InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NLK

Summary

InnateDB Protein

IDBP-293379.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NLK

Protein Name

nemo-like kinase

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000384625

InnateDB Gene

IDBG-36215 (NLK)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:12482967, ECO:0000269PubMed:14960582, ECO:0000269PubMed:15004007, ECO:0000269PubMed:15764709, ECO:0000269PubMed:17952062, ECO:0000269PubMed:20061393, ECO:0000269PubMed:20118921, ECO:0000269PubMed:20874444, ECO:0000269PubMed:21454679}.

Subcellular Localization

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

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 73 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	73 [view]
Protein-Protein	71 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004707	MAP kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0031625	ubiquitin protein ligase binding
GO:0042169	SH2 domain binding

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0016055	Wnt signaling pathway
GO:0018107	peptidyl-threonine phosphorylation
GO:0030178	negative regulation of Wnt signaling pathway
GO:0033136	serine phosphorylation of STAT3 protein
GO:0035556	intracellular signal transduction
GO:0046777	protein autophosphorylation

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005829	cytosol

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt