MAPK6 (mitogen-activated protein kinase 6)
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
15q21.2
LOCUSID
ALIAS
ERK3,HsT17250,PRKM6,p97MAPK
FUSION GENES
Abstract
Review on MAPK6, with data on DNA, on the protein encoded, and where the gene is implicated.
DNA/RNA
Genomic organization of the MAPK6 gene on chromosome 15.
Description
The MAPK6 gene spans 47.01 kb on the long arm of chromosome 15 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 26.45 kb.
Transcription
The MAPK6 transcribed mRNA has 4,186 bp. No splice variants have been reported.
Pseudogene
Database analysis reveals the presence of six MAPK6 pseudogenes localized on four different chromosomes: MAPK6PS1 (8q11.23), MAPK6PS2 (21q21.1), MAPK6PS3 (13q14.13), MAPK6PS4 (8q11.1), MAPK6PS5 (8q23.1) and MAPK6PS6 (10q11.23). All six loci contain intronless copies of MAPK6 and display the features of processed pseudogenes.
Proteins
Schematic representation of the ERK3 protein structure. Kinase, catalytic kinase domain; C34 conserved region in ERK3 and ERK4; SEG, activation loop motif containing the regulatory phosphorylation residue Ser189.
Description
Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. The human ERK3 protein is made of 721 amino acids and contains a typical kinase domain located at the N-terminal extremity. Another region with homology to the MAP kinase ERK4 (C34 domain) has been identified after the kinase domain. The function of the C34 domain is unknown.
Expression
MAPK6 mRNA is expressed ubiquitously. The highest levels of expression are observed in the skeletal muscle and brain. ERK3 is a highly unstable protein, with a half-life of less than one hour, that is constitutively degraded by the ubiquitin-proteasome pathway.
Localisation
ERK3 localizes to the cytoplasm and nucleus of a variety of cultured cells.
Function
Little is known about the regulation and functions of ERK3. Recent studies suggest a potential involvement of the kinase in the control of cell differentiation, cytoskeletal remodelling, cell migration and invasion, DNA repair, and immune response. The best-characterized and validated substrate of ERK3 is the protein kinase MAPKAPK5 (MK5).
Homology
ERK3 display 73% amino acid identity with ERK4 in the kinase domain. ERK4 and ERK3 define a distinct subfamily of MAP kinases.
Mutations
Note
No recurrent mutation in the MAPK6 gene has been reported in cancer.
Implicated in
Entity name
Cancer
Note
Studies have documented the upregulation of MAPK6 mRNA in squamous cell carcinomas of the skin, squamous cell lung carcinoma, and tongue squamous cell carcinoma. Expression of MAPK6 mRNA is also increased in salivary adenoid cystic carcinoma, adrenocortical carcinoma, T-cell acute lymphoblastic leukemia, and acute myeloid leukemia. In lymphomas, reports have suggested an increase of MAPK6 expression in Burkitts lymphoma and a decrease in Hodgkins lymphoma. Downregulation of MAPK6 mRNA level has also been observed in cutaneous melanoma, (colorectal adenocarcinomaand esophageal adenocarcinoma. The significance of these changes remains to be investigated.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 2032290 | 1991 | ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. | Boulton TG et al |
| 22508986 | 2012 | The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology. | Brand F et al |
| 17161475 | 2007 | Atypical mitogen-activated protein kinases: structure, regulation and functions. | Coulombe P et al |
| 15067337 | 2004 | Induction of p97MAPK expression regulates collagen mediated inhibition of proliferation and migration in human squamous cell carcinoma lines. | Crowe DL et al |
| 22505454 | 2012 | ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion. | Long W et al |
| 25002529 | 2014 | The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival. | Marquis M et al |
| 8875998 | 1996 | Primary structure, expression and chromosomal locus of a human homolog of rat ERK3. | Meloche S et al |
| 15538386 | 2004 | Scaffolding by ERK3 regulates MK5 in development. | Schumacher S et al |
| 15577943 | 2004 | Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway. | Seternes OM 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 |
| 10657254 | 2000 | Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDa. | Turgeon B et al |
| 24585635 | 2014 | ERK3 promotes endothelial cell functions by upregulating SRC-3/SP1-mediated VEGFR2 expression. | Wang W et al |
| 7969157 | 1994 | Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3. | Zhu AX et al |
Other Information
Locus ID:
NCBI: 5597
MIM: 602904
HGNC: 6879
Ensembl: ENSG00000069956
Variants:
dbSNP: 5597
ClinVar: 5597
TCGA: ENSG00000069956
COSMIC: MAPK6
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000069956 | ENST00000261845 | Q16659 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
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 |
|---|---|---|---|
| 37057894 | 2023 | ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization. | 5 |
| 37215982 | 2023 | Increased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma. | 2 |
| 37057894 | 2023 | ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization. | 5 |
| 37215982 | 2023 | Increased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma. | 2 |
| 35228660 | 2022 | LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway. | 11 |
| 36250437 | 2022 | miR-128-3p inhibits the inflammation by targeting MAPK6 in penicillin-induced astrocytes. | 5 |
| 35228660 | 2022 | LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway. | 11 |
| 36250437 | 2022 | miR-128-3p inhibits the inflammation by targeting MAPK6 in penicillin-induced astrocytes. | 5 |
| 33070159 | 2021 | ERK3/MAPK6 is required for KRAS-mediated NSCLC tumorigenesis. | 7 |
| 33300070 | 2021 | let7f‑5p attenuates inflammatory injury in in vitro pneumonia models by targeting MAPK6. | 3 |
| 33495824 | 2021 | miR‑653‑5p suppresses the growth and migration of breast cancer cells by targeting MAPK6. | 9 |
| 33579235 | 2021 | ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in non-melanoma skin cancers. | 8 |
| 33070159 | 2021 | ERK3/MAPK6 is required for KRAS-mediated NSCLC tumorigenesis. | 7 |
| 33300070 | 2021 | let7f‑5p attenuates inflammatory injury in in vitro pneumonia models by targeting MAPK6. | 3 |
| 33495824 | 2021 | miR‑653‑5p suppresses the growth and migration of breast cancer cells by targeting MAPK6. | 9 |
Citation
Simon Mathien ; Sylvain Meloche
MAPK6 (mitogen-activated protein kinase 6)
Atlas Genet Cytogenet Oncol Haematol. 2017-03-01
Online version: http://atlasgeneticsoncology.org/gene/43349/mapk6
Historical Card
2008-08-01 MAPK6 (mitogen-activated protein kinase 6) by Sylvain Meloche Affiliation
Institut de Recherche en Immunologie et Cancerologie, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
