Q9ESL4 · M3K20_MOUSE
- ProteinMitogen-activated protein kinase kinase kinase 20
- GeneMap3k20
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids802 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts by catalyzing phosphorylation of MAP kinase kinases, leading to activation of the JNK (MAPK8/JNK1, MAPK9/JNK2 and/or MAPK10/JNK3) and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11042189).
Activates JNK through phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7, and MAP kinase p38 gamma (MAPK12) via phosphorylation of MAP2K3/MKK3 and MAP2K6/MKK6 (PubMed:11042189).
Involved in stress associated with adrenergic stimulation: contributes to cardiac decompensation during periods of acute cardiac stress (By similarity).
May be involved in regulation of S and G2 cell cycle checkpoint by mediating phosphorylation of CHEK2 (By similarity).
Isoform ZAKalpha
Acts as the proximal sensor of ribosome collisions during the ribotoxic stress response (RSR) (PubMed:32289254).
Directly binds to the ribosome by inserting its flexible C-terminus into the ribosomal intersubunit space, thereby acting as a sentinel for colliding ribosomes (By similarity).
Upon ribosome collisions, activates either the stress-activated protein kinase signal transduction cascade or the integrated stress response (ISR), leading to programmed cell death or cell survival, respectively (By similarity).
Dangerous levels of ribosome collisions trigger the autophosphorylation and activation of MAP3K20, which dissociates from colliding ribosomes and phosphorylates MAP kinase kinases, leading to activation of the JNK and MAP kinase p38 pathways that promote programmed cell death (By similarity).
Less dangerous levels of ribosome collisions trigger the integrated stress response (ISR): MAP3K20 activates EIF2AK4/GCN2 independently of its protein-kinase activity, promoting EIF2AK4/GCN2-mediated phosphorylation of EIF2S1/eIF-2-alpha (By similarity).
Also acts as a histone kinase by phosphorylating histone H3 at 'Ser-28' (H3S28ph) (By similarity).
Isoform ZAKbeta
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]This reaction proceeds in the forward direction.
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 kinase kinase 20
- 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 accessionQ9ESL4
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Embryos show polydactyly of the feet (PubMed:26755636).
Defects in stress-activated protein kinase signaling cascade in response to ribotoxic stress, leading to impaired activation of the JNK and MAP kinase p38 pathways (PubMed:27598200).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 45 | Loss of kinase activity. | ||||
Sequence: K → M | ||||||
Mutagenesis | 368 | Causes a split-hand/split-foot phenotype in knockin mice. Gain-of-function mutant that cases a constitutive ribotoxic stress response (RSR). | ||||
Sequence: F → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 32 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-acetylserine | ||||
Sequence: S | ||||||
Modified residue | 2 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000086339 | 2-802 | Mitogen-activated protein kinase kinase kinase 20 | |||
Sequence: SSLGASFVQIKFDDLQFFENCGGGSFGSVYRAKWISQDKEVAVKKLLKIEKEAEILSVLSHRNIIQFYGVILEPPNYGIVTEYASLGSLYDYINSNRSEEMDMEHIMTWATDVAKGMHYLHMEAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHNHTTHMSLVGTFPWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREVPFKGLEGLQVAWLVVEKNERLTIPSSCPRSFAELLHQCWEADAKKRPSFKQIISILESMSNDTNLPDQCNSFLHNKAEWRCEIEATLERLKKLERDLSFKEQELKERERRLKMWEQKLTEQSNTPLLPSFEIGAWTEDDVYFWVQQLVRKGESSVEMSGYASLFKENNITGKRLLLLEEEDLKDMGIVSKGHIIHFKSAIEKLTHDYLNLFHFPPLIKDSGGEPEENEEKIVNLELVFGFHLKPGTGPQDCKWKMYMEMDGDEVAITYIKDVTFNTSLPDAEILKMTKPPFVMEKWIVGIAEDQTVECTVTYENDVRTPKLTKHVHSIQWDRTKPQDEVKAVQLAIQTLFSSSEGNPGSRSDSSADCQWLDTLRMRQIASHTSLQRSQSNPILGSPFFPYFANQDSYAAAVRRTQTPVKYQQITPSINPSRSSSPTQYGLSRNFSSLNLSSRDSGFSSLNDSSSERGRYSDRSRNKYYRGSVSLNSSPKGRYGGKSQHSTPSRERYSGKFYRLPQSALNTHQSPDFKRSPNDHDRRVPRTIPGMPLHPETASKAGEEESRVSEGGWTKVEYRKKTHRQLSAKTSKERTRGNYRGRRNF | ||||||
Modified residue | 3 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 7 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 161 | Phosphothreonine; by autocatalysis | ||||
Sequence: T | ||||||
Modified residue | 165 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 275 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 302 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 434 | In isoform Q9ESL4-2; Phosphoserine | ||||
Sequence: K | ||||||
Modified residue | 453 | In isoform Q9ESL4-2; Phosphoserine | ||||
Sequence: Q | ||||||
Modified residue | 567 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 586 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 587 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 593 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 599 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 628 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 634 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 638 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 649 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 650 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 661 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 685 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 720 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 727 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 733 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 744 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Autophosphorylation in response to ribotoxic stress promotes dissociation from colliding ribosomes and activation (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Developmental stage
Gene expression databases
Interaction
Subunit
Interacts with ZNF33A (By similarity).
Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, MAP3K20 and MAP2K3 (By similarity).
Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and MAP3K20 (By similarity).
Interacts with EIF2AK4/GCN2; promoting EIF2AK4/GCN2 kinase activity (By similarity).
Isoform ZAKalpha
Isoform ZAKbeta
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 16-277 | Protein kinase | ||||
Sequence: LQFFENCGGGSFGSVYRAKWISQDKEVAVKKLLKIEKEAEILSVLSHRNIIQFYGVILEPPNYGIVTEYASLGSLYDYINSNRSEEMDMEHIMTWATDVAKGMHYLHMEAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHNHTTHMSLVGTFPWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREVPFKGLEGLQVAWLVVEKNERLTIPSSCPRSFAELLHQCWEADAKKRPSFKQIISILESMSNDTNLPDQCNSFL | ||||||
Region | 287-308 | Leucine-zipper | ||||
Sequence: IEATLERLKKLERDLSFKEQEL | ||||||
Domain | 339-410 | SAM | ||||
Sequence: WTEDDVYFWVQQLVRKGESSVEMSGYASLFKENNITGKRLLLLEEEDLKDMGIVSKGHIIHFKSAIEKLTHD | ||||||
Compositional bias | 624-668 | Polar residues | ||||
Sequence: YQQITPSINPSRSSSPTQYGLSRNFSSLNLSSRDSGFSSLNDSSS | ||||||
Region | 624-802 | Disordered | ||||
Sequence: YQQITPSINPSRSSSPTQYGLSRNFSSLNLSSRDSGFSSLNDSSSERGRYSDRSRNKYYRGSVSLNSSPKGRYGGKSQHSTPSRERYSGKFYRLPQSALNTHQSPDFKRSPNDHDRRVPRTIPGMPLHPETASKAGEEESRVSEGGWTKVEYRKKTHRQLSAKTSKERTRGNYRGRRNF | ||||||
Region | 670-713 | Sensing domain (S) | ||||
Sequence: RGRYSDRSRNKYYRGSVSLNSSPKGRYGGKSQHSTPSRERYSGK | ||||||
Compositional bias | 680-708 | Polar residues | ||||
Sequence: KYYRGSVSLNSSPKGRYGGKSQHSTPSRE | ||||||
Compositional bias | 730-744 | Basic and acidic residues | ||||
Sequence: FKRSPNDHDRRVPRT | ||||||
Compositional bias | 755-802 | Basic and acidic residues | ||||
Sequence: ASKAGEEESRVSEGGWTKVEYRKKTHRQLSAKTSKERTRGNYRGRRNF | ||||||
Region | 776-802 | C-terminal domain (CTD) | ||||
Sequence: RKKTHRQLSAKTSKERTRGNYRGRRNF |
Domain
Isoform ZAKalpha
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q9ESL4-1
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.
- NameZAKalpha
- SynonymsAlpha
- Length802
- Mass (Da)91,720
- Last updated2001-03-01 v1
- ChecksumD431DF8F312A43CC
Q9ESL4-2
- NameZAKbeta
- SynonymsBeta
- Differences from canonical
Q9ESL4-3
- Name3
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A2ASW6 | A2ASW6_MOUSE | Map3k20 | 74 |
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 171 | in Ref. 2; BAC32371 | ||||
Sequence: P → Q | ||||||
Alternative sequence | VSP_051747 | 285-289 | in isoform 3 | |||
Sequence: CEIEA → WVAPA | ||||||
Alternative sequence | VSP_051748 | 290-802 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_051745 | 332-454 | in isoform ZAKbeta | |||
Sequence: PSFEIGAWTEDDVYFWVQQLVRKGESSVEMSGYASLFKENNITGKRLLLLEEEDLKDMGIVSKGHIIHFKSAIEKLTHDYLNLFHFPPLIKDSGGEPEENEEKIVNLELVFGFHLKPGTGPQD → LPLSARMSEESYFESKTEESNSAEMSCQITAASNGEGHGMNPGLQAMMLMGFGDVFSMNKAGAVLHSGMQINMQAKQNSSKTTCKRRGKKVNMALGFSDFDLSEGDDDDHDGDDAENDVDNSE | ||||||
Alternative sequence | VSP_051746 | 455-802 | in isoform ZAKbeta | |||
Sequence: Missing | ||||||
Compositional bias | 624-668 | Polar residues | ||||
Sequence: YQQITPSINPSRSSSPTQYGLSRNFSSLNLSSRDSGFSSLNDSSS | ||||||
Compositional bias | 680-708 | Polar residues | ||||
Sequence: KYYRGSVSLNSSPKGRYGGKSQHSTPSRE | ||||||
Compositional bias | 730-744 | Basic and acidic residues | ||||
Sequence: FKRSPNDHDRRVPRT | ||||||
Compositional bias | 755-802 | Basic and acidic residues | ||||
Sequence: ASKAGEEESRVSEGGWTKVEYRKKTHRQLSAKTSKERTRGNYRGRRNF |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB049731 EMBL· GenBank· DDBJ | BAB16442.1 EMBL· GenBank· DDBJ | mRNA | ||
AB049732 EMBL· GenBank· DDBJ | BAB16443.1 EMBL· GenBank· DDBJ | mRNA | ||
AK045444 EMBL· GenBank· DDBJ | BAC32371.1 EMBL· GenBank· DDBJ | mRNA | ||
AK132186 EMBL· GenBank· DDBJ | BAE21021.1 EMBL· GenBank· DDBJ | mRNA | ||
BC023718 EMBL· GenBank· DDBJ | AAH23718.1 EMBL· GenBank· DDBJ | mRNA |