STK11 Gene (Protein Coding)

Serine/Threonine Kinase 11

GC19P001177
GIFtS:
49
This gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor. Mutations in this gene have been associated with Peutz-Jeghers syndrome, an autosomal dominant disorder characterized by the growth of polyps in the gastrointestinal tract, pigmented macules on the skin and mouth, and other neoplasms. Alternate t... See more...

Aliases for STK11 Gene

Aliases for STK11 Gene

  • Serine/Threonine Kinase 11 2 3 5
  • LKB1 2 3 4
  • PJS 2 3 4
  • Serine/Threonine-Protein Kinase STK11 3 4
  • Polarization-Related Protein LKB1 2 3
  • Renal Carcinoma Antigen NY-REN-19 3 4
  • Liver Kinase B1 3 4
  • EC 2.7.11.1 4 51
  • HLKB1 3 4
  • Serine/Threonine Kinase 11 (Peutz-Jeghers Syndrome) 2
  • Serine/Threonine-Protein Kinase LKB1 3
  • Serine/Threonine-Protein Kinase 11 3
  • STK11 5

External Ids for STK11 Gene

Previous GeneCards Identifiers for STK11 Gene

  • GC19P001264
  • GC19P001117
  • GC19P001157
  • GC19P001156
  • GC19P000982
  • GC19P001205

Summaries for STK11 Gene

Entrez Gene Summary for STK11 Gene

  • This gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor. Mutations in this gene have been associated with Peutz-Jeghers syndrome, an autosomal dominant disorder characterized by the growth of polyps in the gastrointestinal tract, pigmented macules on the skin and mouth, and other neoplasms. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

CIViC Summary for STK11 Gene

GeneCards Summary for STK11 Gene

STK11 (Serine/Threonine Kinase 11) is a Protein Coding gene. Diseases associated with STK11 include Peutz-Jeghers Syndrome and Testicular Germ Cell Tumor. Among its related pathways are Sweet Taste Signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is DCLK1.

UniProtKB/Swiss-Prot Summary for STK11 Gene

  • 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 Wiki entry for STK11 Gene

Additional gene information for STK11 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for STK11 Gene

Genomics for STK11 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for STK11 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around STK11 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for STK11

Top Transcription factor binding sites by QIAGEN in the STK11 gene promoter:
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • MyoD
  • p53
  • STAT3

Genomic Locations for STK11 Gene

Genomic Locations for STK11 Gene
chr19:1,177,558-1,228,431
(GRCh38/hg38)
Size:
50,874 bases
Orientation:
Plus strand
chr19:1,189,406-1,228,434
(GRCh37/hg19)
Size:
39,029 bases
Orientation:
Plus strand

Genomic View for STK11 Gene

Genes around STK11 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
STK11 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for STK11 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for STK11 Gene

Proteins for STK11 Gene

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  • Protein details for STK11 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15831-STK11_HUMAN
    Recommended name:
    Serine/threonine-protein kinase STK11
    Protein Accession:
    Q15831
    Secondary Accessions:
    • B2RBX7
    • E7EW76

    Protein attributes for STK11 Gene

    Size:
    433 amino acids
    Molecular mass:
    48636 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Cofactor:
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for STK11 Gene

    Alternative splice isoforms for STK11 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for STK11 Gene

Protein Expression for STK11 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for STK11 Gene

Q15831:
  • GTLKISDLGVAEALHPFA
  • IIYTQDFTVPGQV
  • DIWSAGV
  • SVGMDTFIHRIDSTEVIYQPRRKRAKL
  • GSPAFQPPE
  • LHSQGIVH

Post-translational modifications for STK11 Gene

  • Phosphorylated by ATM at Thr-363 following ionizing radiation (IR). Phosphorylation at Ser-428 by RPS6KA1 and/or some PKA is required to inhibit cell growth. Phosphorylation at Ser-428 is also required during neuronal polarization to mediate phosphorylation of BRSK1 and BRSK2 (By similarity). 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-363 mediates CDKN1A degradation (By similarity).
  • Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for STK11 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for STK11

Domains & Families for STK11 Gene

Gene Families for STK11 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for STK11 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for STK11 Gene

GenScript: Design optimal peptide antigens:
  • Serine/threonine kinase 11 (D4P556_HUMAN)
  • Serine/threonine kinase 11 (Q5ZEZ1_HUMAN)
  • STK11 [amino acids 371-433] (Q9NS52_HUMAN)
  • Serine/threonine-protein kinase LKB1 (STK11_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q15831

UniProtKB/Swiss-Prot:

STK11_HUMAN :
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.
Family:
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.
genes like me logo Genes that share domains with STK11: view

Function for STK11 Gene

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Molecular function for STK11 Gene

UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Function:
[Isoform 2]: Has a role in spermiogenesis.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:14976552};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:14976552};.
UniProtKB/Swiss-Prot EnzymeRegulation:
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.
GENATLAS Biochemistry:
serine/threonine kinase 11,with two alternatively spliced isoforms,expressed in all tissues,strongly homolog of Xenopus early embryonic kinase 1 (XEEK1),tumor suppressor gene in hamartomas syndrome and in left sided colon carcinogenesis,mutated in sporadic testicular cancer,malignant melanomas and laryngeal tumors,playing a minor role in the development of ovarian carcinoma

Enzyme Numbers (IUBMB) for STK11 Gene

Phenotypes From GWAS Catalog for STK11 Gene

Gene Ontology (GO) - Molecular Function for STK11 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding IDA 12805220
GO:0002039 p53 binding IDA 11430832
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IEA,TAS --
genes like me logo Genes that share ontologies with STK11: view

Phenotypes for STK11 Gene

MGI mutant phenotypes for STK11:
inferred from 17 alleles
GenomeRNAi human phenotypes for STK11:
genes like me logo Genes that share phenotypes with STK11: view

Human Phenotype Ontology for STK11 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for STK11 Gene

MGI Knock Outs for STK11:

Animal Model Products

CRISPR Products

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Clone Products

  • Addgene plasmids for STK11

No data available for Transcription Factor Targets and HOMER Transcription for STK11 Gene

Localization for STK11 Gene

Subcellular locations from UniProtKB/Swiss-Prot for STK11 Gene

Nucleus. Cytoplasm. Membrane. Mitochondrion. Note=A small fraction localizes at membranes (By similarity). Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). Translocates to the mitochondrion during apoptosis. Translocates to the cytoplasm in response to metformin or peroxynitrite treatment. PTEN promotes cytoplasmic localization. {ECO:0000250}.
[Isoform 2]: Nucleus. Cytoplasm. Note=Predominantly nuclear, but translocates to the cytoplasm in response to metformin or peroxynitrite treatment.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for STK11 gene
Compartment Confidence
extracellular 5
mitochondrion 5
nucleus 5
cytosol 5
plasma membrane 2
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for STK11 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 12805220
GO:0005654 nucleoplasm IDA,TAS --
GO:0005737 cytoplasm IEA,IDA 11430832
GO:0005739 mitochondrion IEA,IDA 11430832
GO:0005829 cytosol IDA,TAS --
genes like me logo Genes that share ontologies with STK11: view

Pathways & Interactions for STK11 Gene

genes like me logo Genes that share pathways with STK11: view

Pathways by source for STK11 Gene

2 Sino Biological pathways for STK11 Gene
1 PharmGKB pathway for STK11 Gene
1 GeneGo (Thomson Reuters) pathway for STK11 Gene
  • Development_Leptin signaling via PI3K-dependent pathway
1 R&D Systems pathway for STK11 Gene
4 Qiagen pathways for STK11 Gene
  • AMPK Enzyme Complex Pathway
  • Molecular Mechanisms of Cancer
  • mTOR Pathway
  • Sperm Motility
1 Cell Signaling Technology pathway for STK11 Gene

SIGNOR curated interactions for STK11 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for STK11 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 regulation of cell growth IEA,ISS --
GO:0001894 tissue homeostasis IEA --
GO:0001944 vasculature development ISS --
GO:0006468 protein phosphorylation IEA,IDA 12805220
GO:0006470 protein dephosphorylation IMP 15731909
genes like me logo Genes that share ontologies with STK11: view

Drugs & Compounds for STK11 Gene

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(47) Drugs for STK11 Gene - From: ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Carboplatin Approved Pharma Antitumor agent that forms platinum-DNA adducts., Platinum 2588
Dexamethasone Approved, Investigational, Vet_approved Pharma Agonist Anti-inflammatory glucocorticoid 2886
Dexamethasone acetate Approved, Investigational, Vet_approved Pharma 2886
Hydroxocobalamin Approved Pharma 437
leucovorin Approved Pharma 3692,1548

(11) Additional Compounds for STK11 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
genes like me logo Genes that share compounds with STK11: view

Transcripts for STK11 Gene

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mRNA/cDNA for STK11 Gene

1 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for STK11

Clone Products

  • Addgene plasmids for STK11

Alternative Splicing Database (ASD) splice patterns (SP) for STK11 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11a · 11b
SP1: -
SP2: -
SP3:
SP4:
SP5: -
SP6: - - - -

Relevant External Links for STK11 Gene

GeneLoc Exon Structure for
STK11

Expression for STK11 Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for STK11 Gene

mRNA expression in normal human tissues for STK11 Gene
mRNA expression by GTEx for STK11 GenemRNA expression by BioGPS for STK11 Gene

Protein differential expression in normal tissues from HIPED for STK11 Gene

This gene is overexpressed in Testis (42.6) and Urine (16.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for STK11 Gene



Protein tissue co-expression partners for STK11 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for STK11

SOURCE GeneReport for Unigene cluster for STK11 Gene:

Hs.515005

mRNA Expression by UniProt/SwissProt for STK11 Gene:

Q15831-STK11_HUMAN
Tissue specificity: Ubiquitously expressed. Strongest expression in testis and fetal liver.

Evidence on tissue expression from TISSUES for STK11 Gene

  • Nervous system(4.7)
  • Liver(4.7)
  • Lung(4.6)
  • Muscle(3.5)
  • Intestine(3.3)
  • Pancreas(3.3)
  • Heart(3.2)
  • Skin(3.1)
  • Kidney(3.1)
  • Blood(3)
  • Lymph node(2.8)
  • Stomach(2.8)
  • Spleen(2.7)
  • Bone marrow(2.6)
  • Thyroid gland(2.6)
  • Adrenal gland(2.5)
  • Eye(2.4)
  • Gall bladder(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for STK11 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • face
  • head
  • lip
  • mouth
  • nose
  • pharynx
  • pituitary gland
Thorax:
  • breast
  • esophagus
Abdomen:
  • appendix
  • biliary tract
  • duodenum
  • gallbladder
  • intestine
  • large intestine
  • liver
  • pancreas
  • small intestine
  • stomach
Pelvis:
  • anus
  • fallopian tube
  • ovary
  • penis
  • prostate
  • rectum
  • testicle
  • ureter
  • uterus
  • vagina
  • vas deferens
  • vulva
Limb:
  • digit
  • finger
  • hand
  • upper limb
General:
  • blood
  • blood vessel
  • hair
  • red blood cell
  • skin
genes like me logo Genes that share expression patterns with STK11: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for STK11 Gene

Orthologs for STK11 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for STK11 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia STK11 30 31
  • 99.23 (n)
 OneToOne