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FLASH GENE
Symbol MKNK2 contributors: mct - updated : 06-05-2015
HGNC name MAP kinase interacting serine/threonine kinase 2
HGNC id 7111
Location 19p13.3      Physical location : 2.037.469 - 2.051.243
Synonym name G protein coupled receptor kinase 7
Synonym symbol(s) GPRK7, MNK2
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 13.77 kb     14 Exon(s)
10 Kb 5' upstream gene genomic sequence study
motif repetitive sequence   ALU   long interspersed repetitive elements
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
text alternatively spliced yielding two splicing isoforms with differing last exons (PMID: 24726367)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 splicing 1778 46.6 414 ubiquitous, nuclear 2014 24726367
  • Mnk2b, which lacks terminal ERK docking site homolog
  • also called isoform B
  • is pro-oncogenic and does not activate MAPK14, while still enhancing EIF4E phosphorylation
  • 14 splicing 3805 51.7 465 cytoplasmic, downregulated in breast, lung, and colon tumors 2014 24726367
  • aslo called isoform A
  • Mnk2a, which contains a MAPK-binding domain
  • is tumor suppressive
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
     stomach   moderately
    Lymphoid/Immunethymus   moderately
     tonsils   moderately
    Nervousnervecranial nerve  predominantly
    Reproductivemale systemprostate  moderately
    Respiratorylung   moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  moderately
    Muscular   moderately
    cell lineage
    cell lines
    fluid/secretion highly in lymph
    at STAGE
    physiological period embryo
    Text moderately in embryo
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a complete serine/threonine kinase domain including a DLG/Asp-Leu-Gly preceded by a DFD (Asp-Phe-Asp) motifs
  • a potential nuclear localization signal (NLS)
  • several potential MAP kinase phosphorylation sites
  • a C terminal ERK docking site homolog
  • conjugated PhosphoP
    mono polymer homomer , monomer
    HOMOLOGY
    interspecies homolog to rattus Mknk2 (94.3 pc)
    homolog to murine Mknk2 (95.4 pc)
    intraspecies paralog to MKNK1, other dependent MAP-kinase dependent kinase
    Homologene
    FAMILY
  • Ser/Thr protein kinase family
  • CATEGORY enzyme , receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • may play a role in the response to environmental stress and cytokines
  • regulating transcription by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap
  • MKNK1, MKNK2 are protein-serine/threonine kinases that are activated by ERK or MAPK14 and phosphorylate EIF4E, which is involved in cap-dependent translation initiation
  • oncogenic role for MKNK1/MKNK2 in tumor development
  • key role for the MKNK1, MKNK2/EIF4E pathway in the regulatory effects of IFNG on normal hematopoiesis
  • plays a unique role, not shared by its closest paralog MKNK1, in limiting protein translation through its negative effect on eIF4G1 Serıı&
  • 8304;&
    8312; phosphorylation and RPS6KB1 activation
  • MKNK1, MKNK2, has a minimal role in T cell development and activation but may regulate non-T cell lineages to control Th1 and Th17 differentiation
  • MKNK1, MKNK2 play important roles in controlling signals involved in mRNA translation
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, translation regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • cell surface receptor linked signal transduction
  • a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor, nucleotide,
  • binding to Mg2+
  • binding to Zn2+ (one ion per subunit)
  • ATP
  • protein
  • estrogen receptor beta (ERB)
  • interacting with the C-terminal regions of EIF4G1 and EIF4G2
  • also binding to dephosphorylated ERK1 and ERK2
  • interacting with ESR2 (variant 1)
  • HNRNPA1 recruitment to stress granules involves MKNK1/MKNK2-dependent phosphorylation of mRNA-bound HNRNPA1
  • MKNK1/MKNK2-EIF4G1 interaction is important for EIF4E phosphorylation
  • previously unrecognized role for BANK1 in CpG-induced responses by splenic B cells on MAPK14 signaling and control of translation initiation of IL6 via MKNK1/MKNK2 and EIF4E
  • MKNK1, MKNK2 increased the binding of EIF4E to the cytoplasmic FMR1-interacting protein 1 (CYFIP1), which binds the fragile-X mental retardation protein, FMR1, a translational repressor
  • MKNK1, MKNK2, can modulate oncogenic translation by regulating EIF4E-EIF4E3 levels and activity in diffuse large B-cell lymphoma (DLBCL)
  • MKNK1, MKNK2 increased the binding of EIF4E to the cytoplasmic FMR1-interacting protein 1 (CYFIP1), which binds the fragile-X mental retardation protein, FMR1, a translational repressor
  • cell & other
    REGULATION
    Other phosphorylated and activated by ERK1, ERK2
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS