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UniProt functional annotation for P49842 | ||
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| UniProt code: P49842. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Serine/threonine-protein kinase that acts as a key regulator of NRAS signaling by mediating phosphorylation of NRAS at 'Ser-89', thereby enhancing NRAS-binding to its downstream effectors. {ECO:0000269|PubMed:30712867}. |
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| Catalytic activity: | |
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:30712867, ECO:0000305|PubMed:9812991}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; Evidence={ECO:0000269|PubMed:30712867, ECO:0000305|PubMed:9812991}; |
| Catalytic activity: | |
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000305|PubMed:9812991}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; Evidence={ECO:0000305|PubMed:9812991}; |
| Cofactor: | |
Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:9812991}; Note=Divalent metal cations. Has a preference for Mn(2+). {ECO:0000269|PubMed:9812991}; |
| Activity regulation: | |
Specifically inhibited by ZT-12-037-01 (1a) (N2- cyclopropyl-N4-(1-isopropylpiperidin-4-yl)- 6,7-dimethoxyquinazoline- 2,4-diamine) (PubMed:30712867). Inhibition by ZT-12-037-01 (1a) blocks oncogenic NRAS-driven melanocyte malignant transformation and melanoma growth (PubMed:30712867). {ECO:0000269|PubMed:30712867}. |
| Subunit: | |
Interacts (via N-terminus) with BAG1. {ECO:0000269|PubMed:15986447}. |
| Subcellular location: | |
Nucleus {ECO:0000269|PubMed:9812991}. |
| Tissue specificity: | |
Monocytes, hepatocytes, epithelial cells, T- and B- lymphocytes. {ECO:0000269|PubMed:8012361}. |
| Disease: | |
Note=Gain-of-function variants in STK19 are involved in NRAS- driven melanomagenesis (PubMed:30712867). Melanoma are malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites (PubMed:30712867). Conditional knockin mice overexpressing Asn-89 variant exhibit hyperpigmentation of the skin, ears, and tail, and the melanin content in skin was significantly increased after tamoxifen induction (PubMed:30712867). Moreover, knockin mice overexpressing Asn- 89 variant promote NRAS 'Arg-61'-driven melanomagenesis (PubMed:30712867). {ECO:0000269|PubMed:30712867}. |
| Similarity: | |
Belongs to the STK19 family. {ECO:0000305}. |
Annotations taken from UniProtKB at the EBI.