Stk11
entrez
314621
canonical
uniprot
D4AE59
canonical
ensembl
ENSRNOG00000014287
resolver
ensembl
ENSRNOG00055032442
resolver
ensembl
ENSRNOG00060031913
resolver
ensembl
ENSRNOG00065019626
resolver
ensp
ENSRNOP00000109626
resolver
genesymbol
Stk11
resolver
genesymbol_syn
Lkb1
resolver
uniprot
A0A0H2UI02
resolver
uniprot
D4A179
resolver
uniprot_entry
STK11_RAT
resolver
uniprot_sec
A0A0H2UI02
resolver
uniprot_sec
D4A179
resolver
activity_regulation
ACTIVITY REGULATION: Activated by forming a complex with STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA (or STRADB)-binding promotes a conformational change of STK11/LKB1 in an active conformation, which is stabilized by CAB39/MO25alpha (or CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK (By similarity). In response to calorie restriction, activated by AXIN1 adapter, promoting association between STK11 and its AMPK substrates PRKAA1 and/or PRKAA2 (By similarity). {ECO:0000250|UniProtKB:Q15831, ECO:0000250|UniProtKB:Q9WTK7}.
uniprot
proteins
amino_acid_sequence
MDVADPQPLGLFPEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLIGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLRRIPNGEANVKKEIQLLRRLRHRNVIQLVDVLYNEEKQKMYMVMEYCVCGMQEMLDSVPEKRFPVCQAHGYFRQLIDGLEYLHSQGIVHKDIKPGNLLLTTNGTLKISDLGVAEALHPFAVDDTCRTSQGSPAFQPPEIANGLDTFSGFKVDIWSAGVTLYNITTGLYPFEGDNIYKLFENIGRGDFTIPCDCAPPLSDLLRGMLEYEPAKRFSIRQIRQHSWFRKKHPLAEALVPIPPSPDTKDRWRSMTVVPYLEDLHGRAEEEEDEDLFDIEDGIIYTQDFTVPGQVLEEEVGQNGQSHSLPKAVCVNGTEPQLSSKVKPEGRPGAANPARKVCSSNKIRRLSACKQQ
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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. {ECO:0000250|UniProtKB:Q15831}.; FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000269|PubMed:18774945}.
uniprot
proteins
mass_dalton
49246
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by ATM at Thr-366 following ionizing radiation (IR). Phosphorylation at Ser-431 by RPS6KA1 and/or some PKA is required to inhibit cell growth. Phosphorylation at Ser-431 is also required during neuronal polarization to mediate phosphorylation of BRSK1 and BRSK2. Phosphorylation by PKC/PRKCZ at Ser-397 in isoform 2 promotes metformin (or peroxynitrite)-induced nuclear export of STK11 and activation of AMPK. UV radiation -induced phosphorylation at Thr-366 mediates CDKN1A degradation. {ECO:0000250|UniProtKB:Q9WTK7}.; PTM: Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro. {ECO:0000269|PubMed:18687677}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
LKB1 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
14511394
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
18687677
uniprot
proteins
pubmed
18774945
uniprot
proteins
pubmed
22673903
uniprot
proteins
sequence_length
436
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18774945}. Cytoplasm {ECO:0000269|PubMed:18774945}. Membrane {ECO:0000269|PubMed:18774945}. Mitochondrion {ECO:0000250|UniProtKB:Q15831}. Late endosome {ECO:0000250|UniProtKB:Q9WTK7}. Note=Translocates to mitochondrion during apoptosis (By similarity). A small fraction localizes at membranes (PubMed:18774945). 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). Translocates to late endosomes in response to calorie restriction (By similarity). {ECO:0000250|UniProtKB:Q15831, ECO:0000250|UniProtKB:Q9WTK7, ECO:0000269|PubMed:18774945}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:18774945}. Cytoplasm {ECO:0000269|PubMed:18774945}. Note=Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). {ECO:0000269|PubMed:18774945}.
uniprot
proteins