Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

STK11 (Q15831) - Overview - Molecular Target Synopsis

Protein


STK11, Serine/threonine-protein kinase STK11
Enzyme Classification 2.7.11.1
UniProt Q15831

Also Known as STK11_HUMAN, STK11, LKB1, PJS

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. Catalytic component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with p53/TP53, SMAD4, STK11IP and WDR6. Interacts with NR4A1. Interacts with NISCH; this interaction may increase STK11 activity. Interacts with PTEN; leading to PTEN phosphorylation. Interacts with SIRT1; the interaction deacetylates STK11. Interacts with CDKN1A.

5WXN
9 RESIDUE FRAGMENT OF
SERINE/THREONINE-PROTEIN KINASE STK11
IN THE STRUCTURE OF
STRUCTURE OF THE LKB1 AND 14-3-3 COMPLEX
RCSB/PDB
Inspect Structure
See all 3D Structures for STK11

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: STK11 is active in the following subcellular-locations: cytoplasm, membrane, mitochondrion, nucleus.
GO terms: STK11 is active in the following subcellular-locations: cytoplasm, cytosol, extracellular exosome, membrane, mitochondrion, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project STK11 has gain in 0 cell-lines, loss in 15 cell-lines and no signal in 990 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HCT_15, OVCAR_5, ACHN

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: G84, LCLC-97TM1, RT4

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, A549

(see details)

RNA Interference


STK11 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HCC70, MDAMB453. (see details)

3D Structures


For STK11 there are:
3 structures (6 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


STK11 has been screened with 360 compounds (579 bioactivities), 9 compounds have bioactivities that show binding affinity of <= 500nM (17 bioactivities). (see details)