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Aliases for NLK Gene

Aliases for NLK Gene

  • Nemo Like Kinase 2 3 5
  • Nemo-Like Kinase 2 4
  • EC 2.7.11.24 4 56
  • Protein LAK1 4
  • EC 2.7.11 56
  • 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 Ectoderm Differentiation and Mesodermal Commitment Pathway. Gene Ontology (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 MAPK7.

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

Additional gene information for NLK Gene

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

Genomics for NLK Gene

GeneHancer (GH) Regulatory Elements for NLK Gene

Promoters and enhancers for NLK Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17I028040 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 556.4 +1.0 1013 4.4 PKNOX1 FOXA2 ARID4B NEUROD1 SIN3A ZBTB7B YY1 E2F8 ZNF143 FOS NLK LOC102724517 LOC105371709 SUPT6H ITM2BP1 LOC101927018 PHF12 ENSG00000202389 ENSG00000251818 SARM1
GH17I027984 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 13.9 -55.5 -55535 3.4 PKNOX1 SMAD1 ARNT ZNF766 E2F8 REST ZNF592 MEF2D SMARCA4 NBN LYRM9 NLK ENSG00000251818 ENSG00000202389 LINC01992 GC17M027891
GH17I027980 Enhancer 1.1 FANTOM5 Ensembl ENCODE 7 -60.6 -60648 2.2 BCOR FOXA2 JUN MAX ZMYM3 BRCA1 RFX5 ADNP RCOR1 FOSL2 ENSG00000251818 ENSG00000202389 NLK PYY2 TNFAIP1 LINC01992 GC17M027891 LYRM9
GH17I027982 Enhancer 0.6 ENCODE 11.3 -58.6 -58636 0.9 GATAD2A HDAC1 USF1 SOX6 BHLHE40 USF2 DACH1 DPF2 MITF CTBP1 NLK ENSG00000202389 ENSG00000251818 LYRM9 PYY2 LGALS9 LINC01992 GC17M027891
GH17I028033 Enhancer 1.1 Ensembl ENCODE 6.1 -7.5 -7451 1.8 PKNOX1 ATF1 ARNT FOS ATF7 CAVIN1 ZNF592 MBD2 MEF2D GMEB1 NLK PYY2 LOC105371709 ENSG00000202389 GC17M028023
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around NLK on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NLK gene promoter:

Genomic Locations for NLK Gene

Genomic Locations for NLK Gene
chr17:28,041,737-28,205,140
(GRCh38/hg38)
Size:
163,404 bases
Orientation:
Plus strand
chr17:26,368,763-26,523,407
(GRCh37/hg19)

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

Selected DME Specific Peptides for NLK Gene

Q9UBE8:
  • TDLLGTP
  • GKRVALKKMPNVFQNL
  • WSVGCIFAE
  • KPGNLLVN
  • WSVGCIFAELLGR
  • LRGLKYLHSA
  • YQILRGLKY
  • LKICDFG
  • PDRPIGYGAFGVVWSVTDPR
  • SCKRVFRE
  • DIWSVGCI
  • FDPSKRI
  • HRDIKPGN
  • LKICDFGLAR

Post-translational modifications for NLK Gene

  • Phosphorylated on Thr-298. Intermolecular autophosphorylation on Thr-298 activates the enzyme.

Other Protein References for NLK Gene

Domains & Families for NLK Gene

Gene Families for NLK Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

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.
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

Phenotypes From GWAS Catalog for NLK Gene

Gene Ontology (GO) - Molecular Function for NLK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding ISS,IEA --
GO:0004672 protein kinase activity TAS,IEA 10863097
GO:0004674 protein serine/threonine kinase activity IEA,TAS --
GO:0004707 MAP kinase activity ISS,IEA --
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

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for NLK

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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NLK gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (3)
  • Nucleoli (3)
  • Nucleus (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NLK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005634 nucleus TAS,ISS --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol 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

Pathways by source for NLK Gene

1 Sino Biological pathway for NLK Gene
1 GeneTex pathway for NLK Gene
1 Cell Signaling Technology pathway for NLK Gene

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:0000165 MAPK cascade IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated ISS --
GO:0006468 protein phosphorylation IEA,ISS --
GO:0007179 transforming growth factor beta receptor signaling pathway IMP 15004007
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 Approved 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:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for NLK

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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



Protein tissue co-expression partners for NLK Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of NLK Gene:

NLK

SOURCE GeneReport for Unigene cluster for NLK Gene:

Hs.208759

Evidence on tissue expression from TISSUES for NLK Gene

  • Nervous system(4.6)
  • Blood(4.3)
  • Eye(2.2)
genes like me logo Genes that share expression patterns with NLK: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
platypus
(Ornithorhynchus anatinus)
Mammalia NLK 34
  • 100 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia NLK 33 34
  • 99.94 (n)
oppossum
(Monodelphis domestica)
Mammalia NLK 34
  • 99 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NLK 33 34
  • 97.53 (n)
cow
(Bos Taurus)
Mammalia NLK 33 34
  • 96.71 (n)
rat
(Rattus norvegicus)
Mammalia Nlk 33
  • 94.5 (n)
mouse
(Mus musculus)
Mammalia Nlk 33 16 34
  • 94.43 (n)
chicken
(Gallus gallus)
Aves NLK 33 34
  • 89.75 (n)
lizard
(Anolis carolinensis)
Reptilia NLK 34
  • 98 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nlk 33
  • 83.4 (n)
Str.7425 33
African clawed frog
(Xenopus laevis)
Amphibia xnlk 33
zebrafish
(Danio rerio)
Actinopterygii nlk2 33 34
  • 77.89 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005898 33
  • 66.58 (n)
fruit fly
(Drosophila melanogaster)
Insecta nmo 35 33 34
  • 65.9 (n)
worm
(Caenorhabditis elegans)
Secernentea lit-1 33 34
  • 62.31 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3781 34
  • 57 (a)
OneToOne
Species where no ortholog for NLK was found in the sources mined by GeneCards:
  • 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

Variants for NLK Gene

Sequence variations from dbSNP and Humsavar for NLK Gene

SNP ID Clin Chr 17 pos Variation AA Info Type
VAR_042273 A glioblastoma multiforme sample p.Ala343Thr
rs1000018096 -- 28,146,449(+) T/C intron_variant
rs1000039716 -- 28,099,639(+) C/T intron_variant
rs1000051167 -- 28,163,458(+) A/G intron_variant
rs1000060068 -- 28,125,300(+) A/G intron_variant

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

Variant ID Type Subtype PubMed ID
esv2678164 CNV deletion 23128226
esv3353471 CNV insertion 20981092
nsv2016 CNV deletion 18451855
nsv522349 CNV gain 19592680

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)

Additional Variant Information for NLK Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NLK

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

Disorders for NLK Gene

Additional Disease Information for NLK

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

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 22 58
  2. Regulation of FOXO1 by TAK1-Nemo-like kinase pathway. (PMID: 20061393) Kim S … Chung J (The Journal of biological chemistry 2010) 3 4 22 58
  3. STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation. (PMID: 15764709) Kojima H … Nakajima K (Proceedings of the National Academy of Sciences of the United States of America 2005) 3 4 22 58
  4. Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK. (PMID: 15082531) Kanei-Ishii C … Ishii S (Genes & development 2004) 3 4 22 58
  5. Stabilization of ATF5 by TAK1-Nemo-like kinase critically regulates the interleukin-1β-stimulated C/EBP signaling pathway. (PMID: 25512613) Zhang ZY … Zhang XD (Molecular and cellular biology 2015) 3 4 58

Products for NLK Gene

Sources for NLK Gene

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