Mus musculus Protein: Nlk | |||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||
InnateDB Protein | IDBP-539119.3 | ||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||
Gene Symbol | Nlk | ||||||||||||||||||||||||
Protein Name | nemo like kinase | ||||||||||||||||||||||||
Synonyms | AI194375; | ||||||||||||||||||||||||
Species | Mus musculus | ||||||||||||||||||||||||
Ensembl Protein | ENSMUSP00000119345 | ||||||||||||||||||||||||
InnateDB Gene | IDBG-203133 (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:10391247, ECO:0000269PubMed:11745377, ECO:0000269PubMed:12482967, ECO:0000269PubMed:12556497, ECO:0000269PubMed:14720327, ECO:0000269PubMed:15004007, ECO:0000269PubMed:15082531, ECO:0000269PubMed:15308626, ECO:0000269PubMed:16055500, ECO:0000269PubMed:17785444, ECO:0000269PubMed:18765672, ECO:0000269PubMed:20118921, ECO:0000269PubMed:20194509, ECO:0000269PubMed:20874444, ECO:0000269PubMed:21118996, ECO:0000269PubMed:9448268}. | ||||||||||||||||||||||||
Subcellular Localization | Nucleus. Cytoplasm. Note=Predominantly nuclear. A smaller fraction is cytoplasmic. | ||||||||||||||||||||||||
Disease Associations | |||||||||||||||||||||||||
Tissue Specificity | Expressed at high levels in the brain, and at lower levels in heart, kidney, lung and liver. {ECO:0000269PubMed:9448268}. | ||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.
They are also associated with 29 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||
PDB ID | MGI:1201387 | ||||||||||||||||||||||||
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 |
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PFAM |
PF00069
PF07714 |
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PRINTS |
PR00109
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PIRSF | |||||||||||||||||||||||||
SMART |
SM00220
SM00219 |
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TIGRFAMs | |||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||
SwissProt | O54949 | ||||||||||||||||||||||||
PhosphoSite | PhosphoSite-O54949 | ||||||||||||||||||||||||
TrEMBL | Q3TV73 | ||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||
Entrez Gene | 18099 | ||||||||||||||||||||||||
UniGene | Mm.9001 | ||||||||||||||||||||||||
RefSeq | NP_032728 | ||||||||||||||||||||||||
MGI ID | |||||||||||||||||||||||||
MGI Symbol | Nlk | ||||||||||||||||||||||||
OMIM | |||||||||||||||||||||||||
CCDS | CCDS25113 | ||||||||||||||||||||||||
HPRD | |||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||
EMBL | AF036332 AK160340 AL591177 AL591376 BC057667 BC058652 | ||||||||||||||||||||||||
GenPept | AAC24499 AAH57667 AAH58652 BAE35746 CAI25549 CAI25603 | ||||||||||||||||||||||||