NS1_INBLE
ID NS1_INBLE Reviewed; 281 AA.
AC P03502;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 23-FEB-2022, entry version 105.
DE RecName: Full=Non-structural protein 1 {ECO:0000255|HAMAP-Rule:MF_04066};
DE Short=NS1 {ECO:0000255|HAMAP-Rule:MF_04066};
DE AltName: Full=NS1A {ECO:0000255|HAMAP-Rule:MF_04066};
GN Name=NS {ECO:0000255|HAMAP-Rule:MF_04066};
OS Influenza B virus (strain B/Lee/1940).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Betainfluenzavirus.
OX NCBI_TaxID=518987;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6283137; DOI=10.1128/jvi.42.1.186-193.1982;
RA Briedis D.J., Lamb R.A.;
RT "Influenza B virus genome: sequences and structural organization of RNA
RT segment 8 and the mRNAs coding for the NS1 and NS2 proteins.";
RL J. Virol. 42:186-193(1982).
RN [2]
RP RNA-BINDING.
RX PubMed=8806538; DOI=10.1006/viro.1996.0453;
RA Wang W., Krug R.M.;
RT "The RNA-binding and effector domains of the viral NS1 protein are
RT conserved to different extents among influenza A and B viruses.";
RL Virology 223:41-50(1996).
RN [3]
RP INTERACTION WITH HUMAN G1P2.
RX PubMed=11157743; DOI=10.1093/emboj/20.3.362;
RA Yuan W., Krug R.M.;
RT "Influenza B virus NS1 protein inhibits conjugation of the interferon
RT (IFN)-induced ubiquitin-like ISG15 protein.";
RL EMBO J. 20:362-371(2001).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF ARG-33; ARG-38; ARG-47; ARG-50; LYS-52;
RP ARG-53; LYS-54; ARG-58; LYS-60; LYS-64; LYS-70; ARG-71; ARG-77; LYS-78;
RP LYS-83 AND LYS-86.
RX PubMed=15479798; DOI=10.1128/jvi.78.21.11574-11582.2004;
RA Donelan N.R., Dauber B., Wang X., Basler C.F., Wolff T., Garcia-Sastre A.;
RT "The N- and C-terminal domains of the NS1 protein of influenza B virus can
RT independently inhibit IRF-3 and beta interferon promoter activation.";
RL J. Virol. 78:11574-11582(2004).
RN [5]
RP REVIEW.
RX PubMed=12758165; DOI=10.1016/s0042-6822(03)00119-3;
RA Krug R.M., Yuan W., Noah D.L., Latham A.G.;
RT "Intracellular warfare between human influenza viruses and human cells: the
RT roles of the viral NS1 protein.";
RL Virology 309:181-189(2003).
CC -!- FUNCTION: Binds and inhibits the conjugation of the ubiquitin-like
CC G1P2/ISG15 protein to its target proteins. Since G1P2/ISG15 is an early
CC antiviral protein, NS1 may inhibit the host antiviral response.
CC Prevents EIF2AK2/PKR activation, either by binding double strand RNA or
CC by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6
CC snRNA. {ECO:0000255|HAMAP-Rule:MF_04066, ECO:0000269|PubMed:15479798}.
CC -!- SUBUNIT: Homodimer. Interacts with and inhibits human G1P2 conjugation
CC by UBE1L. {ECO:0000255|HAMAP-Rule:MF_04066,
CC ECO:0000269|PubMed:11157743}.
CC -!- INTERACTION:
CC P03502; P05161: ISG15; Xeno; NbExp=4; IntAct=EBI-15938710, EBI-746466;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04066}.
CC Host nucleus {ECO:0000255|HAMAP-Rule:MF_04066}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=NS1;
CC IsoId=P03502-1; Sequence=Displayed;
CC Name=NEP; Synonyms=NS2;
CC IsoId=P03511-1; Sequence=External;
CC -!- DOMAIN: Both N-terminus and C-terminus can inhibit IFN-beta promoter
CC activation and IRF-3 nuclear translocation.
CC -!- SIMILARITY: Belongs to the influenza B viruses NS1 family.
CC {ECO:0000255|HAMAP-Rule:MF_04066}.
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DR EMBL; J02096; AAA43756.1; -; Genomic_RNA.
DR PIR; A04093; MNIVA.
DR RefSeq; NP_056666.1; NC_002211.1. [P03502-1]
DR PDB; 1XEQ; X-ray; 2.10 A; A/B=1-103.
DR PDB; 3R66; X-ray; 2.30 A; A/B=1-103.
DR PDB; 3RT3; X-ray; 2.01 A; C=1-103.
DR PDB; 3SDL; X-ray; 2.29 A; A/B=1-103.
DR PDB; 6J62; X-ray; 2.49 A; C=1-103.
DR PDB; 6JH0; X-ray; 2.40 A; A/C=1-103.
DR PDB; 6JH1; X-ray; 3.00 A; A/B=1-103.
DR PDBsum; 1XEQ; -.
DR PDBsum; 3R66; -.
DR PDBsum; 3RT3; -.
DR PDBsum; 3SDL; -.
DR PDBsum; 6J62; -.
DR PDBsum; 6JH0; -.
DR PDBsum; 6JH1; -.
DR BMRB; P03502; -.
DR SMR; P03502; -.
DR DIP; DIP-59701N; -.
DR IntAct; P03502; 1.
DR DNASU; 26824008; -.
DR GeneID; 26824008; -.
DR KEGG; vg:26824008; -.
DR EvolutionaryTrace; P03502; -.
DR Proteomes; UP000008158; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0039579; P:suppression by virus of host ISG15-protein conjugation; IEA:UniProtKB-KW.
DR GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR HAMAP; MF_04066; INFV_NS1; 1.
DR InterPro; IPR004208; NS1.
DR InterPro; IPR009068; S15_NS1_RNA-bd.
DR Pfam; PF02942; Flu_B_NS1; 1.
DR PIRSF; PIRSF003938; Flu_B_NS1; 1.
DR SUPFAM; SSF47060; SSF47060; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Host cytoplasm; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host ISG15 by virus; Inhibition of host PKR by virus;
KW Interferon antiviral system evasion; Reference proteome; RNA-binding;
KW Viral immunoevasion.
FT CHAIN 1..281
FT /note="Non-structural protein 1"
FT /id="PRO_0000078960"
FT REGION 1..103
FT /note="G1P2-binding"
FT REGION 1..93
FT /note="RNA-binding and homodimerization"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT MOTIF 50..55
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT MUTAGEN 33
FT /note="R->A: Partial loss of dsRNA-binding and no effect on
FT inhibition of IFN-beta promoter; when associated with A-
FT 38."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 38
FT /note="R->A: Partial loss of dsRNA-binding and no effect on
FT inhibition of IFN-beta promoter; when associated with A-
FT 33."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 47
FT /note="R->A: Complete loss of dsRNA-binding and 40% loss of
FT inhibition of IFN-beta promoter; when associated with A-
FT 50."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 50
FT /note="R->A: Complete loss of dsRNA-binding and 40% loss of
FT inhibition of IFN-beta promoter; when associated with A-
FT 47."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 52
FT /note="K->A: Partial loss of dsRNA-binding and 15% loss of
FT inhibition of IFN-beta promoter; when associated with A-53
FT and A-54."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 53
FT /note="R->A: Partial loss of dsRNA-binding and 15% loss of
FT inhibition of IFN-beta promoter; when associated with A-52
FT and A-54."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 54
FT /note="K->A: Partial loss of dsRNA-binding and 15% loss of
FT inhibition of IFN-beta promoter; when associated with A-52
FT and A-53."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 58
FT /note="R->A: Complete loss of dsRNA-binding and 20% loss of
FT inhibition of IFN-beta promoter; when associated with A-60
FT and A-64."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 60
FT /note="K->A: Complete loss of dsRNA-binding and 20% loss of
FT inhibition of IFN-beta promoter; when associated with A-58
FT and A-64."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 64
FT /note="K->A: Complete loss of dsRNA-binding and 20% loss of
FT inhibition of IFN-beta promoter; when associated with A-58
FT and A-60."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 70
FT /note="K->A: No effect on dsRNA-binding and inhibition of
FT IFN-beta promoter; when associated with A-71."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 71
FT /note="R->A: No effect on dsRNA-binding and inhibition of
FT IFN-beta promoter; when associated with A-70."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 77
FT /note="R->A: Complete loss of dsRNA-binding and inhibition
FT of IFN-beta promoter; when associated with A-78."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 78
FT /note="K->A: Complete loss of dsRNA-binding and inhibition
FT of IFN-beta promoter; when associated with A-77."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 83
FT /note="K->A: No effect on dsRNA-binding and 45% loss of
FT inhibition of IFN-beta promoter; when associated with A-
FT 86."
FT /evidence="ECO:0000269|PubMed:15479798"
FT MUTAGEN 86
FT /note="K->A: No effect on dsRNA-binding and 45% loss of
FT inhibition of IFN-beta promoter; when associated with A-
FT 83."
FT /evidence="ECO:0000269|PubMed:15479798"
FT HELIX 16..36
FT /evidence="ECO:0007829|PDB:3RT3"
FT HELIX 42..63
FT /evidence="ECO:0007829|PDB:3RT3"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:3RT3"
FT HELIX 74..90
FT /evidence="ECO:0007829|PDB:3RT3"
FT HELIX 93..100
FT /evidence="ECO:0007829|PDB:3RT3"
SQ SEQUENCE 281 AA; 32067 MW; 09C376EA400CA73F CRC64;
MADNMTTTQI EVGPGATNAT INFEAGILEC YERFSWQRAL DYPGQDRLHR LKRKLESRIK
THNKSEPENK RMSLEERKAI GVKMMKVLLF MDPSAGIEGF EPYCVKNPST SKCPNYDWTD
YPPTPGKYLD DIEEEPENVD HPIEVVLRDM NNKDARQKIK DEVNTQKEGK FRLTIKRDIR
NVLSLRVLVN GTFLKHPNGD KSLSTLHRLN AYDQNGGLVA KLVATDDRTV EDEKDGHRIL
NSLFERFDEG HSKPIRAAET AVGVLSQFGQ EHRLSPEEGD N
