MAPK4 (mitogen-activated protein kinase 4)
2017-03-01 Simon Mathien , Sylvain Meloche AffiliationInstitute of Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec H3C 3J7, Canada; [email protected]; [email protected]
Identity
HGNC
LOCATION
18q21.1
LOCUSID
ALIAS
ERK-4,ERK4,PRKM4,p63-MAPK,p63MAPK
FUSION GENES
Abstract
Review on MAPK4, with data on DNA, on the protein encoded, and where the gene is implicated.
DNA/RNA
Figure 1. Genomic organization of the MAPK4 gene on chromosome 18.
Description
The MAPK4 gene spans 171.7 kb on the long arm of chromosome 18 and is transcribed in the centromere-to-telomere orientation. The gene is composed of 6 exons with the translation initiation codon located in exon 2. The first two exons are separated by a long intron of 102.8 kb.
Transcription
The MAPK4 transcribed mRNA has 4,736 bp. No splice variants have been reported.
Pseudogene
None.
Proteins
Figure 2. Schematic representation of the ERK4 protein structure. Kinase, catalytic kinase domain; C34 conserved region in ERK3 and ERK4; SEG, activation loop motif containing the regulatory phosphorylation residue Ser186.
Description
Extracellular signal-regulated kinase 4 (ERK4) is an atypical member of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. The human ERK4 protein is made of 587 amino acids and contains a typical kinase domain located at the N-terminal extremity. Another region with homology to the MAP kinase ERK3 (C34 domain) has been identified after the kinase domain. The function of the C34 domain is unknown.
Expression
MAPK4 mRNA is expressed to the highest level in the brain. Other sites of expression include the heart, lung, kidney, intestine, pancreas, parathyroid gland, prostate, thymus, ovary, eye and ear.
Localisation
ERK4 localizes to the cytoplasm and nucleus of a variety of cultured cells.
Function
Little is known about the regulation and functions of ERK4. The only known substrate of ERK4 is the protein kinase MAPKAPK5 (MK5).
Homology
ERK4 display 73% amino acid identity with ERK3 in the kinase domain. ERK4 and ERK3 define a distinct subfamily of MAP kinases.
Mutations
Note
The R114C/H mutation has been reported in several types of cancer (colorectal adenocarcinoma, diffuse glioma, non-small cell lung cancer, cutaneous melanoma, stomach adenocarcinoma, uterine carcinosarcoma). The functional impact of this mutation on the expression or activity of ERK4 is not known.
Implicated in
Entity name
Cancer
Note
Analysis of copy number alterations (CNAs) from TCGA datasets show that MAPK4 gene is deleted in several adenocarcinomas, includingprostate, esophageal, stomach and lung adenocarcinomas. Also, a chromosomal subregion containing the MAPK4 gene is deleted with high frequency (23%) in pancreatic adenocarcinoma. On the other hand, MAPK4 is amplified with low frequency in neuroendocrine prostate cancer, diffuse large B-cell lymphoma and sarcomas. Interrogation of the Oncomine database reveals that expression of MAPK4 mRNA is downregulated in breast and prostate cancer. Consistent with CNA analysis, MAPK4 mRNA is upregulated in diffuse large B-cell lymphoma.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16971392 | 2006 | Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4. | Aberg E et al |
| 17161475 | 2007 | Atypical mitogen-activated protein kinases: structure, regulation and functions. | Coulombe P et al |
| 1319925 | 1992 | Heterogeneous expression of four MAP kinase isoforms in human tissues. | Gonzalez FA et al |
| 16973613 | 2006 | Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5. | Kant S et al |
| 16080956 | 2005 | Genome-wide aberrations in pancreatic adenocarcinoma. | Nowak NJ et al |
| 12504858 | 2002 | The protein kinase ERK3 is encoded by a single functional gene: genomic analysis of the ERK3 gene family. | Turgeon B et al |
Other Information
Locus ID:
NCBI: 5596
MIM: 176949
HGNC: 6878
Ensembl: ENSG00000141639
Variants:
dbSNP: 5596
ClinVar: 5596
TCGA: ENSG00000141639
COSMIC: MAPK4
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000141639 | ENST00000400384 | P31152 |
| ENSG00000141639 | ENST00000540640 | B4DEW2 |
| ENSG00000141639 | ENST00000588540 | K7EN18 |
| ENSG00000141639 | ENST00000592595 | K7ELV1 |
Expression (GTEx)
Pathways
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA284 | MAP2K7 | Gene | Pathway | associated | 20124951 | ||
| PA30584 | MAP2K1 | Gene | Pathway | associated | 20124951 | ||
| PA30587 | MAP2K2 | Gene | Pathway | associated | 20124951 | ||
| PA30588 | MAP2K3 | Gene | Pathway | associated | 20124951 | ||
| PA30589 | MAP2K4 | Gene | Pathway | associated | 20124951 | ||
| PA30590 | MAP2K5 | Gene | Pathway | associated | 20124951 | ||
| PA30591 | MAP2K6 | Gene | Pathway | associated | 20124951 | ||
| PA7000 | sorafenib | Chemical | Pathway | associated | 20124951 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37494889 | 2024 | Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis. | 0 |
| 37494889 | 2024 | Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis. | 0 |
| 37531320 | 2023 | Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy. | 0 |
| 38279470 | 2023 | LINC00467 enhanced the proliferative, migratory and invasive ability of breast cancer cells by targeting miR-18a/b-5p/MAPK4 axis. | 0 |
| 37531320 | 2023 | Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy. | 0 |
| 38279470 | 2023 | LINC00467 enhanced the proliferative, migratory and invasive ability of breast cancer cells by targeting miR-18a/b-5p/MAPK4 axis. | 0 |
| 35017531 | 2022 | MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade. | 11 |
| 36073321 | 2022 | Promotor methylation status of MAPK4 is a novel epigenetic biomarker for prognosis of recurrence in patients with thymic epithelial tumors. | 4 |
| 35017531 | 2022 | MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade. | 11 |
| 36073321 | 2022 | Promotor methylation status of MAPK4 is a novel epigenetic biomarker for prognosis of recurrence in patients with thymic epithelial tumors. | 4 |
| 33586682 | 2021 | MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT. | 26 |
| 33586682 | 2021 | MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT. | 26 |
| 32711558 | 2020 | MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer. | 12 |
| 33155194 | 2020 | MiR-127-3p inhibits proliferation of ovarian cancer in rats through down-regulating MAPK4. | 6 |
| 32711558 | 2020 | MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer. | 12 |
Citation
Simon Mathien ; Sylvain Meloche
MAPK4 (mitogen-activated protein kinase 4)
Atlas Genet Cytogenet Oncol Haematol. 2017-03-01
Online version: http://atlasgeneticsoncology.org/gene/41293/mapk4
Historical Card
2008-03-01 MAPK4 (mitogen-activated protein kinase 4) by Sylvain Meloche Affiliation
Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada
