LipidDB ID

LipidDB-10090-00604

Entry Name

UniProt Accession

Q9WTK7; B3VBP0; Q3TAE0;

Theoretical PI

6.4

Molecular Weight

49266.53

Genbank Protein ID

AAD22100.1; AAD31044.1; ACE73833.1; AAD55368.1; AAD55368.1; AAD55368.1; AAD55368.1; AAD55368.1; AAD55368.1; AAD55368.1; AAD55368.1; AAD55368.1; AAF21370.1; BAA76749.1; BAE42728.1; BAE43050.1; BAE42977.1; AAH52379.1;

Genbank Nucleotide ID

AF129870; AF145287; EU730638; AF145296; AF145288; AF145289; AF145290; AF145291; AF145292; AF145293; AF145294; AF145295; AF151711; AB015801; AK171909; AK172528; AK172385; BC052379;

Protein Name

Serine/threonine-protein kinase STK11

Protein Synonyms/Alias

2.7.11.1; Liver kinase B1 homolog; LKB1; mLKB1;

Gene Name

Stk11

Gene Synonyms/Alias

Lkb1;

Created Date

28-NOV-2006

Organism

Mus musculus (Mouse)

NCBI Taxa ID

10090

Reference

[1] Sapkota GP, Kieloch A, Lizcano JM, Lain S, Arthur JS, Williams MR, Morrice N, Deak M, Alessi DR. Phosphorylation of the protein kinase mutated in Peutz-Jegherscancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent proteinkinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth. J Biol Chem. 2001 Jun 1;276(22):19469-82. Epub 2001 Jan 31. PubMedPMID: 11297520.[PMID:11297520]
[2] Collins SP, Reoma JL, Gamm DM, Uhler MD. LKB1, a novel serine/threonineprotein kinase and potential tumour suppressor, is phosphorylated bycAMP-dependent protein kinase (PKA) and prenylated in vivo. Biochem J. 2000 Feb1;345 Pt 3:673-80.[PMID:10642527]
[3] Sapkota GP, Boudeau J, Deak M, Kieloch A, Morrice N, Alessi DR. Identificationand characterization of four novel phosphorylation sites (Ser31, Ser325, Thr336and Thr366) on LKB1/STK11, the protein kinase mutated in Peutz-Jeghers cancersyndrome. Biochem J. 2002 Mar 1;362(Pt 2):481-90.[PMID:11853558]

Functional Description

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.

Sequence Annotation

Domain: 49 309 Protein kinase.
Nucleotide-binding: 55 63 ATP.
Region: 45 90 Sufficient for interaction with SIRT1.
Active site: 176 176 Proton acceptor.
Binding site: 78 78 ATP.
Modified residue: 31 31 Phosphoserine.
Modified residue: 44 44 N6-acetyllysine.
Modified residue: 48 48 N6-acetyllysine.
Modified residue: 96 96 N6-acetyllysine.
Modified residue: 97 97 N6-acetyllysine.
Modified residue: 189 189 Phosphothreonine; by autocatalysis.
Modified residue: 296 296 N6-acetyllysine.
Modified residue: 311 311 N6-acetyllysine.
Modified residue: 325 325 Phosphoserine.
Modified residue: 336 336 Phosphothreonine; by autocatalysis.
Modified residue: 366 366 Phosphothreonine; by ATM andautocatalysis.
Modified residue: 420 420 N6-acetyllysine.
Modified residue: 426 426 N6-acetyllysine.
Modified residue: 431 431 Phosphoserine; by autocatalysis, PKA,PKC/PRKCZ and RPS6KA1.
Modified residue: 433 433 Cysteine methyl ester.
Modified residue: 434 434 N6-acetyllysine.

Protein Length

436 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005737; C:cytoplasm; IDA:UniProtKB
GO:0005829; C:cytosol; IDA:UniProtKB
GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl
GO:0016020; C:membrane; IDA:UniProtKB
GO:0005739; C:mitochondrion; ISS:UniProtKB
GO:0005634; C:nucleus; IDA:UniProtKB
GO:0036398; C:TCR signalosome; IDA:MGI
GO:0005524; F:ATP binding; ISS:UniProtKB
GO:0030275; F:LRR domain binding; IPI:UniProtKB
GO:0000287; F:magnesium ion binding; ISS:UniProtKB
GO:0002039; F:p53 binding; ISS:UniProtKB
GO:0030295; F:protein kinase activator activity; IDA:UniProtKB
GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB
GO:0032147; P:activation of protein kinase activity; IDA:MGI
GO:0043276; P:anoikis; IEA:Ensembl
GO:0006914; P:autophagy; IEA:UniProtKB-KW
GO:0007409; P:axonogenesis; IMP:UniProtKB
GO:0060070; P:canonical Wnt signaling pathway; IMP:MGI
GO:0007050; P:cell cycle arrest; ISS:UniProtKB
GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW
GO:0030010; P:establishment of cell polarity; IMP:UniProtKB
GO:0042593; P:glucose homeostasis; IMP:UniProtKB
GO:0051645; P:Golgi localization; IMP:MGI
GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISS:UniProtKB
GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB
GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IMP:MGI
GO:0050772; P:positive regulation of axonogenesis; IGI:MGI
GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl
GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:MGI
GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL
GO:0045059; P:positive thymic T cell selection; IMP:MGI
GO:0046777; P:protein autophosphorylation; IDA:UniProtKB
GO:0051291; P:protein heterooligomerization; IEA:Ensembl
GO:0006468; P:protein phosphorylation; ISS:UniProtKB
GO:0001558; P:regulation of cell growth; IDA:UniProtKB
GO:0051896; P:regulation of protein kinase B signaling; IMP:MGI
GO:0030111; P:regulation of Wnt signaling pathway; IMP:MGI
GO:0033762; P:response to glucagon; IEA:Ensembl
GO:0010212; P:response to ionizing radiation; IDA:UniProtKB
GO:0033993; P:response to lipid; IEA:Ensembl
GO:0007286; P:spermatid development; IMP:UniProtKB
GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW
GO:0050852; P:T cell receptor signaling pathway; IMP:MGI
GO:0036399; P:TCR signalosome assembly; IMP:MGI
GO:0001894; P:tissue homeostasis; IMP:MGI
GO:0001944; P:vasculature development; IMP:UniProtKB

Interpro

InterPro; IPR020636; Ca/CaM-dep_Ca-dep_prot_Kinase
InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR002290; Ser/Thr_dual-sp_kinase
InterPro; IPR008271; Ser/Thr_kinase_AS

Pfam

Pfam; PF00069; Pkinase;

SMART

SMART; SM00220; S_TKc;

PROSITE

PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00108; PROTEIN_KINASE_ST;

PRINTS