviral NS1, U94, is found in human herpesvirus 6 variants A and B (HHV-6A and HHV-6B, respectively) which do not replicate by "rolling hairpin"mecanism. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation [ , ]. | Name | NS1 nuclease, NS1-Nuc domain, parvovirinae |
| Short Name | NS1-Nuc | Type | Domain |
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