Tchem NLK Serine/threonine-protein kinase NLK

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Serine/threonine-protein Kinase Nlk

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Mapk Family / Nmo Subfamily / Serine/threonine-protein Kinase Nlk

Protein Summary

Description

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).

Uniprot Accession IDs

• Q9UBE8
• B2RCX1
• Q2PNI9
• Q6P2A3

Gene Name

• NLK

Ensembl ID

• ENST00000407008
• ENSP00000384625
• ENSG00000087095

Symbol

• LAK1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	0.85
virus perturbation	0.83
transcription factor	0.79
disease perturbation	0.74

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 84.66   (req: < 5)

Gene RIFs: 47   (req: <= 3)

Antibodies: 357   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 84.66   (req: >= 5)

Gene RIFs: 47   (req: > 3)

Antibodies: 357   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (4)

Explore Active Ligands

1 – 4 of 4

CHEMBL10

NLKTchem Kinase

Kd : 7.6

CHEMBL248757

NLKTchem Kinase

IC50 : 5.78999996

CHEMBL1230122

NLKTchem Kinase

Kd : 8.22

CHEMBL278041

NLKTchem Kinase

Kd : 7.55

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	nemo like kinase	VGNC:9477	739132
Macaque	nemo like kinase		677693
Mouse	nemo like kinase	MGI:1201387	18099
Rat	nemo like kinase	RGD:1561602	497961
Dog	nemo like kinase	VGNC:43841	491160

Species	Name	OMA	EggNOG	Inparanoid
Chimp	nemo like kinase
Macaque	nemo like kinase
Mouse	nemo like kinase
Rat	nemo like kinase
Dog	nemo like kinase

Protein Structure (0 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

AF-Q9UBE8-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

Pathways (35)

Reactome (4)

KEGG (4)

PathwayCommons (17)

WikiPathways (10)

Beta-catenin independent WNT signaling (R-HSA-3858494)

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Find Similar Targets

Items per page:

5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Beta-catenin independent WNT signaling	146 targets	R-HSA-3858494
Reactome	Ca2+ pathway	61 targets	R-HSA-4086398
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by WNT	299 targets	R-HSA-195721

Name	Explore in Pharos	Explore in Source
Beta-catenin independent WNT signaling	146 targets	R-HSA-3858494
Ca2+ pathway	61 targets	R-HSA-4086398
Signal Transduction	2704 targets	R-HSA-162582
Signaling by WNT	299 targets	R-HSA-195721

Gene Ontology Terms (23)

Functions (8)

Components (4)

Processes (11)

Find Similar Targets

Items per page:

10

1 – 8 of 8

GO Term	Evidence	Assigned by
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
ATP binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
magnesium ion binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
MAP kinase activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
SH2 domain binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
protein kinase activity	Traceable Author Statement (TAS)	ProtInc
protein serine/threonine kinase activity	Traceable Author Statement (TAS)	Reactome

Protein-Protein Interactions (140)

Explore Interacting Targets

1 – 10 of 140

• See Interactions on String-DB

SHANK2

Tbio

Novelty: 0.00710548

p_int: 0.999999993

p_ni: 6e-9

p_wrong: 1e-9

Score: 0.461

Data Source: BioPlex,STRINGDB

FAM222B

Tdark

Novelty: 2.41126839

p_int: 0.999699398

p_ni: 8e-9

p_wrong: 0.000300595

Score: 0.439

Data Source: BioPlex,STRINGDB

TRPS1

Tbio

Family: TF

Novelty: 0.0075626

p_int: 0.997681991

p_ni: 0.002307712

p_wrong: 0.000010297

Score: 0.46

Data Source: BioPlex,STRINGDB

WDCP

Tdark

Novelty: 0.29184907

p_int: 0.994630837

p_ni: 0.005369159

p_wrong: 5e-9

Score: 0.439

Data Source: BioPlex,STRINGDB

ISCA1

Tbio

Novelty: 0.01288069

p_int: 0.966481404

p_ni: 0.01597736

p_wrong: 0.017541235

Data Source: BioPlex

FAM222A

Tdark

Novelty: 0.41466126

p_int: 0.963653587

p_ni: 8.3e-8

p_wrong: 0.03634633

Score: 0.517

Data Source: BioPlex,STRINGDB

CNOT2

Tbio

Novelty: 0.01886737

p_int: 0.893303971

p_ni: 0.106665701

p_wrong: 0.000030328

Score: 0.439

Data Source: BioPlex,STRINGDB

ZNF593

Tbio

Novelty: 0.45276787

p_int: 0.876803942

p_ni: 0.046659239

p_wrong: 0.076536819

Data Source: BioPlex

TCF7L2

Tbio

Family: TF

Novelty: 0.00178694

Score: 0.988

Data Source: Reactome,STRINGDB

LEF1

Tchem

Family: TF

Novelty: 0.00168638

Score: 0.986

Data Source: Reactome,STRINGDB

Publication Statistics

PubMed Score  84.66

PubMed score by year

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PubTator Score  56.12

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

Show Full Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

Find similar targets by:

UniProt Keyword Find Similar Targets

ATP-binding
Complete proteome
Cytoplasm
Kinase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging