NS2_HRSVA
ID NS2_HRSVA Reviewed; 124 AA.
AC P04543; Q77YB6;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 23-FEB-2022, entry version 87.
DE RecName: Full=Non-structural protein 2;
DE Short=NS2;
DE AltName: Full=Non-structural protein 1B;
GN Name=1B; Synonyms=NS2;
OS Human respiratory syncytial virus A (strain A2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX NCBI_TaxID=11259;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2998021; DOI=10.1016/0042-6822(85)90384-8;
RA Collins P.L., Wertz G.W.;
RT "Nucleotide sequences of the 1B and 1C nonstructural protein mRNAs of human
RT respiratory syncytial virus.";
RL Virology 143:442-451(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=4009789; DOI=10.1128/jvi.55.1.101-110.1985;
RA Elango N., Satake M., Venkatesan S.;
RT "mRNA sequence of three respiratory syncytial virus genes encoding two
RT nonstructural proteins and a 22K structural protein.";
RL J. Virol. 55:101-110(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7747420; DOI=10.1006/viro.1995.1178;
RA Connors M., Crowe J.E. Jr., Firestone C.Y., Murphy B.R., Collins P.L.;
RT "A cold-passaged, attenuated strain of human respiratory syncytial virus
RT contains mutations in the F and L genes.";
RL Virology 208:478-484(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=9035372; DOI=10.1007/bf00366988;
RA Crowe J.E. Jr., Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R.;
RT "Acquisition of the ts phenotype by a chemically mutagenized cold-passaged
RT human respiratory syncytial virus vaccine candidate results from the
RT acquisition of a single mutation in the polymerase (L) gene.";
RL Virus Genes 13:269-273(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Cold-passage attenuated;
RX PubMed=9557743; DOI=10.1128/jvi.72.5.4467-4471.1998;
RA Whitehead S.S., Juhasz K., Firestone C.Y., Collins P.L., Murphy B.R.;
RT "Recombinant respiratory syncytial virus (RSV) bearing a set of mutations
RT from cold-passaged RSV is attenuated in chimpanzees.";
RL J. Virol. 72:4467-4471(1998).
RN [6]
RP SUBUNIT.
RX PubMed=8864205; DOI=10.1016/0168-1702(96)01327-5;
RA Evans J.E., Cane P.A., Pringle C.R.;
RT "Expression and characterisation of the NS1 and NS2 proteins of respiratory
RT syncytial virus.";
RL Virus Res. 43:155-161(1996).
RN [7]
RP FUNCTION.
RX PubMed=15047850; DOI=10.1128/jvi.78.8.4363-4369.2004;
RA Spann K.M., Tran K.C., Chi B., Rabin R.L., Collins P.L.;
RT "Suppression of the induction of alpha, beta, and lambda interferons by the
RT NS1 and NS2 proteins of human respiratory syncytial virus in human
RT epithelial cells and macrophages.";
RL J. Virol. 78:4363-4369(2004).
RN [8]
RP FUNCTION.
RX PubMed=15827150; DOI=10.1128/jvi.79.9.5353-5362.2005;
RA Spann K.M., Tran K.C., Collins P.L.;
RT "Effects of nonstructural proteins NS1 and NS2 of human respiratory
RT syncytial virus on interferon regulatory factor 3, NF-kappaB, and
RT proinflammatory cytokines.";
RL J. Virol. 79:5353-5362(2005).
RN [9]
RP FUNCTION.
RX PubMed=17151097; DOI=10.1128/jvi.01420-06;
RA Bitko V., Shulyayeva O., Mazumder B., Musiyenko A., Ramaswamy M.,
RA Look D.C., Barik S.;
RT "Nonstructural proteins of respiratory syncytial virus suppress premature
RT apoptosis by an NF-kappaB-dependent, interferon-independent mechanism and
RT facilitate virus growth.";
RL J. Virol. 81:1786-1795(2007).
RN [10]
RP FUNCTION.
RX PubMed=17251292; DOI=10.1128/jvi.02303-06;
RA Elliott J., Lynch O.T., Suessmuth Y., Qian P., Boyd C.R., Burrows J.F.,
RA Buick R., Stevenson N.J., Touzelet O., Gadina M., Power U.F.,
RA Johnston J.A.;
RT "Respiratory syncytial virus NS1 protein degrades STAT2 by using the
RT Elongin-Cullin E3 ligase.";
RL J. Virol. 81:3428-3436(2007).
RN [11]
RP FUNCTION, AND INTERACTION WITH HOST DDX58.
RX PubMed=19193793; DOI=10.1128/jvi.02434-08;
RA Ling Z., Tran K.C., Teng M.N.;
RT "Human respiratory syncytial virus nonstructural protein NS2 antagonizes
RT the activation of beta interferon transcription by interacting with RIG-
RT I.";
RL J. Virol. 83:3734-3742(2009).
RN [12]
RP SUBCELLULAR LOCATION, DOMAIN, SUBUNIT, INTERACTION WITH HOST MAP1B, AND
RP INTERACTION WITH NS1.
RX PubMed=21795342; DOI=10.1128/jvi.00413-11;
RA Swedan S., Andrews J., Majumdar T., Musiyenko A., Barik S.;
RT "Multiple functional domains and complexes of the two nonstructural
RT proteins of human respiratory syncytial virus contribute to interferon
RT suppression and cellular location.";
RL J. Virol. 85:10090-10100(2011).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23877405; DOI=10.1038/cr.2013.98;
RA Goswami R., Majumdar T., Dhar J., Chattopadhyay S., Bandyopadhyay S.K.,
RA Verbovetskaya V., Sen G.C., Barik S.;
RT "Viral degradasome hijacks mitochondria to suppress innate immunity.";
RL Cell Res. 23:1025-1042(2013).
RN [14]
RP FUNCTION.
RX PubMed=26557722; DOI=10.1155/2015/738547;
RA Zheng J., Yang P., Tang Y., Pan Z., Zhao D.;
RT "Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and
RT SOCS3 in the Different Manner from Endogenous IFN Signaling.";
RL J. Immunol. Res. 2015:738547-738547(2015).
RN [15]
RP REVIEW.
RX PubMed=31622448; DOI=10.1371/journal.ppat.1007984;
RA Sedeyn K., Schepens B., Saelens X.;
RT "Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional
RT disrupters of innate immune responses.";
RL PLoS Pathog. 15:e1007984-e1007984(2019).
RN [16]
RP REVIEW.
RX PubMed=32509597; DOI=10.3389/fcimb.2020.00225;
RA Thornhill E.M., Verhoeven D.;
RT "Respiratory Syncytial Virus's Non-structural Proteins: Masters of
RT Interference.";
RL Front. Cell. Infect. Microbiol. 10:225-225(2020).
CC -!- FUNCTION: Plays a major role in antagonizing the type I IFN-mediated
CC antiviral response (PubMed:15047850). Acts cooperatively with NS1 to
CC repress activation and nuclear translocation of host IFN-regulatory
CC factor IRF3 (PubMed:15827150). Interacts with the host cytoplasmic
CC sensor of viral nucleic acids DDX58/RIG-I and prevents the interaction
CC with its downstream partner MAVS (PubMed:19193793). Together with NS2,
CC participates in the proteasomal degradation of host STAT2, IRF3, IRF7,
CC TBK1 and DDX58 through a NS-degradasome involving CUL2 and Elongin-C
CC (PubMed:17251292, PubMed:23877405). The degradasome requires an intact
CC mitochondrial MAVS (PubMed:23877405). Induces host SOCS1 expression
CC (PubMed:26557722). Induces activation of NF-kappa-B. Suppresses
CC premature apoptosis by an NF-kappa-B-dependent, interferon-independent
CC mechanism promoting continued viral replication (PubMed:17151097).
CC {ECO:0000269|PubMed:15047850, ECO:0000269|PubMed:15827150,
CC ECO:0000269|PubMed:17151097, ECO:0000269|PubMed:17251292,
CC ECO:0000269|PubMed:19193793, ECO:0000269|PubMed:23877405,
CC ECO:0000269|PubMed:26557722}.
CC -!- SUBUNIT: Monomer (instable) (PubMed:8864205). Homomultimer
CC (PubMed:8864205). Heteromultimer with NS1 (PubMed:21795342). Interacts
CC with host DDX58 (via N-terminus); this interaction prevents host
CC signaling pathway involved in interferon production (PubMed:19193793).
CC Interacts with host MAP1B/microtubule-associated protein 1B
CC (PubMed:21795342). {ECO:0000269|PubMed:19193793,
CC ECO:0000269|PubMed:21795342, ECO:0000269|PubMed:8864205}.
CC -!- INTERACTION:
CC P04543; O95786: DDX58; Xeno; NbExp=2; IntAct=EBI-3648048, EBI-995350;
CC -!- SUBCELLULAR LOCATION: Host mitochondrion {ECO:0000269|PubMed:21795342,
CC ECO:0000269|PubMed:23877405}. Note=Most NS2 resides in the mitochondria
CC as a heteromer with NS1. {ECO:0000269|PubMed:21795342,
CC ECO:0000269|PubMed:23877405}.
CC -!- DOMAIN: The DNLP motif has IFN suppressive functions like binding to
CC host MAP1B. {ECO:0000269|PubMed:21795342}.
CC -!- SIMILARITY: Belongs to the pneumovirus non-structural protein 2 family.
CC {ECO:0000305}.
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DR EMBL; M11486; AAB59851.1; -; Genomic_RNA.
DR EMBL; U50362; AAB86657.1; -; Genomic_RNA.
DR EMBL; U50363; AAB86669.1; -; Genomic_RNA.
DR EMBL; U63644; AAC55963.1; -; Genomic_RNA.
DR EMBL; AF035006; AAC14895.1; -; Genomic_RNA.
DR PIR; B94336; MNNZ1B.
DR SMR; P04543; -.
DR IntAct; P04543; 1.
DR Proteomes; UP000007678; Genome.
DR Proteomes; UP000134464; Genome.
DR Proteomes; UP000181145; Genome.
DR Proteomes; UP000181262; Genome.
DR Proteomes; UP000181559; Genome.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity; IEA:UniProtKB-KW.
DR GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR GO; GO:0039557; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity; IEA:UniProtKB-KW.
DR GO; GO:0039723; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity; IEA:UniProtKB-KW.
DR InterPro; IPR004336; RSV_NS2.
DR Pfam; PF03113; RSV_NS2; 1.
PE 1: Evidence at protein level;
KW Host mitochondrion; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host IRF3 by virus; Inhibition of host IRF7 by virus;
KW Inhibition of host RIG-I by virus; Inhibition of host RLR pathway by virus;
KW Inhibition of host STAT2 by virus; Inhibition of host TBK1 by virus;
KW Inhibition of host TLR pathway by virus;
KW Interferon antiviral system evasion;
KW Modulation of host cell apoptosis by virus; Reference proteome;
KW Viral immunoevasion.
FT CHAIN 1..124
FT /note="Non-structural protein 2"
FT /id="PRO_0000142789"
FT MOTIF 121..124
FT /note="DLNP; interaction with MAP1B"
FT /evidence="ECO:0000269|PubMed:21795342"
FT CONFLICT 55
FT /note="R -> K (in Ref. 1; AAB59851)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 124 AA; 14702 MW; C14DF0FE9C9E5512 CRC64;
MDTTHNDNTP QRLMITDMRP LSLETIITSL TRDIITHKFI YLINHECIVR KLDERQATFT
FLVNYEMKLL HKVGSTKYKK YTEYNTKYGT FPMPIFINHD GFLECIGIKP TKHTPIIYKY
DLNP
