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FLASH GENE
Symbol MKNK1 contributors: mct/npt - updated : 06-05-2015
HGNC name MAP kinase-interacting serine/threonine kinase 1
HGNC id 7110
Location 1p33      Physical location : 47.023.090 - 47.069.966
Synonym name
  • MAP kinase interacting kinase 1
  • mitogen-activated protein kinase signal-integrating kinases
  • EIF4E kinase
  • Synonym symbol(s) MNK1
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 46.89 kb     14 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 2816 - 465 - 2009 19650764
  • also called MNK1A
  • different kinase activity between MNK1A and MNK1B is independent of the phosphorylation status of the activation loop residues
  • activity of MNK1A is tightly regulated by signalling through ERK (extracellular-signal-regulated kinase) and MAPK14
  • longer C-terminus of MNK1A represses the basal activity and T (activation)-loop phosphorylation of this isoenzyme while allowing both properties to be stimulated by upstream MAPK signalling
  • 12 splicing 2618 - 347 - 2009 19650764
  • also called MNK1B
  • having much higher basal eIF4E kinase activity than MNK1A
  • crucial role of the 12 AAs, particularly the Ala344, in the C-terminal specific region of Mnk1b (Mnk1bSR), on the kinase activity of the protein
  • higher basal activity than MNK1A
  • short C-terminus of MNK1B confers on it a 'default' behaviour of substantial, but unregulated, activity
  • 13 - 2693 - 424 - 2009 19650764
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   highly
    Endocrinepancreas   predominantly Homo sapiens
    Lymphoid/Immunespleen   highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine  Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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, motifs for binding to MAPKs
  • HOMOLOGY
    interspecies homolog to murine Mknk1
    intraspecies paralog to MKNK2
    Homologene
    FAMILY
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • active form of MKNK1 localises to centrosomes, spindle microtubules and the midbody
  • basic FUNCTION
  • may be playing a role in the myeloid differentiation
  • playing a role in the AML fusion protein-associated differentiation block
  • 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
  • may play a role in the induction of senescence
  • MNK1 activity is required for abscission
  • 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
  • appears to be an important regulator of neutrophil responses
  • 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
  • is a novel pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance and EIF4E phosphorylation
  • MKNK1, MKNK2 play important roles in controlling signals involved in mRNA translation
  • is a key component of BDNF-mediated translational regulation in neurons
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • component of the eukaryotic initiation complex EIF4F with EIF4A, EIF4E, EIF4EBP1, EIF4EBP2, EIF4EBP3, PABPC1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphorylated by ERK1, ERK2
  • interacting with SPRY2 (MKNK1-mediated serine phosphorylation of SPRY2 constitutes a regulatory mechanism to extend the temporal range of SPRY activity)
  • HNRNPA1 recruitment to stress granules involves MKNK1/MKNK2-dependent phosphorylation of mRNA-bound HNRNPA1
  • target gene of several leukemogenic fusion proteins in AML
  • PRKCA activation elicits a cascade of orchestrated phosphorylation events that may modulate EIF4G1 structure and control interaction with MKNK1
  • regulates the phosphorylation and the subcellular distribution of HNRNPA1
  • is a direct PTF1A target
  • 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
  • BDNF induces the release of CYFIP1 from EIF4E, and this depends on MNKNK1
  • cell & other
  • displayed by adenovirus from eIF4G subsequently inhibiting EIF4E phosphorylation
  • REGULATION
    Other recruited by eIF4G to the initiation complex to phosphorylate eIF4E
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    induces the formation of multinucleated cells, which can be rescued by expressing a form of MNK1 that is resistant to RNA interference
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    pharmacologic inhibition of the MKNK1, MKNK2 may be therapeutically useful blast crisis chronic myeloid leukemia
    immunologyinflammatory 
    in numerous chronic inflammatory disorders, MNK1 could represent an attractive therapeutic target
    ANIMAL & CELL MODELS