P45984 · MK09_HUMAN
- ProteinMitogen-activated protein kinase 9
- GeneMAPK9
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids424 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 MAPK9/JNK2 (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572).
In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:10376527).
In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 (PubMed:15805466).
Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 (PubMed:17525747, PubMed:21364637).
In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells (PubMed:19290929).
Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels (PubMed:19290929).
Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption (PubMed:20595622).
When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway (PubMed:19675674).
Participates also in neurite growth in spiral ganglion neurons (By similarity).
Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity).
Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMitogen-activated protein kinase 9
- EC number
- Short namesMAP kinase 9; MAPK 9
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP45984
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_042260 | 13 | in a colorectal adenocarcinoma sample; somatic mutation; dbSNP:rs1762231480 | |||
Sequence: V → M | ||||||
Natural variant | VAR_042261 | 56 | in a head & Neck squamous cell carcinoma sample; somatic mutation | |||
Sequence: K → N | ||||||
Natural variant | VAR_042262 | 246 | in dbSNP:rs35421153 | |||
Sequence: A → T | ||||||
Natural variant | VAR_025175 | 268 | in dbSNP:rs35693958 | |||
Sequence: G → A | ||||||
Natural variant | VAR_042263 | 366 | in dbSNP:rs55736180 | |||
Sequence: R → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 348 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000186273 | 1-424 | UniProt | Mitogen-activated protein kinase 9 | |||
Sequence: MSDSKCDSQFYSVQVADSTFTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRPFQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIHMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQLGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSKMLVIDPDKRISVDEALRHPYITVWYDPAEAEAPPPQIYDAQLEEREHAIEEWKELIYKEVMDWEERSKNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR | |||||||
Modified residue | 183 | UniProt | Phosphothreonine; by MAP2K7 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 183 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 185 | UniProt | Phosphotyrosine; by MAP2K4 | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 185 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 188 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Interacts with DCLK2 (By similarity).
Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway (By similarity).
Interacts with NFATC4 (PubMed:17875713).
Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN (PubMed:10376527).
Interacts with BCL10 (PubMed:17189706).
Interacts with CTNNB1 and GSK3B (PubMed:19675674).
Interacts with MAPKBP1 (PubMed:28089251).
Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-355'. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (By similarity).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 26-321 | Protein kinase | ||||
Sequence: YQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRPFQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIHMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQLGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSKMLVIDPDKRISVDEALRHPYI | ||||||
Motif | 183-185 | TXY | ||||
Sequence: TPY | ||||||
Region | 368-424 | Disordered | ||||
Sequence: KNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR | ||||||
Compositional bias | 376-416 | Polar residues | ||||
Sequence: PSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDAS |
Domain
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
P45984-1
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
- Length424
- Mass (Da)48,139
- Last updated2006-01-24 v2
- Checksum9C15DA79981290AF
P45984-2
- NameAlpha-1
- Differences from canonical
- 378-424: DAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR → AQMQQ
P45984-3
- NameBeta-1
P45984-4
- NameBeta-2
- Differences from canonical
- 216-230: GELVKGCVIFQGTDH → AEMVLHKVLFPGRDY
P45984-5
- Name5
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 51 | in Ref. 1; AAA56831 and 3; AAC50606/AAC50608/AAC50609 | ||||
Sequence: N → S | ||||||
Alternative sequence | VSP_004834 | 216-230 | in isoform Beta-1 and isoform Beta-2 | |||
Sequence: GELVKGCVIFQGTDH → AEMVLHKVLFPGRDY | ||||||
Alternative sequence | VSP_041908 | 230-242 | in isoform 5 | |||
Sequence: HIDQWNKVIEQLG → RILPRDLGPAMLS | ||||||
Alternative sequence | VSP_041909 | 243-424 | in isoform 5 | |||
Sequence: Missing | ||||||
Compositional bias | 376-416 | Polar residues | ||||
Sequence: PSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDAS | ||||||
Sequence conflict | 377 | in Ref. 2; AAA74740 | ||||
Sequence: S → P | ||||||
Alternative sequence | VSP_004835 | 378-424 | in isoform Alpha-1 and isoform Beta-1 | |||
Sequence: DAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR → AQMQQ |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L31951 EMBL· GenBank· DDBJ | AAA56831.1 EMBL· GenBank· DDBJ | mRNA | ||
U09759 EMBL· GenBank· DDBJ | AAA74740.1 EMBL· GenBank· DDBJ | mRNA | ||
U34821 EMBL· GenBank· DDBJ | AAC50606.1 EMBL· GenBank· DDBJ | mRNA | ||
U35002 EMBL· GenBank· DDBJ | AAC50608.1 EMBL· GenBank· DDBJ | mRNA | ||
U35003 EMBL· GenBank· DDBJ | AAC50609.1 EMBL· GenBank· DDBJ | mRNA | ||
EU927388 EMBL· GenBank· DDBJ | ACH57450.1 EMBL· GenBank· DDBJ | mRNA | ||
CR536580 EMBL· GenBank· DDBJ | CAG38817.1 EMBL· GenBank· DDBJ | mRNA | ||
AK289638 EMBL· GenBank· DDBJ | BAF82327.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ066599 EMBL· GenBank· DDBJ | AAY46156.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB451302 EMBL· GenBank· DDBJ | BAG70116.1 EMBL· GenBank· DDBJ | mRNA | ||
AB451355 EMBL· GenBank· DDBJ | BAG70169.1 EMBL· GenBank· DDBJ | mRNA | ||
AC008610 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC104115 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471165 EMBL· GenBank· DDBJ | EAW53759.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471165 EMBL· GenBank· DDBJ | EAW53757.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471165 EMBL· GenBank· DDBJ | EAW53758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471165 EMBL· GenBank· DDBJ | EAW53762.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC032539 EMBL· GenBank· DDBJ | AAH32539.1 EMBL· GenBank· DDBJ | mRNA |