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MAP2K4 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3.
CIViC holds 2 clinical evidence items and 0 assertions across 2 variants, naming Selumetinib and PLX8725. Open Targets scores its association with cancer at 0.77 (direct and indirect evidence; datatypes literature 0.95, animal model 0.27, genetic association 0.29, somatic mutation 0.97). IntOGen calls it a driver in 15 cohorts (4 activating, 11 loss-of-function), covering Invasive Breast Carcinoma, Cholangiocarcinoma, Colorectal Adenocarcinoma, Oesophagogastric Adenocarcinoma, Oesophageal Squamous Cell Carcinoma, Hepatocellular Carcinoma and others.
In plain words · MAP2K4 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
MAP2K4 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway.
No product in this corpus aims at MAP2K4 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA MAP2K4: RNA low tissue specificity; high antibody staining in 1 normal tissue. Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Colorectal cancer, Pancreatic ductal adenocarcinoma, Gastric & gastro-oesophageal junction cancer, Oesophageal cancer, Hepatocellular carcinoma, Skin cancer (all types) and more); Open Targets associates it with 1 specific cancer type at or above 0.5 (breast adenocarcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P45985; CIViC gene MAP2K4; IntOGen MAP2K4; Human Protein Atlas MAP2K4 tissue; Open Targets ENSG00000065559 associations
First described 1995. Earliest sequence paper UniProt cites for the protein: Derijard et al, Science, 1995, "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms". Source.
Sources: HGNC HGNC:6844 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P45985 (protein name, function text, keywords and locations (REST API)); CIViC gene MAP2K4 (2 evidence items, 0 assertions, 2 variants; diseases: Cancer, Uterus Leiomyosarcoma (GraphQL API, CC0)); Open Targets ENSG00000065559 (association with cancer (MONDO_0004992) 0.77; per-cancer scores at or above 0.5: melanoma 0.51, skin cancer 0.52, breast cancer 0.72, biliary tract cancer 0.50 (GraphQL API, CC0)); IntOGen MAP2K4 (driver in 15 cohorts (Act 4, LoF 11); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. Location: Cytoplasm; Nucleus (UniProt). Locus 17p12 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Breast, Endometrium, Hippocampus, Kidney, Placenta, Thyroid gland.
No cancer stained high; medium in ovarian cancer, thyroid cancer, urothelial cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query for this target: (TITLE:"MAP2K4" OR ABSTRACT:"MAP2K4" OR TITLE:"mitogen-activated protein kinase kinase 4" OR ABSTRACT:"mitogen-activated protein kinase kinase 4" OR TITLE:"Dual specificity mitogen-activated protein kinase kinase 4" OR ABSTRACT:"Dual specificity mitogen-activated protein kinase kinase 4" OR TITLE:"MEK4" OR ABSTRACT:"MEK4" OR TITLE:"JNKK1" OR ABSTRACT:"JNKK1" OR TITLE:"PRKMK4" OR ABSTRACT:"PRKMK4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MAP2K4, not a curated reading list.
Shares Biliary tract cancer (all types), Oesophageal cancer, Skin cancer (all types), Hepatocellular carcinoma.
Shares Biliary tract cancer (all types), Oesophageal cancer, Skin cancer (all types), CIViC.
Shares Biliary tract cancer (all types), Oesophageal cancer, Hepatocellular carcinoma, CIViC.
Shares Biliary tract cancer (all types), Hepatocellular carcinoma, CIViC, IntOGen.
Shares Biliary tract cancer (all types), Oesophageal cancer, Skin cancer (all types), CIViC.
Shares Biliary tract cancer (all types), Skin cancer (all types), IntOGen, Breast cancer (all types).
Shares Biliary tract cancer (all types), Oesophageal cancer, Skin cancer (all types), Hepatocellular carcinoma.
Shares Biliary tract cancer (all types), IntOGen, Open Targets Platform, Pancreatic ductal adenocarcinoma.