Reviewed,
UniProtKB/Swiss-Prot O08648 (M3K4_MOUSE)
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October 13, 2009.
Version 86.
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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: Mitogen-activated protein kinase kinase kinase 4 EC=2.7.11.25 Alternative name(s): MAPK/ERK kinase kinase 4 Short name=MEK kinase 4 Short name=MEKK 4 | ||||
| Gene names |
| ||||
| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 1597 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. Ref.1 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium. |
| Enzyme regulation | N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and prevening interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1494 By similarity. |
| Subunit structure | Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1. Ref.1 Ref.3 |
| Subcellular location | Cytoplasm › perinuclear region. Note: Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles. |
| Tissue specificity | Widely expressed. High expression was found in skeletal muscle, kidney, testis followed by heart brain and lung. Low expression was found in spleen. |
| Sequence similarities | Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing |
| Ligand | ATP-binding Magnesium Metal-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro |
| Cellular component | perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activityInferred from electronic annotation. Source: EC magnesium ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform A (identifier: O08648-1) 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. | ||||||
| Isoform B (identifier: O08648-2) The sequence of this isoform differs from the canonical sequence as follows: 1162-1213: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1597 | 1597 | Mitogen-activated protein kinase kinase kinase 4 | PRO_0000086248 | |||||
Regions | |||||||||
| Domain | 1332 – 1590 | 259 | Protein kinase | ||||||
| Nucleotide binding | 1338 – 1346 | 9 | ATP By similarity | ||||||
| Compositional bias | 1178 – 1182 | 5 | Poly-Ala | ||||||
Sites | |||||||||
| Active site | 1452 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 1361 | 1 | ATP | ||||||
Amino acid modifications | |||||||||
| Modified residue | 492 | 1 | Phosphoserine Ref.4 | ||||||
| Modified residue | 1494 | 1 | Phosphothreonine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1162 – 1213 | 52 | Missing in isoform B. | VSP_004885 | |||||
Experimental info | |||||||||
| Mutagenesis | 1361 | 1 | K → A: Loss of kinase activity. Ref.1 | ||||||
| Sequence conflict | 363 – 364 | 2 | SL → NS in AAC08286. Ref.2 | ||||||
| Sequence conflict | 473 | 1 | T → A in AAC08286. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway." Gerwins P., Blank J.L., Johnson G.L. J. Biol. Chem. 272:8288-8295(1997) [PubMed: 9079650] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), FUNCTION, INTERACTION WITH CDC42, MUTAGENESIS OF LYS-1361. Tissue: Brain. |
| [2] | "Characterization of the C3 YAC contig from proximal mouse chromosome 17 and analysis of allelic expression of genes flanking the imprinted Igf2r gene." Schweifer N., Valk P.J., Delwel R., Cox R., Francis F., Meier-Ewert S., Lehrach H., Barlow D.P. Genomics 43:285-297(1997) [PubMed: 9268631] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 363-1049. Strain: C57BL/6. Tissue: Ectoplacental cone. |
| [3] | "The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms." Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C. J. Biol. Chem. 279:39366-39373(2004) [PubMed: 15262978] [Abstract] Cited for: INTERACTION WITH AXIN1 AND DIXDC1. |
| [4] | "Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-492, MASS SPECTROMETRY. Tissue: Liver. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U85607 mRNA. Translation: AAC53126.1. U85608 mRNA. Translation: AAC53127.1. U66240 mRNA. Translation: AAC08286.1. | |
| IPI | IPI00623304. IPI00875136. |
| UniGene | Mm.28587 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1H0U based on UniProtKB P24941. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | O08648. |
PTM databases | |
| PhosphoSite | O08648. |
Proteomic databases | |
| PRIDE | O08648. |
Genome annotation databases | |
| Ensembl | ENSMUST00000074585; ENSMUSP00000074170; ENSMUSG00000014426; Mus musculus. [Genome view] ENSMUST00000089058; ENSMUSP00000086459; ENSMUSG00000014426; Mus musculus. [Genome view] |
| UCSC | uc008ako.1. mouse. |
Organism-specific databases | |
| MGI | MGI:1346875. Map3k4. |
Phylogenomic databases | |
| HOGENOM | O08648. |
| HOVERGEN | O08648. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.25. 244. |
Gene expression databases | |
| ArrayExpress | O08648. |
| Bgee | O08648. |
| CleanEx | MM_MAP3K4. |
| Genevestigator | O08648. |
| GermOnline | ENSMUSG00000014426. Mus musculus. |
Family and domain databases | |
| InterPro | IPR015747. MAPKKK4. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view] |
| PANTHER | PTHR22986:SF60. MAPKKK4. 1 hit. |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00220. S_TKc. 1 hit. [Graphical view] |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| SOURCE | Search... |
Entry information
| Entry name | M3K4_MOUSE | ||||||||
| Accession | Primary (citable) accession number: O08648 Secondary accession number(s): O08649, O70124 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |
