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Protein

MAP kinase-interacting serine/threonine-protein kinase 2

Gene

Mknk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Enhances the formation of EIF4F complex in pachytene spermatocytes, thus promoting mRNA translation during spermatogenesis. Displays a high basal kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As2O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Mg2+1 Publication
  • Zn2+By similarityNote: Binds 1 zinc ion per monomer.By similarity

Enzyme regulationi

Inhibited by CGP57380 and staurosporine.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei113ATPPROSITE-ProRule annotation1
Active sitei205Proton acceptorPROSITE-ProRule annotation1
Binding sitei209StaurosporineBy similarity1
Metal bindingi299ZincBy similarity1
Metal bindingi311ZincBy similarity1
Metal bindingi314ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi90 – 98ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cellular response to arsenic-containing substance Source: MGI
  • extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • hemopoiesis Source: MGI
  • intracellular signal transduction Source: UniProtKB
  • peptidyl-serine phosphorylation Source: GO_Central
  • protein autophosphorylation Source: GO_Central
  • protein phosphorylation Source: UniProtKB
  • regulation of translation Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Translation regulation

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
MAP kinase-interacting serine/threonine-protein kinase 2 (EC:2.7.11.1)
Alternative name(s):
MAP kinase signal-integrating kinase 2
Short name:
MAPK signal-integrating kinase 2
Short name:
Mnk2
Gene namesi
Name:Mknk2
Synonyms:Mnk2
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:894279. Mknk2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi238D → A: Loss of activity. 1 Publication1
Mutagenesisi438L → A: Reduced phosphorylation. 1 Publication1
Mutagenesisi440Q → R: Reduced MAPK3/ERK1 and MAPK1/ERK2-binding. 1 Publication1
Mutagenesisi446S → A or D: Normal MAPK3/ERK1 and MAPK1/ERK2-binding. 1 Publication1
Mutagenesisi448S → A: Normal MAPK3/ERK1 and MAPK1/ER2K-binding. 1 Publication1
Mutagenesisi448S → D: Reduced MAPK3/ERK1 and MAPK1/ER2K-binding. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863371 – 459MAP kinase-interacting serine/threonine-protein kinase 2Add BLAST459

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei74PhosphoserineCombined sources1 Publication1
Modified residuei244PhosphothreonineBy similarity1
Modified residuei249PhosphothreonineBy similarity1
Modified residuei379PhosphothreonineBy similarity1
Modified residuei431Phosphoserine1 Publication1
Modified residuei434Phosphoserine1 Publication1
Modified residuei446Phosphoserine1 Publication1
Modified residuei450Phosphothreonine1 Publication1

Post-translational modificationi

Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As2O3 treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14 (By similarity). Dephosphorylated by PP2A.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8CDB0.
PaxDbiQ8CDB0.
PRIDEiQ8CDB0.

PTM databases

iPTMnetiQ8CDB0.
PhosphoSitePlusiQ8CDB0.

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined, with high levels in skeletal muscle and low levels in brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000020190.
CleanExiMM_MKNK2.
ExpressionAtlasiQ8CDB0. baseline and differential.
GenevisibleiQ8CDB0. MM.

Interactioni

Subunit structurei

Interacts with ESR2 and EIF4E in the nucleus (By similarity). Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Mapk1P6308523EBI-646209,EBI-397697
Traf2P394293EBI-646209,EBI-520016

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201432. 2 interactors.
IntActiQ8CDB0. 3 interactors.
MINTiMINT-1524069.
STRINGi10090.ENSMUSP00000003433.

Structurei

3D structure databases

ProteinModelPortaliQ8CDB0.
SMRiQ8CDB0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini84 – 368Protein kinasePROSITE-ProRule annotationAdd BLAST285

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni160 – 162Staurosporine bindingBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi60 – 66Nuclear localization signalBy similarity7
Motifi438 – 442MAP kinase binding5

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0607. Eukaryota.
ENOG410XQA9. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000231140.
HOVERGENiHBG106949.
InParanoidiQ8CDB0.
KOiK04372.
OMAiVQKKTAE.
OrthoDBiEOG091G0G1X.
PhylomeDBiQ8CDB0.
TreeFamiTF314050.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q8CDB0-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVQKRTAELQ GFHRSFKGQN PFELAFSLDL AQHRDSDFSP QCEARPDMPS
60 70 80 90 100
SQPIDIPDAK KRGRKKKRCR ATDSFSGRFE DVYQLQEDVL GEGAHARVQT
110 120 130 140 150
CVNLITNQEY AVKIIEKQLG HIRSRVFREV EMLYQCQGHR NVLELIEFFE
160 170 180 190 200
EEDRFYLVFE KMRGGSILSH IHRRRHFNEL EASVVVQDVA SALDFLHNKG
210 220 230 240 250
IAHRDLKPEN ILCEHPNQVS PVKICDFDLG SGIKLNGDCS PISTPELLTP
260 270 280 290 300
CGSAEYMAPE VVEAFSEEAS IYDKRCDLWS LGVILYILLS GYPPFVGHCG
310 320 330 340 350
SDCGWDRGEA CPACQNMLFE SIQEGKYEFP DKDWSHISFA AKDLISKLLV
360 370 380 390 400
RDAKQRLSAA QVLQHPWVQG CAPENTLPTP LVLQRNSCAK DLTSFAAEAI
410 420 430 440 450
AMNRQLAQCE EDAGQDQPVV IRATSRCLQL SPPSQSKLAQ RRQRASLSAT

PVVLVGDRA
Length:459
Mass (Da):51,633
Last modified:March 7, 2006 - v3
Checksum:i5252C711AD99729A
GO
Isoform 2 (identifier: Q8CDB0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-256: Missing.

Note: No experimental confirmation available.
Show »
Length:250
Mass (Da):27,770
Checksum:iF0B92AE4C5841C85
GO

Sequence cautioni

The sequence AAH10256 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB25570 differs from that shown. Reason: Frameshift at position 439.Curated
The sequence CAA71966 differs from that shown. Reason: Frameshift at position 31.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti256Y → D in BAB25570 (PubMed:16141072).Curated1
Sequence conflicti349L → P in BAB25570 (PubMed:16141072).Curated1
Sequence conflicti454L → I in BAB25570 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00735548 – 256Missing in isoform 2. 1 PublicationAdd BLAST209

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB164081 mRNA. Translation: BAD18852.1.
AK008277 mRNA. Translation: BAB25570.2. Frameshift.
AK030830 mRNA. Translation: BAC27151.2.
AK154235 mRNA. Translation: BAE32453.1.
Y11092 mRNA. Translation: CAA71966.1. Frameshift.
BC010256 mRNA. Translation: AAH10256.1. Different initiation.
CCDSiCCDS24030.2. [Q8CDB0-1]
RefSeqiNP_067437.2. NM_021462.4. [Q8CDB0-1]
XP_006513379.1. XM_006513316.1. [Q8CDB0-1]
XP_017169313.1. XM_017313824.1.
UniGeneiMm.42126.
Mm.486332.

Genome annotation databases

EnsembliENSMUST00000200082; ENSMUSP00000143508; ENSMUSG00000020190. [Q8CDB0-1]
GeneIDi17347.
KEGGimmu:17347.
UCSCiuc007gef.3. mouse. [Q8CDB0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB164081 mRNA. Translation: BAD18852.1.
AK008277 mRNA. Translation: BAB25570.2. Frameshift.
AK030830 mRNA. Translation: BAC27151.2.
AK154235 mRNA. Translation: BAE32453.1.
Y11092 mRNA. Translation: CAA71966.1. Frameshift.
BC010256 mRNA. Translation: AAH10256.1. Different initiation.
CCDSiCCDS24030.2. [Q8CDB0-1]
RefSeqiNP_067437.2. NM_021462.4. [Q8CDB0-1]
XP_006513379.1. XM_006513316.1. [Q8CDB0-1]
XP_017169313.1. XM_017313824.1.
UniGeneiMm.42126.
Mm.486332.

3D structure databases

ProteinModelPortaliQ8CDB0.
SMRiQ8CDB0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201432. 2 interactors.
IntActiQ8CDB0. 3 interactors.
MINTiMINT-1524069.
STRINGi10090.ENSMUSP00000003433.

PTM databases

iPTMnetiQ8CDB0.
PhosphoSitePlusiQ8CDB0.

Proteomic databases

EPDiQ8CDB0.
PaxDbiQ8CDB0.
PRIDEiQ8CDB0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000200082; ENSMUSP00000143508; ENSMUSG00000020190. [Q8CDB0-1]
GeneIDi17347.
KEGGimmu:17347.
UCSCiuc007gef.3. mouse. [Q8CDB0-1]

Organism-specific databases

CTDi2872.
MGIiMGI:894279. Mknk2.

Phylogenomic databases

eggNOGiKOG0607. Eukaryota.
ENOG410XQA9. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000231140.
HOVERGENiHBG106949.
InParanoidiQ8CDB0.
KOiK04372.
OMAiVQKKTAE.
OrthoDBiEOG091G0G1X.
PhylomeDBiQ8CDB0.
TreeFamiTF314050.

Miscellaneous databases

ChiTaRSiMknk2. mouse.
PROiQ8CDB0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020190.
CleanExiMM_MKNK2.
ExpressionAtlasiQ8CDB0. baseline and differential.
GenevisibleiQ8CDB0. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMKNK2_MOUSE
AccessioniPrimary (citable) accession number: Q8CDB0
Secondary accession number(s): O08606, Q75PY0, Q9D893
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: March 7, 2006
Last modified: November 2, 2016
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.