Protein: Serine/threonine-protein kinase STK11 (EC 2.7.11.1) (Liver kinase B1 homolog) (LKB1) (mLKB1) (Q9WTK7)
Organism: Mus musculus (Mouse)
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. 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.
Subcellular location: Nucleus. Cytoplasm. Membrane. Mitochondrion {ECO:0000250}. Note=Translocates to mitochondrion during apoptosis (By similarity). A small fraction localizes at membranes. Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). PTEN promotes cytoplasmic localization (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). {ECO:0000250}.
Sequence: MDVADPEPLGLFSEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLIGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLRRIPNGEANVKKEIQLLRRLRHRNVIQLVDVLYNEEKQKMYMVMEYCVCGMQEMLDSVPEKRFPVCQAHGYFRQLIDGLEYLHSQGIVHKDIKPGNLLLTTNGTLKISDLGVAEALHPFAVDDTCRTSQGSPAFQPPEIANGLDTFSGFKVDIWSAGVTLYNITTGLYPFEGDNIYKLFENIGRGDFTIPCDCGPPLSDLLRGMLEYEPAKRFSIRQIRQHSWFRKKHPLAEALVPIPPSPDTKDRWRSMTVVPYLEDLHGRAEEEEEEDLFDIEDGIIYTQDFTVPGQVLEEEVGQNGQSHSLPKAVCVNGTEPQLSSKVKPEGRPGTANPARKVCSSNKIRRLSACKQQ
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [28-339]
- IPR039154: Serine/Threonine kinase LKB1, catalytic domain (domain) [55-309]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [172-184]
- IPR017441: Protein kinase, ATP binding site (binding_site) [55-78]
- IPR000719: Protein kinase domain (domain) [49-309]
Interaction partners: - STE20-related kinase adapter protein alpha
- Calcium-binding protein 39
- Axin-1
- STE20-related kinase adapter protein beta
- Calcium-binding protein 39-like
- 5'-AMP-activated protein kinase subunit gamma-1
- 5'-AMP-activated protein kinase subunit beta-2
- 5'-AMP-activated protein kinase subunit gamma-2
- 5'-AMP-activated protein kinase catalytic subunit alpha-1
- 5'-AMP-activated protein kinase subunit beta-1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0044877 (protein-containing complex binding), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0004672 (protein kinase activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004674 (protein serine/threonine kinase activity), GO:0016301 (kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0009653 (anatomical structure morphogenesis), GO:0007163 (establishment or maintenance of cell polarity), GO:0019222 (regulation of metabolic process), GO:0008283 (cell population proliferation), GO:0051301 (cell division), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0050793 (regulation of developmental process), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0006950 (response to stress), GO:0007017 (microtubule-based process), GO:0048523 (negative regulation of cellular process), GO:0061351 (neural precursor cell proliferation), GO:0048729 (tissue morphogenesis), GO:0030010 (establishment of cell polarity), GO:0009611 (response to wounding), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0008285 (negative regulation of cell population proliferation), GO:0048513 (animal organ development), GO:0060255 (regulation of macromolecule metabolic process), GO:0000226 (microtubule cytoskeleton organization), GO:0009891 (positive regulation of biosynthetic process), GO:0008356 (asymmetric cell division), GO:0035295 (tube development), GO:0048598 (embryonic morphogenesis), GO:0042127 (regulation of cell population proliferation), GO:0009888 (tissue development), GO:0031325 (positive regulation of cellular metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0016043 (cellular component organization), GO:0009790 (embryo development), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0008284 (positive regulation of cell population proliferation), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0035239 (tube morphogenesis), GO:0007405 (neuroblast proliferation), GO:0060562 (epithelial tube morphogenesis), GO:0021915 (neural tube development), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0021915 (neural tube development), GO:0051246 (regulation of protein metabolic process), GO:0035088 (establishment or maintenance of apical/basal cell polarity), GO:0002009 (morphogenesis of an epithelium), GO:0016331 (morphogenesis of embryonic epithelium), GO:0050678 (regulation of epithelial cell proliferation), GO:0010468 (regulation of gene expression), GO:0050679 (positive regulation of epithelial cell proliferation), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0022008 (neurogenesis), GO:0051254 (positive regulation of RNA metabolic process), GO:0048568 (embryonic organ development), GO:0007399 (nervous system development), GO:0050680 (negative regulation of epithelial cell proliferation), GO:0008544 (epidermis development), GO:0031326 (regulation of cellular biosynthetic process), GO:0060606 (tube closure), GO:0051247 (positive regulation of protein metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0060429 (epithelium development), GO:0006996 (organelle organization), GO:0030182 (neuron differentiation), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0009792 (embryo development ending in birth or egg hatching), GO:0001838 (embryonic epithelial tube formation), GO:0043009 (chordate embryonic development), GO:0031399 (regulation of protein modification process), GO:0001892 (embryonic placenta development), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0001843 (neural tube closure), GO:0007010 (cytoskeleton organization), GO:0060070 (canonical Wnt signaling pathway), GO:0030216 (keratinocyte differentiation), GO:0001841 (neural tube formation), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0048699 (generation of neurons), GO:0009913 (epidermal cell differentiation), GO:0031401 (positive regulation of protein modification process), GO:0042325 (regulation of phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0045893 (positive regulation of DNA-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:0014020 (primary neural tube formation), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0001934 (positive regulation of protein phosphorylation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0030054 (cell junction), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)