P45983 · MK08_HUMAN
- ProteinMitogen-activated protein kinase 8
- GeneMAPK8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids427 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971).
Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198).
Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198).
Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637).
In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239).
Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871).
Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity).
In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity).
Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:16581800, PubMed:17296730, PubMed:20027304).
Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).
Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973).
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity).
Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296).
In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity).
Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201).
Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560).
Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315).
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 8
- EC number
- Short namesMAP kinase 8; MAPK 8
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP45983
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 55 | Abolished protein kinase activity. | ||||
Sequence: K → D | ||||||
Natural variant | VAR_042258 | 171 | in a renal clear cell carcinoma sample; somatic mutation | |||
Sequence: G → S | ||||||
Natural variant | VAR_042259 | 177 | in a glioblastoma multiforme sample; somatic mutation; dbSNP:rs2043278229 | |||
Sequence: G → R | ||||||
Mutagenesis | 183 | Phosphorylation blocked. | ||||
Sequence: T → A | ||||||
Mutagenesis | 185 | Phosphorylation blocked. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_050592 | 365 | in dbSNP:rs45483593 | |||
Sequence: E → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 388 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_0000186262 | 1-427 | UniProt | Mitogen-activated protein kinase 8 | |||
Sequence: MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSKMLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEVMDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR | |||||||
Modified residue | 116 | UniProt | S-nitrosocysteine | ||||
Sequence: C | |||||||
Modified residue (large scale data) | 178 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 179 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
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 | |||||||
Modified residue | 301 | UniProt | In isoform P45983-5; Phosphoserine | ||||
Sequence: M | |||||||
Modified residue | 377 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 377 | UniProt | In isoform P45983-2; Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 377 | UniProt | In isoform P45983-3; Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by TAOK2 (PubMed:17158878).
May be phosphorylated at Thr-183 and Tyr-185 by MAP3K1/MEKK1 (PubMed:17761173).
Phosphorylated form is more concentrated at synapses than none-phosphorylated (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8IP1/JIP1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK9/JNK2 (By similarity).
Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 (PubMed:15693750).
These proteins also bind other components of the JNK signaling pathway. Interacts with TP53 and WWOX (PubMed:12514174).
Interacts with JAMP (By similarity).
Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs under both normal growth conditions and immediately upon heat shock (PubMed:10747973).
Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells (By similarity).
Interacts with NFATC4 (PubMed:17875713).
Interacts with MECOM; regulates JNK signaling (PubMed:10856240).
Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates (PubMed:21660049).
Interacts with GRIPAP1 (PubMed:17761173).
Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-355'. Interacts with STMN2, STMN3 and STMN4 (By similarity).
Interacts with HSF4 (PubMed:16581800).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P45983 | CBL P22681 | 2 | EBI-286483, EBI-518228 | |
BINARY | P45983 | CLDN6 P56747 | 3 | EBI-286483, EBI-12955011 | |
BINARY | P45983 | DUSP8 Q13202 | 3 | EBI-286483, EBI-6380262 | |
BINARY | P45983 | H2AX P16104 | 3 | EBI-286483, EBI-494830 | |
BINARY | P45983 | JUN P05412 | 5 | EBI-286483, EBI-852823 | |
BINARY | P45983 | MAP2K4 P45985 | 3 | EBI-286483, EBI-447868 | |
BINARY | P45983 | MAP2K7 O14733-2 | 3 | EBI-286483, EBI-492627 | |
BINARY | P45983 | MAPK8IP1 Q9UQF2 | 8 | EBI-286483, EBI-78404 | |
XENO | P45983 | Mapk8ip1 Q9WVI9-1 | 2 | EBI-286483, EBI-288461 | |
BINARY | P45983 | MAPK9 P45984 | 5 | EBI-286483, EBI-713568 | |
BINARY | P45983 | PIK3R1 P27986 | 6 | EBI-286483, EBI-79464 | |
BINARY | P45983 | RPTOR Q8N122 | 6 | EBI-286483, EBI-1567928 | |
BINARY | P45983-1 | JUN P05412 | 2 | EBI-288687, EBI-852823 | |
BINARY | P45983-4 | DUSP10 Q9Y6W6 | 3 | EBI-18121963, EBI-3443946 | |
BINARY | P45983-4 | DUSP16 Q9BY84 | 3 | EBI-18121963, EBI-3443956 |
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: YQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSKMLVIDASKRISVDEALQHPYI | ||||||
Motif | 183-185 | TXY | ||||
Sequence: TPY | ||||||
Region | 371-427 | Disordered | ||||
Sequence: VIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR | ||||||
Compositional bias | 381-414 | Polar residues | ||||
Sequence: AAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDS |
Domain
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
P45983-1
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.
- Name2
- SynonymsJNK1-alpha-2
- Length427
- Mass (Da)48,296
- Last updated1997-11-01 v2
- Checksum94FB6BE0358B9B60
P45983-2
- Name1
- SynonymsJNK1-alpha-1
- Differences from canonical
- 380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ
P45983-3
- Name3
- SynonymsJNK1-beta-1
P45983-4
- Name4
- SynonymsJNK1-beta-2
P45983-5
- Name5
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9J762 | C9J762_HUMAN | MAPK8 | 142 | ||
C9JWQ4 | C9JWQ4_HUMAN | MAPK8 | 40 | ||
A0A3B3IRW7 | A0A3B3IRW7_HUMAN | MAPK8 | 169 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_054554 | 206-281 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_004831 | 208 | in isoform 3 and isoform 4 | |||
Sequence: L → I | ||||||
Alternative sequence | VSP_004832 | 219-230 | in isoform 3 and isoform 4 | |||
Sequence: VCHKILFPGRDY → IKGGVLFPGTDH | ||||||
Alternative sequence | VSP_004833 | 380-427 | in isoform 1, isoform 3 and isoform 5 | |||
Sequence: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ | ||||||
Compositional bias | 381-414 | Polar residues | ||||
Sequence: AAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L26318 EMBL· GenBank· DDBJ | AAA36131.1 EMBL· GenBank· DDBJ | mRNA | ||
U34822 EMBL· GenBank· DDBJ | AAC50607.1 EMBL· GenBank· DDBJ | mRNA | ||
U35004 EMBL· GenBank· DDBJ | AAC50610.1 EMBL· GenBank· DDBJ | mRNA | ||
U35005 EMBL· GenBank· DDBJ | AAC50611.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ234352 EMBL· GenBank· DDBJ | ABB29981.1 EMBL· GenBank· DDBJ | mRNA | ||
AC016397 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC074325 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AB451231 EMBL· GenBank· DDBJ | BAG70045.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471187 EMBL· GenBank· DDBJ | EAW93132.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471187 EMBL· GenBank· DDBJ | EAW93129.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471187 EMBL· GenBank· DDBJ | EAW93130.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471187 EMBL· GenBank· DDBJ | EAW93133.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471187 EMBL· GenBank· DDBJ | EAW93134.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471187 EMBL· GenBank· DDBJ | EAW93136.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC144063 EMBL· GenBank· DDBJ | AAI44064.1 EMBL· GenBank· DDBJ | mRNA |