{PDOC51966}
{PS51966; COV_VIROPORIN_3A_TM}
{PS51967; COV_VIROPORIN_3A_CD}
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* Coronavirus (CoV) 3a-like viroporin transmembrane (TM) and cytosolic (CD) domains profiles *
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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.  The  ideal  hosts  of  AlphaCoV  and
BetaCoV are  mammals, and GammaCoV primarily infects birds, while DeltaCoV has
been identified in both mammals and birds. SARS, SARS-CoV-2, BatCoV RaTG13 and
Bat-SARS-like coronavirus  (BATSL-CoVZXC21  and  BAT-SL-CoVZC45) belong to the
Sarbecovirus subgenus of BetaCoV [E1].

All coronaviruses  have a similar genomic structure. At the 5' end, two-thirds
of the genome comprises two large open reading frames (ORFs) (ORF1a and ORF1b)
encoding the coronavirus replicase, which is highly conserved among genera. At
the 3'  end, the genome encodes four structural proteins (S, E, M and N) and a
variable number  of  accessory  proteins. Accessory proteins play an important
role in virus–host interactions, especially in antagonizing or regulating host
immunity and  virus  adaptation to the host. There are large variations in the
number of  accessory  proteins  (1–10)  among  coronaviruses.  The  number  of
accessory proteins  of  the  AlphaCoVs  is  relatively lower, between 1 and 5,
while BetaCoVs   have   3–5   accessory  proteins,  except  for  SARS-CoV  and
SARS-CoV-2, which  possess  the largest number of accessory proteins among all
coronaviruses (10  and  9, respectively). 3a-like accessory proteins are found
in multiple  AlphaCoV  and  BetaCoV lineages that infect bats and humans. They
are transmembrane  proteins  of the viroporin family that form ion channels in
the host   membrane   and   have   been   implicated  in  inducing  apoptosis,
pathogenicity, and virus release. The induction of cytokine storms in COVID-19
patients might be linked to ORF3a mediated activation of inflammasome. 3a-like
viroporins contain  a  transmembrane  domain  (TM) and a cytosolic domain (CD)
[1,2,3,4,5,6,7].

The 3a-like viroporin TM domain is composed of three helices and the CD domain
of two anti-parallel beta-sheets forming a beta-sandwich (see <PDB:6XDC>). The
3a-like viroporin forms a dimer and the six transmembrane helices of the dimer
form an ion channel with polar/charged residues in the interior of the channel
capable of conducting cations [3].

The profiles  we developed cover respectively the entire CoV 3a-like viroporin
TM and CD domains.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: March 2021 / First entry.

[ 1] Arya R., Kumari S., Pandey B., Mistry H., Bihani S.C., Das A.,
     Prashar V., Gupta G.D., Panicker L., Kumar M.
     "Structural insights into SARS-CoV-2 proteins."
     J. Mol. Biol. 433:166725-166725(2021).
     PubMed=33245961; DOI=10.1016/j.jmb.2020.11.024
[ 2] Azad G.K., Khan P.K.
     "Variations in Orf3a protein of SARS-CoV-2 alter its structure and
     function."
     Biochem. Biophys. Rep. 26:100933-100933(2021).
     PubMed=33527091; DOI=10.1016/j.bbrep.2021.100933
[ 3] Kern D.M., Sorum B., Hoel C.M., Sridharan S., Remis J.P., Toso D.B.,
     Brohawn S.G.
     "Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid
     nanodiscs."
     bioRxiv 0:0-0(2020).
     PubMed=32587976; DOI=10.1101/2020.06.17.156554
[ 4] Shang J., Han N., Chen Z., Peng Y., Li L., Zhou H., Ji C., Meng J.,
     Jiang T., Wu A.
     "Compositional diversity and evolutionary pattern of coronavirus
     accessory proteins."
     Brief. Bioinform. 0:0-0(2020).
     PubMed=33126244; DOI=10.1093/bib/bbaa262
[ 5] McClenaghan C., Hanson A., Lee S.-J., Nichols C.G.
     "Coronavirus Proteins as Ion Channels: Current and Potential
     Research."
     Front. Immunol. 11:573339-573339(2020).
     PubMed=33154751; DOI=10.3389/fimmu.2020.573339
[ 6] Chen I.-Y., Moriyama M., Chang M.-F., Ichinohe T.
     "Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates
     the NLRP3 Inflammasome."
     Front. Microbiol. 10:50-50(2019).
     PubMed=30761102; DOI=10.3389/fmicb.2019.00050
[ 7] Ouzounis C.A.
     "A recent origin of Orf3a from M protein across the coronavirus
     lineage arising by sharp divergence."
     Comput. Struct. Biotechnol. J. 18:4093-4102(2020).
     PubMed=33363705; DOI=10.1016/j.csbj.2020.11.047
[E1] https://viralzone.expasy.org/30?outline=all_by_species

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