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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
    Physical map
    AKR1A1 1p33-p32 aldo-keto reductase family 1, member A1 (aldehyde reductase) NASP 1p34.1 nuclear autoantigenic sperm protein (histone-binding) FLJ33084 1p34.1 hypothetical protein FLJ33084 SP192 1p34.1 hypothetical protein SP192 LOC51249 1p34.1 hypothetical protein LOC51249 IPP 1p34-p32 intracisternal A particle-promoted polypeptide MAST205 1p33 intracisternal A particle-promoted polypeptide PIK3R3 1p34.1 phosphoinositide-3-kinase, regulatory subunit, polypeptide 3 (p55, gamma) LOC388627 1 LOC388627 TSPAN-1 1p34.1 tetraspan 1 FLJ20277 RAD54L 1p32 RAD54-like (S. cerevisiae) MUF1 1p34.1 RAD54-like (S. cerevisiae) UQCRH 1p34.1 ubiquinol-cytochrome c reductase hinge protein MGC22960 1p34 MGC22960 gene FAAH 1p35-p34 fatty acid amide hydrolase LOC391036 1 similar to vitamin D3 hydroxylase associated protein LOC388628 1 hypothetical gene supported by BC021746 OTX3 1p34.1 orthodenticle homolog 3 (Drosophila) FLJ32011 1p34.1 hypothetical protein FLJ32011 MKNK1 1p34.1 MAP kinase-interacting serine/threonine kinase 1 MOB3C ATPAF1 1p33-p32.3 ATP synthase mitochondrial F1 complex assembly factor 1 LOC374973 1p34.1 LOC374973 KIAA0494 1pter-p22.1 LOC374973 CYP4B1 1p34-p12 cytochrome P450, family 4, subfamily B, polypeptide 1 LOC388629 1 similar to cytochrome P450 4Z1 CYP4Z2P 1p34.1-p33 cytochrome P450 4Z2 pseudogene CYP4A11 1p36.1-p32.1 cytochrome P450, family 4, subfamily A, polypeptide 11 CYP4X1 1p33 likely ortholog of rat cytochrome P450 4X1 CYP4Z1 1p33 cytochrome P450 4Z1 LOC284541 1p33 similar to fatty acid omega-hydroxylase CYP4A11 MAP17 1p33 membrane-associated protein 17 TAL1 1p32 T-cell acute lymphocytic leukemia 1 SIL 1p33-p32 TAL1 (SCL) interrupting locus UMP-CMPK  UMP-CMP kinase
    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