STK11 | Serine/threonine-protein kinase STK11
 
image/svg+xmlExtracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion None Kinase Substrate Both Localization legend

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Sequence Viewer
Gene
Synonyms
LKB1 PJS
Protein Name
Serine/threonine-protein kinase STK11
UniProt ID
Q15831 [go to UniProt ] [go to PDBe-KB ]
Ensembl Gene ID
NCBI Gene ID
Molecular Weight
48636
Protein Length
433
Protein Domain
3D Structure
(PDB ID : 2wtk)
Target by Small Molecules
Protein-protein Interaction Database
Gene Expression
Drugs and Diseases
Enzyme Class
2.7.11.1; (BRENDA)
Catalytic Site
Catalytic Activity
ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]
Localization
Nucleus,Cytoplasm,Membrane,Mitochondrion;Isoform 2: Nucleus,Cytoplasm;
Function
Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. In vein endothelial cells, inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite (in vitro). Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316).Isoform 2: Has a role in spermiogenesis.
Gene Ontology
GO:0005737; GO:0005829; GO:0070062; GO:0016020; GO:0005739; GO:0005654; GO:0005634; GO:0005524; GO:0030275; GO:0000287; GO:0002039; GO:0030295; GO:0004674; GO:0032147; GO:0043276; GO:0006914; GO:0007409; GO:0060070; GO:0007050; GO:0006974; GO:0071493; GO:0097484; GO:0030010; GO:0042593; GO:0051645; GO:0072332; GO:0090090; GO:0030308; GO:0008285; GO:0120163; GO:0060770; GO:1904262; GO:0010508; GO:0050772; GO:1900182; GO:0030511; GO:0045059; GO:0046777; GO:0006470; GO:0006468; GO:0001558; GO:0048814; GO:0051896; GO:1901796; GO:0010212; GO:0007283; GO:0050852; GO:0001894; GO:0001944


Gene Ontology (click on any section to view sub-classification)