NSP1_ROTP5
ID NSP1_ROTP5 Reviewed; 486 AA.
AC Q84940; Q85037;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 23-FEB-2022, entry version 68.
DE RecName: Full=Non-structural protein 1 {ECO:0000255|HAMAP-Rule:MF_04088};
DE Short=NSP1 {ECO:0000255|HAMAP-Rule:MF_04088};
DE AltName: Full=NCVP2 {ECO:0000255|HAMAP-Rule:MF_04088};
DE AltName: Full=Non-structural RNA-binding protein 53 {ECO:0000255|HAMAP-Rule:MF_04088};
DE Short=NS53 {ECO:0000255|HAMAP-Rule:MF_04088};
OS Rotavirus A (strain RVA/Pig/United States/OSU/1977/G5P9[7]) (RV-A)
OS (Rotavirus A (strain Ohio State University)).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=10915;
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8030275; DOI=10.1006/viro.1994.1471;
RA Dunn S.J., Cross T.L., Greenberg H.B.;
RT "Comparison of the rotavirus nonstructural protein NSP1 (NS53) from
RT different species by sequence analysis and northern blot hybridization.";
RL Virology 203:178-183(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7996134; DOI=10.1099/0022-1317-75-12-3413;
RA Xu L.I., Tian Y., Tarlow O., Harbour D.A., McCrae M.A.;
RT "Molecular biology of rotaviruses. IX. Conservation and divergence in
RT genome segment 5.";
RL J. Gen. Virol. 75:3413-3421(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8629937; DOI=10.1007/bf01718584;
RA Kojima K., Taniguchi K., Kobayashi N.;
RT "Species-specific and interspecies relatedness of NSP1 sequences in human,
RT porcine, bovine, feline, and equine rotavirus strains.";
RL Arch. Virol. 141:1-12(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND FUNCTION.
RX PubMed=17251580; DOI=10.1099/vir.0.82255-0;
RA Graff J.W., Ewen J., Ettayebi K., Hardy M.E.;
RT "Zinc-binding domain of rotavirus NSP1 is required for proteasome-dependent
RT degradation of IRF3 and autoregulatory NSP1 stability.";
RL J. Gen. Virol. 88:613-620(2007).
RN [5]
RP FUNCTION, INTERACTION WITH HOST CUL1; CUL3 AND BTRC, PHOSPHORYLATION, AND
RP MUTAGENESIS OF CYS-42 AND GLU-486.
RX PubMed=28851847; DOI=10.1128/mbio.01213-17;
RA Davis K.A., Morelli M., Patton J.T.;
RT "Rotavirus NSP1 Requires Casein Kinase II-Mediated Phosphorylation for
RT Hijacking of Cullin-RING Ligases.";
RL MBio 8:0-0(2017).
CC -!- FUNCTION: Plays a role in the inhibition of host innate immunity by
CC inducing the degradation of key host factors required to activate
CC interferon production such as IRF3, IRF5 or IRF7. Associates with
CC components of cullin RING ligases (CRLs) including CUL1 or CUL3, which
CC are essential multisubunit ubiquitination complexes, to modulate their
CC activities. Recognizes the host NF-kappa-B regulator BTRC through the
CC presence of a DSGXS motif in the C-terminal substrate recognition
CC domain. {ECO:0000255|HAMAP-Rule:MF_04088, ECO:0000269|PubMed:17251580,
CC ECO:0000269|PubMed:28851847}.
CC -!- SUBUNIT: Interacts (via C-terminus) with host IRF3; this interaction
CC leads to IRF3 degradation. Interacts with host IRF7; this interaction
CC leads to IRF7 degradation. Interacts with host CUL1 and CUL3. Interacts
CC with host BTRC. {ECO:0000255|HAMAP-Rule:MF_04088}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm, host cytoskeleton
CC {ECO:0000255|HAMAP-Rule:MF_04088}.
CC -!- DOMAIN: The integrity of the zinc-binding domain in NSP1 is important
CC for degradation of host IRF3. {ECO:0000255|HAMAP-Rule:MF_04088}.
CC -!- DOMAIN: The pLxIS motif targets host IRF3 for degradation; however
CC phosphorylation of NSP1 pLxIS motif is not required for its activity.
CC {ECO:0000255|HAMAP-Rule:MF_04088}.
CC -!- PTM: The C-terminal region is phosphorylated by host CKII/CSNK2A1.
CC Phosphorylation of the DSGXS motif is essential for host NF-kappa-B
CC inhibition. {ECO:0000255|HAMAP-Rule:MF_04088,
CC ECO:0000269|PubMed:28851847}.
CC -!- SIMILARITY: Belongs to the rotavirus NSP1 family. {ECO:0000255|HAMAP-
CC Rule:MF_04088}.
CC -!- CAUTION: NSP1 has been shown (PubMed:17251580) to be almost unable to
CC bind and degrade IRF3 in cell culture. However, this does not implies
CC that it is the case in vivo, since the down-regulation of host
CC antiviral state is not essential for the virus in cell culture and the
CC used cells were not of porcine origin. {ECO:0000305|PubMed:17251580}.
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DR EMBL; U08432; AAA50495.1; -; Genomic_RNA.
DR EMBL; Z12107; CAA78092.1; -; Genomic_RNA.
DR EMBL; D38153; BAA20544.1; -; Genomic_RNA.
DR PIR; S31805; S31805.
DR IntAct; Q84940; 19.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-UniRule.
DR GO; GO:0044163; C:host cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-UniRule.
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-UniRule.
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-UniRule.
DR HAMAP; MF_04088; ROTA_NSP1; 1.
DR InterPro; IPR002148; Rotavirus_NSP1.
DR Pfam; PF00981; Rota_NS53; 1.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host cytoskeleton; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host IRF3 by virus; Inhibition of host IRF7 by virus;
KW Inhibition of host NF-kappa-B by virus;
KW Inhibition of host RLR pathway by virus;
KW Interferon antiviral system evasion; Metal-binding; Phosphoprotein;
KW RNA-binding; Viral immunoevasion.
FT CHAIN 1..486
FT /note="Non-structural protein 1"
FT /id="PRO_0000367822"
FT REGION 1..81
FT /note="RNA-binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088"
FT REGION 42..79
FT /note="Zinc-binding domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088"
FT REGION 82..176
FT /note="Important for cytoskeleton localization"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088"
FT REGION 317..486
FT /note="Interaction with host IRF3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088"
FT MOTIF 479..483
FT /note="IKBKB-like degron (ILD) motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088,
FT ECO:0000269|PubMed:28851847"
FT MOTIF 480..483
FT /note="pLxIS motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088"
FT MUTAGEN 42
FT /note="C->A: Complete loss of interaction with host CUL1
FT and CUL3."
FT /evidence="ECO:0000269|PubMed:28851847"
FT MUTAGEN 486
FT /note="E->Q: Complete loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:28851847"
FT CONFLICT 102
FT /note="Y -> F (in Ref. 2; CAA78092)"
FT CONFLICT 227
FT /note="H -> R (in Ref. 2; CAA78092)"
FT CONFLICT 250
FT /note="S -> N (in Ref. 2; CAA78092)"
FT CONFLICT 321
FT /note="C -> S (in Ref. 2; CAA78092)"
FT CONFLICT 370
FT /note="E -> Q (in Ref. 2; CAA78092)"
FT CONFLICT 449..450
FT /note="DT -> TR (in Ref. 2; CAA78092)"
FT CONFLICT 478..479
FT /note="YD -> CN (in Ref. 2; CAA78092)"
SQ SEQUENCE 486 AA; 57235 MW; E42BAC8CDF5BF666 CRC64;
MATFKDACYY YKRINKLNHA VLKLGVNDTW RPSPPTKYKG WCLDCCQHTD LTYCRGCTMY
HVCQWCSQYG RCFLDNEPHL LRMRTFKNEV TKDDLMNLVD MYDTLFPMNQ KIVDKFINNT
RQHKCRNECV NQWYNHLLMP ITLQSLSIEL DGDVYYIFGY YDDMNNVNQT PFSFVNLVDI
YDKLLLDDVN FTRMSFLPVT LQQEYALRYF SKSRFISEQR KCVSDSHFSI NVLENLHNPS
FKMQITRNCS ELSSDWNGAC KLVKDTSAYF NILKTSHVEF YSISTRCRVF TQRKLKIASK
LIKPNYITSN HRTSATEVHN CKWCSINSSY TVWNDFRVKK IYDNIFNFLR ALVKSNVNVG
HCSSQEKIYE CVENILDVCD NEKWKTSVTK IFNYLEPVEL NAVNYVLFNH EVNWDVINVL
VQSIGKVPQI LTLNDVTTIM QSIIYEWFDT KYMRNTPMTT FTVDKLRRLC TGSKTVDYDS
GISDVE
