NS1_HRSVA
ID NS1_HRSVA Reviewed; 139 AA.
AC P0DOE9; P04544; Q77YB7;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 23-FEB-2022, entry version 24.
DE RecName: Full=Non-structural protein 1;
DE Short=NS1;
DE AltName: Full=Non-structural protein 1C;
GN Name=1C; Synonyms=NS1;
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, AND INTERACTION WITH M PROTEIN.
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=9445048; DOI=10.1128/jvi.72.2.1452-1461.1998;
RA Atreya P.L., Peeples M.E., Collins P.L.;
RT "The NS1 protein of human respiratory syncytial virus is a potent inhibitor
RT of minigenome transcription and RNA replication.";
RL J. Virol. 72:1452-1461(1998).
RN [8]
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 [9]
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 [10]
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 [11]
RP INTERACTION WITH HOST ELOC AND CUL2, AND 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 [12]
RP FUNCTION.
RX PubMed=19625398; DOI=10.1128/jvi.00715-09;
RA Swedan S., Musiyenko A., Barik S.;
RT "Respiratory syncytial virus nonstructural proteins decrease levels of
RT multiple members of the cellular interferon pathways.";
RL J. Virol. 83:9682-9693(2009).
RN [13]
RP SUBCELLULAR LOCATION, DOMAIN, SUBUNIT, INTERACTION WITH HOST MAP1B, AND
RP INTERACTION WITH NS2.
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 [14]
RP FUNCTION.
RX PubMed=21533073; DOI=10.1371/journal.ppat.1001336;
RA Munir S., Hillyer P., Le Nouen C., Buchholz U.J., Rabin R.L., Collins P.L.,
RA Bukreyev A.;
RT "Respiratory syncytial virus interferon antagonist NS1 protein suppresses
RT and skews the human T lymphocyte response.";
RL PLoS Pathog. 7:e1001336-e1001336(2011).
RN [15]
RP INTERACTION WITH HOST IRF3, AND FUNCTION.
RX PubMed=21632562; DOI=10.1099/vir.0.032987-0;
RA Ren J., Liu T., Pang L., Li K., Garofalo R.P., Casola A., Bao X.;
RT "A novel mechanism for the inhibition of interferon regulatory factor-3-
RT dependent gene expression by human respiratory syncytial virus NS1
RT protein.";
RL J. Gen. Virol. 92:2153-2159(2011).
RN [16]
RP MUTAGENESIS OF 22-VAL--CYS-29.
RX PubMed=21600055; DOI=10.1186/1743-422x-8-252;
RA Straub C.P., Lau W.H., Preston F.M., Headlam M.J., Gorman J.J.,
RA Collins P.L., Spann K.M.;
RT "Mutation of the elongin C binding domain of human respiratory syncytial
RT virus non-structural protein 1 (NS1) results in degradation of NS1 and
RT attenuation of the virus.";
RL Virol. J. 8:252-252(2011).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST MAVS.
RX PubMed=22383950; DOI=10.1371/journal.pone.0029386;
RA Boyapalle S., Wong T., Garay J., Teng M., San Juan-Vergara H.,
RA Mohapatra S., Mohapatra S.;
RT "Respiratory syncytial virus NS1 protein colocalizes with mitochondrial
RT antiviral signaling protein MAVS following infection.";
RL PLoS ONE 7:E29386-E29386(2012).
RN [18]
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 [19]
RP FUNCTION.
RX PubMed=24480984; DOI=10.1159/000357327;
RA Xu X., Zheng J., Zheng K., Hou Y., Zhao F., Zhao D.;
RT "Respiratory syncytial virus NS1 protein degrades STAT2 by inducing SOCS1
RT expression.";
RL Intervirology 57:65-73(2014).
RN [20]
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 [21]
RP MUTAGENESIS OF TYR-125 AND 132-LEU-LEU-133.
RX PubMed=28665409; DOI=10.1038/nmicrobiol.2017.101;
RA Chatterjee S., Luthra P., Esaulova E., Agapov E., Yen B.C., Borek D.M.,
RA Edwards M.R., Mittal A., Jordan D.S., Ramanan P., Moore M.L., Pappu R.V.,
RA Holtzman M.J., Artyomov M.N., Basler C.F., Amarasinghe G.K., Leung D.W.;
RT "Structural basis for human respiratory syncytial virus NS1-mediated
RT modulation of host responses.";
RL Nat. Microbiol. 2:17101-17101(2017).
RN [22]
RP INTERACTION WITH HOST TRIM25, AND FUNCTION.
RX PubMed=30558248; DOI=10.3390/v10120716;
RA Ban J., Lee N.R., Lee N.J., Lee J.K., Quan F.S., Inn K.S.;
RT "Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I
RT Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling.";
RL Viruses 10:0-0(2018).
RN [23]
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 [24]
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 by degrading or inhibiting multiple cellular factors
CC required for either IFN induction or response pathways
CC (PubMed:15047850). Acts cooperatively with NS2 to repress activation
CC and nuclear translocation of host IFN-regulatory factor IRF3
CC (PubMed:15827150). Also disrupts the association of IRF3 with CREBBP
CC (PubMed:21632562). Interacts with host mitochondrial-associated
CC membrane (MAM) MAVS and prevents the interaction with DDX58/RIG-I
CC (PubMed:22383950) (Probable). Interacts with TRIM25 to suppress TRIM25-
CC mediated DDX58 ubiquitination and thereby DDX58-MAVS interaction
CC (PubMed:30558248). Together with NS2, participates in the proteasomal
CC degradation of host STAT2, IRF3, IRF7, TBK1 and DDX58/RIG-I through a
CC NS-degradasome involving CUL2 and Elongin-C (PubMed:17251292,
CC PubMed:23877405). The degradasome requires an intact mitochondrial MAVS
CC (PubMed:23877405). Decreases the levels of host TRAF3 and IKBKE/IKK-
CC epsilon (PubMed:19625398). As functions other than disruptions of the
CC type I IFN-mediated antiviral signaling pathways, induces host SOCS1
CC and SOCS3 expression (PubMed:24480984, PubMed:26557722). Suppresses
CC premature apoptosis by an NF-kappa-B-dependent, interferon-independent
CC mechanism and thus facilitates virus growth (PubMed:17151097).
CC Additionally, NS1 may serve some inhibitory role in viral transcription
CC and RNA replication (PubMed:9445048). Suppresses proliferation and
CC activation of host CD103+ CD8+ cytotoxic T-lymphocytes and Th17 helper
CC T-lymphocytes (PubMed:21533073). {ECO:0000269|PubMed:15047850,
CC ECO:0000269|PubMed:15827150, ECO:0000269|PubMed:17151097,
CC ECO:0000269|PubMed:17251292, ECO:0000269|PubMed:19625398,
CC ECO:0000269|PubMed:21533073, ECO:0000269|PubMed:21632562,
CC ECO:0000269|PubMed:22383950, ECO:0000269|PubMed:23877405,
CC ECO:0000269|PubMed:24480984, ECO:0000269|PubMed:26557722,
CC ECO:0000269|PubMed:30558248, ECO:0000269|PubMed:9445048,
CC ECO:0000305|PubMed:23877405}.
CC -!- SUBUNIT: Monomer (PubMed:8864205). Homomultimer (PubMed:21795342,
CC PubMed:8864205). Heteromultimer with NS2 (PubMed:21795342). Interacts
CC with the matrix protein M (PubMed:8864205). Interacts with host ELOC
CC and CUL2; this interaction allows NS1 to form an active E3 ligase with
CC ELOC and CUL2 (PubMed:17251292). Interacts with host IRF3; this
CC interaction leads to the disrupted association of IRF3 with CREBBP and
CC thus reduced binding of IRF3 to the IFN-beta promoter
CC (PubMed:21632562). Interacts with host MAVS; this interaction prevents
CC MAVS binding to DDX58 and inhibits signaling pathway leading to
CC interferon production (PubMed:22383950). Interacts with host
CC MAP1B/microtubule-associated protein 1B (PubMed:21795342). Interacts
CC with host TRIM25 (via SPRY domain); this interaction suppresses DDX58
CC ubiquitination and results in decreased interaction between DDX58 and
CC MAVS (PubMed:30558248). {ECO:0000269|PubMed:17251292,
CC ECO:0000269|PubMed:21632562, ECO:0000269|PubMed:21795342,
CC ECO:0000269|PubMed:22383950, ECO:0000269|PubMed:30558248,
CC ECO:0000269|PubMed:8864205}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:22383950}.
CC Host mitochondrion {ECO:0000269|PubMed:22383950,
CC ECO:0000269|PubMed:23877405}. Host nucleus
CC {ECO:0000269|PubMed:21795342}. Note=Most NS1 resides in the
CC mitochondria as a heteromer with NS2. {ECO:0000269|PubMed:21795342,
CC ECO:0000269|PubMed:23877405}.
CC -!- DOMAIN: N-terminus is important for IKBKE/IKK-epsilon reduction
CC (PubMed:21795342). The DNLP motif has IFN suppressive functions like
CC binding to host MAP1B (PubMed:21795342). {ECO:0000269|PubMed:21795342}.
CC -!- SIMILARITY: Belongs to the pneumovirus non-structural protein 1 family.
CC {ECO:0000305}.
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DR EMBL; M11486; AAB59850.1; -; Genomic_RNA.
DR EMBL; U50362; AAB86656.1; -; Genomic_RNA.
DR EMBL; U50363; AAB86668.1; -; Genomic_RNA.
DR EMBL; U63644; AAC55962.1; -; Genomic_RNA.
DR EMBL; AF035006; AAC14894.1; -; Genomic_RNA.
DR PIR; A94336; MNNZ1C.
DR SMR; P0DOE9; -.
DR IntAct; P0DOE9; 220.
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:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039504; P:suppression by virus of host adaptive immune response; 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:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS 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; IPR005099; Pneumo_NS1.
DR Pfam; PF03438; Pneumo_NS1; 1.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host mitochondrion; Host nucleus; Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
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 MAVS by virus; Inhibition of host RIG-I by virus;
KW Inhibition of host RLR pathway by virus; Inhibition of host STAT2 by virus;
KW Inhibition of host TBK1 by virus; 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..139
FT /note="Non-structural protein 1"
FT /id="PRO_0000142783"
FT MOTIF 136..139
FT /note="DLNP; interaction with MAP1B"
FT /evidence="ECO:0000269|PubMed:21795342"
FT MUTAGEN 22..29
FT /note="VALLKITC->AALAKITA: Mislocalizes NS1 to lysosomes."
FT /evidence="ECO:0000269|PubMed:21600055"
FT MUTAGEN 125
FT /note="Y->A: Decreased viral RNA replication and loss of
FT inhibition of IFN-beta production."
FT /evidence="ECO:0000269|PubMed:28665409"
FT MUTAGEN 132
FT /note="L->A: Decreased viral RNA replication and loss of
FT inhibition of IFN-beta production."
FT /evidence="ECO:0000269|PubMed:28665409"
FT MUTAGEN 133
FT /note="L->A: Decreased viral RNA replication and loss of
FT inhibition of IFN-beta production."
FT /evidence="ECO:0000269|PubMed:28665409"
SQ SEQUENCE 139 AA; 15567 MW; EBCC69B09BC46B6D CRC64;
MGSNSLSMIK VRLQNLFDND EVALLKITCY TDKLIHLTNA LAKAVIHTIK LNGIVFVHVI
TSSDICPNNN IVVKSNFTTM PVLQNGGYIW EMMELTHCSQ PNGLLDDNCE IKFSKKLSDS
TMTNYMNQLS ELLGFDLNP
