The Global Phosphorylation Landscape of SARS-CoV-2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the enveloped positive-sense RNA viruses. In the ongoing pandemic no vaccine has been approved as of yet. The Phosphorylation Landscape of SARS-CoV-2 Infection presented here is a step towards a deeper understanding of virus-host relationship and vaccine development.1

During a COVID-19 infection both, host and viral proteins, undergo major changes in phosphorylation. The virus tries to alter activities of e.g. kinases in order to influence cellular signaling to its benefits. The map on the left is based on the SARS-CoV-2 virus-host protein-protein interaction map of Gordon et al.2 and shows 40 human proteins which are significantly differentially phosphorylated across infection at least two time points. Viral proteins are shown as green diamonds. Interacting human proteins are shown as gray or respectively dark grey circles . PHs emanate from human proteins, colored by change compared with uninfected control samples (red, increase; blue, decrease) at each time point (0, 2, 4, 8, 12, and 24 h after infection) in a clockwise fashion.

The SARS-CoV-2 N protein is known to interact with several RNA-processing proteins that are differentially phosphorylated during infection, including LARP1 and RRP9. Here LARP1 phosphorylation decreases on several sites, which is known to consequently increase LARP1 affinity for 3' untranslated regions (UTRs) of mRNAs encoding ribosomal proteins, driving inhibition of human protein synthesis.3 In addition, Nsp8 interacts with LARP7 and MEPCE which are important regulators of RNA polymerase II-mediated transcription elongation as part of the 7SK small nuclear ribonucleoprotein particle (snRNP) complex. Their phosphorylation may influence positive transcription elongation factor b (PTEFb [CDK9]) and transcriptional regulation of the virus.4

10 of the 40 interacting proteins are kinases, a decrease in activity for MARK2 and PRKACA were observed while CK2 shows increased activity. The changes in kinase activity offer insights into the biology of viral infection and possible attack points to fight an infection. Therefore kinases are predestined as drug targets and further research may lead to  development of novel therapeutics relevant for future virus pandemics.

SARS-CoV-2 Structural Proteins: SARS-CoV-2 Spike Protein, SARS-CoV-2 N Protein, SARS-CoV-2 E Protein, SARS-CoV-2 M Protein,

SARS-CoV Viral Proteins: , , , , , , ,

All SARS-CoV-2 Non-Structural Proteins: SARS-CoV-2 Non-Structural Proteins

SARS-CoV-2 Antibodies: anti-SARS-CoV-2 Antibodies

References:

  1.  Bouhaddou et al.The Global Phosphorylation Landscape of SARS-CoV-2 Infection, Cell (2020), doi.org/10.1016/j.cell.2020.06.034
  2. David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O’Meara, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, N. J. K. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing. Nature. (2020).
  3. Hong, S., Freeberg, M.A., Han, T., Kamath, A., Yao, Y., Fukuda, T., Suzuki, T., Kim, J.K., and Inoki, K. . LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs. (2017) eLife 6, e25237.
  4. Mbonye, U.R., Wang, B., Gokulrangan, G., Chance, M.R., and Karn, J. . Phosphorylation of HEXIM1 at Tyr271 and Tyr274 Promotes Release of PTEFb from the 7SK snRNP Complex and Enhances Proviral HIV Gene Expression. Proteomics 15, 2078–2086. (2015)

SARS-CoV-2 Virus-Human Interacting Proteins

Antigens in this category:
LARP1 (La Ribonucleoprotein Domain Family, Member 1): LARP1 antibodies   LARP1 Proteins
MARK1 (MAP/microtubule Affinity-Regulating Kinase 1): MARK1 antibodies MARK1 ELISA Kits MARK1 Proteins
MARK2 - MAP/microtubule Affinity-Regulating Kinase 2: MARK2 antibodies   MARK2 Proteins
PRKACA (Protein Kinase A, alpha): PRKACA antibodies PRKACA ELISA Kits PRKACA Proteins
PRKAR2A - Protein Kinase, CAMP-Dependent, Regulatory, Type II, alpha: PRKAR2A antibodies   PRKAR2A Proteins
PRKAR2B - Protein Kinase, CAMP-Dependent, Regulatory, Type II, beta: PRKAR2B antibodies PRKAR2B ELISA Kits PRKAR2B Proteins
RRP9 - Ribosomal RNA Processing 9, Small Subunit (SSU) Processome Component, Homolog (Yeast): RRP9 antibodies   RRP9 Proteins
APOL2 - Apolipoprotein L 2: APOL2 antibodies APOL2 ELISA Kits APOL2 Proteins
ATP13A3 (ATPase Type 13A3): ATP13A3 antibodies    
BRD2 (Bromodomain Containing 2): BRD2 antibodies   BRD2 Proteins
CENPF (Centromere Protein F): CENPF antibodies CENPF ELISA Kits  
CCL11 (Chemokine (C-C Motif) Ligand 11):      
CCL13 - Chemokine (C-C Motif) Ligand 13: CCL13 antibodies CCL13 ELISA Kits CCL13 Proteins
CCL2 - Chemokine (C-C Motif) Ligand 2: CCL2 antibodies CCL2 ELISA Kits CCL2 Proteins
CCL20 (Chemokine (C-C Motif) Ligand 20): CCL20 antibodies CCL20 ELISA Kits CCL20 Proteins
CLCC1 - Chloride Channel CLIC-Like 1: CLCC1 antibodies CLCC1 ELISA Kits CLCC1 Proteins
CIT (Citron (Rho-Interacting, serine/threonine Kinase 21)): CIT antibodies   CIT Proteins
CCDC86 - Coiled-Coil Domain Containing 86: CCDC86 antibodies CCDC86 ELISA Kits CCDC86 Proteins
CRTC3 (CREB Regulated Transcription Coactivator 3): CRTC3 antibodies CRTC3 ELISA Kits CRTC3 Proteins
DNMT1 - DNA (Cytosine-5)-Methyltransferase 1: DNMT1 antibodies DNMT1 ELISA Kits DNMT1 Proteins
ERC1 (ELKS/RAB6-Interacting/CAST Family Member 1): ERC1 antibodies ERC1 ELISA Kits ERC1 Proteins
HECTD1 (HECT Domain Containing 1): HECTD1 antibodies   HECTD1 Proteins
HDAC2 - Histone Deacetylase 2: HDAC2 antibodies HDAC2 ELISA Kits HDAC2 Proteins
LARP4B (La Ribonucleoprotein Domain Family, Member 4B): LARP4B antibodies    
LARP7 (La Ribonucleoprotein Domain Family, Member 7): LARP7 antibodies LARP7 ELISA Kits LARP7 Proteins
MPHOSPH10 - M-Phase phosphoprotein 10 (U3 Small Nucleolar Ribonucleoprotein): MPHOSPH10 antibodies MPHOSPH10 ELISA Kits MPHOSPH10 Proteins
MAP7D1 (MAP7 Domain Containing 1): MAP7D1 antibodies    
MEPCE (Methylphosphate Capping Enzyme): MEPCE antibodies MEPCE ELISA Kits MEPCE Proteins
MIB1 - Mindbomb E3 Ubiquitin Protein Ligase 1: MIB1 antibodies   MIB1 Proteins
MYCBP2 (MYC Binding Protein 2): MYCBP2 antibodies    
NKAP (NFKB Activating Protein): NKAP antibodies NKAP ELISA Kits NKAP Proteins
NEK9 - NIMA (Never in Mitosis Gene A)- Related Kinase 9: NEK9 antibodies NEK9 ELISA Kits NEK9 Proteins
NUP210 (Nucleoporin 210kDa): NUP210 antibodies   NUP210 Proteins
NUP214 (Nucleoporin 214kDa): NUP214 antibodies NUP214 ELISA Kits  
PKP2 - Plakophilin 2: PKP2 antibodies PKP2 ELISA Kits  
PLEKHA5 (Pleckstrin Homology Domain Containing, Family A Member 5): PLEKHA5 antibodies    
SUN2 (Sad1 and UNC84 Domain Containing 2): SUN2 antibodies   SUN2 Proteins
SNIP1 (Smad Nuclear Interacting Protein 1): SNIP1 antibodies SNIP1 ELISA Kits SNIP1 Proteins
STOML2 (Stomatin (EPB72)-Like 2): STOML2 antibodies STOML2 ELISA Kits STOML2 Proteins
TOR1AIP1 (Torsin A Interacting Protein 1): TOR1AIP1 antibodies   TOR1AIP1 Proteins
UBAP2L (Ubiquitin Associated Protein 2-Like): UBAP2L antibodies    
ZC3H18 (Zinc Finger CCCH-Type Containing 18):      
ZDHHC5 (Zinc Finger, DHHC-Type Containing 5): ZDHHC5 antibodies