NSP1_ROTS4
ID NSP1_ROTS4 Reviewed; 496 AA.
AC Q99FX5; Q99FX4;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 23-FEB-2022, entry version 63.
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/SA11-4F/G3P6[1]) (RV-A) (Simian Agent 11 (strain
OS 4F)).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=36436;
OH NCBI_TaxID=9544; Macaca mulatta (Rhesus macaque).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=11160712; DOI=10.1128/jvi.75.5.2076-2086.2001;
RA Patton J.T., Taraporewala Z.F., Chen D., Chizhikov V., Jones M.T.,
RA Elhelu A., Collins M., Kearney K., Wagner M., Hoshino Y., Gouvea V.;
RT "Effect of intragenic rearrangement and changes in the 3' consensus
RT sequence on NSP1 expression and rotavirus replication.";
RL J. Virol. 75:2076-2086(2001).
RN [2]
RP RNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=8189533; DOI=10.1128/jvi.68.6.3990-4000.1994;
RA Hua J.J., Chen X., Patton J.T.;
RT "Deletion mapping of the rotavirus metalloprotein NS53 (NSP1): the
RT conserved cysteine-rich region is essential for virus-specific RNA
RT binding.";
RL J. Virol. 68:3990-4000(1994).
RN [3]
RP FUNCTION, AND INTERACTION WITH HUMAN IRF3.
RX PubMed=15741273; DOI=10.1073/pnas.0408376102;
RA Barro M., Patton J.T.;
RT "Rotavirus nonstructural protein 1 subverts innate immune response by
RT inducing degradation of IFN regulatory factor 3.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:4114-4119(2005).
RN [4]
RP 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, AND INTERACTION WITH HUMAN IRF7.
RX PubMed=17301153; DOI=10.1128/jvi.02498-06;
RA Barro M., Patton J.T.;
RT "Rotavirus NSP1 inhibits expression of type I interferon by antagonizing
RT the function of interferon regulatory factors IRF3, IRF5, and IRF7.";
RL J. Virol. 81:4473-4481(2007).
RN [6]
RP FUNCTION, AND INTERACTION WITH HOST CUL1 AND CUL3.
RX PubMed=27099313; DOI=10.1128/jvi.00704-16;
RA Lutz L.M., Pace C.R., Arnold M.M.;
RT "Rotavirus NSP1 Associates with Components of the Cullin RING Ligase Family
RT of E3 Ubiquitin Ligases.";
RL J. Virol. 90:6036-6048(2016).
RN [7] {ECO:0007744|PDB:5JEO, ECO:0007744|PDB:5JER}
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 478-496 IN COMPLEX WITH HOST
RP IRF3, FUNCTION, INTERACTION WITH HOST IRF3, DOMAIN, AND MUTAGENESIS OF
RP GLU-482; PHE-484; LEU-486; ILE-488 AND SER-489.
RX PubMed=27302953; DOI=10.1073/pnas.1603269113;
RA Zhao B., Shu C., Gao X., Sankaran B., Du F., Shelton C.L., Herr A.B.,
RA Ji J.Y., Li P.;
RT "Structural basis for concerted recruitment and activation of IRF-3 by
RT innate immune adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E3403-E3412(2016).
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. {ECO:0000255|HAMAP-Rule:MF_04088,
CC ECO:0000269|PubMed:15741273, ECO:0000269|PubMed:17251580,
CC ECO:0000269|PubMed:17301153, ECO:0000269|PubMed:27099313,
CC ECO:0000269|PubMed:27302953}.
CC -!- SUBUNIT: Interacts (via C-terminus pLxIS motif) with host IRF3; this
CC interaction leads to IRF3 degradation. Interacts with host IRF7; this
CC interaction leads to IRF7 degradation. Interacts with host CUL1 and
CC CUL3. {ECO:0000255|HAMAP-Rule:MF_04088, ECO:0000269|PubMed:15741273,
CC ECO:0000269|PubMed:17301153, ECO:0000269|PubMed:27302953}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm, host cytoskeleton
CC {ECO:0000255|HAMAP-Rule:MF_04088, ECO:0000269|PubMed:8189533}.
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:0000269|PubMed:27302953}.
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 -!- SIMILARITY: Belongs to the rotavirus NSP1 family. {ECO:0000255|HAMAP-
CC Rule:MF_04088}.
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DR EMBL; AF290883; AAK14071.1; -; Genomic_RNA.
DR EMBL; AF290884; AAK14072.1; -; Genomic_RNA.
DR PDB; 5JEO; X-ray; 1.72 A; B=479-494.
DR PDB; 5JER; X-ray; 2.91 A; B/D/F/H=479-494.
DR PDBsum; 5JEO; -.
DR PDBsum; 5JER; -.
DR SMR; Q99FX5; -.
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: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 3D-structure; 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 RLR pathway by virus;
KW Interferon antiviral system evasion; Metal-binding; RNA-binding;
KW Viral immunoevasion.
FT CHAIN 1..496
FT /note="Non-structural protein 1"
FT /id="PRO_0000367820"
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..177
FT /note="Important for cytoskeleton localization"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088"
FT REGION 321..496
FT /note="Interaction with host IRF3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04088"
FT MOTIF 486..489
FT /note="pLxIS motif"
FT /evidence="ECO:0000269|PubMed:27302953"
FT VARIANT 479
FT /note="T -> I (in strain: Isolate 5S)"
FT VARIANT 480..496
FT /note="Missing (in strain: Isolate 5S)"
FT MUTAGEN 482
FT /note="E->A: Reduced Interaction with host IRF3."
FT /evidence="ECO:0000269|PubMed:27302953"
FT MUTAGEN 484
FT /note="F->A: Abolished interaction with host IRF3."
FT /evidence="ECO:0000269|PubMed:27302953"
FT MUTAGEN 486
FT /note="L->A: Abolished interaction with host IRF3."
FT /evidence="ECO:0000269|PubMed:27302953"
FT MUTAGEN 488
FT /note="I->A: Impaired ability to degrade host IRF3."
FT /evidence="ECO:0000269|PubMed:27302953"
FT MUTAGEN 489
FT /note="S->A: Does not affect ability to degrade host IRF3."
FT /evidence="ECO:0000269|PubMed:27302953"
SQ SEQUENCE 496 AA; 58565 MW; 5877EA0A0C078CAD CRC64;
MATFKDACFH YRRLTALNRR LCNIGANSIC MPVPDAKIKG WCLECCQIAD LTHCYGCSLP
HVCKWCVQNR RCFLDNEPHL LKLRTVKHPI TKDKLQCIID LYNIIFPIND KVIRKFERMI
KQRKCRNQYK IEWYNHLLLP ITLNAAAFKF DENNLYYVFG LYEKSVSDIY APYRIVNFIN
EFDKLLLDDI NFTRMSNLPI ELRNHYAKKY FQLSRLPSSK LKQIYFSDFT KETVIFNTYT
KTPGRSIYRN VTEFNWRDEL ELYSDLKNDK NKLIAAMMTS KYTRFYAHDN NFGRLKMTIF
ELGHHCQPNY VASNHPGNAS DIQYCKWCNI KYFLSKIDWR IRDMYNLLME FIKDCYKSNV
NVGHCSSVEN IYPLIKRLIW SLFTNHMDQT IEEVFNHMSP VSVEGTNVIM LILGLNISLY
NEIKRTLNVD SIPMVLNLNE FSSIVKSISS KWYNVDELDK LPMSIKSTEE LIEMKNSGTL
TEEFELLISN SEDDNE
