Relation Results

Summary

Name	rep
Full Name	Replicase polyprotein 1ab
Synonyms	pp1ab, ORF1ab polyprotein, Non-structural protein 1, nsp1, p65 homolog, EC 3.4.19.12, EC 3.4.22.-, Non-structural protein 3, nsp3, PL2-PRO, 3CLp, EC 3.4.22.69, Main protease, Mpro, Non-structural protein 5, nsp5, SARS coronavirus main proteinase, nsp9, RNA-capping enzyme subunit nsp9, Growth factor-like peptide, GFL, RdRp, EC 2.7.7.48, EC 2.7.7.50, Non-structural protein 12, nsp12, EC 3.6.4.12, EC 3.6.4.13, Non-structural protein 13, nsp13, EC 2.1.1.56, EC 3.1.13.-, Non-structural protein 14, nsp14, Proofreading exoribonuclease nsp14, ExoN, NendoU, Non-structural protein 15, nsp15, Non-structural protein 16, nsp16 \|
Primary ID	P0C6X7
Links	- -
Type	protein
Relations	17
Inhibitors	FGFR1
Function	[Isoform Replicase polyprotein 1ab]: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. {ECO:0000305}.; [Host translation inhibitor nsp1]: Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371). {ECO:0000269\|PubMed:23035226, ECO:0000269\|PubMed:30943371}.; [Non-structural protein 2]: May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2 (PubMed:19640993). Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses (PubMed:19640993). {ECO:0000269\|PubMed:19640993}.; [Papain-like protease nsp3]: Responsible for the cleavages located at the N-terminus of the replicase polyprotein (PubMed:16306590). In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:16306590, PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling (PubMed:19369340, PubMed:24622840). {ECO:0000269\|PubMed:16306590, ECO:0000269\|PubMed:17692280, ECO:0000269\|PubMed:19369340, ECO:0000269\|PubMed:23943763, ECO:0000269\|PubMed:24622840, ECO:0000303\|PubMed:24410069}.; [Non-structural protein 4]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763). Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV. {ECO:0000269\|PubMed:23943763, ECO:0000303\|PubMed:24410069}.; [3C-like proteinase nsp5]: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. May cleave human NLRP1 in lung epithelial cells, thereby activating the NLRP1 inflammasome pathway (PubMed:35594856). Also able to bind an ADP-ribose-1''-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH. {ECO:0000255\|PROSITE-ProRule:PRU00772, ECO:0000269\|PubMed:16226257, ECO:0000269\|PubMed:35594856}.; [Non-structural protein 6]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:24991833, PubMed:24410069). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24991833, PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833). {ECO:0000269\|PubMed:24991833, ECO:0000303\|PubMed:24410069}.; [Non-structural protein 7]: Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. {ECO:0000269\|PubMed:22039154}.; [Non-structural protein 8]: Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. {ECO:0000269\|PubMed:22039154}.; [Viral protein genome-linked nsp9]: Forms a primer, NSP9-pU, which is utilized by the polymerase for the initiation of RNA chains. Interacts with ribosome signal recognition particle RNA (SRP). Together with NSP8, suppress protein integration into the cell membrane, thereby disrupting host immune defenses. {ECO:0000250\|UniProtKB:P0DTD1}.; [Non-structural protein 10]: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation. {ECO:0000269\|PubMed:22022266, ECO:0000269\|PubMed:22635272}.; [RNA-directed RNA polymerase nsp12]: RNA-directed RNA polymerase that catalyzes the transcription of viral genomic and subgenomic RNAs (PubMed:22791111). Acts in complex with nsp7 and nsp8 to transcribe both the minus and positive strands of genomic RNA. The kinase-like NiRAN domain of NSP12 attaches one or more nucleotides to the amino terminus of NSP9, forming a covalent RNA-protein intermediate that serves as transcription/replication primer. Subgenomic RNAs (sgRNAs) are formed by discontinuous transcription: The polymerase has the ability to pause at transcription-regulating sequences (TRS) and jump to the leader TRS, resulting in a major deletion. This creates a series of subgenomic RNAs that are replicated, transcribed and translated. In addition, Nsp12 is a subunit of the viral RNA capping enzyme that catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. Subsequently, the NiRAN domain transfers RNA to GDP, and forms the core cap structure GpppA-RNA. {ECO:0000250\|UniProtKB:P0DTD1, ECO:0000269\|PubMed:22791111}.; [Helicase nsp13]: Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium. {ECO:0000269\|PubMed:12917423, ECO:0000269\|PubMed:22615777}.; [Guanine-N7 methyltransferase nsp14]: Plays a role in viral RNA synthesis through two distinct activities. The N7-guanine methyltransferase activity plays a role in the formation of the cap structure GpppA-RNA (PubMed:20421945, PubMed:34845015). The proofreading exoribonuclease reduces the sensitivity of the virus to RNA mutagens during replication (PubMed:16549795, PubMed:22635272, PubMed:23966862, PubMed:29511076, PubMed:21593585). This activity acts on both ssRNA and dsRNA in a 3'-5' direction. {ECO:0000269\|PubMed:16549795, ECO:0000269\|PubMed:20421945, ECO:0000269\|PubMed:21593585, ECO:0000269\|PubMed:22635272, ECO:0000269\|PubMed:23966862, ECO:0000269\|PubMed:29511076, ECO:0000269\|PubMed:34845015}.; [Uridylate-specific endoribonuclease nsp15]: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (PubMed:28158275, PubMed:18045871). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (PubMed:16828802). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (PubMed:28158275, PubMed:18045871). {ECO:0000269\|PubMed:16828802, ECO:0000269\|PubMed:18045871, ECO:0000269\|PubMed:28158275}.; [2'-O-methyltransferase nsp16]: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs (PubMed:18417574, PubMed:22022266, PubMed:20421945). N7-methyl guanosine cap is a prerequisite for binding of nsp16 (PubMed:18417574). Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system (PubMed:18417574, PubMed:22022266, PubMed:20421945). {ECO:0000269\|PubMed:18417574, ECO:0000269\|PubMed:20421945, ECO:0000269\|PubMed:22022266, ECO:0000305}.