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Protein

Dual specificity mitogen-activated protein kinase kinase 6

Gene

map2k6

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Phosphorylation by MAP2K6 asymmetrically activates p38 on one side of the blastodisc, an event which is necessary for blastomere cleavage.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.Curated

Enzyme regulationi

Activated by dual phosphorylation on Ser-234 and Thr-238 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei109 – 1091ATP
Active sitei206 – 2061Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi86 – 949ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-DRE-168638. NOD1/2 Signaling Pathway.
R-DRE-2559580. Oxidative Stress Induced Senescence.
R-DRE-446652. Interleukin-1 signaling.
R-DRE-450302. activated TAK1 mediates p38 MAPK activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 6By similarity (EC:2.7.12.2)
Short name:
MAP kinase kinase 6By similarity
Short name:
MAPKK 6By similarity
Alternative name(s):
Mitogen-activated protein kinase kinase 31 Publication
Short name:
zMKK3Imported
Gene namesi
Name:map2k6By similarity
Synonyms:map2k3Imported
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Chromosome 12

Organism-specific databases

ZFINiZDB-GENE-010202-3. map2k6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi109 – 1091K → A: Acts as dominant negative. Inhibits activation of MAP kinase p38 and disrupts cleavage. 1 Publication
Mutagenesisi234 – 2385SVAKT → EVAKE: Constitutively active. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 361361Dual specificity mitogen-activated protein kinase kinase 6PRO_0000345633Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei234 – 2341Phosphoserine; by MAPK3By similarity
Modified residuei238 – 2381Phosphothreonine; by MAPK3By similarity

Post-translational modificationi

Weakly autophosphorylated (By similarity). Phosphorylated at Ser-234 and Thr-238 by the majority of M3Ks.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9DGE0.

Expressioni

Developmental stagei

Expressed both maternally and zygotically. Zygotic expression continues throughout development.1 Publication

Gene expression databases

BgeeiQ9DGE0.
ExpressionAtlasiQ9DGE0. differential.

Interactioni

Subunit structurei

Dimer. Interacts (via its D domain) with its MAP kinase substrates. Interacts (via its DVD domain) with MAP3Ks activators.By similarity

Protein-protein interaction databases

STRINGi7955.ENSDARP00000111296.

Structurei

3D structure databases

ProteinModelPortaliQ9DGE0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini80 – 341262Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 4617D domainBy similarityAdd
BLAST
Regioni338 – 36124DVD domainBy similarityAdd
BLAST

Domaini

The DVD domain (residues 338-361) 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 (By similarity).By similarity
The D domain (residues 30-46) contains a conserved docking site and is required for the binding to MAPK substrates.By similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0984. Eukaryota.
ENOG410XT3F. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ9DGE0.
OrthoDBiEOG7J9VPW.
PhylomeDBiQ9DGE0.
TreeFamiTF350701.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9DGE0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGGSDKESK VFCDSPSPNP KGEMSVPSNV RGKKKLPKEL KLPKEVFEKP
60 70 80 90 100
APAPTPPRDL DSKAYVTIGE KNFVVKADDL EQIGELGRGA YGVVDKMRHV
110 120 130 140 150
PSGVIMAVKR IRATVNTQEQ KRLLMDLDIS MRTVDCFYTV TFYGALFREG
160 170 180 190 200
DVWICMELMD TSLDKFYKQV HEKGKTIPED ILGKITVSIV KALEHLHSNL
210 220 230 240 250
SVIHRDVKPS NVLINMQGQV KMCDFGISGY LVDSVAKTMD AGCKPYMAPE
260 270 280 290 300
RINPETNQKG YNVKSDIWSL GITMIELAIL RFPYDSWGTP FQQLKQVVEE
310 320 330 340 350
PSPQLPADRF SADFVDFTSQ CLRKNSTERP TYTELMQHPF FTLHDSKDTD
360
VASFVKTILG D
Length:361
Mass (Da):40,594
Last modified:September 2, 2008 - v2
Checksum:iD942485DE14864B9
GO

Sequence cautioni

The sequence AAH71285.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti28 – 281S → SNV in BAB11809 (PubMed:10995439).Curated
Sequence conflicti28 – 281S → SNV in AAH44129 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB030899 mRNA. Translation: BAB11809.1.
BC044129 mRNA. Translation: AAH44129.1.
BC071285 mRNA. Translation: AAH71285.1. Different initiation.
RefSeqiNP_001299799.1. NM_001312870.1.
UniGeneiDr.150491.

Genome annotation databases

EnsembliENSDART00000171268; ENSDARP00000141647; ENSDARG00000099184.
GeneIDi65239.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB030899 mRNA. Translation: BAB11809.1.
BC044129 mRNA. Translation: AAH44129.1.
BC071285 mRNA. Translation: AAH71285.1. Different initiation.
RefSeqiNP_001299799.1. NM_001312870.1.
UniGeneiDr.150491.

3D structure databases

ProteinModelPortaliQ9DGE0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi7955.ENSDARP00000111296.

Proteomic databases

PaxDbiQ9DGE0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSDART00000171268; ENSDARP00000141647; ENSDARG00000099184.
GeneIDi65239.

Organism-specific databases

CTDi5608.
ZFINiZDB-GENE-010202-3. map2k6.

Phylogenomic databases

eggNOGiKOG0984. Eukaryota.
ENOG410XT3F. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ9DGE0.
OrthoDBiEOG7J9VPW.
PhylomeDBiQ9DGE0.
TreeFamiTF350701.

Enzyme and pathway databases

ReactomeiR-DRE-168638. NOD1/2 Signaling Pathway.
R-DRE-2559580. Oxidative Stress Induced Senescence.
R-DRE-446652. Interleukin-1 signaling.
R-DRE-450302. activated TAK1 mediates p38 MAPK activation.

Miscellaneous databases

NextBioi20902036.
PROiQ9DGE0.

Gene expression databases

BgeeiQ9DGE0.
ExpressionAtlasiQ9DGE0. differential.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Asymmetric p38 activation in zebrafish: its possible role in symmetric and synchronous cleavage."
    Fujii R., Yamashita S., Hibi M., Hirano T.
    J. Cell Biol. 150:1335-1348(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF LYS-109 AND 234-SER--THR-238.
    Tissue: Embryo1 Publication.
  2. NIH - Zebrafish Gene Collection (ZGC) project
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: ABImported.
    Tissue: EmbryoImported.

Entry informationi

Entry nameiMP2K6_DANRE
AccessioniPrimary (citable) accession number: Q9DGE0
Secondary accession number(s): Q6IQW6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: September 2, 2008
Last modified: May 11, 2016
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be a Map2k3 protein but sequence analysis shows closer similarity to the Map2k6 proteins.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.