InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: STK11

Summary

InnateDB Protein

IDBP-13952.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

STK11

Protein Name

serine/threonine kinase 11

Synonyms

hLKB1; LKB1; PJS;

Species

Homo sapiens

Ensembl Protein

ENSP00000324856

InnateDB Gene

IDBG-13950 (STK11)

Protein Structure

UniProt Annotation

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). {ECO:0000269PubMed:11430832, ECO:0000269PubMed:12805220, ECO:0000269PubMed:14517248, ECO:0000269PubMed:14976552, ECO:0000269PubMed:15016379, ECO:0000269PubMed:15733851, ECO:0000269PubMed:15987703, ECO:0000269PubMed:17108107, ECO:0000269PubMed:18321849, ECO:0000269PubMed:21317932}.Isoform 2: Has a role in spermiogenesis. {ECO:0000250}.

Subcellular Localization

Nucleus. Cytoplasm. Membrane {ECO:0000250}. 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 {ECO:0000269PubMed:23612973}. Cytoplasm {ECO:0000269PubMed:23612973}. Note=Predominantly nuclear, but translocates to the cytoplasm in response to metformin or peroxynitrite treatment.

Disease Associations

Peutz-Jeghers syndrome (PJS) [MIM:175200]: An autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. {ECO:0000269PubMed:10408777, ECO:0000269PubMed:12372054, ECO:0000269PubMed:21411391, ECO:0000269PubMed:9425897, ECO:0000269PubMed:9428765, ECO:0000269PubMed:9760200, ECO:0000269PubMed:9837816}. Note=The disease is caused by mutations affecting the gene represented in this entry.Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. {ECO:0000269PubMed:9605748}. Note=The gene represented in this entry may be involved in disease pathogenesis.Note=Defects in STK11 are associated with some sporadic cancers, especially lung cancers. Frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Defects promote lung cancerigenesis process, especially lung cancer progression and metastasis. Confers lung adenocarcinoma the ability to trans- differentiate into squamous cell carcinoma. Also able to promotes lung cancer metastasis, via both cancer-cell autonomous and non- cancer-cell autonomous mechanisms.

Tissue Specificity

Ubiquitously expressed. Strongest expression in testis and fetal liver.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 71 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	71 [view]
Protein-Protein	69 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0002039	p53 binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030275	LRR domain binding
GO:0030295	protein kinase activator activity
GO:0032403	protein complex binding

Biological Process

GO:0001558	regulation of cell growth
GO:0001894	tissue homeostasis
GO:0001944	vasculature development
GO:0006112	energy reserve metabolic process
GO:0006468	protein phosphorylation
GO:0006914	autophagy
GO:0006974	cellular response to DNA damage stimulus
GO:0007050	cell cycle arrest
GO:0007286	spermatid development
GO:0007409	axonogenesis
GO:0008285	negative regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0010212	response to ionizing radiation
GO:0030010	establishment of cell polarity
GO:0030111	regulation of Wnt signaling pathway
GO:0030308	negative regulation of cell growth
GO:0030511	positive regulation of transforming growth factor beta receptor signaling pathway
GO:0032147	activation of protein kinase activity
GO:0033762	response to glucagon
GO:0033993	response to lipid
GO:0036399	TCR signalosome assembly
GO:0042304	regulation of fatty acid biosynthetic process
GO:0042593	glucose homeostasis
GO:0043276	anoikis
GO:0043434	response to peptide hormone
GO:0044281	small molecule metabolic process
GO:0045059	positive thymic T cell selection
GO:0045722	positive regulation of gluconeogenesis
GO:0046777	protein autophosphorylation
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0050772	positive regulation of axonogenesis
GO:0050852	T cell receptor signaling pathway
GO:0051291	protein heterooligomerization
GO:0051645	Golgi localization
GO:0051896	regulation of protein kinase B signaling
GO:0060070	canonical Wnt signaling pathway
GO:0060770	negative regulation of epithelial cell proliferation involved in prostate gland development
GO:0072332	intrinsic apoptotic signaling pathway by p53 class mediator

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0016020	membrane
GO:0036398	TCR signalosome
GO:0043234	protein complex
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt