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NS1_HRSS2
ID   NS1_HRSS2               Reviewed;         139 AA.
AC   P0DOE8; P04544; Q77YB7;
DT   12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2017, sequence version 1.
DT   03-AUG-2022, entry version 20.
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 S-2) (HRSV-S2).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX   NCBI_TaxID=410078;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9032893; DOI=10.1016/s0264-410x(96)00136-3;
RA   Tolley K.P., Marriott A.C., Simpson A., Plows D.J., Matthews D.A.,
RA   Longhurst S.J., Evans J.E., Johnson J.L., Cane P.A., Easton A.J.,
RA   Pringle C.R.;
RT   "Identification of mutations contributing to the reduced virulence of a
RT   modified strain of respiratory syncytial virus.";
RL   Vaccine 14:1637-1646(1996).
RN   [2]
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   [3]
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. Acts
CC       cooperatively with NS2 to repress activation and nuclear translocation
CC       of host IFN-regulatory factor IRF3. Also disrupts the association of
CC       IRF3 with CREBBP. Interacts with host mitochondrial-associated membrane
CC       (MAM) MAVS and prevents the interaction with DDX58/RIG-I. Interacts
CC       with TRIM25 to suppress TRIM25-mediated DDX58 ubiquitination and
CC       thereby DDX58-MAVS interaction. Together with NS2, participates in the
CC       proteasomal degradation of host STAT2, IRF3, IRF7, TBK1 and DDX58/RIG-I
CC       through a NS-degradasome involving CUL2 and Elongin-C. The degradasome
CC       requires an intact mitochondrial MAVS. Decreases the levels of host
CC       TRAF3 and IKBKE/IKK-epsilon. As functions other than disruptions of the
CC       type I IFN-mediated antiviral signaling pathways, induces host SOCS1
CC       and SOCS3 expression. Suppresses premature apoptosis by an NF-kappa-B-
CC       dependent, interferon-independent mechanism and thus facilitates virus
CC       growth. Additionally, NS1 may serve some inhibitory role in viral
CC       transcription and RNA replication. Suppresses proliferation and
CC       activation of host CD103+ CD8+ cytotoxic T-lymphocytes and Th17 helper
CC       T-lymphocytes. {ECO:0000250|UniProtKB:P0DOE9}.
CC   -!- SUBUNIT: Monomer. Homomultimer. Heteromultimer with NS2. Interacts with
CC       the matrix protein M. Interacts with host ELOC and CUL2; this
CC       interaction allows NS1 to form an active E3 ligase with ELOC and CUL2.
CC       Interacts with host IRF3; this interaction leads to the disrupted
CC       association of IRF3 with CREBBP and thus reduced binding of IRF3 to the
CC       IFN-beta promoter. Interacts with host MAVS; this interaction prevents
CC       MAVS binding to DDX58 and inhibits signaling pathway leading to
CC       interferon production. Interacts with host MAP1B/microtubule-associated
CC       protein 1B. Interacts with host TRIM25 (via SPRY domain); this
CC       interaction suppresses DDX58 ubiquitination and results in decreased
CC       interaction between DDX58 and MAVS. {ECO:0000250|UniProtKB:P0DOE9}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250|UniProtKB:P0DOE9}.
CC       Host mitochondrion {ECO:0000250|UniProtKB:P0DOE9}. Host nucleus
CC       {ECO:0000250|UniProtKB:P0DOE9}. Note=Most NS1 resides in the
CC       mitochondria as a heteromer with NS2. {ECO:0000250|UniProtKB:P0DOE9}.
CC   -!- DOMAIN: N-terminus is important for IKBKE/IKK-epsilon reduction. The
CC       DNLP motif has IFN suppressive functions like binding to host MAP1B.
CC       {ECO:0000250|UniProtKB:P0DOE9}.
CC   -!- SIMILARITY: Belongs to the pneumovirus non-structural protein 1 family.
CC       {ECO:0000305}.
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DR   EMBL; U39662; AAC57020.1; -; Genomic_RNA.
DR   SMR; P0DOE8; -.
DR   Proteomes; UP000113393; 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   3: Inferred from homology;
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_0000439634"
FT   MOTIF           136..139
FT                   /note="DLNP; interaction with MAP1B"
FT                   /evidence="ECO:0000250|UniProtKB:P0DOE9"
SQ   SEQUENCE   139 AA;  15567 MW;  EBCC69B09BC46B6D CRC64;
     MGSNSLSMIK VRLQNLFDND EVALLKITCY TDKLIHLTNA LAKAVIHTIK LNGIVFVHVI
     TSSDICPNNN IVVKSNFTTM PVLQNGGYIW EMMELTHCSQ PNGLLDDNCE IKFSKKLSDS
     TMTNYMNQLS ELLGFDLNP
 
 
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