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FLASH GENE
Symbol NLK contributors: mct/npt - updated : 02-01-2017
HGNC name nemo-like kinase
HGNC id 29858
Location 17q11.2      Physical location : 26.369.687 - 26.523.402
Synonym name protein LAK1
Synonym symbol(s) DKFZp761G1211, FLJ21033, LAK1
EC.number 2.7.11.24
DNA
TYPE functioning gene
STRUCTURE 153.72 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 3555 - 527 - 2002 12039044
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineparathyroid   highly
Lymphoid/Immunelymph node   highly
Nervousbrain    
Urinarykidney    
Visualeyeretina  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 289 AA kinase domain
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • MAP kinase subfamily
  • CATEGORY regulatory , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • may play a novel role in the regulatory of SMAD4 through phosphorylation
  • suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex
  • suppresses Notch signalling by interfering with formation of the Notch active transcriptional complexconserved serine/threonine kinase that suppresses beta-catenin/T-cell factor (TCF) complex transcriptional activity through phosphorylation of TCF
  • its expression is altered during prostate cancer progression and is involved in regulation of AR signaling in these cells
  • induces apoptosis in glioma cells via activation of caspases
  • potentially serves as a conserved molecular link between core planar cell polarity factors and E-cadherin-CTNNB complexes, promoting cell motility
  • potential clock kinase
  • suppressor of tumor necrosis factor (TNF)-induced NFKB1 signaling by inhibiting the phosphorylation of IKBKB
  • NLK mediates aberrant erythropoiesis in Diamond Blackfan Anemia (DBA)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • transforming growth factor-beta-activated kinase (MAP3K7)-Nemo-like kinase (NLK) pathway negatively regulates FOXO1
  • a component
  • homodimerization of NLK is required for its activation and nuclear localization (dimerization is an initial key event required for the functional activation of NLK)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds and phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain
  • is a DAPK3 -binding partner and DAPK3 regulates NLK-mediated repression of canonical Wnt/beta-catenin signaling
  • functions as a pivotal negative regulator in TNF-induced activation of NFKB1 via disrupting the interaction of MAP3K7 with IKBKB
  • nuclear localization of NLK was mediated through direct interaction with HSPB1 which further protected cancer cells from apoptosis
  • cell & other
    REGULATION
    activated by Wnt1-induced MAP3K7 stimulation
    intermolecular autophosphorylation of NLK dimers at Thr-286
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    associated with poor prognosis in glioma
    tumoral     --low  
    in prostate cancer metastases in comparison to normal prostate epithelium and primary cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    upregulating NLK expression could be developed for treatment of glioma
    blood  
    potential target for therapy in Diamond Blackfan Anemia (DBA)
    ANIMAL & CELL MODELS