{PDOC51947}
{PS51947; NIRAN}
{BEGIN}
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* Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile *
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Positive-stranded RNA  (+RNA)  viruses  that  belong  to the order Nidovirales
infect a  wide range of vertebrates (families Arteriviridae and Coronaviridae)
or invertebrates (Mesoniviridae and Roniviridae). Examples of nidoviruses with
high economic and societal impact are the arterivirus porcine reproductive and
respiratory syndrome  virus  (PRRSV)  and  the  zoonotic  coronaviruses (CoVs)
causing severe  acute  respiratory  syndrome  (SARS),  Middle East respiratory
syndrome (MERS) and Covid-19 (SARS-CoV-2) in humans.

In all  nidoviruses,  at least two-thirds of the capacity of the polycistronic
genome is occupied by the two large open reading frames (ORFs; 1a and 1b) that
together constitute  the  replicase  gene. The two polyproteins produced, pp1a
(ORF1a-encoded) and  pp1ab  (ORF1a/ORF1b-encoded), are processed to a dozen or
more proteins  by  the  virus’  main  protease (3CLpro, encoded in ORF1a) (see
<PDOC51442>) with  possible  involvement of other protease(s). These and other
proteins form  a  membrane-bound  replication-transcription complex (RTC) that
invariably includes  two  key  ORF1b-encoded  subunits:  the RNA-dependent RNA
polymerase (RdRp)   and   a   superfamily   1   helicase  domain  (HEL1)  (see
<PDOC51657>), which  is fused with a multinuclear Zn-binding domain (ZBD) (see
<PDOC51652>). The  RNA-dependent  RNA  polymerase (RdRp) domain of nidoviruses
resides in  a  cleavage  product  of  the  replicase  polyprotein  named  non-
structural protein (nsp) 12 in coronaviruses and nsp9 in arteriviruses. In all
nidoviruses, the  C-terminal  RdRp  domain is linked to a conserved N-terminal
domain, which  has  been  coined  NiRAN (nidovirus RdRp-associated nucleotidyl
transferase). The  NiRAN domain has an essential nucleotidylation activity and
its potential  functions  in  nidovirus  replication may include RNA ligation,
protein-primed RNA  synthesis,  and  the guanylyl-transferase function that is
necessary for mRNA capping [1,2,3,4,5].

The NiRAN  domain  is  characterized by an alpha + beta fold composed of eight
alpha helices and a five stranded beta-sheet (see <PDB:7BTF>). In addition, an
N-terminal beta-hairpin  interacts  with the palm subdomain of the RdRp domain
[5,6].

The profile we developed covers the entire Nidovirus NiRAN 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] Lehmann K.C., Gulyaeva A., Zevenhoven-Dobbe J.C., Janssen G.M.C.,
     Ruben M., Overkleeft H.S., van Veelen P.A., Samborskiy D.V.,
     Kravchenko A.A., Leontovich A.M., Sidorov I.A., Snijder E.J.,
     Posthuma C.C., Gorbalenya A.E.
     "Discovery of an essential nucleotidylating activity associated with a
     newly delineated conserved domain in the RNA polymerase-containing
     protein of all nidoviruses."
     Nucleic. Acids. Res. 43:8416-8434(2015).
     PubMed=26304538; DOI=10.1093/nar/gkv838
[ 2] Posthuma C.C., Te Velthuis A.J.W., Snijder E.J.
     "Nidovirus RNA polymerases: Complex enzymes handling exceptional RNA
     genomes."
     Virus. Res. 234:58-73(2017).
     PubMed=28174054; DOI=10.1016/j.virusres.2017.01.023
[ 3] Kirchdoerfer R.N., Ward A.B.
     "Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8
     co-factors."
     Nat. Commun. 10:2342-2342(2019).
     PubMed=31138817; DOI=10.1038/s41467-019-10280-3
[ 4] Saberi A., Gulyaeva A.A., Brubacher J.L., Newmark P.A.,
     Gorbalenya A.E.
     "A planarian nidovirus expands the limits of RNA genome size."
     PLoS Pathog. 14:E1007314-E1007314(2018).
     PubMed=30383829; DOI=10.1371/journal.ppat.1007314
[ 5] Romano M., Ruggiero A., Squeglia F., Maga G., Berisio R.
     "A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA
     Synthesis, Proofreading and Final Capping."
     Cells 9:0-0(2020).
     PubMed=32443810; DOI=10.3390/cells9051267
[ 6] Gao Y., Yan L., Huang Y., Liu F., Zhao Y., Cao L., Wang T., Sun Q.,
     Ming Z., Zhang L., Ge J., Zheng L., Zhang Y., Wang H., Zhu Y., Zhu C.,
     Hu T., Hua T., Zhang B., Yang X., Li J., Yang H., Liu Z., Xu W.,
     Guddat L.W., Wang Q., Lou Z., Rao Z.
     "Structure of the RNA-dependent RNA polymerase from COVID-19 virus."
     Science 368:779-782(2020).
     PubMed=32277040; DOI=10.1126/science.abb7498

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