Host-pathogen interaction of human coronaviruses - MAPK signaling (WP4877)

Homo sapiens

This pathway describes the activation of the human MAPK signaling system during human coronavirus infection, per Fung and Liu, Figure 7 [10.1146/annurev-micro-020518-115759]. The MAPK signaling system regulates response to different environmental stimuli, e.g. inflammation due to infection. Its downstream effects include regulation of cell cycle, apoptosis, differentiation and immune response. During coronavirus infection, three MAPK signaling pathways were studied and described. The p38 pathway (MAPK11 - MAPK14) leads to stimulation of apoptosis via CHOP (DDIT3) while the ERK pathway (MAPK1 and MAPK3) counteracts apoptosis stimulation and supports cell survival by stimulating ATF2 and FOS. The JNK pathway (MAPK 8 - MAPK10) inhibits cell survival protein BCL2, thus stimulating apoptosis but also stimulating the AP1 complex that leads to the production of effectors to fight the infection. The interplay of apoptosis stimulation and cell survival is not yet fully understood in SARS-CoV-2 infection.


Friederike Ehrhart , Egon Willighagen , Alex Pico , Rex D A B , Kristina Hanspers , Marvin Martens , Martina Summer-Kutmon , Eric Weitz , Finterly Hu , Denise Slenter , and Isabel Wassink


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Homo sapiens




Pathway Ontology

signaling pathway p38 MAPK signaling pathway

Disease Ontology

viral infectious disease severe acute respiratory syndrome COVID-19


Label Type Compact URI Comment
MAP3K1 GeneProduct ensembl:ENSG00000095015 MEKK1
MAP3K9 GeneProduct ensembl:ENSG00000006432 MLK1
MAP3K10 GeneProduct ensembl:ENSG00000130758 MLK2
MAP3K11 GeneProduct ensembl:ENSG00000173327 MLK3
MAPK9 GeneProduct ncbigene:5601 JNK
JUN GeneProduct ensembl:ENSG00000177606 AP1
FOS GeneProduct ensembl:ENSG00000170345 AP1
MAPK11 GeneProduct ncbigene:5600 p38
MAPK13 GeneProduct ncbigene:5603 p38
DDIT3 GeneProduct ensembl:ENSG00000175197 CHOP
MAPK12 GeneProduct ncbigene:6300 p38
MAP3K4 GeneProduct ensembl:ENSG00000085511 MEKK4
MAPK3 GeneProduct ncbigene:5595 ERK1
MAP2K7 GeneProduct ensembl:ENSG00000076984 MKK7
MAPK1 GeneProduct ncbigene:5594 ERK2
ATF2 GeneProduct ensembl:ENSG00000115966
MAPK8 GeneProduct ncbigene:5599 JNK
MAP2K4 GeneProduct ensembl:ENSG00000065559 MKK4
MAP2K3 GeneProduct ensembl:ENSG00000034152 MKK3
EIF4E GeneProduct ensembl:ENSG00000151247
MAPK14 GeneProduct ensembl:ENSG00000112062 p38
MAP2K1 GeneProduct ensembl:ENSG00000169032 MKK1
RPS6KA3 GeneProduct ensembl:ENSG00000177189 RSK
FOS GeneProduct ensembl:ENSG00000170345 c-FOS
BCL2 GeneProduct ensembl:ENSG00000171791
MAPK10 GeneProduct ncbigene:5602 JNK
RPS6KA2 GeneProduct ensembl:ENSG00000071242 RSK
MAP2K6 GeneProduct ensembl:ENSG00000108984 MKK6
MAP2K2 GeneProduct ensembl:ENSG00000126934 MKK2
RPS6KA1 GeneProduct ensembl:ENSG00000117676 RSK
RAF1 GeneProduct ensembl:ENSG00000132155
IFI27 GeneProduct ncbigene:3429
BST2 GeneProduct ncbigene:684
JUNB GeneProduct ncbigene:3726
IFI27 GeneProduct ncbigene:3429
BST2 GeneProduct ncbigene:684
S Protein wikidata:Q89458416
orf3a Protein uniprot:P59632
orf3b Protein uniprot:P59633
orf7a Protein uniprot:P59635
S Protein wikidata:Q89458416
orf3a Protein uniprot:P59632
orf7a Protein uniprot:P59635
N Protein wikidata:Q89457519
orf3b Protein uniprot:P59633
orf6 Protein uniprot:P59634
IFITM2 Protein ensembl:ENSG00000185201
IFITM3 Protein ensembl:ENSG00000142089
IFITM1 Protein ensembl:ENSG00000185885
IFITM2 Protein ensembl:ENSG00000185201
IFITM3 Protein ensembl:ENSG00000142089
IFITM1 Protein ensembl:ENSG00000185885


  1. Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19 [Internet]. Huang L, Shi Y, Gong B, Jiang L, Liu X, Yang J, et al. Cold Spring Harbor Laboratory; 2020. Available from: DOI Scholia
  2. Human Coronavirus: Host-Pathogen Interaction. Fung TS, Liu DX. Annu Rev Microbiol. 2019 Sep 8;73:529–57. PubMed Europe PMC Scholia