STK11

Gene Information
 
Gene Symbol
STK11
 
Aliases
LKB1, PJS, hLKB1
 
Entrez Gene ID
 
Gene Name
Serine/threonine kinase 11
 
Chromosomal Location
19p13.3
 
HGNC ID
 
Summary
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)
 
GeneCards ID
 
UniGene
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

Gene Ontology (GO)

GO ID Ontology Definition Evidence Reference
GO:0006468 Biological process Protein phosphorylation IDA 12805220
GO:0008285 Biological process Negative regulation of cell proliferation IMP 17216128
GO:0030511 Biological process Positive regulation of transforming growth factor beta receptor signaling pathway IMP 18311138
GO:0043276 Biological process Anoikis IMP 19622832
GO:0046777 Biological process Protein autophosphorylation IDA 11430832
Protein Information
 
Protein Name
Serine/threonine-protein kinase STK11
 
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, leading to promote 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 and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2: it thereby regulates 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, 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 neurons 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 p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways
 
Refseq Proteins
 
UniProt
 
PDB
 
InterPro
 
Pfam
Pfam Accession Pfam ID
PF00069 Pkinase Protein kinase domain
 
KEGG
 
OMIM
 
Phenotype MIM ID

Associated Diseases

Diseases References
Ovulatory response 18000088
   
References
 
Primary:
 
Supporting Literature:
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
 
Ovulatory response 
C allele SNP in STK11 gene 
NIH criteria 
Related 
 
The study found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin. 

Unreviewed Literature:

PubMed / PMC ID
Title Type of study
26147831
Polycystic ovary syndrome (PCOS) with melanocytic mucosal macules: the role of STK11 gene polymorphisms in PCOS and Peutz-Jeghers syndrome. 
Clinical study 
23786328
Diverse roles of metformin during peri-implantation development: revisiting novel molecular mechanisms underlying clinical implications. 
Effect of treatment 

 

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