Tchem NLK 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

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

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: 93.87   (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: 93.87   (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: 16

Tclin

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

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (5)

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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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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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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Approved Drugs (0)

No approved drugs found

Active Ligands (16)

Explore Active Ligands

1 – 10 of 16

TG-100572

NLKTchem Kinase

pKd : 9.05

OTS-167

NLKTchem Kinase

pKd : 7.55

SB203580

NLKTchem Kinase

pKd : 7.6

SID103905151

NLKTchem Kinase

pKi : 8.4

SID103904296

NLKTchem Kinase

pKi : 7.9

SID103904857

NLKTchem Kinase

pKi : 8.1

SID103904366

NLKTchem Kinase

pKi : 9.2

SID103904361

NLKTchem Kinase

pKi : 7.7

SID103904362

NLKTchem Kinase

pKi : 8

SID103904357

NLKTchem Kinase

pKi : 8

Protein-Protein Interactions (140)

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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

Nearest Tclin Targets (3)

Explore Nearest Tclin Targets

Upstream (1)

Downstream (2)

1 – 1 of 1

IL1R1

Tclin

Family:  Other

KEGG Distance:  3

Common Pathways:  1

1: MAPK signaling pathway

Pathways (35)

Reactome (4)

KEGG (4)

PathwayCommons (17)

WikiPathways (10)

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

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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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (23)

Functions (8)

Components (4)

Processes (11)

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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

Disease Associations (null)

No disease associations found

GWAS Traits (10)

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5

1 – 5 of 10

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood protein measurement	EFO_0007937	4	3	4		80.7
sporadic amyotrophic lateral sclerosis	EFO_0001357	1	1	0	1.2	52.5
breast cancer anti-estrogen resistance protein 3 measurement	EFO_0008040	1	1	1		48.8
OCIA domain-containing protein 1 measurement	EFO_0008252	1	1	1		47.2
macrophage scavenger receptor types I and II measurement	EFO_0008222	1	1	1		40.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 10

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood protein measurement	EFO_0007937	4		80.7
sporadic amyotrophic lateral sclerosis	EFO_0001357	0	1.2	52.5
breast cancer anti-estrogen resistance protein 3 measurement	EFO_0008040	1		48.8
OCIA domain-containing protein 1 measurement	EFO_0008252	1		47.2
macrophage scavenger receptor types I and II measurement	EFO_0008222	1		40.4

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UniProt Keyword Find Similar Targets

No Header	No Header
ATP-binding
Complete proteome
Cytoplasm
Kinase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism

GWAS Trait Find Similar Targets

No Header	No Header
Abelson tyrosine-protein kinase 2 measurement
blood protein measurement
body mass index
breast cancer anti-estrogen resistance protein 3 measurement
macrophage scavenger receptor types I and II measurement
non-receptor tyrosine-protein kinase TYK2 measurement
OCIA domain-containing protein 1 measurement
serine/threonine-protein kinase 17B measurement
sporadic amyotrophic lateral sclerosis
vascular endothelial growth factor A measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

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

Publication Statistics

PubMed Score 93.87

PubMed score by year

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PubTator Score 56.12

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Related Publications

Text Mined References (72)

GeneRif Annotations (47)

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PMID	Year	Title