Protein Domain : NSP3, first ubiquitin-like (Ubl) domain, coronavirus IPR044357

Type	Domain
Description	Non-structural protein NSP3 (also known as nsp3) is a multi-domain protein, the largest product of ORF1a which encodes the poyprotein 1a/1ab (pp1a/1ab). NSP3 comprises up to 16 different domains and regions, their organisation differs between coronaviruses (CoV). However, eight domains and two transmembrane regions are conserved in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (hypervariable region), a macrodomain (X domain), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2pro, depending on the CoV there are one or two PLpro), the NSP3 ectodomain (3Ecto, also called "zinc-finger domain"), as well as the domains Y1 and CoV-Y of unknown function. NSP3 is released from pp1a/1ab by the papain-like protease domain(s), which is (are) part of NSP3 itself. NSP3 is an essential component of the replication/transcription complex (RTC) as it acts as a scaffold protein to interact with itself and to bind other viral NSPs or host proteins. The RTC associates with host ER membranes producing convoluted membranes and double-membrane vesicles. It is also involved in post-translational modifications of host proteins to antagonise its innate immune response [ , ].Nsp3 comprises various domains of functional and structural importance for virus replication, the organization of which differs between CoV genera, due to duplication or absence of some domains [ ]. Two ubiquitin-like domains, Ubl1 and Ubl2 (Nsp3a and the N-terminal domain of Nsp3d), exist within Nsp3 of all CoVs. The known functional roles of Nsp3a Ubl in CoVs are related to single-stranded (ssRNA) binding and interacting with the nucleocapsid (N) protein [, ]. Nsp3d Ubl is immediately adjacent to the N terminus of the PLpro (or PL2Pro) domain in CoV polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection [, , , ]. In addition to the four β-strands and two α-helices that are common to ubiquitin-like folds, the Nsp3a Ubl domain contains two short helices [, ]. The Nsp3d Ubl domain comprises five β-strands, one α-helix, and one 3(10)-helix [, , ]. This entry represents a domain covering the entire CoV Nsp3a and Nsp3d first Ubl domain. NSP3a interacts with numerous other proteins involved in replication and transcription and may serve as a scaffolding protein for these processes. The Ubl1 domain interacts with N protein to co-localise genomic RNA with the nascent replicase-transcriptase complex at the earliest stages of infection, essential for the virus []. This Ubl1 domain may bind ssRNA with AUA patterns. The C-terminal Glu-rich subdomain is best described as a flexible tail attached to the globular UB1 subdomain [].
Short Name	NSP3_Ubl1_dom_CoV