HelmholtzZentrum munich
WCMC

Connecting genetic risk to disease endpoints through the human blood plasma proteome

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 410

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
MAPKAPK3 trans Discovery rs17844003 13:46,670,347 T/C 0.20 994 -0.377 0.055 1.2×10-11 -1.120 8.2×10-12 2.1×10-11

 

Regional association plots

MAP kinase-activated protein kinase 3 (MAPKAPK3)

 

Boxplots and histograms for top associations

MAP kinase-activated protein kinase 3 (MAPKAPK3)

inverse-normalized probe levels log2 transformed probe levels raw probe levels
Discovery study

MAP kinase-activated protein kinase 3 (MAPKAPK3)

Target (abbrv.) MAPKAPK3
Target (full name) MAP kinase-activated protein kinase 3
Somalogic ID (Sequence ID) SL004765 (3822-54_2)
Entrez Gene Symbol MAPKAPK3
UniProt ID Q16644
UniProt Comment
  • Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression.
Biomarker applications (based on IPA annotation)
  • unspecified application
Wiki Pathways
  • FAS pathway and Stress induction of HSP regulation
  • Serotonin HTR1 Group and FOS Pathway
Pathway Interaction Database
  • Signaling mediated by p38-alpha and p38-beta
  • p38 signaling mediated by MAPKAP kinases
Reactome
  • Oxidative Stress Induced Senescence
  • VEGFA-VEGFR2 Pathway
  • activated TAK1 mediates p38 MAPK activation
  • p38MAPK events
Pathway Studio
  • ADRA1A → IL6 production
  • AngiotensinR → CREB/ELK-SRF/TP53 signaling
  • CHRM1 → IL2 production
  • CNR1/2 → IL1B/2/4/6/10 production
  • CannabinoidR → AP-1/EGR signaling
  • CholinergicRm → CREB/ELK-SRF signaling
  • DopamineR2 → AP-1/CREB/ELK-SRF signaling
  • EDNRA/B → vascular motility
  • EGFR → AP-1/CREB/ELK-SRF/MYC signaling
  • EndothelinRa → AP-1/CREB signaling
  • EndothelinRb → AP-1/CREB/ELK-SRF signaling
  • ErythropoietinR → AP-1/CREB/MYC signaling
  • FGFR → AP-1/CREB/CREBBP/ELK-SRF/MYC signaling
  • GRM1/5 → CREB signaling
  • HGFR → AP-1/CREB/MYC signaling
  • HTR1 → IL6 production
  • HTR5 → TNF production
  • ICAM1 → AP-1/CREB/ELK-SRF signaling
  • NGFR → AP-1/CEBPB/CREB/ELK-SRF/TP53 signaling
  • NTRK → AP-1/CREB/ELK-SRF/MYC/SMAD3/TP53 signaling
  • Nociception-related DRD2 expression targets
  • PTAFR → AP-1/ATF1/CREB/ERK-SRF signaling
  • SerotoninR1 → FOS signaling
  • Summarized nociception-related expression targets
  • T-cell receptor → ATF/CREB signaling
  • TGFBR → CREB/ELK-SRF signaling
  • TNFR → CREB/ELK-SRF signaling
  • TNFRSF1A → CREB/ELK-SRF signaling
  • ThrombinR → AP-1/CREB/ELK-SRF/SP1 signaling
  • ThrombopoietinR → AP-1/CREB/ELK-SRF/MYC signaling
  • VEGFR → AP-1/CREB/MYC signaling
  • VEGFR → ATF/CREB/ELK-SRF signaling
  • VasopressinR1 → CREB/ELK-SRF/AP-1/EGR signaling
  • VasopressinR2 → CREB/ELK-SRF/AP-1/EGR signaling

All locus annotations are based on the sentinel SNP (rs17844003).
Download the detailed results of SNiPA's block annotation (PDF)

Linked genes

Genes hit or close-by
  • CPB2 carboxypeptidase B2 (plasma)
  • CPB2-AS1 CPB2 antisense RNA 1
eQTL genes
  • ZC3H13 zinc finger CCCH-type containing 13
  • CPB2-AS1 CPB2 antisense RNA 1

 

Results from other genome-wide association studies

No associations available.