Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

MAPK15 (Q8TD08) - Overview - Molecular Target Synopsis


MAPK15, Mitogen-activated protein kinase 15
Enzyme Classification
UniProt Q8TD08

Also Known as MK15_HUMAN, MAPK15, ERK7, ERK8

Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:22948227, PubMed:24618899, PubMed:29021280, PubMed:21847093, PubMed:20733054). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:20638370, PubMed:19166846). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). Interacts with CSK/c-Src, ABL1, RET and TGFB1I1 (PubMed:11875070, PubMed:16484222, PubMed:16624805). Interacts with GABARAP, MAP1LC3B and GABARAPL1; controls, in a kinase-dependent fashion, both basal and starvation-induced autophagy (PubMed:22948227). Interacts with ESRRA; promotes re-localization of ESRRA to the cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA transcriptional activity (PubMed:21190936). Interacts with PCNA; the interaction is chromatin binding- and kinase activity-dependent and prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2 (PubMed:20733054). Interacts with DVL2 (By similarity). Interacts with CLIC3; MAPK15 does not phosphorylates CLIC3 (By similarity).

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: MAPK15 is active in the following subcellular-locations: autophagosome, cell junction, centriole, centrosome, cilium basal body, cytoplasm, cytoplasmic vesicle, cytoskeleton, golgi apparatus, microtubule organizing center, nucleus, spindle, tight junction.
GO terms: MAPK15 is active in the following subcellular-locations: autophagosome, bicellular tight junction, cell-cell junction, centriole, ciliary basal body, cytoplasm, cytoplasmic vesicle, extracellular region, Golgi apparatus, meiotic spindle, nucleus.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project MAPK15 has gain in 9 cell-lines, loss in 2 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: HS578T, A498, ACHN

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MDA-MB-134-VI, SJCRH30, LXFL529

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, NHLF

(see details)

RNA Interference

MAPK15 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: KPD, KNS42. (see details)

3D Structures

At greater than 35% identity similarity to MAPK15 there are:
216 structures (250 chains) solved
178 are solved in complex with at least one small molecule ligand
4 are solved with an approved drug

MAPK15 is solved in complex with the approved drug(s):


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

MAPK15 has been screened with 408 compounds (545 bioactivities), 23 compounds have bioactivities that show binding affinity of <= 500nM (33 bioactivities). (see details)