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Protein

MAP kinase-interacting serine/threonine-protein kinase 2

Gene

MKNK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As2O3-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.9 Publications

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:

Activity regulationi

Inhibited by CGP57380 and staurosporine. Activated by phosphorylation in a negative-feedback regulatory manner in response to chemotherapy (e.g. cytarabine) and thus impairs the generation of antileukemic responses.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei113ATPPROSITE-ProRule annotation1
Active sitei205Proton acceptorPROSITE-ProRule annotation1
Binding sitei209Staurosporine1 Publication1
Metal bindingi299Zinc2 Publications1
Metal bindingi311Zinc2 Publications1
Metal bindingi314Zinc2 Publications1

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Translation regulation
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ9HBH9
SIGNORiQ9HBH9

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:GPRK7, MNK2
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000099875.14
HGNCiHGNC:7111 MKNK2
MIMi605069 gene
neXtProtiNX_Q9HBH9

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi228D → G: Reduced phosphorylation. 1 Publication1
Mutagenesisi244T → A: Loss of kinase activity; when associated with T-249. 1 Publication1
Mutagenesisi249T → A: Loss of kinase activity; when associated with T-244. 1 Publication1
Mutagenesisi379T → D: Constitutively active. 1 Publication1

Organism-specific databases

DisGeNETi2872
OpenTargetsiENSG00000099875
PharmGKBiPA30830

Chemistry databases

ChEMBLiCHEMBL4204
GuidetoPHARMACOLOGYi2105

Polymorphism and mutation databases

BioMutaiMKNK2
DMDMi90102033

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863361 – 465MAP kinase-interacting serine/threonine-protein kinase 2Add BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei74PhosphoserineBy similarity1
Modified residuei244Phosphothreonine1 Publication1
Modified residuei249Phosphothreonine1 Publication1
Modified residuei379Phosphothreonine1 Publication1
Modified residuei437PhosphoserineBy similarity1
Modified residuei440PhosphoserineBy similarity1
Modified residuei452PhosphoserineCombined sources1

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. Dephosphorylated by PP2A.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9HBH9
PaxDbiQ9HBH9
PeptideAtlasiQ9HBH9
PRIDEiQ9HBH9
ProteomicsDBi81554
81555 [Q9HBH9-2]

PTM databases

iPTMnetiQ9HBH9
PhosphoSitePlusiQ9HBH9

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined. Isoform 2 is expressed at higher levels in the ovary than is isoform 1.1 Publication

Gene expression databases

BgeeiENSG00000099875 Expressed in 232 organ(s), highest expression level in vagina
CleanExiHS_MKNK2
ExpressionAtlasiQ9HBH9 baseline and differential
GenevisibleiQ9HBH9 HS

Organism-specific databases

HPAiCAB037253
HPA021875
HPA070499

Interactioni

Subunit structurei

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. Isoform 1 interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation. Isoform 2 interacts with ESR2 and EIF4E in the nucleus.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAPK14Q165393EBI-2864341,EBI-73946

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109130, 39 interactors
IntActiQ9HBH9, 35 interactors
STRINGi9606.ENSP00000250896

Chemistry databases

BindingDBiQ9HBH9

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9HBH9
SMRiQ9HBH9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HBH9

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini84 – 388Protein kinasePROSITE-ProRule annotationAdd BLAST305

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni160 – 162Staurosporine binding3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi60 – 66Nuclear localization signal7
Motifi444 – 448MAP kinase bindingBy similarity5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0607 Eukaryota
ENOG410XQA9 LUCA
GeneTreeiENSGT00900000140876
HOVERGENiHBG106949
InParanoidiQ9HBH9
KOiK04372
OMAiEAIAMNR
OrthoDBiEOG091G0G1X
PhylomeDBiQ9HBH9

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
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
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 11 Publication (identifier: Q9HBH9-1) [UniParc]FASTAAdd to basket
Also known as: 2a1 Publication

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
MVQKKPAELQ GFHRSFKGQN PFELAFSLDQ PDHGDSDFGL QCSARPDMPA
60 70 80 90 100
SQPIDIPDAK KRGKKKKRGR ATDSFSGRFE DVYQLQEDVL GEGAHARVQT
110 120 130 140 150
CINLITSQEY AVKIIEKQPG HIRSRVFREV EMLYQCQGHR NVLELIEFFE
160 170 180 190 200
EEDRFYLVFE KMRGGSILSH IHKRRHFNEL EASVVVQDVA SALDFLHNKG
210 220 230 240 250
IAHRDLKPEN ILCEHPNQVS PVKICDFDLG SGIKLNGDCS PISTPELLTP
260 270 280 290 300
CGSAEYMAPE VVEAFSEEAS IYDKRCDLWS LGVILYILLS GYPPFVGRCG
310 320 330 340 350
SDCGWDRGEA CPACQNMLFE SIQEGKYEFP DKDWAHISCA AKDLISKLLV
360 370 380 390 400
RDAKQRLSAA QVLQHPWVQG CAPENTLPTP MVLQRNSCAK DLTSFAAEAI
410 420 430 440 450
AMNRQLAQHD EDLAEEEAAG QGQPVLVRAT SRCLQLSPPS QSKLAQRRQR
460
ASLSSAPVVL VGDHA
Length:465
Mass (Da):51,875
Last modified:March 7, 2006 - v3
Checksum:iD6D4BE6C541012B1
GO
Isoform 21 Publication (identifier: Q9HBH9-2) [UniParc]FASTAAdd to basket
Also known as: 2b1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     386-414: NSCAKDLTSFAAEAIAMNRQLAQHDEDLA → WDSHFLLPPHPCRIHVRPGGLVRTVTVNE
     415-465: Missing.

Show »
Length:414
Mass (Da):46,711
Checksum:iBA5E7C107CB3FD43
GO
Isoform 31 Publication (identifier: Q9HBH9-3)
Sequence is not available
Length:
Mass (Da):
Isoform 41 Publication (identifier: Q9HBH9-4)
Sequence is not available
Length:
Mass (Da):
Isoform 51 Publication (identifier: Q9HBH9-5)
Sequence is not available
Length:
Mass (Da):

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EJ98K7EJ98_HUMAN
MAP kinase-interacting serine/threo...
MKNK2
176Annotation score:
K7EIN7K7EIN7_HUMAN
MAP kinase-interacting serine/threo...
MKNK2
129Annotation score:
Q9NV89Q9NV89_HUMAN
MAP kinase-interacting serine/threo...
MKNK2
158Annotation score:
K7ELG3K7ELG3_HUMAN
MAP kinase-interacting serine/threo...
MKNK2
73Annotation score:
K7EK27K7EK27_HUMAN
MAP kinase-interacting serine/threo...
MKNK2
82Annotation score:
K7ELN0K7ELN0_HUMAN
MAP kinase-interacting serine/threo...
MKNK2
76Annotation score:
K7EMP5K7EMP5_HUMAN
MAP kinase-interacting serine/threo...
MKNK2
43Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti261V → L in AAF17226 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05164810Q → K. Corresponds to variant dbSNP:rs3746101Ensembl.1
Natural variantiVAR_04080573D → N1 PublicationCorresponds to variant dbSNP:rs56158214Ensembl.1
Natural variantiVAR_051649428R → Q. Corresponds to variant dbSNP:rs34475638Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007353386 – 414NSCAK…DEDLA → WDSHFLLPPHPCRIHVRPGG LVRTVTVNE in isoform 2. 3 PublicationsAdd BLAST29
Alternative sequenceiVSP_007354415 – 465Missing in isoform 2. 3 PublicationsAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF237775 mRNA Translation: AAG26336.1
AF237776 mRNA Translation: AAG26337.1
AF125532 mRNA Translation: AAF17226.1
BC073140 mRNA Translation: AAH73140.1
CCDSiCCDS12079.1 [Q9HBH9-2]
CCDS12080.1 [Q9HBH9-1]
RefSeqiNP_060042.2, NM_017572.3 [Q9HBH9-2]
NP_951009.1, NM_199054.2 [Q9HBH9-1]
UniGeneiHs.515032

Genome annotation databases

EnsembliENST00000250896; ENSP00000250896; ENSG00000099875 [Q9HBH9-1]
ENST00000309340; ENSP00000309485; ENSG00000099875 [Q9HBH9-2]
ENST00000591601; ENSP00000467811; ENSG00000099875 [Q9HBH9-1]
GeneIDi2872
KEGGihsa:2872
UCSCiuc002lus.3 human [Q9HBH9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF237775 mRNA Translation: AAG26336.1
AF237776 mRNA Translation: AAG26337.1
AF125532 mRNA Translation: AAF17226.1
BC073140 mRNA Translation: AAH73140.1
CCDSiCCDS12079.1 [Q9HBH9-2]
CCDS12080.1 [Q9HBH9-1]
RefSeqiNP_060042.2, NM_017572.3 [Q9HBH9-2]
NP_951009.1, NM_199054.2 [Q9HBH9-1]
UniGeneiHs.515032

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AC3X-ray2.10A72-385[»]
2AC5X-ray3.20A72-385[»]
2HW7X-ray2.71A72-385[»]
6CJ5X-ray2.80A72-385[»]
6CJEX-ray3.36A72-385[»]
6CJHX-ray3.60A72-385[»]
6CJWX-ray3.38A72-385[»]
6CJYX-ray3.05A72-385[»]
6CK3X-ray2.90A72-385[»]
6CK6X-ray3.32A72-385[»]
6CKIX-ray2.95A72-385[»]
ProteinModelPortaliQ9HBH9
SMRiQ9HBH9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109130, 39 interactors
IntActiQ9HBH9, 35 interactors
STRINGi9606.ENSP00000250896

Chemistry databases

BindingDBiQ9HBH9
ChEMBLiCHEMBL4204
GuidetoPHARMACOLOGYi2105

PTM databases

iPTMnetiQ9HBH9
PhosphoSitePlusiQ9HBH9

Polymorphism and mutation databases

BioMutaiMKNK2
DMDMi90102033

Proteomic databases

EPDiQ9HBH9
PaxDbiQ9HBH9
PeptideAtlasiQ9HBH9
PRIDEiQ9HBH9
ProteomicsDBi81554
81555 [Q9HBH9-2]

Protocols and materials databases

DNASUi2872
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250896; ENSP00000250896; ENSG00000099875 [Q9HBH9-1]
ENST00000309340; ENSP00000309485; ENSG00000099875 [Q9HBH9-2]
ENST00000591601; ENSP00000467811; ENSG00000099875 [Q9HBH9-1]
GeneIDi2872
KEGGihsa:2872
UCSCiuc002lus.3 human [Q9HBH9-1]

Organism-specific databases

CTDi2872
DisGeNETi2872
EuPathDBiHostDB:ENSG00000099875.14
GeneCardsiMKNK2
HGNCiHGNC:7111 MKNK2
HPAiCAB037253
HPA021875
HPA070499
MIMi605069 gene
neXtProtiNX_Q9HBH9
OpenTargetsiENSG00000099875
PharmGKBiPA30830
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0607 Eukaryota
ENOG410XQA9 LUCA
GeneTreeiENSGT00900000140876
HOVERGENiHBG106949
InParanoidiQ9HBH9
KOiK04372
OMAiEAIAMNR
OrthoDBiEOG091G0G1X
PhylomeDBiQ9HBH9

Enzyme and pathway databases

SignaLinkiQ9HBH9
SIGNORiQ9HBH9

Miscellaneous databases

ChiTaRSiMKNK2 human
EvolutionaryTraceiQ9HBH9
GeneWikiiMKNK2
GenomeRNAii2872
PROiPR:Q9HBH9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000099875 Expressed in 232 organ(s), highest expression level in vagina
CleanExiHS_MKNK2
ExpressionAtlasiQ9HBH9 baseline and differential
GenevisibleiQ9HBH9 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
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
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMKNK2_HUMAN
AccessioniPrimary (citable) accession number: Q9HBH9
Secondary accession number(s): Q6GPI3
, Q9HBH8, Q9UHR0, Q9Y2N6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: March 7, 2006
Last modified: September 12, 2018
This is version 173 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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