{PDOC51946}
{PS51946; COV_NSP4C}
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* Coronavirus Nsp4 C-terminal (Nsp4C) 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). Nsp4 is an approximately 500-amino-acid replicase
subunit that  is released by the combined activity of the main and papain-like
proteases. An N-terminal transmembrane region (amino acids 1-30) is presumably
followed by  a large lumenal domain (amino acids 30-280), three closely spaced
additional transmembrane  regions  (amino  acids  280-400)  and  finally  a C-
terminal domain  of about 100 residues that is exposed at the cytoplasmic face
of the  membrane.  Nsp4  plays  important  role in coronavirus replication and
double membrane  vesicles  (DMVs)  formation, and the transmembrane regions of
Nsp4 are  involved  in association of the coronavirus replication complex with
cellular membranes.  The  Nsp4C  domain  could  be  engaged in protein-protein
interactions [1,2].

The Nsp4C  structure  contains  six  short beta-strands, beta1-beta6, and four
alpha-helices, alpha1-alpha4.  Strands  beta1  and beta2 and strands beta3 and
beta5 form  small  two-stranded  antiparallel sheets (see <PDB:3GZF>). Strands
beta4 and    beta6  could participate in the formation of a dimer interface or
interact with  other partner molecules to help to stabilize the Nsp4 molecule.
Nsp4C has  nine  conserved  and  two  nonconserved  residues  which  form  the
hydrophobic core of the structure [1,2].

The profile we developed covers the entire CoV Nsp4C 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] Xu X., Lou Z., Ma Y., Chen X., Yang Z., Tong X., Zhao Q., Xu Y.,
     Deng H., Bartlam M., Rao Z.
     "Crystal structure of the C-terminal cytoplasmic domain of
     non-structural protein  4 from mouse hepatitis virus A59."
     PLoS One. 4:E6217-E6217(2009).
     PubMed=19593433; DOI=10.1371/journal.pone.0006217
[ 2] Manolaridis I., Wojdyla J.A., Panjikar S., Snijder E.J.,
     Gorbalenya A.E., Berglind H., Nordlund P., Coutard B., Tucker P.A.
     "Structure of the C-terminal domain of nsp4 from feline coronavirus."
     Acta Crystallogr. D. Biol. Crystallogr. 65:839-846(2009).
     PubMed=19622868; DOI=10.1107/S0907444909018253
[E1] https://viralzone.expasy.org/30?outline=all_by_species

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