Q8CE90 · MP2K7_MOUSE
- ProteinDual specificity mitogen-activated protein kinase kinase 7
- GeneMap2k7
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids535 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK. Isoforms 3 and 4 have lower basal activity but a higher level of inducible activation, than isoforms 2, 6, 7 and 8.
Features
Showing features for site, binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDual specificity mitogen-activated protein kinase kinase 7
- EC number
- Short namesMAP kinase kinase 7; MAPKK 7
- 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 accessionQ8CE90
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 27 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000271406 | 2-535 | Dual specificity mitogen-activated protein kinase kinase 7 | |||
Sequence: AASSLEQKLSRLEAKLKQENREARRRIDLNLDISPQRPRPIIVITLSPAPAPSQRAALQLPLANDGGSRSPSSESSPQHPTPPTRPRHMLGLPSTLFTPRSMESIEIDQKLQEIMKQTGYLTIGGQRYQAEINDLENLGEMGSGTCGQVWKMRFRKTGHIIAVKQMRRSGNKEENKRILMDLDVVLKSHDCPYIVQCFGTFITNTDVFIAMELMGTCAEKLKKRMQGPIPERILGKMTVAIVKALYYLKEKHGVIHRDVKPSNILLDERGQIKLCDFGISGRLVDSKAKTRSAGCAAYMAPERIDPPDPTKPDYDIRADVWSLGISLVELATGQFPYKNCKTDFEVLTKVLQEEPPLLPGHMGFSGDFQSFVKDCLTKDHRKRPKYNKLLEHSFIKHYEILEVDVASWFKDVMAKTESPRTSGVLSQHHLPFFSTSVTWGAWPLAAQTPFQSGVIRCRGRVPSPRRATGGSGGQPCVCAGGPGPSFTEMGPSPSPMLSNTFFTPDPGACPGASTWGLPRRRLCQLLTTSTPGCC | ||||||
Modified residue | 287 | Phosphoserine; by MAP3K | ||||
Sequence: S | ||||||
Modified residue | 291 | Phosphothreonine; by MAP3K | ||||
Sequence: T | ||||||
Modified residue | 427 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Activated by phosphorylation on Ser-287 and Thr-291 by MAP kinase kinase kinases (MAP3Ks).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed at high levels in brain, lung, liver, skeletal muscle, kidney, and testis and at lower levels in the heart and spleen.
Developmental stage
Expressed at high levels in the brain, spinal cord, eyes, muscle, lungs, vertebrae, and intestine and at lower levels in the heart and livers at 12.5 dpc. At later stages of embryogenesis (14.5 dpc, 16.5 dpc, and 18.5 dpc) high levels were found in the brain, retina, bone marrow, skin, intestine, lung epithelium and the epithelial layers lining the olfactory cavity and developing teeth and whiskers.
Gene expression databases
Interaction
Subunit
Interacts with RASSF7, the interaction promotes phosphorylation. Interacts with VRK2 (By similarity).
Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 (By similarity).
Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1 and MAP3K1/MEKK1 (By similarity).
Interacts with SH3RF1, MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642).
Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103).
Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 (By similarity).
Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1 and MAP3K1/MEKK1 (By similarity).
Interacts with SH3RF1, MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642).
Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for coiled coil, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Coiled coil | 2-30 | |||||
Sequence: AASSLEQKLSRLEAKLKQENREARRRIDL | ||||||
Region | 37-73 | D domain | ||||
Sequence: QRPRPIIVITLSPAPAPSQRAALQLPLANDGGSRSPS | ||||||
Region | 63-93 | Disordered | ||||
Sequence: LANDGGSRSPSSESSPQHPTPPTRPRHMLGL | ||||||
Domain | 136-396 | Protein kinase | ||||
Sequence: LENLGEMGSGTCGQVWKMRFRKTGHIIAVKQMRRSGNKEENKRILMDLDVVLKSHDCPYIVQCFGTFITNTDVFIAMELMGTCAEKLKKRMQGPIPERILGKMTVAIVKALYYLKEKHGVIHRDVKPSNILLDERGQIKLCDFGISGRLVDSKAKTRSAGCAAYMAPERIDPPDPTKPDYDIRADVWSLGISLVELATGQFPYKNCKTDFEVLTKVLQEEPPLLPGHMGFSGDFQSFVKDCLTKDHRKRPKYNKLLEHSFI | ||||||
Region | 393-416 | DVD domain | ||||
Sequence: HSFIKHYEILEVDVASWFKDVMAK |
Domain
The DVD domain (residues 393-413) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
The D domain (residues 37-73) contains a conserved docking site and is required for the binding to MAPK substrates.
Sequence similarities
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 8 isoforms produced by Alternative splicing.
Q8CE90-1
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
- Length535
- Mass (Da)59,312
- Last updated2003-03-01 v1
- ChecksumA96DA75565E3CD0F
Q8CE90-2
- Name2
- Synonymsa, beta 1
Q8CE90-3
- Name3
- Synonymsalpha 2
Q8CE90-4
- Name4
- Synonymsalpha 1
Q8CE90-5
- Name5
- Synonymsb
Q8CE90-6
- Name6
- Synonymsb, gamma 1
Q8CE90-7
- Name7
- Synonymsgamma 2
Q8CE90-8
- Name8
- Synonymsbeta 2
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A140LHN8 | A0A140LHN8_MOUSE | Map2k7 | 79 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_052264 | 1-45 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_052265 | 1-89 | in isoform 3 and isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_052266 | 42-58 | in isoform 2 and isoform 8 | |||
Sequence: IIVITLSPAPAPSQRAA → T | ||||||
Alternative sequence | VSP_052267 | 46-57 | in isoform 5 | |||
Sequence: TLSPAPAPSQRA → MLTPFMPLVFNSP | ||||||
Sequence conflict | 47 | in Ref. 5; AAB63448 | ||||
Sequence: L → T | ||||||
Sequence conflict | 166 | in Ref. 6; BAC27272 | ||||
Sequence: Q → K | ||||||
Sequence conflict | 211 | in Ref. 4; AAC16274 | ||||
Sequence: A → V | ||||||
Sequence conflict | 217 | in Ref. 1; AAB81848 | ||||
Sequence: T → I | ||||||
Sequence conflict | 396 | in Ref. 5; AAD15819/AAD15821/AAD15823 | ||||
Sequence: I → II | ||||||
Sequence conflict | 418 | in Ref. 1; AAB81848 | ||||
Sequence: E → D | ||||||
Alternative sequence | VSP_052268 | 435 | in isoform 2, isoform 4, isoform 5 and isoform 6 | |||
Sequence: S → R | ||||||
Alternative sequence | VSP_052270 | 436-519 | in isoform 3, isoform 7 and isoform 8 | |||
Sequence: TSVTWGAWPLAAQTPFQSGVIRCRGRVPSPRRATGGSGGQPCVCAGGPGPSFTEMGPSPSPMLSNTFFTPDPGACPGASTWGLP → GSLEESPTSPPSPKSFPLSPAIPQAQAEWVSGR | ||||||
Alternative sequence | VSP_052269 | 436-535 | in isoform 2, isoform 4, isoform 5 and isoform 6 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_052271 | 520-535 | in isoform 3, isoform 7 and isoform 8 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF026216 EMBL· GenBank· DDBJ | AAB81848.1 EMBL· GenBank· DDBJ | mRNA | ||
U74463 EMBL· GenBank· DDBJ | AAC53364.1 EMBL· GenBank· DDBJ | mRNA | ||
U74464 EMBL· GenBank· DDBJ | AAC53365.1 EMBL· GenBank· DDBJ | mRNA | ||
AB005654 EMBL· GenBank· DDBJ | BAA24383.1 EMBL· GenBank· DDBJ | mRNA | ||
AF022112 EMBL· GenBank· DDBJ | AAC16274.1 EMBL· GenBank· DDBJ | mRNA | ||
AF022113 EMBL· GenBank· DDBJ | AAC16275.1 EMBL· GenBank· DDBJ | mRNA | ||
U93030 EMBL· GenBank· DDBJ | AAB63447.1 EMBL· GenBank· DDBJ | mRNA | ||
U93031 EMBL· GenBank· DDBJ | AAB63448.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF060943 EMBL· GenBank· DDBJ | AAD15819.1 EMBL· GenBank· DDBJ | mRNA | ||
AF060944 EMBL· GenBank· DDBJ | AAD15820.1 EMBL· GenBank· DDBJ | mRNA | ||
AF060945 EMBL· GenBank· DDBJ | AAD15821.1 EMBL· GenBank· DDBJ | mRNA | ||
AF060946 EMBL· GenBank· DDBJ | AAD15822.1 EMBL· GenBank· DDBJ | mRNA | ||
AF060947 EMBL· GenBank· DDBJ | AAD15823.1 EMBL· GenBank· DDBJ | mRNA | ||
AK028772 EMBL· GenBank· DDBJ | BAC26111.1 EMBL· GenBank· DDBJ | mRNA | ||
AK031137 EMBL· GenBank· DDBJ | BAC27272.1 EMBL· GenBank· DDBJ | mRNA | ||
AK165184 EMBL· GenBank· DDBJ | BAE38066.1 EMBL· GenBank· DDBJ | mRNA | ||
BC070467 EMBL· GenBank· DDBJ | AAH70467.1 EMBL· GenBank· DDBJ | mRNA |