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

MAPK10 (P53779) - Overview - Molecular Target Synopsis

Protein


MAPK10, Mitogen-activated protein kinase 10
Enzyme Classification 2.7.11.24
UniProt P53779

Also Known as MK10_HUMAN, MAPK10, JNK3, JNK3A, PRKM10, SAPK1B

Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Interacts with MAPKBP1 (By similarity). Binds to at least four scaffolding proteins, MAPK8IP1/JIP1, MAPK8IP2/JIP2, MAPK8IP3/JIP3/JSAP1 and SPAG9/MAPK8IP4/JIP4. These proteins also bind other components of the JNK signaling pathway. Interacts with HDAC9. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. Interacts with SARM1.

6EQ9
CRYSTAL STRUCTURE OF JNK3 IN COMPLEX WITH AMP-PCP
RCSB/PDB
Inspect Structure
See all 3D Structures for MAPK10

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MAPK10 is active in the following subcellular-locations: cytoplasm, membrane, mitochondrion, nucleus.
GO terms: MAPK10 is active in the following subcellular-locations: cytoplasm, cytosol, glutamatergic synapse, mitochondrion, neuron projection, nucleoplasm, nucleus, perikaryon, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAPK10 has gain in 0 cell-lines, loss in 4 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: U251, SF_295, SN12C

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: RL, KARPAS-422, SU-DHL-4

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: HSMM, NHLF, HMEC

(see details)

RNA Interference


MAPK10 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: PEO14, ASPC1. (see details)

3D Structures


For MAPK10 there are:
51 structures (60 chains) solved
47 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

MAPK10 is solved in complex with the approved drug(s):

AMP/ADENOSINE PHOSPHATE (4KKE_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAPK10 has been screened with 1860 compounds (2407 bioactivities), 534 compounds have bioactivities that show binding affinity of <= 500nM (612 bioactivities). (see details)