Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

MAPK15 (Q8TD08) - Overview - Molecular Target Synopsis

Protein


MAPK15, Mitogen-activated protein kinase 15
Enzyme Classification 2.7.11.24
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.

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, intracellular, meiotic spindle, nucleus.



UniProt
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:
211 structures (250 chains) solved
173 are solved in complex with at least one small molecule ligand
3 are solved with an approved drug

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

DX4/THIOGUANINE (4XOY_A, 4XP3_A),
BEZ/BENZOIC ACID (5WP1_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAPK15 has been screened with 219 compounds (289 bioactivities), 18 compounds have bioactivities that show binding affinity of <= 500nM (27 bioactivities). (see details)