MAPK15

MAPK15
Identifiers
Aliases	MAPK15, ERK7, ERK8, mitogen-activated protein kinase 15
External IDs	MGI: 2652894 HomoloGene: 16371 GeneCards: MAPK15
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q24.3 Start 143,716,340 bp[1] End 143,722,458 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 D3 Start 75,865,618 bp[2] End 75,871,003 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube left lobe of thyroid gland left uterine tube right lobe of thyroid gland right lung anterior pituitary skin of abdomen upper lobe of left lung body of pancreas canal of the cervix Top expressed in spermatocyte rib spermatid seminiferous tubule proximal tubule islet of Langerhans esophagus lip respiratory epithelium olfactory epithelium More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity nucleotide binding SH3 domain binding MAP kinase activity protein serine/threonine kinase activity protein binding ATP binding protein kinase activity kinase activity chromatin binding Cellular component intracellular anatomical structure extracellular region nucleus cytoplasm autophagosome centriole cell-cell junction axoneme ciliary basal body Golgi apparatus meiotic spindle spindle cytoskeleton bicellular tight junction cell junction cytoplasmic vesicle cell projection Biological process positive regulation of telomere capping phosphorylation positive regulation of telomere maintenance via telomerase protein phosphorylation positive regulation of telomerase activity MAPK cascade protein autophosphorylation regulation of gene expression regulation of autophagy protein localization to ciliary transition zone regulation of COPII vesicle coating endoplasmic reticulum organization negative regulation of cell migration dopamine uptake regulation of cilium assembly positive regulation of metaphase/anaphase transition of meiosis I positive regulation of spindle assembly cellular response to DNA damage stimulus positive regulation of cell population proliferation intracellular signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 225689 332110 Ensembl ENSG00000181085 ENSG00000274205 ENSMUSG00000063704 UniProt Q8TD08 Q80Y86 RefSeq (mRNA) NM_139021 NM_177922 RefSeq (protein) NP_620590 NP_808590 Location (UCSC) Chr 8: 143.72 – 143.72 Mb Chr 15: 75.87 – 75.87 Mb PubMed search [3] [4]
Wikidata
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Mitogen-activated protein kinase 15, also known as MAPK15, ERK7, or ERK8, is an enzyme that in humans is encoded by the MAPK15 gene.^[5][6]

Evolutionarily, MAPK15 is conserved in a number of species, including P. troglodytes, B. taurus, M. musculus, R. norvegicus, D. rerio, D. melanogaster, C. elegans, and X. laevis.^[6]

Function

The protein encoded by this gene is a member of the MAP (mitogen-activated protein) kinase family. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), and are involved in signaling cascades that regulate a number of cellular processes, including proliferation, differentiation, and transcriptional regulation. MAPK15 is often referred to as ERK7 or ERK8, and the latter two share 69% amino acid sequence similarity; at least one study has suggested that the two are, in fact, distinct proteins.

In vertebrate models, ERK8 is not constitutively active, and exhibits relatively low basal kinase activity.^[7] It contains two SH3 (SRC homology 3) binding motifs in its C-terminal region, and is likely activated by an SRC-dependent signaling pathway.^[5] SRC is a non-receptor tyrosine kinase (and proto-oncogene) that has been implicated in cancer growth and progression in humans when it is overexpressed. The exact function of MAPK15 is unknown, though a number of studies have implicated the enzyme in various cellular pathways.

Specifically, MAPK15 expression is significantly reduced in human lung and breast carcinomas, and MAPK15 down-regulation is correlated with increased cell motility.^[7] MAPK15 has also been found to negatively regulate protein O-glycosylation with acetyl galactosamine (GalNAc), a process in which a sugar molecule is covalently attached to an oxygen atom on an amino acid residue.^[7] Mammalian MAPK15 is a putative regulator of the cellular localization and transcriptional activity of estrogen-related receptor alpha (ERRa), as well as an inhibitor of proliferating cell nuclear antigen (PCNA) degradation.^[8][9] PCNA is critical for DNA replication, and is an essential factor in protecting genome stability. MAPK15 has also been shown to regulate ciliogenesis in X. laevis (African clawed frog) embryos by phosphorylating an actin regulator called CapZIP.^[10]

Interactions

MAPK15 has been demonstrated to interact with gamma-aminobutyric acid receptor-associated protein (GABARAP) and microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A, or LC3) in a process that stimulates autophagy.^[11] A number of additional proteins also interact with MAPK15, including cyclin-dependent kinase 2 (CDK2), mitogen-activated protein kinase 12 (MAPK12), and lactotransferrin (LTF), among many others.^[6]

Clinical significance

Due to its role in protecting genomic integrity and cell motility, MAPK15 has been identified as a potential target for cancer therapeutics.^[12] Additionally, given the putative role that MAPK15 plays in the regulation of ciliogenesis, it may be an ideal target for diseases related to human ciliary defects (often called ciliopathies).

References

Further reading

External links

• MAP Kinase Resource Archived 2021-04-15 at the Wayback Machine