GSK3 phosphorylates nucleoprotein

Stable Identifier
Reaction [transition]
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Phosphorylation of nucleoprotein
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Phosphorylation of SARS-Cov-2 nucleocapsid is catalyzed by glycogen synthase kinase 3 (GSK3) and several other host cell kinases. Phosphorylated N forms a liquid-like compartment, possibly suited for viral genome processing (Carlson et al, 2020). GSK3 phosphorylations depend on priming phosphorylations on at least two sites by SRPK1/2 protein kinases (Heaton et al, 2020).

Three proteomics papers show varying sites for phosphorylations on N that can be explained by specific phosphorylation catalyzed by GSK3 when primed by phosphorylations on S188 and S206. The sites S176, S180, S184, S194, T198 and S202 are supported by at least two of the three papers (Bouhaddou et al, 2020; Davidson et al, 2020; Klann et al, 2020). Another analysis found S176 phosphorylated in about half of the cases (Supekar et al, 2021)..
Literature References
PubMed ID Title Journal Year
32637943 Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein

Howard, CJ, Hartooni, N, Ghent, CM, Carlson, CR, Morgan, DO, Asfaha, JB

bioRxiv 2020
32723359 Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein

Williamson, MK, Ellis, J, Heesom, KJ, Lewis, PA, Matthews, DA, Zambon, M, Carroll, MW, Shoemark, D, Davidson, AD, Lewis, S, Hiscox, JA

Genome Med 2020
32877642 Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication

Ciesek, S, Cinatl, J, Tascher, G, Münch, C, Bojkova, D, Klann, K

Mol Cell 2020
32645325 The Global Phosphorylation Landscape of SARS-CoV-2 Infection

Beltrao, P, Fischer, ER, Koh, C, Vignuzzi, M, Johnson, JR, Richards, AL, Bouhaddou, M, Melnyk, JE, Meyer, B, O'Neal, MC, Guo, JZ, Lim, JK, Shoichet, B, Dugourd, A, Hernandez-Armenta, C, Fabius, JM, McBride, T, Obernier, K, Kim, M, Leach, AR, Manners, EJ, Weigang, S, Moreno, E, Cakir, M, Soucheray, M, Cai, Y, Knerr, J, Hüttenhain, R, Patil, T, Polacco, BJ, Muralidharan, M, Hardy, A, Mathy, CJP, Nilsson-Payant, BE, Grosse, R, Quintero, D, Li, Q, Goff, M, Miorin, L, Stevenson, E, Swaney, DL, Tutuncuoglu, B, Mullins, RD, Shokat, KM, Rezelj, VV, Zhou, Y, Batra, J, Jang, G, Bouhaddou, S, Krogan, NJ, Tran, QD, Modak, M, tenOever, BR, White, KM, Dunham, A, de Wit, E, Robinot, R, Gaulton, A, Kochs, G, Xu, J, Saez-Rodriguez, J, Valdeolivas, A, García-Sastre, A, Félix, E, Vallet, T, Shi, Y, Memon, D, Gordon, DE, Broadhurst, DJ, Ulferts, S, Kaake, RM, Klippsten, S, Kortemme, T, Ott, M, Rojc, A, Chang, JCJ, Hiatt, J, Correa Marrero, M

Cell 2020
32817937 The FDA-approved drug Alectinib compromises SARS-CoV-2 nucleocapsid phosphorylation and inhibits viral infection in vitro

Chaparian, RR, Bulaon, DK, Anand, SK, Johnson, JL, Shobana-Ganesh, K, Trimarco, JD, Liberatore, KM, Levy, TM, Nilsson-Payant, BE, Getz, G, Beausoleil, SA, Weinstein, H, Tata, PR, Kavanagh-Williamson, M, Matthews, D, Yaron, TM, Chen, SB, Lee, G, Kerelsky, A, Lin, TY, Heesom, K, Cohen, BM, Mercadante, MN, Blenis, J, Possemato, AP, Zhu, X, Tkachev, SL, Hamele, CE, Piskounova, E, Smith, CM, Davidson, AD, Harding, AT, He, L, Heaton, BE, Jordan, TX, Burke, KN, Cantley, LC, Kastenhuber, ER, tenOever, BR, Tata, A, Aguet, F, Elemento, O, Hornbeck, PV, Schwartz, RE, Heaton, NS

bioRxiv 2020
33997890 Variable posttranslational modifications of severe acute respiratory syndrome coronavirus 2 nucleocapsid protein

Shajahan, A, Moremen, KW, Heiss, C, Azadi, P, Rouhani, DS, Supekar, NT, Chapla, DG, Gleinich, AS

Glycobiology 2021
Catalyst Activity

protein serine/threonine kinase activity of GSK3 [cytosol]

This event is regulated
Negatively by
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
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