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UniProtKB - Q9HBH9 (MKNK2_HUMAN)

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Protein

MAP kinase-interacting serine/threonine-protein kinase 2

Gene

MKNK2

Organism
Homo sapiens (Human)
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. 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:
  • Mg2+1 Publication
  • Zn2+Note: Binds 1 zinc ion per subunit.

Enzyme 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

Complete GO annotation...

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • cellular response to arsenic-containing substance Source: UniProtKB
  • extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • hemopoiesis Source: UniProtKB
  • 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...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:7111. MKNK2.

Subcellular locationi

Isoform 2 :
Isoform 1 :

GO - Cellular componenti

Complete GO annotation...

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.

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.
CleanExiHS_MKNK2.
ExpressionAtlasiQ9HBH9. baseline and differential.
GenevisibleiQ9HBH9. HS.

Organism-specific databases

HPAiCAB037253.
HPA021875.
HPA053989.

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

Complete GO annotation...

Protein-protein interaction databases

BioGridi109130. 38 interactors.
IntActiQ9HBH9. 33 interactors.
STRINGi9606.ENSP00000250896.

Chemistry databases

BindingDBiQ9HBH9.

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi74 – 76Combined sources3
Turni79 – 81Combined sources3
Beta strandi83 – 85Combined sources3
Beta strandi94 – 102Combined sources9
Beta strandi104 – 106Combined sources3
Beta strandi109 – 116Combined sources8
Helixi123 – 135Combined sources13
Beta strandi145 – 151Combined sources7
Beta strandi154 – 160Combined sources7
Helixi167 – 174Combined sources8
Helixi179 – 198Combined sources20
Helixi208 – 210Combined sources3
Beta strandi211 – 214Combined sources4
Beta strandi216 – 219Combined sources4
Beta strandi221 – 224Combined sources4
Helixi254 – 256Combined sources3
Helixi259 – 264Combined sources6
Helixi267 – 272Combined sources6
Helixi273 – 275Combined sources3
Helixi276 – 290Combined sources15
Helixi312 – 324Combined sources13
Helixi331 – 334Combined sources4
Helixi339 – 348Combined sources10
Turni353 – 355Combined sources3
Helixi359 – 364Combined sources6
Turni366 – 368Combined sources3

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[»]
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

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.Curated

Phylogenomic databases

eggNOGiKOG0607. Eukaryota.
ENOG410XQA9. LUCA.
GeneTreeiENSGT00830000128274.
HOVERGENiHBG106949.
InParanoidiQ9HBH9.
KOiK04372.
OMAiEAIAMNR.
OrthoDBiEOG091G0G1X.
PhylomeDBiQ9HBH9.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
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

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):–

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

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.

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: June 7, 2017
This is version 164 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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families