| UniProt ID | NLK_HUMAN | |
|---|---|---|
| UniProt AC | Q9UBE8 | |
| Protein Name | Serine/threonine-protein kinase NLK | |
| Gene Name | NLK | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 527 | |
| Subcellular Localization | Nucleus. Cytoplasm. Predominantly nuclear. A smaller fraction is cytoplasmic (By similarity).. | |
| Protein 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] | |
| Protein Sequence | MSLCGARANAKMMAAYNGGTSAAAAGHHHHHHHHLPHLPPPHLHHHHHPQHHLHPGSAAAVHPVQQHTSSAAAAAAAAAAAAAMLNPGQQQPYFPSPAPGQAPGPAAAAPAQVQAAAAATVKAHHHQHSHHPQQQLDIEPDRPIGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSCKRVFRELKMLCFFKHDNVLSALDILQPPHIDYFEEIYVVTELMQSDLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEELDESRHMTQEVVTQYYRAPEILMGSRHYSNAIDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTPSLEAMRTACEGAKAHILRGPHKQPSLPVLYTLSSQATHEAVHLLCRMLVFDPSKRISAKDALAHPYLDEGRLRYHTCMCKCCFSTSTGRVYTSDFEPVTNPKFDDTFEKNLSSVRQVKEIIHQFILEQQKGNRVPLCINPQSAAFKSFISSTVAQPSEMPPSPLVWE | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 274 | Phosphorylation | PGNLLVNSNCVLKIC CCCEEECCCCEEEEC | 24.91 | - | |
| 294 | Phosphorylation | RVEELDESRHMTQEV CHHHHHHHHCCCHHH | 27.44 | 30177828 | |
| 298 | Phosphorylation | LDESRHMTQEVVTQY HHHHHCCCHHHHHHH | 18.56 | 23401153 | |
| 303 | Phosphorylation | HMTQEVVTQYYRAPE CCCHHHHHHHHCCHH | 18.94 | 30177828 | |
| 305 | Phosphorylation | TQEVVTQYYRAPEIL CHHHHHHHHCCHHHH | 5.88 | 30177828 | |
| 306 | Phosphorylation | QEVVTQYYRAPEILM HHHHHHHHCCHHHHH | 7.18 | 30177828 | |
| 315 | Phosphorylation | APEILMGSRHYSNAI CHHHHHCCCCCCCHH | 11.26 | 24719451 | |
| 367 | Phosphorylation | PSLEAMRTACEGAKA CCHHHHHHHHHHHHH | 23.68 | - | |
| 373 | Ubiquitination | RTACEGAKAHILRGP HHHHHHHHHHHHCCC | 51.89 | - | |
| 385 | Phosphorylation | RGPHKQPSLPVLYTL CCCCCCCCCCEEEEC | 42.69 | - | |
| 419 | Ubiquitination | PSKRISAKDALAHPY HHHCCCHHHHHCCCC | 36.42 | - | |
| 434 | Phosphorylation | LDEGRLRYHTCMCKC CCCCCEEEEEEEEEE | 13.18 | - | |
| 459 | Phosphorylation | TSDFEPVTNPKFDDT ECCCCCCCCCCCCHH | 57.42 | 24719451 | |
| 462 | Ubiquitination | FEPVTNPKFDDTFEK CCCCCCCCCCHHHHH | 64.59 | - | |
| 469 | Ubiquitination | KFDDTFEKNLSSVRQ CCCHHHHHCHHHHHH | 60.02 | - | |
| 472 | Phosphorylation | DTFEKNLSSVRQVKE HHHHHCHHHHHHHHH | 35.86 | 24719451 | |
| 522 | Phosphorylation | QPSEMPPSPLVWE-- CCCCCCCCCCCCC-- | 25.62 | 17344846 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 298 | T | Phosphorylation | Kinase | NLK | Q9UBE8 | GPS |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of NLK_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-298 AND SER-522, ANDMASS SPECTROMETRY. | |
| "Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-298, AND MASSSPECTROMETRY. | |
