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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: -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

Caution

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

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)DescriptionActionsGraphical viewLength
Binding sitei109ATP1
Active sitei206Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi86 – 94ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processStress response, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-DRE-168638 NOD1/2 Signaling Pathway
R-DRE-2559580 Oxidative Stress Induced Senescence
R-DRE-450302 activated TAK1 mediates p38 MAPK activation
R-DRE-9020702 Interleukin-1 signaling

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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi109K → A: Acts as dominant negative. Inhibits activation of MAP kinase p38 and disrupts cleavage. 1 Publication1
Mutagenesisi234 – 238SVAKT → EVAKE: Constitutively active. 1 Publication5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003456331 – 361Dual specificity mitogen-activated protein kinase kinase 6Add BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei234Phosphoserine; by MAPK3By similarity1
Modified residuei238Phosphothreonine; by MAPK3By similarity1

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
PRIDEiQ9DGE0

Expressioni

Developmental stagei

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

Gene expression databases

BgeeiENSDARG00000099184
ExpressionAtlasiQ9DGE0 baseline and 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
SMRiQ9DGE0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 341Protein kinasePROSITE-ProRule annotationAdd BLAST262

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 46D domainBy similarityAdd BLAST17
Regioni338 – 361DVD domainBy similarityAdd BLAST24

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

Phylogenomic databases

eggNOGiKOG0984 Eukaryota
ENOG410XT3F LUCA
GeneTreeiENSGT00760000119199
HOGENOMiHOG000234206
HOVERGENiHBG108518
InParanoidiQ9DGE0
KOiK04433
OMAiWGTPFEQ
PhylomeDBiQ9DGE0
TreeFamiTF350701

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

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 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28S → SNV in BAB11809 (PubMed:10995439).Curated1
Sequence conflicti28S → SNV in AAH44129 (Ref. 2) Curated1

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
KEGGidre:65239

Similar proteinsi

Entry informationi

Entry nameiMP2K6_DANRE
AccessioniPrimary (citable) accession number: Q9DGE0
Secondary accession number(s): Q6IQW6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: September 2, 2008
Last modified: March 28, 2018
This is version 117 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health