Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Serine/threonine-protein kinase STK11



Mus musculus (Mouse)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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. 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).5 Publications
Isoform 2: Has a role in spermiogenesis.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity


Mg2+By similarity, Mn2+By similarity

Enzyme regulationi

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).By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei78ATPCurated1
Active sitei176Proton acceptorPROSITE-ProRule annotationBy similarity1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi55 – 63ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • LRR domain binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • p53 binding Source: UniProtKB
  • protein kinase activator activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • activation of protein kinase activity Source: MGI
  • anoikis Source: MGI
  • autophagy Source: UniProtKB-KW
  • axonogenesis Source: UniProtKB
  • canonical Wnt signaling pathway Source: MGI
  • cell cycle arrest Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to UV-B Source: UniProtKB
  • dendrite extension Source: MGI
  • establishment of cell polarity Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • Golgi localization Source: MGI
  • intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
  • negative regulation of lipid biosynthetic process Source: MGI
  • negative regulation of TORC1 signaling Source: MGI
  • peptidyl-serine phosphorylation Source: GO_Central
  • peptidyl-threonine phosphorylation Source: GO_Central
  • positive regulation of autophagy Source: MGI
  • positive regulation of axonogenesis Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of protein localization to nucleus Source: MGI
  • positive regulation of protein serine/threonine kinase activity Source: MGI
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • positive thymic T cell selection Source: MGI
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of cell growth Source: UniProtKB
  • regulation of dendrite morphogenesis Source: MGI
  • regulation of protein kinase B signaling Source: MGI
  • regulation of Wnt signaling pathway Source: MGI
  • response to ionizing radiation Source: UniProtKB
  • spermatid development Source: UniProtKB
  • spermatogenesis Source: UniProtKB-KW
  • T cell receptor signaling pathway Source: MGI
  • TCR signalosome assembly Source: MGI
  • tissue homeostasis Source: MGI
  • vasculature development Source: UniProtKB


Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Autophagy, Cell cycle, Differentiation, DNA damage, Spermatogenesis
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase STK11 (EC:
Alternative name(s):
Liver kinase B1 homolog
Short name:
Short name:
Gene namesi
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1341870. Stk11.

Subcellular locationi

  • Nucleus
  • Cytoplasm
  • Membrane
  • Mitochondrion By similarity

  • 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).By similarity
Isoform 2 :
  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta).By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular exosome Source: MGI
  • membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • TCR signalosome Source: MGI

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice die in utero 8.5 to 9.5 dpc due to severe defects in their vasculature: embryos show neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development is also severely affected; the mutant placentas exhibit defective labyrinth layer development and the fetal vessels fail to invade the placenta. Male mice specifically lacking isoform 2 are sterile (PubMed:18774945). A specifically deletion in liver results in hyperglycemia with increased gluconeogenic and lipogenic gene expression due to loss of AMPK phosphorylation and subsequent dephosphorylation of CRTC2/TORC2 (PubMed:16308421). Use of a conditional allele, leads to defects in defects in axon formation with a thinner cortical wall and larger lateral ventricles in the brain cortex (PubMed:17482548). Heterozygous mice develop multiple gastric adenomatous polyps, with polyps remarkably similar to hamartomas of PJS patients both macroscopically and histologically. Polyps in the heterozygous mice are detected at 5 months, and cause premature lethality progressively from 8 months onwards. Polyps are most frequently observed in the stomach where they typically concentrate close to the pylorus. Polyps in the small and large intestine are significantly less frequent. The histology of the polyps in the heterozygous mice is remarkably similar to PJS polyps including the relative contribution of well-differentiated epithelium, and a prominent smooth muscle component. Ptgs2/Cox2 is highly up-regulated in heterozygous mice polyps concomitantly with activation of the extracellular signal-regulated kinases Mapk1/Erk2 and Mapk3/Erk1: treatment with celecoxib Ptgs2/Cox2 inhibitor significantly reduces the total polyp burden.9 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi31S → A: No change in kinase activity; when associated with A-325; A-336 and A-366. 1 Publication1
Mutagenesisi78K → I: Loss of kinase activity. 1
Mutagenesisi194D → A: Loss of kinase activity and descreased phosphorylation. 1 Publication1
Mutagenesisi325S → A: No change in kinase activity; when associated with A-31; A-336 and A-366. 1 Publication1
Mutagenesisi336T → A: Abolishes ability to suppress cell growth. Decreased phosphorylation; when associated with A-366. No change in kinase activity; when associated with A-31; A-325 and A-366. 1 Publication1
Mutagenesisi366T → A: Diminished interaction with CDKN1A and impaired ability to repair UV-induced DNA damage by affecting CDKN1A UV-induced degradation. Decreased phosphorylation; when associated with A-336. No change in kinase activity; when associated with A-31; A-325 and A-336. 4 Publications1
Mutagenesisi431S → A: Does not prevent S-farnesylation. Defects in neuron polarization. 4 Publications1
Mutagenesisi433C → A: Does not affect nuclear localization. Does not prevent phosphorylation at S-431. 3 Publications1

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002600321 – 433Serine/threonine-protein kinase STK11Add BLAST433
PropeptideiPRO_0000422301434 – 436Removed in mature form3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei31PhosphoserineCombined sources1 Publication1
Modified residuei44N6-acetyllysineBy similarity1
Modified residuei48N6-acetyllysineBy similarity1
Modified residuei96N6-acetyllysineBy similarity1
Modified residuei97N6-acetyllysineBy similarity1
Modified residuei189Phosphothreonine; by autocatalysisBy similarity1
Modified residuei296N6-acetyllysineBy similarity1
Modified residuei311N6-acetyllysineBy similarity1
Modified residuei325Phosphoserine1 Publication1
Modified residuei336Phosphothreonine; by autocatalysis1 Publication1
Modified residuei366Phosphothreonine; by ATM and autocatalysis4 Publications1
Modified residuei403PhosphoserineBy similarity1
Modified residuei420N6-acetyllysineBy similarity1
Lipidationi422S-palmitoyl cysteine1 Publication1
Modified residuei426N6-acetyllysineBy similarity1
Modified residuei431Phosphoserine; by autocatalysis, PKA, PKC/PRKCZ and RPS6KA14 Publications1
Modified residuei433Cysteine methyl ester1 Publication1
Lipidationi433S-farnesyl cysteine3 Publications1
Modified residuei434N6-acetyllysineBy similarity1

Post-translational modificationi

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-428 promotes peroxynitrite-induced nuclear export of STK11, leading to PTEN activation and subsequent inhibition of AKT signaling. Phosphorylation by PKC/PRKCZ at Ser-399 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.8 Publications
Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.1 Publication

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Palmitate, Phosphoprotein, Prenylation

Proteomic databases


PTM databases



Tissue specificityi

Widely expressed. Isoform 2 is predominantly expressed in testis (at protein level).3 Publications

Developmental stagei

Ubiquitously expressed 7-11 dpc. Present in nucleated embryonic blood cells from 9 dpc. Restricted to gastrointestinal tract, testis and lung from days 15-19 dpc.2 Publications

Gene expression databases

ExpressionAtlasiQ9WTK7. baseline and differential.
GenevisibleiQ9WTK7. MM.


Subunit structurei

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 (By similarity). Interacts with NISCH; this interaction may increase STK11 activity (By similarity). Interacts with PTEN, leading to PTEN phosphorylation (By similarity). Interacts with SIRT1; the interaction deacetylates STK11 (By similarity). Interacts with CDKN1A.By similarity2 Publications

GO - Molecular functioni

  • LRR domain binding Source: UniProtKB
  • p53 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi203541. 4 interactors.
IntActiQ9WTK7. 3 interactors.


3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini49 – 309Protein kinasePROSITE-ProRule annotationAdd BLAST261


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni45 – 90Sufficient for interaction with SIRT1By similarityAdd BLAST46

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.

Family and domain databases

InterProiView protein in InterPro
IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 16 Publications (identifier: Q9WTK7-1) [UniParc]FASTAAdd to basket
Also known as: LKB1(L)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
60 70 80 90 100
110 120 130 140 150
160 170 180 190 200
210 220 230 240 250
260 270 280 290 300
310 320 330 340 350
360 370 380 390 400
410 420 430
Mass (Da):49,267
Last modified:November 1, 1999 - v1
Isoform 21 Publication (identifier: Q9WTK7-2) [UniParc]FASTAAdd to basket
Also known as: LKB1(S)

The sequence of this isoform differs from the canonical sequence as follows:
     416-436: Missing.

Show »
Mass (Da):46,494

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti95V → L in BAE42728 (PubMed:10400995).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_052222374 – 415QVLEE…RPGTA → VEEAAEAGLSEDACDTCMWK SQGAGLPGEEPEEGFGALV in isoform 2. 2 PublicationsAdd BLAST42
Alternative sequenceiVSP_052223416 – 436Missing in isoform 2. 2 PublicationsAdd BLAST21

Sequence databases

Select the link destinations:
Links Updated
AF129870 mRNA. Translation: AAD22100.1.
AF145287 mRNA. Translation: AAD31044.1.
EU730638 mRNA. Translation: ACE73833.1.
, AF145288, AF145289, AF145290, AF145291, AF145292, AF145293, AF145294, AF145295 Genomic DNA. Translation: AAD55368.1.
AF151711 mRNA. Translation: AAF21370.1.
AB015801 mRNA. Translation: BAA76749.1.
AK171909 mRNA. Translation: BAE42728.1.
AK172528 mRNA. Translation: BAE43050.1.
AK172385 mRNA. Translation: BAE42977.1.
BC052379 mRNA. Translation: AAH52379.1.
CCDSiCCDS35974.1. [Q9WTK7-1]
CCDS78854.1. [Q9WTK7-2]
RefSeqiNP_001288782.1. NM_001301853.1. [Q9WTK7-2]
NP_001288783.1. NM_001301854.1.
NP_035622.1. NM_011492.4. [Q9WTK7-1]

Genome annotation databases

EnsembliENSMUST00000003152; ENSMUSP00000003152; ENSMUSG00000003068. [Q9WTK7-1]
ENSMUST00000144883; ENSMUSP00000114195; ENSMUSG00000003068. [Q9WTK7-2]
ENSMUST00000213772; ENSMUSP00000150488; ENSMUSG00000003068. [Q9WTK7-2]
UCSCiuc007gbt.2. mouse. [Q9WTK7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSTK11_MOUSE
AccessioniPrimary (citable) accession number: Q9WTK7
Secondary accession number(s): B3VBP0, Q3TAE0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 1, 1999
Last modified: June 7, 2017
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome


  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families