{PDOC51958}
{PS51958; NENDOU}
{BEGIN}
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* Nidoviral uridylate-specific endoribonuclease (NendoU) 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 nonstructural  proteins  (Nsps)  by  the  virus’  main  protease (3CLpro,
encoded in  ORF1a)  (see  <PDOC51442>)  with  possible  involvement  of  other
protease(s). Among  the  Nsps  found  in Nidovirales, nonstructural protein 15
(nsp15) from  coronaviruses  and  Nsp11  from arteriviruses participate in the
viral replication  process  and in the evasion of the host immune system. They
contain in  their C-terminal region a conserved endoribonuclease domain called
nidoviral uridylate-specific    endoribonuclease    (NendoU)   with   cleavage
specificity for  single-  and double-stranded RNA 5' of uridine nucleotides to
produce a  2'-3'-cyclic  phosphate  end  product.  The  NendoU  domain  is not
conserved in  those  nidovirus  branches  that replicate in invertebrate hosts
(Mesoniviridae, Roniviridae),  suggesting  specific  roles in vertebrate hosts
[1,2,3,4,5,6,7,8].

The NendoU  domain  packs into two beta-sheets which constitute the catalytic-
site cleft  located  at one side of the domain. A group of small alpha-helices
packed at  the  other side of the domain face the concave surface of the beta-
sheets. The  active  site, located in the shallow groove between the two beta-
sheets, carries  the  catalytic  triad  made  of  two  histidines and a lysine
[4,5,6,7,8].

The profile we developed covers the entire NendoU domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2021 / First entry.

[ 1] Snijder E.J., Decroly E., Ziebuhr J.
     "The Nonstructural Proteins Directing Coronavirus RNA Synthesis and
     Processing."
     Adv. Virus. Res. 96:59-126(2016).
     PubMed=27712628; DOI=10.1016/bs.aivir.2016.08.008
[ 2] Zheng A., Shi Y., Shen Z., Wang G., Shi J., Xiong Q., Fang L.,
     Xiao S., Fu Z.F., Peng G.
     "Insight into the evolution of nidovirus endoribonuclease based on the
     finding that nsp15 from porcine Deltacoronavirus functions as a
     dimer."
     J. Biol. Chem. 293:12054-12067(2018).
     PubMed=29887523; DOI=10.1074/jbc.RA118.003756
[ 3] Cao J., Wu C.-C., Lin T.L.
     "Turkey coronavirus non-structure protein NSP15--an
     endoribonuclease."
     Intervirology 51:342-351(2008).
     PubMed=19023218; DOI=10.1159/000175837
[ 4] Xu X., Zhai Y., Sun F., Lou Z., Su D., Xu Y., Zhang R., Joachimiak A.,
     Zhang X.C., Bartlam M., Rao Z.
     "New antiviral target revealed by the hexameric structure of mouse
     hepatitis virus nonstructural protein nsp15."
     J. Virol. 80:7909-7917(2006).
     PubMed=16873248; DOI=10.1128/JVI.00525-06
[ 5] Joseph J.S., Saikatendu K.S., Subramanian V., Neuman B.W.,
     Buchmeier M.J., Stevens R.C., Kuhn P.
     "Crystal structure of a monomeric form of severe acute respiratory
     syndrome coronavirus endonuclease nsp15 suggests a role for
     hexamerization as an allosteric switch."
     J. Virol. 81:6700-6708(2007).
     PubMed=17409150; DOI=10.1128/JVI.02817-06
[ 6] Zhang M., Li X., Deng Z., Chen Z., Liu Y., Gao Y., Wu W., Chen Z.
     "Structural Biology of the Arterivirus nsp11 Endoribonucleases."
     J. Virol. 91:0-0(2017).
     PubMed=27795409; DOI=10.1128/JVI.01309-16
[ 7] Zhang L., Li L., Yan L., Ming Z., Jia Z., Lou Z., Rao Z.
     "Structural and Biochemical Characterization of Endoribonuclease Nsp15
     Encoded by  Middle East Respiratory Syndrome Coronavirus."
     J. Virol. 92:0-0(2018).
     PubMed=30135128; DOI=10.1128/JVI.00893-18
[ 8] Kim Y., Jedrzejczak R., Maltseva N.I., Wilamowski M., Endres M.,
     Godzik A., Michalska K., Joachimiak A.
     "Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2."
     Protein. Sci. 29:1596-1605(2020).
     PubMed=32304108; DOI=10.1002/pro.3873

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