Q8CE90 (MP2K7_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 92.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Dual specificity mitogen-activated protein kinase kinase 7 Short name=MAP kinase kinase 7 Short name=MAPKK 7 EC=2.7.12.2 Alternative name(s): JNK-activating kinase 2 MAPK/ERK kinase 7 Short name=MEK 7 c-Jun N-terminal kinase kinase 2 Short name=JNK kinase 2 Short name=JNKK 2 | ||||
| Gene names |
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| Organism | Mus musculus (Mouse) [Reference proteome] | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus![]() |
Protein attributes
| Sequence length | 535 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| 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 proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.10 Ref.11 |
| Catalytic activity | |
| Cofactor | |
| Enzyme 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. Ref.5 |
| Subunit structure | 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 MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. Ref.8 Ref.9 |
| Subcellular location | |
| Tissue specificity | Expressed at high levels in brain, lung, liver, skeletal muscle, kidney, and testis and at lower levels in the heart and spleen. Ref.1 Ref.2 Ref.4 |
| 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 E12.5. At later stages of embryogenesis (E14.5, E16.5, and E18.5) 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. Ref.1 |
| 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. |
| Post-translational modification | Activated by phosphorylation on Ser-287 and Thr-291 by MAP kinase kinase kinases (MAP3Ks). |
| Sequence similarities | Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain. |
Ontologies
Alternative products
| This entry describes 8 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 Ref.6 (identifier: 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. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 2 Ref.2 Ref.5 Ref.6 (identifier: Q8CE90-2) Also known as: a; beta 1; The sequence of this isoform differs from the canonical sequence as follows: 42-58: IIVITLSPAPAPSQRAA → T 435-435: S → R 436-535: Missing. | ||||||
| Isoform 3 Ref.3 Ref.5 (identifier: Q8CE90-3) Also known as: alpha 2; The sequence of this isoform differs from the canonical sequence as follows: 1-89: Missing. 436-519: TSVTWGAWPL...CPGASTWGLP → GSLEESPTSPPSPKSFPLSPAIPQAQAEWVSGR 520-535: Missing. | ||||||
| Isoform 4 Ref.5 (identifier: Q8CE90-4) Also known as: alpha 1; The sequence of this isoform differs from the canonical sequence as follows: 1-89: Missing. 435-435: S → R 436-535: Missing. | ||||||
| Isoform 5 Ref.2 (identifier: Q8CE90-5) Also known as: b; The sequence of this isoform differs from the canonical sequence as follows: 1-45: Missing. 46-57: TLSPAPAPSQRA → MLTPFMPLVFNSP 435-435: S → R 436-535: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 6 Ref.1 Ref.5 Ref.7 (identifier: Q8CE90-6) Also known as: b; gamma 1; The sequence of this isoform differs from the canonical sequence as follows: 435-435: S → R 436-535: Missing. | ||||||
| Isoform 7 Ref.5 (identifier: Q8CE90-7) Also known as: gamma 2; The sequence of this isoform differs from the canonical sequence as follows: 436-519: TSVTWGAWPL...CPGASTWGLP → GSLEESPTSPPSPKSFPLSPAIPQAQAEWVSGR 520-535: Missing. | ||||||
| Isoform 8 Ref.5 (identifier: Q8CE90-8) Also known as: beta 2; The sequence of this isoform differs from the canonical sequence as follows: 42-58: IIVITLSPAPAPSQRAA → T 436-519: TSVTWGAWPL...CPGASTWGLP → GSLEESPTSPPSPKSFPLSPAIPQAQAEWVSGR 520-535: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 535 | 535 | Dual specificity mitogen-activated protein kinase kinase 7 | PRO_0000271406 | |||||
Regions | |||||||||
| Domain | 136 – 396 | 261 | Protein kinase | ||||||
| Nucleotide binding | 142 – 150 | 9 | ATP By similarity UniProtKB Q13131 | ||||||
| Region | 37 – 73 | 37 | D domain By similarity | ||||||
| Region | 393 – 416 | 24 | DVD domain By similarity | ||||||
| Coiled coil | 2 – 30 | 29 | Potential | ||||||
Sites | |||||||||
| Active site | 259 | 1 | Proton acceptor By similarity UniProtKB Q13131 | ||||||
| Binding site | 165 | 1 | ATP By similarity UniProtKB Q13131 | ||||||
| Site | 60 – 61 | 2 | Cleavage; by anthrax lethal factor By similarity UniProtKB O14733 | ||||||
| Site | 92 – 93 | 2 | Cleavage; by anthrax lethal factor By similarity UniProtKB O14733 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 287 | 1 | Phosphoserine; by MAP3K By similarity | ||||||
| Modified residue | 291 | 1 | Phosphothreonine; by MAP3K By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 89 | 89 | Missing in isoform 3 and isoform 4. Ref.3 Ref.5 | VSP_052265 | |||||
| Alternative sequence | 1 – 45 | 45 | Missing in isoform 5. Ref.2 | VSP_052264 | |||||
| Alternative sequence | 42 – 58 | 17 | IIVIT…SQRAA → T in isoform 2 and isoform 8. Ref.2 Ref.5 Ref.6 | VSP_052266 | |||||
| Alternative sequence | 46 – 57 | 12 | TLSPA…PSQRA → MLTPFMPLVFNSP in isoform 5. Ref.2 | VSP_052267 | |||||
| Alternative sequence | 435 | 1 | S → R in isoform 2, isoform 4, isoform 5 and isoform 6. Ref.1 Ref.2 Ref.5 Ref.6 Ref.7 | VSP_052268 | |||||
| Alternative sequence | 436 – 535 | 100 | Missing in isoform 2, isoform 4, isoform 5 and isoform 6. Ref.1 Ref.2 Ref.5 Ref.6 Ref.7 | VSP_052269 | |||||
| Alternative sequence | 436 – 519 | 84 | TSVTW…TWGLP → GSLEESPTSPPSPKSFPLSP AIPQAQAEWVSGR in isoform 3, isoform 7 and isoform 8. Ref.3 Ref.5 | VSP_052270 | |||||
| Alternative sequence | 520 – 535 | 16 | Missing in isoform 3, isoform 7 and isoform 8. Ref.3 Ref.5 | VSP_052271 | |||||
Experimental info | |||||||||
| Sequence conflict | 47 | 1 | L → T in AAB63448. Ref.5 | ||||||
| Sequence conflict | 166 | 1 | Q → K in BAC27272. Ref.6 | ||||||
| Sequence conflict | 211 | 1 | A → V in AAC16274. Ref.4 | ||||||
| Sequence conflict | 217 | 1 | T → I in AAB81848. Ref.1 | ||||||
| Sequence conflict | 396 | 1 | I → II in AAD15819. Ref.5 | ||||||
| Sequence conflict | 396 | 1 | I → II in AAD15821. Ref.5 | ||||||
| Sequence conflict | 396 | 1 | I → II in AAD15823. Ref.5 | ||||||
| Sequence conflict | 418 | 1 | E → D in AAB81848. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Activation of stress-activated protein kinases/c-Jun N-terminal protein kinases (SAPKs/JNKs) by a novel mitogen-activated protein kinase kinase (MKK7)." Yao Z., Diener K., Wang X.S., Zukowski M., Matsumoto G., Zhou G., Mo R., Sasaki T., Nishina H., Hui C.C., Tan T.-H., Woodgett J.P., Penninger J.M. J. Biol. Chem. 272:32378-32383(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. |
| [2] | "MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous." Holland P.M., Magali S., Campbell J.S., Noselli S., Cooper J.A. J. Biol. Chem. 272:24994-24998(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 5), FUNCTION, TISSUE SPECIFICITY. |
| [3] | "A novel SAPK/JNK kinase, MKK7, stimulated by TNFalpha and cellular stresses." Moriguchi T., Toyoshima F., Masuyama N., Hanafusa H., Gotoh Y., Nishida E. EMBO J. 16:7045-7053(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), FUNCTION. |
| [4] | "Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli." Foltz I.N., Gerl R.E., Wieler J.S., Luckach M., Salmon R.A., Schrader J.W. J. Biol. Chem. 273:9344-9351(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-311 (ISOFORMS 2/6), FUNCTION, TISSUE SPECIFICITY. Tissue: B-cell and Thymus. |
| [5] | "The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases." Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J. Mol. Cell. Biol. 19:1569-1581(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 6; 7 AND 8), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 47-535 (ISOFORM 6), FUNCTION, ENZYME REGULATION, PHOSPHORYLATION, SUBCELLULAR LOCATION. Strain: CD-1. Tissue: Testis. |
| [6] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Fetal forelimb, Fetus and Skin. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6). Strain: C57BL/6. Tissue: Eye. |
| [8] | "A mammalian scaffold complex that selectively mediates MAP kinase activation." Whitmarsh A.J., Cavanagh J., Tournier C., Yasuda J., Davis R.J. Science 281:1671-1674(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAPK8IP1/JIP1. |
| [9] | "Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3." Kelkar N., Gupta S., Dickens M., Davis R.J. Mol. Cell. Biol. 20:1030-1043(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAPK8IP3/JIP3. |
| [10] | "MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines." Tournier C., Dong C., Turner T.K., Jones S.N., Flavell R.A., Davis R.J. Genes Dev. 15:1419-1426(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [11] | "Different properties of SEK1 and MKK7 in dual phosphorylation of stress-induced activated protein kinase SAPK/JNK in embryonic stem cells." Kishimoto H., Nakagawa K., Watanabe T., Kitagawa D., Momose H., Seo J., Nishitai G., Shimizu N., Ohata S., Tanemura S., Asaka S., Goto T., Fukushi H., Yoshida H., Suzuki A., Sasaki T., Wada T., Penninger J.M., Nishina H., Katada T. J. Biol. Chem. 278:16595-16601(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [12] | "Differential regulation and properties of MAPKs." Raman M., Chen W., Cobb M.H. Oncogene 26:3100-3112(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ENZYME REGULATION. |
| [13] | "Diverse physiological functions of MKK4 and MKK7 during early embryogenesis." Asaoka Y., Nishina H. J. Biochem. 148:393-401(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION. |
| [14] | "The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7." Haeusgen W., Herdegen T., Waetzig V. Eur. J. Cell Biol. 90:536-544(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON REGULATION, REVIEW ON FUNCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF026216 mRNA. Translation: AAB81848.1. U74463 mRNA. Translation: AAC53364.1. U74464 mRNA. Translation: AAC53365.1. AB005654 mRNA. Translation: BAA24383.1. AF022112 mRNA. Translation: AAC16274.1. AF022113 mRNA. Translation: AAC16275.1. U93030 mRNA. Translation: AAB63447.1. U93031 Genomic DNA. Translation: AAB63448.1. AF060943 mRNA. Translation: AAD15819.1. AF060944 mRNA. Translation: AAD15820.1. AF060945 mRNA. Translation: AAD15821.1. AF060946 mRNA. Translation: AAD15822.1. AF060947 mRNA. Translation: AAD15823.1. AK028772 mRNA. Translation: BAC26111.1. AK031137 mRNA. Translation: BAC27272.1. AK165184 mRNA. Translation: BAE38066.1. BC070467 mRNA. Translation: AAH70467.1. |
| IPI | IPI00117840. IPI00228989. IPI00280475. IPI00749972. IPI00816840. IPI00816864. IPI00816890. IPI00816911. |
| RefSeq | NP_001036022.1. NM_001042557.2. NP_001157644.1. NM_001164172.1. NP_036074.2. NM_011944.3. |
| UniGene | Mm.3906. |
3D structure databases | |
| HSSP | HSSP built from PDB template 1S9I based on UniProtKB P36507. |
| ProteinModelPortal | Q8CE90. |
| SMR | Q8CE90. Positions 80-418. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q8CE90. 2 interactions. |
PTM databases | |
| PhosphoSite | Q8CE90. |
Proteomic databases | |
| PaxDb | Q8CE90. |
| PRIDE | Q8CE90. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENSMUST00000003027; ENSMUSP00000003027; ENSMUSG00000002948. ENSMUST00000062686; ENSMUSP00000054512; ENSMUSG00000002948. ENSMUST00000110994; ENSMUSP00000106622; ENSMUSG00000002948. ENSMUST00000110995; ENSMUSP00000106623; ENSMUSG00000002948. ENSMUST00000110996; ENSMUSP00000106624; ENSMUSG00000002948. ENSMUST00000110998; ENSMUSP00000106626; ENSMUSG00000002948. ENSMUST00000110999; ENSMUSP00000106627; ENSMUSG00000002948. ENSMUST00000145165; ENSMUSP00000117418; ENSMUSG00000002948. |
| GeneID | 26400. |
| KEGG | mmu:26400. |
| UCSC | uc009kti.2. mouse. uc009ktj.2. mouse. uc009ktk.2. mouse. uc009ktm.2. mouse. uc009ktn.2. mouse. |
Organism-specific databases | |
| CTD | 5609. |
| MGI | MGI:1346871. Map2k7. |
Phylogenomic databases | |
| eggNOG | COG0515. |
| GeneTree | ENSGT00690000101918. |
| HOVERGEN | HBG108518. |
| InParanoid | Q8CE90. |
| KO | K04431. |
| OMA | FKMSSLE. |
Gene expression databases | |
| Bgee | Q8CE90. |
| CleanEx | MM_MAP2K7. |
| Genevestigator | Q8CE90. |
Family and domain databases | |
| InterPro | IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view] |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| SMART | SM00220. S_TKc. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChiTaRS | MAP2K7. mouse. |
| NextBio | 304359. |
| SOURCE | Search... |
Entry information
| Entry name | MP2K7_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q8CE90 Secondary accession number(s): O35406 Q9R1Z6 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
