{PDOC51942}
{PS51942; BCOV_NSP3C_C}
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* Betacoronavirus Nsp3c-C domain profile *
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Coronaviruses (CoVs)  are  enveloped  positive-strand  RNA viruses that infect
many species, including humans, other mammals, and birds. After infection, the
host may   develop  respiratory,  bowel,  liver,  and  neurological  diseases.
Coronaviruses are divided into four genera: Alphacoronavirus, Betacoronavirus,
Gammacoronavirus, and  Deltacoronavirus.  SARS,  SARS-CoV-2, BatCoV RaTG13 and
Bat-SARS-like coronavirus  (BATSL-CoVZXC21  and  BAT-SL-CoVZC45) belong to the
Sarbecovirus subgenus of Betacoronavirus [E1].

The CoV  replicase  gene encodes two overlapping polyproteins, termed pp1a and
pp1ab, which  mediate  viral  replication  and transcription. The polypeptides
pp1a and  pp1ab  are  processed  by  the action of a main protease (Nsp5) (see
<PDOC51442>) and of one or two papain-like proteases (PLpro) (see <PDOC51124>)
found in  Nsp3  into  non-structural  proteins (Nsps) to form the replication/
transcription complex (RTC). Among these, Nsp3 is a glycosylated, multidomain,
integral membrane  protein.  Nsp3 plays many roles in the viral life cycle. It
can act  as a scaffold protein to interact with itself and to bind other viral
Nsps or  host  proteins.  In  particular, Nsp3 is essential for RTC formation.
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 [1]. The Nsp3c-C (or SUD-C), which
is conserved  across  multiple beta-CoVs, is a Domain Preceding Ubl2 and PLpro
(DPUP). The  Nsp3c-C domain adopts a frataxin fold or double-wing motif, which
is an  alpha+beta  fold  that is associated with protein/protein interactions,
DNA binding,  and  metal  ion  binding.  The  Nsp3c-C  domain binds to single-
stranded RNA  and  recognizes purine bases more strongly than pyrimidine bases
[2,3,4].

The Nsp3c-C  domain  consists  of  an  antiparallel beta-sheet with two alpha-
helices at  the  N-  and  C-termini  that  pack  on one side of the sheet (see
<PDB:2KQW>) [1,2,3,,4].

The profile we developed covers the entire Nsp3c-C domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: October 2020 / First entry.

[ 1] Lei J., Kusov Y., Hilgenfeld R.
     "Nsp3 of coronaviruses: Structures and functions of a large
     multi-domain protein."
     Antiviral. Res. 149:58-74(2018).
     PubMed=29128390; DOI=10.1016/j.antiviral.2017.11.001
[ 2] Johnson M.A., Chatterjee A., Neuman B.W., Wuethrich K.
     "SARS coronavirus unique domain: three-domain molecular architecture
     in solution and RNA binding."
     J. Mol. Biol. 400:724-742(2010).
     PubMed=20493876; DOI=10.1016/j.jmb.2010.05.027
[ 3] Chen Y., Savinov S.N., Mielech A.M., Cao T., Baker S.C., Mesecar A.D.
     "X-ray Structural and Functional Studies of the Three Tandemly Linked
     Domains of Non-structural Protein 3 (nsp3) from Murine Hepatitis Virus
     Reveal Conserved Functions."
     J. Biol. Chem. 290:25293-25306(2015).
     PubMed=26296883; DOI=10.1074/jbc.M115.662130
[ 4] Hammond R.G., Tan X., Johnson M.A.
     "SARS-unique fold in the Rousettus bat coronavirus HKU9."
     Protein. Sci. 26:1726-1737(2017).
     PubMed=28580734; DOI=10.1002/pro.3208
[E1] https://viralzone.expasy.org/30?outline=all_by_species

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