UniProtKB - P0DTC6 (NS6_SARS2)
ORF6 protein
6
Functioni
Disrupts bidirectional nucleocytoplasmic transport by interacting with the host RAE1-NUP98 complex (PubMed:33360543, PubMed:33849972).
Disrupts cell nuclear import complex formation by tethering karyopherin alpha 2 and karyopherin beta 1 to the membrane (PubMed:32979938).
Retention of import factors at the ER/Golgi membrane leads to a loss of transport into the nucleus (By similarity).
Prevents STAT1 nuclear translocation in response to interferon signaling, thus blocking the expression of interferon stimulated genes (ISGs) that display multiple antiviral activities (PubMed:33097660).
Suppresses IFN-beta production possibly by blocking IRF3 nuclear translocation (PubMed:32979938).
Might induce accumulation of host HNRNPA1 (PubMed:33360543).
By similarity4 PublicationsGO - Biological processi
- suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity Source: UniProtKB-KW
- suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity Source: UniProtKB-KW
- suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
Keywordsi
Enzyme and pathway databases
SIGNORi | P0DTC6 |
Names & Taxonomyi
Protein namesi | Recommended name: ORF6 proteinShort name: ORF6 Alternative name(s): Accessory protein 6 Non-structural protein 6 Short name: ns6 Protein X3 |
Gene namesi | ORF Names:6 |
Organismi | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2) |
Taxonomic identifieri | 2697049 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Pisuviricota › Pisoniviricetes › Nidovirales › Cornidovirineae › Coronaviridae › Orthocoronavirinae › Betacoronavirus › Sarbecovirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Subcellular locationi
- Host endoplasmic reticulum membrane By similarity1 Publication
- Host Golgi apparatus membrane By similarity1 Publication
- Host cytoplasm By similarity Note: Localizes to virus-induced vesicular structures called double membrane vesicles.By similarity
Keywords - Cellular componenti
Host cytoplasm, Host endoplasmic reticulum, Host Golgi apparatus, Host membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 16 | Missing : Retains interaction with human NUP98-RAE1 complex. Increases down-regulation of protein expression of newly transcribed genes in host cell. 1 PublicationAdd BLAST | 16 | |
Mutagenesisi | 22 – 30 | Missing : Retains interaction with human NUP98-RAE1 complex. Increases down-regulation of protein expression of newly transcribed genes in host cell. 1 Publication | 9 | |
Mutagenesisi | 38 – 61 | Missing : Loss of interaction with human NUP98-RAE1 complex which suppresses the down-regulation of protein expression of newly transcribed genes in the host cell. 1 PublicationAdd BLAST | 24 | |
Mutagenesisi | 50 – 61 | Missing : Loss of interaction with human NUP98-RAE1 complex which suppresses the down-regulation of protein expression of newly transcribed genes in the host cell. 1 PublicationAdd BLAST | 12 | |
Mutagenesisi | 58 | M → A: Loss of interaction with human NUP98-RAE1 complex which suppresses the mRNA accumulation in the nucleus, the down-regulation of protein expression of newly transcribed genes in the host cell and blockade on nuclear import on a broad range of host factors. 1 Publication | 1 | |
Mutagenesisi | 58 | M → R: Complete loss of binding to the NUP98-RAE1 complex and IFN antagonistic function. 1 Publication | 1 | |
Mutagenesisi | 61 | D → DYP: Does not affect repression of reporter protein expression. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000449653 | 1 – 61 | ORF6 proteinAdd BLAST | 61 |
Interactioni
Subunit structurei
May interact with nsp8 (By similarity).
Interacts with protein ORF9b (By similarity).
Interacts (via C-terminus) with the host NUP98-RAE1 complex; this interaction disrupts the host nuclear import (PubMed:33097660, PubMed:33360543, PubMed:33849972).
Interacts with host KPNA2; this interaction may inhibit IFN-beta production by blocking IRF3 nuclear translocation (PubMed:32979938).
By similarity4 PublicationsBinary interactionsi
P0DTC6
Protein-protein interaction databases
BioGRIDi | 4383870, 681 interactors |
IntActi | P0DTC6, 82 interactors |
Structurei
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Family and domain databases
InterProi | View protein in InterPro IPR022736, NS6_bCoV |
Pfami | View protein in Pfam PF12133, bCoV_NS6, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MFHLVDFQVT IAEILLIIMR TFKVSIWNLD YIINLIIKNL SKSLTENKYS
60
QLDEEQPMEI D
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 2 | F → H in strain: Eta/B.1.525. Curated | 1 | |
Natural varianti | 3 | Missing in strain: Eta/B.1.525. Curated | 1 | |
Natural varianti | 61 | D → L in strain: Omicron/BA.2. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | MN908947 Genomic RNA Translation: QHD43420.1 |
RefSeqi | YP_009724394.1, NC_045512.2 |
Genome annotation databases
GeneIDi | 43740572 |
KEGGi | vg:43740572 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | MN908947 Genomic RNA Translation: QHD43420.1 |
RefSeqi | YP_009724394.1, NC_045512.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
7VPH | X-ray | 2.80 | I/J/K/X | 41-61 | [»] | |
ModBasei | Search... | |||||
SWISS-MODEL-Workspacei | Submit a new modelling project... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4383870, 681 interactors |
IntActi | P0DTC6, 82 interactors |
Genome annotation databases
GeneIDi | 43740572 |
KEGGi | vg:43740572 |
Enzyme and pathway databases
SIGNORi | P0DTC6 |
Miscellaneous databases
PROi | PR:P0DTC6 |
Family and domain databases
InterProi | View protein in InterPro IPR022736, NS6_bCoV |
Pfami | View protein in Pfam PF12133, bCoV_NS6, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NS6_SARS2 | |
Accessioni | P0DTC6Primary (citable) accession number: P0DTC6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 22, 2020 |
Last sequence update: | April 22, 2020 | |
Last modified: | May 25, 2022 | |
This is version 11 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families