ID   NS2_HRSV1               Reviewed;         124 AA.
AC   P24569;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-1992, sequence version 1.
DT   03-AUG-2022, entry version 60.
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 B (strain 18537).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX   NCBI_TaxID=11251;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2525176; DOI=10.1099/0022-1317-70-6-1539;
RA   Johnson P.R., Collins P.L.;
RT   "The 1B (NS2), 1C (NS1) and N proteins of human respiratory syncytial virus
RT   (RSV) of antigenic subgroups A and B: sequence conservation and divergence
RT   within RSV genomic RNA.";
RL   J. Gen. Virol. 70:1539-1547(1989).
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. Acts cooperatively with NS1 to repress activation
CC       and nuclear translocation of host IFN-regulatory factor IRF3. Interacts
CC       with the host cytoplasmic sensor of viral nucleic acids DDX58/RIG-I and
CC       prevents the interaction with its downstream partner MAVS. Together
CC       with NS2, participates in the proteasomal degradation of host STAT2,
CC       IRF3, IRF7, TBK1 and DDX58 through a NS-degradasome involving CUL2 and
CC       Elongin-C. The degradasome requires an intact mitochondrial MAVS.
CC       Induces host SOCS1 expression. Induces activation of NF-kappa-B.
CC       Suppresses premature apoptosis by an NF-kappa-B-dependent, interferon-
CC       independent mechanism promoting continued viral replication.
CC       {ECO:0000250|UniProtKB:P04543}.
CC   -!- SUBUNIT: Monomer (instable). Homomultimer. Heteromultimer with NS1.
CC       Interacts with host DDX58 (via N-terminus); this interaction prevents
CC       host signaling pathway involved in interferon production. Interacts
CC       with host MAP1B/microtubule-associated protein 1B.
CC       {ECO:0000250|UniProtKB:P04543}.
CC   -!- SUBCELLULAR LOCATION: Host mitochondrion
CC       {ECO:0000250|UniProtKB:P04543}. Note=Most NS2 resides in the
CC       mitochondria as a heteromer with NS1. {ECO:0000250|UniProtKB:P04543}.
CC   -!- DOMAIN: The DNLP motif has IFN suppressive functions like binding to
CC       host MAP1B. {ECO:0000250|UniProtKB:P04543}.
CC   -!- SIMILARITY: Belongs to the pneumovirus non-structural protein 2 family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; D00736; BAA00636.1; -; Genomic_RNA.
DR   PIR; B32063; MNNZ15.
DR   SMR; P24569; -.
DR   PRIDE; P24569; -.
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   3: Inferred from homology;
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; Viral immunoevasion.
FT   CHAIN           1..124
FT                   /note="Non-structural protein 2"
FT                   /id="PRO_0000142788"
FT   MOTIF           121..124
FT                   /note="DLNP; interaction with MAP1B"
FT                   /evidence="ECO:0000250|UniProtKB:P04543"
SQ   SEQUENCE   124 AA;  14624 MW;  526F8C2C6553C1DA CRC64;
     MSTTNDNTTM QRLMITDMRP LSMESIITSL TKEIITHKFI YLINNECIVR KLDERQATFT
     FLVNYEMKLL HKVGSTIYKK YTEYNTKYGT FPMPIFINHD GFLECIGIKP TKHTPIIYKY
     DLNP