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Aliases for NLK Gene

Aliases for NLK Gene

  • Nemo Like Kinase 2
  • Nemo-Like Kinase 2 3 4 5
  • EC 2.7.11.24 4 63
  • Protein LAK1 4
  • EC 2.7.11 63
  • LAK1 4

External Ids for NLK Gene

Previous GeneCards Identifiers for NLK Gene

  • GC17P026225
  • GC17P028269
  • GC17P026515
  • GC17P026514
  • GC17P023393
  • GC17P026369
  • GC17P022577

Summaries for NLK Gene

GeneCards Summary for NLK Gene

NLK (Nemo Like Kinase) is a Protein Coding gene. Among its related pathways are Signaling by GPCR and ERK Signaling. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAPK1.

UniProtKB/Swiss-Prot for NLK Gene

  • Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Activation of this pathway causes binding to and phosphorylation of the histone methyltransferase SETDB1. The NLK-SETDB1 complex subsequently interacts with PPARG, leading to methylation of PPARG target promoters at histone H3K9 and transcriptional silencing. The resulting loss of PPARG target gene transcription inhibits adipogenesis and promotes osteoblastogenesis in mesenchymal stem cells (MSCs). Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613).

Gene Wiki entry for NLK Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NLK Gene

Genomics for NLK Gene

Regulatory Elements for NLK Gene

Promoters for NLK Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around NLK on UCSC Golden Path with GeneCards custom track

Genomic Location for NLK Gene

Chromosome:
17
Start:
28,041,737 bp from pter
End:
28,205,140 bp from pter
Size:
163,404 bases
Orientation:
Plus strand

Genomic View for NLK Gene

Genes around NLK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NLK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NLK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NLK Gene

Proteins for NLK Gene

  • Protein details for NLK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UBE8-NLK_HUMAN
    Recommended name:
    Serine/threonine-protein kinase NLK
    Protein Accession:
    Q9UBE8
    Secondary Accessions:
    • B2RCX1
    • Q2PNI9
    • Q6P2A3

    Protein attributes for NLK Gene

    Size:
    527 amino acids
    Molecular mass:
    58283 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer. Homodimerization is required for intermolecular autophosphorylation, kinase activation and nuclear localization (By similarity). May interact with components of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes (By similarity). Interacts with LEF1, MEF2A, MYBL1 and MYBL2 (By similarity). Interacts with the upstream activating kinases HIPK2 and MAP3K7/TAK1. Interaction with MAP3K7/TAK1 seems to be indirect, and may be mediated by other proteins such as STAT3, TAB1 and TAB2. Interacts with and phosphorylates a number of transcription factors including FOXO1, FOXO3, FOXO4, MYB, NOTCH1 and TCF7L2/TCF4. Interacts with DAPK3/ZIPK, and this interaction may disrupt interaction with transcription factors such as TCF7L2/TCF4. Forms a transcriptional repressor complex with CHD7, PPARG and SETDB1. Interacts with RNF138/NARF. Interacts with ATF5; the interaction stabilizes ATF5 at the protein level in a kinase-independent manner (PubMed:25512613).
    SequenceCaution:
    • Sequence=AAD56013.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAF04857.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=ABC40748.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAG37718.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

neXtProt entry for NLK Gene

Proteomics data for NLK Gene at MOPED

Post-translational modifications for NLK Gene

  • Phosphorylated on Thr-298. Intermolecular autophosphorylation on Thr-298 activates the enzyme.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NLK Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for NLK Gene

Gene Families for NLK Gene

Suggested Antigen Peptide Sequences for NLK Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9UBE8

UniProtKB/Swiss-Prot:

NLK_HUMAN :
  • Contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-298) is sufficient for kinase activation. This mode of activation contrasts with that of classical MAP kinases, which contain a TXY activation loop motif in which phosphorylation of both the threonine and tyrosine residues is required for kinase activation.
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
Domain:
  • Contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-298) is sufficient for kinase activation. This mode of activation contrasts with that of classical MAP kinases, which contain a TXY activation loop motif in which phosphorylation of both the threonine and tyrosine residues is required for kinase activation.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
genes like me logo Genes that share domains with NLK: view

Function for NLK Gene

Molecular function for NLK Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-298 (By similarity). Activated by the non-canonical Wnt signaling pathway, in which WNT5A treatment leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Other cytokines such as IL6 may also activate this regulatory circuit.
UniProtKB/Swiss-Prot Function:
Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Activation of this pathway causes binding to and phosphorylation of the histone methyltransferase SETDB1. The NLK-SETDB1 complex subsequently interacts with PPARG, leading to methylation of PPARG target promoters at histone H3K9 and transcriptional silencing. The resulting loss of PPARG target gene transcription inhibits adipogenesis and promotes osteoblastogenesis in mesenchymal stem cells (MSCs). Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613).

Enzyme Numbers (IUBMB) for NLK Gene

Gene Ontology (GO) - Molecular Function for NLK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IEA,ISS --
GO:0008134 transcription factor binding IPI 16714285
GO:0031625 ubiquitin protein ligase binding IPI 16714285
genes like me logo Genes that share ontologies with NLK: view
genes like me logo Genes that share phenotypes with NLK: view

Animal Models for NLK Gene

MGI Knock Outs for NLK:

Animal Model Products

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NLK Gene

Localization for NLK Gene

Subcellular locations from UniProtKB/Swiss-Prot for NLK Gene

Nucleus. Cytoplasm. Note=Predominantly nuclear. A smaller fraction is cytoplasmic (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NLK Gene COMPARTMENTS Subcellular localization image for NLK gene
Compartment Confidence
cytosol 5
nucleus 5
peroxisome 1

Gene Ontology (GO) - Cellular Components for NLK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with NLK: view

Pathways & Interactions for NLK Gene

genes like me logo Genes that share pathways with NLK: view

SIGNOR curated interactions for NLK Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for NLK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IEA,ISS --
GO:0006468 protein phosphorylation IEA,ISS --
GO:0018107 peptidyl-threonine phosphorylation IEA,ISS --
GO:0030178 negative regulation of Wnt signaling pathway IEA,ISS --
GO:0046777 protein autophosphorylation IEA --
genes like me logo Genes that share ontologies with NLK: view

Drugs & Compounds for NLK Gene

(3) Drugs for NLK Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Nutra 0
genes like me logo Genes that share compounds with NLK: view

Transcripts for NLK Gene

Unigene Clusters for NLK Gene

Nemo-like kinase:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NLK Gene

No ASD Table

Relevant External Links for NLK Gene

GeneLoc Exon Structure for
NLK
ECgene alternative splicing isoforms for
NLK

Expression for NLK Gene

mRNA expression in normal human tissues for NLK Gene

mRNA differential expression in normal tissues according to GTEx for NLK Gene

This gene is overexpressed in Brain - Cortex (x5.0) and Brain - Frontal Cortex (BA9) (x5.0).

Protein differential expression in normal tissues from HIPED for NLK Gene

This gene is overexpressed in Brain (49.1) and Retina (19.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for NLK Gene



SOURCE GeneReport for Unigene cluster for NLK Gene Hs.208759

genes like me logo Genes that share expression patterns with NLK: view

Protein tissue co-expression partners for NLK Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA Expression by UniProt/SwissProt for NLK Gene

Orthologs for NLK Gene

This gene was present in the common ancestor of animals.

Orthologs for NLK Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia NLK 35
  • 96.71 (n)
  • 100 (a)
NLK 36
  • 100 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NLK 35
  • 97.53 (n)
  • 99.81 (a)
NLK 36
  • 100 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nlk 35
  • 94.43 (n)
  • 99.81 (a)
Nlk 16
Nlk 36
  • 100 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia NLK 35
  • 99.94 (n)
  • 100 (a)
NLK 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nlk 35
  • 94.5 (n)
  • 99.81 (a)
oppossum
(Monodelphis domestica)
Mammalia NLK 36
  • 99 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NLK 36
  • 100 (a)
OneToOne
chicken
(Gallus gallus)
Aves NLK 35
  • 89.75 (n)
  • 98.67 (a)
NLK 36
  • 99 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NLK 36
  • 98 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nlk 35
  • 83.4 (n)
  • 94.85 (a)
Str.7425 35
African clawed frog
(Xenopus laevis)
Amphibia xnlk 35
zebrafish
(Danio rerio)
Actinopterygii nlk2 35
  • 77.89 (n)
  • 98.47 (a)
nlk2 36
  • 94 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta nmo 37
  • 78 (a)
nmo 35
  • 65.9 (n)
  • 80.31 (a)
nmo 36
  • 77 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005898 35
  • 66.58 (n)
  • 80.05 (a)
worm
(Caenorhabditis elegans)
Secernentea lit-1 35
  • 62.31 (n)
  • 66.41 (a)
lit-1 36
  • 47 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3781 36
  • 57 (a)
OneToOne
Species with no ortholog for NLK:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NLK Gene

ENSEMBL:
Gene Tree for NLK (if available)
TreeFam:
Gene Tree for NLK (if available)

Paralogs for NLK Gene

Paralogs for NLK Gene

genes like me logo Genes that share paralogs with NLK: view

Variants for NLK Gene

Sequence variations from dbSNP and Humsavar for NLK Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
rs11871287 - 28,122,674(+) TCTGG(C/T)CTCTT nc-transcript-variant, reference, missense
VAR_042273 A glioblastoma multiforme sample
rs1242299 -- 28,189,182(+) cccaa(A/G)catat intron-variant
rs2045620 -- 28,073,659(+) TCCCA(G/T)TTTAG intron-variant
rs2048752 -- 28,176,869(+) AAACA(C/T)ACAAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NLK Gene

Variant ID Type Subtype PubMed ID
nsv2016 CNV Loss 18451855
nsv522349 CNV Gain 19592680
esv2678164 CNV Deletion 23128226

Variation tolerance for NLK Gene

Residual Variation Intolerance Score: 23.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.59; 12.76% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NLK Gene

HapMap Linkage Disequilibrium report
NLK

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NLK Gene

Disorders for NLK Gene

Relevant External Links for NLK

Genetic Association Database (GAD)
NLK
Human Genome Epidemiology (HuGE) Navigator
NLK
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NLK

No disorders were found for NLK Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NLK Gene

Publications for NLK Gene

  1. Characterization of the Fugu rubripes NLK and FN5 genes flanking the NF1 (Neurofibromatosis type 1) gene in the 5' direction and mapping of the human counterparts. (PMID: 10863097) Kehrer-Sawatzki H. … Krone W. (Gene 2000) 2 3 4 23 67
  2. Regulation of FOXO1 by TAK1-Nemo-like kinase pathway. (PMID: 20061393) Kim S. … Chung J. (J. Biol. Chem. 2010) 3 23
  3. Targeted disruption of Nemo-like kinase inhibits tumor cell growth by simultaneous suppression of cyclin D1 and CDK2 in human hepatocellular carcinoma. (PMID: 20512928) Jung K.H. … Nam S.W. (J. Cell. Biochem. 2010) 3 23
  4. Human SMAD4 is phosphorylated at Thr9 and Ser138 by interacting with NLK. (PMID: 19690946) Shi Y. … Huo K. (Mol. Cell. Biochem. 2010) 3 23
  5. TAB2 scaffolds TAK1 and NLK in repressing canonical Wnt signaling. (PMID: 20194509) Li M. … Li L. (J. Biol. Chem. 2010) 3 23

Products for NLK Gene

Sources for NLK Gene

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