IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Proceedings of the National Academy of Sciences of the United States of America 2021 imex curation Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins Coronavirus - Interactions investigated in the context of Coronavirus darst@rockefeller.edu,campbee@rockefeller.edu Only protein-protein interactions imex curation in vitro In vitro 3d-em 3D electron microscopy 3D-EM electron tomog structure determination identification by structure determination identification by structure determination structure determination Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins darst@rockefeller.edu,campbee@rockefeller.edu Accepted 2021-JUN-28 AT 07:46 BST AT 07:46 BST by KALPANAP Proceedings of the National Academy of Sciences of the United States of America 2021 Only protein-protein interactions imex curation imex curation Mock publication and experiment for abstract interactions that are not interaction evidences. Mock publication and experiment for abstract interactions that are not interaction evidences. unspecified method Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Proceedings of the National Academy of Sciences of the United States of America 2021 imex curation Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins Coronavirus - Interactions investigated in the context of Coronavirus darst@rockefeller.edu,campbee@rockefeller.edu Only protein-protein interactions imex curation in vitro In vitro ms of complexes mass spectrometry studies of complexes ms of complexes fingerprinting peptide massfingerprinting fingerprinting Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins darst@rockefeller.edu,campbee@rockefeller.edu Accepted 2021-JUN-28 AT 07:46 BST AT 07:46 BST by KALPANAP Proceedings of the National Academy of Sciences of the United States of America 2021 Only protein-protein interactions imex curation imex curation Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Proceedings of the National Academy of Sciences of the United States of America 2021 imex curation Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins Coronavirus - Interactions investigated in the context of Coronavirus darst@rockefeller.edu,campbee@rockefeller.edu Only protein-protein interactions imex curation in vitro In vitro emsa electrophoretic mobility shift assay Gel retardation assay band shift band shift Gel retardation assay emsa weight by staining molecular weight estimation by staining weight by staining Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins Nsp13 (PRO_0000449630) added separately when ROLE = ancillary, as I do not think I can do that when part of the complex? darst@rockefeller.edu,campbee@rockefeller.edu Accepted 2021-JUN-28 AT 07:46 BST AT 07:46 BST by KALPANAP Proceedings of the National Academy of Sciences of the United States of America 2021 Only protein-protein interactions imex curation imex curation Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Proceedings of the National Academy of Sciences of the United States of America 2021 imex curation Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins Coronavirus - Interactions investigated in the context of Coronavirus darst@rockefeller.edu,campbee@rockefeller.edu Only protein-protein interactions imex curation in vitro In vitro crosslink cross-linking study crosslink weight autoradiogra molecular weight estimation by autoradiography weight autoradiogra Malone B., Chen J., Wang Q., Llewellyn E., Choi YJ., Olinares PDB., Cao X., Hernandez C., Eng ET., Chait BT., Shaw DE., Landick R., Darst SA., Campbell EA. Virus - Publications including interactions involving viral proteins Exposure to UV light results in an increase in covalent linkage between 4-thioU and a (radiolabelled) cytidine residue. darst@rockefeller.edu,campbee@rockefeller.edu Accepted 2021-JUN-28 AT 07:46 BST AT 07:46 BST by KALPANAP Proceedings of the National Academy of Sciences of the United States of America 2021 Only protein-protein interactions imex curation imex curation p_strand_38_mer rna ribonucleic acid RNA rna chemical synthesis Chemical synthesis (Chemical synthesis) CGCGUAGCAUGCUACGUCAUUCUCCUAAGAAGCUACCC btc6_p_strand_41_mer rna ribonucleic acid RNA rna chemical synthesis Chemical synthesis (Chemical synthesis) CGCGUAGCAUGCUACGUCAUUCUCCUAAGAAGCUACCCCCC p0dtd1-pro_0000449626 Non-structural protein 8 rep ORF1ab polyprotein 1a-1b protein protein SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 2019-nCoV AIASEFSSLPSYAAFATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVIPDYNTYKNTCDGTTFTYASALWEIQQVVDADSKIVQLSEISMDNSPNLAWPLIVTALRANSAVKLQ 3943 4140 rtc_t_strand_3'_nc_045512.2 rna ribonucleic acid RNA rna chemical synthesis Chemical synthesis (Chemical synthesis) CUAUCCCCAUGUGAUUUUAAUAGCUUCUUAGGAGAAUGACGUAGCAUGCUACGCG NC_045512.2 residues 29831 - 29870 3' end p0dtd1-pro_0000449630 Helicase nsp13 rep ORF1ab polyprotein 1a-1b protein protein SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 2019-nCoV AVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNAPGCDVTDVTQLYLGGMSYYCKSHKPPISFPLCANGQVFGLYKNTCVGSDNVTDFNAIATCDWTNAGDYILANTCTERLKLFAAETLKATEETFKLSYGIATVREVLSDRELHLSWEVGKPRPPLNRNYVFTGYRVTKNSKVQIGEYTFEKGDYGDAVVYRGTTTYKLNVGDYFVLTSHTVMPLSAPTLVPQEHYVRITGLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKCSRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRTLLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINRPQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKVGILCIMSDRDLYDKLQFTSLEIPRRNVATLQ 5325 5925 p0dtd1-pro_0000449629 RNA-directed RNA polymerase nsp12 rep ORF1ab polyprotein 1a-1b protein protein SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 2019-nCoV SADAQSFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKTNCCRFQEKDEDDNLIDSYFVVKRHTFSNYQHEETIYNLLKDCPAVAKHDFFKFRIDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDFVENPDILRVYANLGERVRQALLKTVQFCDAMRNAGIVGVLTLDNQDLNGNWYDFGDFIQTTPGSGVPVVDSYYSLLMPILTLTRALTAESHVDTDLTKPYIKWDLLKYDFTEERLKLFDRYFKYWDQTYHPNCVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVENPHLMGWDYPKCDRAMPNMLRIMASLVLARKHTTCCSLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQHRLYECLYRNRDVDTDFVNEFYAYLRKHFSMMILSDDAVVCFNSTYASQGLVASIKNFKSVLYYQNNVFMSEAKCWTETDLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 4393 5324 p0dtd1-pro_0000449625 Non-structural protein 7 rep ORF1ab polyprotein 1a-1b protein protein SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 2019-nCoV SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRATLQ 3860 3942 p_strand_35_mer rna ribonucleic acid RNA rna chemical synthesis Chemical synthesis (Chemical synthesis) CGCGUAGCAUGCUACGUCAUUCUCCUAAGAAGCUA btc5_p_strand_40_mer rna ribonucleic acid RNA rna chemical synthesis Chemical synthesis (Chemical synthesis) CGCGUAGCAUGCUACGUCAUUCUCCUAAGAAGCUACCCCC btc5_p_strand_40_mer-nsp7_nsp8_nsp12_sars2-1 1 14 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) 20 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) physical association physical association Supplementary Table 1 cannot add CP RTC as a complex because stoichiomentry is not the same as in CP. btc5_p_strand_40_mer-nsp7_nsp8_nsp12_sars2-2 1 14 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 20 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) physical association physical association Supplementary Table 1 btc5_p_strand_40_mer-nsp7_nsp8_nsp12_sars2-3 1 14 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 28 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) 9 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) physical association physical association Supplementary Table 1 btc5_p_strand_40_mer-nsp7_nsp8_nsp12_sars2-4 4 13 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 20 unspecified role unspecified role prey prey purified purified P0DTD1-PRO_0000449629:p.Asp760Ala mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain D A 35 Mon Jun 28 17:12:02 BST 2021 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp760Ala' ecoli Escherichia coli (strain K12) physical association physical association 1B, Lane 1, Supp. figure 1A lanes 1+3 The holo-RdRp (nsp7/nsp82/nsp12) bound the RTC scaffold in the presence or absence of nsp13 and ADP + AlF3. nsp7_nsp8_nsp12_sars2-p_strand_35_mer-1 4 13 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 28 unspecified role unspecified role prey prey purified purified P0DTD1-PRO_0000449629:p.Asp760Ala mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain D A 41 Mon Jun 28 17:39:35 BST 2021 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp760Ala' ecoli Escherichia coli (strain K12) physical association physical association 1B, Lane 4, supp. figure 1A lanes 5 + 7 The holo-RdRp (nsp7/nsp82/nsp12) bound the RTC scaffold in the presence or absence of nsp13 and ADP + AlF3. btc5_p_strand_40_mer-nsp7_nsp8_nsp12_sars2-5 4 14 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role ancillary ancillary purified purified ecoli Escherichia coli (strain K12) 20 unspecified role unspecified role prey prey purified purified P0DTD1-PRO_0000449629:p.Asp760Ala mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain D A 35 Mon Jun 28 17:37:24 BST 2021 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp760Ala' ecoli Escherichia coli (strain K12) physical association physical association 1B, Lane 6, Supp. figure 1A lanes 6 + 8. Nsp13 was required for efficient binding to the BTC scaffolds. Interaction was seen in the presence of ADP + AlF3. nsp7_nsp8_nsp12_sars2-p_strand_35_mer-2 4 6 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role ancillary ancillary purified purified ecoli Escherichia coli (strain K12) 20 unspecified role unspecified role prey prey purified purified ecoli Escherichia coli (strain K12) physical association physical association 1B, Lane 5 Interaction was seen in the presence of ADP + AlF3. p_strand_35_mer-nsp7_nsp8_nsp12_sars2-1 4 14 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 20 unspecified role unspecified role prey prey purified purified P0DTD1-PRO_0000449629:p.Asp760Ala mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain D A 35 ecoli Escherichia coli (strain K12) physical association physical association Supp. figure 1A, lane 4 The holo-RdRp with nsp12-D760A does not require nsp13 to bind the BTC5 scaffold. btc5_p_strand_40_mer-nsp7_nsp8_nsp12_sars2-6 3 7 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 10 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) 20 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) physical association physical association Supplementary Figure 1 B/C btc5_p_strand_40_mer-rtc_sars2-1 3 7 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 28 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) 9 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) physical association physical association Supplementary figure 1 B/C p_strand_35_mer-nsp7_nsp8_nsp12_sars2-2 5 13 unspecified role unspecified role bait bait 4-thio-Uracil rna chemical modification RNA chemical modification RNA chemical modification post-transcriptional modification rna chemical modification certain certain sequence position certain certain certain sequence position certain Cytidine_radiolabel 32p radiolabel 32p radiolabel P32 32P 32P P32 certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 20 unspecified role unspecified role prey prey purified purified P0DTD1-PRO_0000449629:p.Asp760Ala mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain D A 35 Mon Jun 28 17:08:24 BST 2021 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp760Ala' ecoli Escherichia coli (strain K12) 69 70 physical association physical association Supp. figure 5A, lanes 1,4, S5B, Lane 1 Interaction was seen in the presence of ATP and UV light. p_strand_35_mer-nsp7_nsp8_nsp12_sars2-3 5 13 unspecified role unspecified role bait bait 4-thio-Uracil rna chemical modification RNA chemical modification RNA chemical modification post-transcriptional modification rna chemical modification certain certain sequence position certain certain certain sequence position certain Cytidine_radiolabel 32p radiolabel 32p radiolabel P32 32P 32P P32 certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 28 unspecified role unspecified role prey prey purified purified P0DTD1-PRO_0000449629:p.Asp760Ala mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain D A 41 Mon Jun 28 17:36:15 BST 2021 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp760Ala' ecoli Escherichia coli (strain K12) 76 77 physical association physical association Supp. figure 5A, lanes 2,(3), 5-10, S5B, Lane 2 Interaction was seen in the and presence and absence of ATP and UV light, although reduced in the absence of UV. For the D760A mutant the absence of UV resulted in a much greater reduction in binding than for WT. Cross-linking of the p-RNA to nsp12 was substantially increased by the addition of nsp13 with ATP. nsp7-nsp8-nsp12_sars2 SARS-CoV-2 polymerase complex NSP7:2xNSP8:NSP12 replication-transcription complex replication and transcription complex RTC central RTC C-RTC holo-RdRp complex holo-RNA-dependent RNA polymerase complex 8 enzyme enzyme nsp7_nsp8 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 11 enzyme enzyme nsp7_nsp8 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 8 enzyme enzyme nsp8_nsp12 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 12 unspecified role unspecified role nsp8_nsp12 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 87 82 85 82 87 83 85 83 physical association physical association SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 2019-nCoV stable complex stable complex physical interaction evidence used in manual assertion physical interaction evidence used in manual assertion IPI inferred from physical interaction RNA-directed 5'-3' RNA polymerase of the SARS-CoV-2 coronavirus which consists of the main polymerase protein NSP12 and a stoichiometric variant of the primase complex (CPX-5690). Extends partially double-stranded RNA templates and is probably also required for transcription initiation, though the mechanism for this has yet to be determined. Complex formation enhances dsRNA binding of the individual protomers. Heterotetramer Severe acute respiratory syndrome (SARS) [EFO:0000694]: A viral respiratory infection caused by the SARS coronavirus. It is transmitted through close person-to-person contact. It is manifested with high fever, headache, dry cough and myalgias. It may progress to pneumonia and cause death. Primase complex without polymerase has a different stoichiometry (8:8). NSP12 possesses conserved motifs involved in template binding, NTP binding, and polymerization that assume a structure resembling a cupped “right hand”. The NSP7-NSP8 heterodimer binds to the index finger loop and may facilitates the interaction of NSP12 with additional components of the RNA synthesis machinery. The second NSP8 molecule binds close to the RNA template-binding channel. Accepted 2020-APR-20 by ORCHARD coronavirus rtc_sars2 SARS-CoV-2 replication and transcription complex NSP7:2xNSP8:NSP12:2xNSP13 mini RTC RTC replication-transcription complex E-RTC elongation RTC 10 enzyme enzyme nsp8_nsp12_nsp13 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 10 enzyme enzyme nsp8_nsp13_binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 8 enzyme enzyme nsp7_nsp8_nsp13 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 11 enzyme enzyme nsp7_nsp8_nsp13 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 8 enzyme enzyme nsp8_nsp12_nsp13 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 12 unspecified role unspecified role nsp8_nsp12 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 89 96 94 91 89 93 96 91 93 98 94 93 98 physical association physical association SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 2019-nCoV stable complex stable complex physical interaction evidence used in manual assertion physical interaction evidence used in manual assertion IPI inferred from physical interaction Replication and transcription complex (RTC) of the SARS-CoV-2 coronavirus which consists of the polymerase complex (CPX-5742) and 2 helicase molecules (nsp13). Although coronavirus nsp13s have been proposed to unwind RNA in the 5' to 3' direction, the 5' extension of template RNA is fed into the active site of SARS-CoV-2 nsp13 in the 3' to 5' direction. RNA polymerase has been known to possess a “backtrack” feature, in which the productive elongation and translocation complexes are in the same conformation to facilitate reversible backward motion during RNA synthesis. The SARS-CoV-2 RTC structure suggests it has the same function here. The nsp12 nucleotidyltransferase (NiRAN) domain possesses guanylyltransferase activity, catalyzing the formation of the cap core structure (GpppA) on the nascent mRNA. ADP-Mg2+ binds in the catalytic site of this domain. Heterohexamer Severe acute respiratory syndrome (SARS) [EFO:0000694]: A viral respiratory infection caused by the SARS coronavirus. It is transmitted through close person-to-person contact. It is manifested with high fever, headache, dry cough and myalgias. It may progress to pneumonia and cause death. One of the nsp13 molecules stabilizes the overall architecture of the complex by interacting with both nsp7-nsp8-nsp12-RNA and the second nsp13 protein. This anchors the 5'-extension of RNA template, and enables continue transcription using the 5′ leader as a template, possibly by a second RTC complex. Orientation shifts of nsp13 results in its variable interactions with other components of this complex. While the second nsp13 molecule strongly binds to nsp12, the first makes only a weak hydrophobic contact. nsp9 monomer (P0DTD1-PRO_0000449627, not dimer CPX-5687) inhibits nsp12 guanylyltransferase activity. coronavirus Accepted 2021-FEB-15 by ORCHARD