Q8CDB0 · MKNK2_MOUSE
- ProteinMAP kinase-interacting serine/threonine-protein kinase 2
- GeneMknk2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids459 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Enhances the formation of EIF4F complex in pachytene spermatocytes, thus promoting mRNA translation during spermatogenesis. Displays a high basal kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As2O3-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 zinc ion per monomer.
Activity regulation
Inhibited by CGP57380 and staurosporine.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 90-98 | ATP (UniProtKB | ChEBI) | ||||
Sequence: LGEGAHARV | ||||||
Binding site | 113 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 160-162 | staurosporine (UniProtKB | ChEBI) | ||||
Sequence: EKM | ||||||
Active site | 205 | Proton acceptor | ||||
Sequence: D | ||||||
Binding site | 209 | staurosporine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 299 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 311 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 314 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Cellular Component | PML body | |
Molecular Function | ATP binding | |
Molecular Function | calcium-dependent protein serine/threonine kinase activity | |
Molecular Function | calmodulin binding | |
Molecular Function | calmodulin-dependent protein kinase activity | |
Molecular Function | metal ion binding | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | cellular response to arsenic-containing substance | |
Biological Process | extrinsic apoptotic signaling pathway in absence of ligand | |
Biological Process | hemopoiesis | |
Biological Process | intracellular signal transduction | |
Biological Process | protein phosphorylation | |
Biological Process | regulation of translation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMAP kinase-interacting serine/threonine-protein kinase 2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8CDB0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 238 | Loss of activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 438 | Reduced phosphorylation. | ||||
Sequence: L → A | ||||||
Mutagenesis | 440 | Reduced MAPK3/ERK1 and MAPK1/ERK2-binding. | ||||
Sequence: Q → R | ||||||
Mutagenesis | 446 | Normal MAPK3/ERK1 and MAPK1/ERK2-binding. | ||||
Sequence: S → A or D | ||||||
Mutagenesis | 448 | Normal MAPK3/ERK1 and MAPK1/ER2K-binding. | ||||
Sequence: S → A | ||||||
Mutagenesis | 448 | Reduced MAPK3/ERK1 and MAPK1/ER2K-binding. | ||||
Sequence: S → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 15 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000086337 | 1-459 | MAP kinase-interacting serine/threonine-protein kinase 2 | |||
Sequence: MVQKRTAELQGFHRSFKGQNPFELAFSLDLAQHRDSDFSPQCEARPDMPSSQPIDIPDAKKRGRKKKRCRATDSFSGRFEDVYQLQEDVLGEGAHARVQTCVNLITNQEYAVKIIEKQLGHIRSRVFREVEMLYQCQGHRNVLELIEFFEEEDRFYLVFEKMRGGSILSHIHRRRHFNELEASVVVQDVASALDFLHNKGIAHRDLKPENILCEHPNQVSPVKICDFDLGSGIKLNGDCSPISTPELLTPCGSAEYMAPEVVEAFSEEASIYDKRCDLWSLGVILYILLSGYPPFVGHCGSDCGWDRGEACPACQNMLFESIQEGKYEFPDKDWSHISFAAKDLISKLLVRDAKQRLSAAQVLQHPWVQGCAPENTLPTPLVLQRNSCAKDLTSFAAEAIAMNRQLAQCEEDAGQDQPVVIRATSRCLQLSPPSQSKLAQRRQRASLSATPVVLVGDRA | ||||||
Modified residue | 74 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 244 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 249 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 379 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 431 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 434 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 446 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 450 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As2O3 treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14 (By similarity).
Dephosphorylated by PP2A
Dephosphorylated by PP2A
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed in all tissues examined, with high levels in skeletal muscle and low levels in brain.
Gene expression databases
Interaction
Subunit
Interacts with ESR2 and EIF4E in the nucleus (By similarity).
Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation
Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8CDB0 | Mapk1 P63085 | 23 | EBI-646209, EBI-397697 | |
BINARY | Q8CDB0 | Traf2 P39429 | 3 | EBI-646209, EBI-520016 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 37-67 | Disordered | ||||
Sequence: DFSPQCEARPDMPSSQPIDIPDAKKRGRKKK | ||||||
Motif | 60-66 | Nuclear localization signal | ||||
Sequence: KKRGRKK | ||||||
Domain | 84-368 | Protein kinase | ||||
Sequence: QLQEDVLGEGAHARVQTCVNLITNQEYAVKIIEKQLGHIRSRVFREVEMLYQCQGHRNVLELIEFFEEEDRFYLVFEKMRGGSILSHIHRRRHFNELEASVVVQDVASALDFLHNKGIAHRDLKPENILCEHPNQVSPVKICDFDLGSGIKLNGDCSPISTPELLTPCGSAEYMAPEVVEAFSEEASIYDKRCDLWSLGVILYILLSGYPPFVGHCGSDCGWDRGEACPACQNMLFESIQEGKYEFPDKDWSHISFAAKDLISKLLVRDAKQRLSAAQVLQHPWV | ||||||
Motif | 438-442 | MAP kinase binding | ||||
Sequence: LAQRR |
Sequence similarities
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q8CDB0-1
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.
- Name1
- Length459
- Mass (Da)51,633
- Last updated2006-03-07 v3
- Checksum5252C711AD99729A
Q8CDB0-2
- Name2
- Differences from canonical
- 48-256: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0R4IZX7 | A0A0R4IZX7_MOUSE | Mknk2 | 412 | ||
A0A0G2JGQ2 | A0A0G2JGQ2_MOUSE | Mknk2 | 40 | ||
A0A0G2JGS6 | A0A0G2JGS6_MOUSE | Mknk2 | 118 | ||
A0A0G2JDJ0 | A0A0G2JDJ0_MOUSE | Mknk2 | 49 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_007355 | 48-256 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 256 | in Ref. 2; BAB25570 | ||||
Sequence: Y → D | ||||||
Sequence conflict | 349 | in Ref. 2; BAB25570 | ||||
Sequence: L → P | ||||||
Sequence conflict | 454 | in Ref. 2; BAB25570 | ||||
Sequence: L → I |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB164081 EMBL· GenBank· DDBJ | BAD18852.1 EMBL· GenBank· DDBJ | mRNA | ||
AK008277 EMBL· GenBank· DDBJ | BAB25570.2 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AK030830 EMBL· GenBank· DDBJ | BAC27151.2 EMBL· GenBank· DDBJ | mRNA | ||
AK154235 EMBL· GenBank· DDBJ | BAE32453.1 EMBL· GenBank· DDBJ | mRNA | ||
Y11092 EMBL· GenBank· DDBJ | CAA71966.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
BC010256 EMBL· GenBank· DDBJ | AAH10256.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |