Q61831 · MK10_MOUSE
- ProteinMitogen-activated protein kinase 10
- GeneMapk10
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids464 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory 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-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692).
Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (By similarity).
Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (By similarity).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax for the enzyme. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity).
Inhibited by HDAC9
Inhibited by HDAC9
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | glutamatergic synapse | |
Cellular Component | mitochondrion | |
Cellular Component | nucleus | |
Cellular Component | perikaryon | |
Cellular Component | plasma membrane | |
Cellular Component | postsynaptic density | |
Cellular Component | postsynaptic Golgi apparatus | |
Molecular Function | ATP binding | |
Molecular Function | JUN kinase activity | |
Molecular Function | protein serine kinase activity | |
Biological Process | JNK cascade | |
Biological Process | locomotor rhythm | |
Biological Process | negative regulation of transcription by RNA polymerase II | |
Biological Process | neurotransmitter receptor transport to postsynaptic membrane | |
Biological Process | protein phosphorylation | |
Biological Process | regulation of circadian rhythm | |
Biological Process | response to light stimulus | |
Biological Process | vesicle-mediated transport in synapse |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMitogen-activated protein kinase 10
- EC number
- Short namesMAP kinase 10; MAPK 10
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ61831
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Lipid-anchor
Note: Palmitoylation regulates MAPK10 trafficking to cytoskeleton (By similarity).
Recruited to the mitochondria in the presence of SARM1
Recruited to the mitochondria in the presence of SARM1
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000186278 | 1-464 | Mitogen-activated protein kinase 10 | |||
Sequence: MSLHFLYYCSEPTLDVKIAFCQGFDKHVDVSSIAKHYNMSKSKVDNQFYSVEVGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRHKILFPGRSYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVENRPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPVKRISVDDALQHPYINVWYDPAEVEAPPPQIYDKQLDEREHTIEEWKELIYKEVMNSEEKTKNGVVKSQPSPSGAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLEASAGPLGCCR | ||||||
Modified residue | 221 | Phosphothreonine; by MAP2K7 | ||||
Sequence: T | ||||||
Modified residue | 223 | Phosphotyrosine; by MAP2K4 | ||||
Sequence: Y | ||||||
Lipidation | 462 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Lipidation | 463 | S-palmitoyl cysteine | ||||
Sequence: C |
Post-translational modification
Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro (By similarity).
Palmitoylation regulates subcellular location and axonal development.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Brain (at protein level). Expressed specifically in neurons of the hippocampus, cortex, cerebellum, brainstem, and spinal cord. Seems to be also found in testis, and very weakly in the heart.
Developmental stage
Expression begins in day 11.5 dpc embryos, and is localized in both the rostral spinal cord and rhombencephalon. In 12.5-13 dpc embryos, it is found throughout the telencephalon. By day 17.5, JNK3 is also expressed in neurons of dorsal root and sensory ganglia and at lower levels in neurons of the myenteric plexus and the developing heart.
Interaction
Subunit
Interacts with MAPK8IP1/JIP-1, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP4 (By similarity).
Interacts with HDAC9 and MAPKBP1 (PubMed:10471813, PubMed:16611996).
Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5 (By similarity).
Interacts with SARM1 (PubMed:17724133).
Interacts with JUND; interaction is inhibited in the presence of MEN1 (By similarity).
Interacts with HDAC9 and MAPKBP1 (PubMed:10471813, PubMed:16611996).
Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5 (By similarity).
Interacts with SARM1 (PubMed:17724133).
Interacts with JUND; interaction is inhibited in the presence of MEN1 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q61831 | Mapk8ip3 Q9ESN9-2 | 4 | EBI-400741, EBI-9549291 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 64-359 | Protein kinase | ||||
Sequence: YQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRHKILFPGRSYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVENRPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPVKRISVDDALQHPYI | ||||||
Motif | 221-223 | TXY | ||||
Sequence: TPY | ||||||
Compositional bias | 405-454 | Polar residues | ||||
Sequence: TKNGVVKSQPSPSGAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLE | ||||||
Region | 405-464 | Disordered | ||||
Sequence: TKNGVVKSQPSPSGAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLEASAGPLGCCR |
Domain
The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Sequence similarities
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q61831-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameAlpha-2
- Length464
- Mass (Da)52,532
- Last updated1997-11-01 v2
- Checksum4313335AC2E9D2E6
Q61831-2
- NameAlpha-1
- Differences from canonical
- 418-464: GAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLEASAGPLGCCR → AQVQQ
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q3TQZ7 | Q3TQZ7_MOUSE | Mapk10 | 418 | ||
Q80W80 | Q80W80_MOUSE | Mapk10 | 464 | ||
Q80W82 | Q80W82_MOUSE | Mapk10 | 422 | ||
A0A5F8MP75 | A0A5F8MP75_MOUSE | Mapk10 | 478 | ||
Q8C9D4 | Q8C9D4_MOUSE | Mapk10 | 464 | ||
E9QN59 | E9QN59_MOUSE | Mapk10 | 494 | ||
A0A0G2JG69 | A0A0G2JG69_MOUSE | Mapk10 | 178 | ||
A0A0G2JGL2 | A0A0G2JGL2_MOUSE | Mapk10 | 252 | ||
A0A0G2JEJ8 | A0A0G2JEJ8_MOUSE | Mapk10 | 173 |
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 267 | in Ref. 2; BAA85877 | ||||
Sequence: S → D | ||||||
Sequence conflict | 345 | in Ref. 2; BAA85877 | ||||
Sequence: V → A | ||||||
Compositional bias | 405-454 | Polar residues | ||||
Sequence: TKNGVVKSQPSPSGAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLE | ||||||
Sequence conflict | 412 | in Ref. 2; BAA85877 | ||||
Sequence: S → G | ||||||
Sequence conflict | 418-423 | in Ref. 2 | ||||
Sequence: GAAVNS → AQVQQ | ||||||
Alternative sequence | VSP_004840 | 418-464 | in isoform Alpha-1 | |||
Sequence: GAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLEASAGPLGCCR → AQVQQ |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L35236 EMBL· GenBank· DDBJ | AAB37741.1 EMBL· GenBank· DDBJ | mRNA | ||
AB005665 EMBL· GenBank· DDBJ | BAA85877.1 EMBL· GenBank· DDBJ | mRNA |