STK11
entrez
6794
canonical
uniprot
Q15831
canonical
ensembl
ENSG00000118046
resolver
ensp
ENSP00000324856
resolver
ensp
ENSP00000498804
resolver
genesymbol
STK11
resolver
genesymbol_syn
LKB1
resolver
genesymbol_syn
PJS
resolver
hgnc
HGNC:11389
resolver
uniprot
A0A0S2Z4D1
resolver
uniprot
B2RBX7
resolver
uniprot
E7EW76
resolver
uniprot_entry
A0A0S2Z4D1_HUMAN
resolver
uniprot_entry
STK11_HUMAN
resolver
uniprot_sec
B2RBX7
resolver
uniprot_sec
E7EW76
resolver
activity_regulation
ACTIVITY REGULATION: 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 (PubMed:19892943). Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK (PubMed:22983157). In response to calorie restriction, activated by AXIN1 adapter, promoting association between STK11 and its AMPK substrates PRKAA1 and/or PRKAA2 (By similarity). {ECO:0000250|UniProtKB:Q9WTK7, ECO:0000269|PubMed:19892943, ECO:0000269|PubMed:22983157}.
uniprot
proteins
amino_acid_sequence
MEVVDPQQLGMFTEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLIGKYLMGDLLGEGSYGKVKEVLDSETLCRRAVKILKKKKLRRIPNGEANVKKEIQLLRRLRHKNVIQLVDVLYNEEKQKMYMVMEYCVCGMQEMLDSVPEKRFPVCQAHGYFCQLIDGLEYLHSQGIVHKDIKPGNLLLTTGGTLKISDLGVAEALHPFAADDTCRTSQGSPAFQPPEIANGLDTFSGFKVDIWSAGVTLYNITTGLYPFEGDNIYKLFENIGKGSYAIPGDCGPPLSDLLKGMLEYEPAKRFSIRQIRQHSWFRKKHPPAEAPVPIPPSPDTKDRWRSMTVVPYLEDLHGADEDEDLFDIEDDIIYTQDFTVPGQVPEEEASHNGQRRGLPKAVCMNGTEAAQLSTKSRAEGRAPNPARKACSASSKIRRLSACKQQ
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:10408777, ECO:0000269|PubMed:12372054, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:21411391, ECO:0000269|PubMed:9425897, ECO:0000269|PubMed:9428765, ECO:0000269|PubMed:9760200, ECO:0000269|PubMed:9837816}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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:0000269|PubMed:9605748, ECO:0000269|PubMed:9887330}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: 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 promote lung cancer metastasis, via both cancer-cell autonomous and non-cancer-cell autonomous mechanisms.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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 (PubMed:12805220, PubMed:14517248, PubMed:14976552, PubMed:15016379, PubMed:15733851). 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 (PubMed:12805220, PubMed:14517248, PubMed:14976552, PubMed:15016379, PubMed:15733851). Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53 (PubMed:11430832, PubMed:15987703). 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 (PubMed:14976552). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton (PubMed:15016379). Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification (PubMed:14976552). Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation (PubMed:11430832, PubMed:17108107, PubMed:21317932). 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 (PubMed:11430832, PubMed:17108107, PubMed:21317932). 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 (PubMed:11430832, PubMed:17108107, PubMed:21317932). Regulates UV radiation-induced DNA damage response mediated by CDKN1A (PubMed:25329316). 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). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.; FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000250|UniProtKB:Q9WTK7}.
uniprot
proteins
mass_dalton
48636
uniprot
proteins
mutagenesis
MUTAGEN 44; /note="K->R: No effect on kinase activity."; /evidence="ECO:0000269|PubMed:18687677"; MUTAGEN 48; /note="K->Q: No effect on basal nucleocytoplasmic localization, but fails to translocate to the cytoplasm when coexpressed with SIRT1."; /evidence="ECO:0000269|PubMed:18687677"; MUTAGEN 48; /note="K->R: Enhanced phosphorylation at Thr-336 and Ser-428, enhanced cytoplasmic localization and increased kinase activity."; /evidence="ECO:0000269|PubMed:18687677"; MUTAGEN 74; /note="R->A: Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-204."; /evidence="ECO:0000269|PubMed:19892943"; MUTAGEN 78; /note="K->I: Loss of kinase activity, leading to greatly reduced autophosphorylation."; /evidence="ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:9837816"; MUTAGEN 78; /note="K->M: Loss of kinase activity, leading to reduced autophosphorylation and acting as a dominant-negative mutant."; /evidence="ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:9837816"; MUTAGEN 96; /note="K->R: No effect on kinase activity."; /evidence="ECO:0000269|PubMed:18687677"; MUTAGEN 97; /note="K->R: No effect on kinase activity."; /evidence="ECO:0000269|PubMed:18687677"; MUTAGEN 189; /note="T->A: Reduced phosphorylation."; /evidence="ECO:0000269|PubMed:11430832"; MUTAGEN 194; /note="D->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:19892943"; MUTAGEN 204; /note="F->A: No effect. Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-74."; /evidence="ECO:0000269|PubMed:19892943"; MUTAGEN 428; /note="S->A,E: No effect on kinase activity."; /evidence="ECO:0000269|PubMed:18854309
uniprot
proteins
post_translational_modification
PTM: 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-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). {ECO:0000250|UniProtKB:Q9WTK7, ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:18854309}.; PTM: Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro. {ECO:0000269|PubMed:18687677}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
LKB1 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10079245
uniprot
proteins
pubmed
10201537
uniprot
proteins
pubmed
10208439
uniprot
proteins
pubmed
10408777
uniprot
proteins
pubmed
10429654
uniprot
proteins
pubmed
10508479
uniprot
proteins
pubmed
11212897
uniprot
proteins
pubmed
11430832
uniprot
proteins
pubmed
11741830
uniprot
proteins
pubmed
12097271
uniprot
proteins
pubmed
12372054
uniprot
proteins
pubmed
12533684
uniprot
proteins
pubmed
12805220
uniprot
proteins
pubmed
14517248
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14976552
uniprot
proteins
pubmed
15016379
uniprot
proteins
pubmed
15021901
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15733851
uniprot
proteins
pubmed
15987703
uniprot
proteins
pubmed
17108107
uniprot
proteins
pubmed
17216128
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17384680
uniprot
proteins
pubmed
17676035
uniprot
proteins
pubmed
17711506
uniprot
proteins
pubmed
18321849
uniprot
proteins
pubmed
18594528
uniprot
proteins
pubmed
18687677
uniprot
proteins
pubmed
18854309
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19892943
uniprot
proteins
pubmed
20559149
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21317932
uniprot
proteins
pubmed
21380642
uniprot
proteins
pubmed
21396365
uniprot
proteins
pubmed
21411391
uniprot
proteins
pubmed
22983157
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23572524
uniprot
proteins
pubmed
23612973
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25329316
uniprot
proteins
pubmed
31519760
uniprot
proteins
pubmed
9425897
uniprot
proteins
pubmed
9428765
uniprot
proteins
pubmed
9537235
uniprot
proteins
pubmed
9605748
uniprot
proteins
pubmed
9683800
uniprot
proteins
pubmed
9731485
uniprot
proteins
pubmed
9760200
uniprot
proteins
pubmed
9809980
uniprot
proteins
pubmed
9837816
uniprot
proteins
pubmed
9887330
uniprot
proteins
sequence_length
433
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18854309}. Cytoplasm {ECO:0000269|PubMed:18854309}. Membrane {ECO:0000250|UniProtKB:Q9WTK7}. Mitochondrion {ECO:0000269|PubMed:11430832}. Late endosome {ECO:0000250|UniProtKB:Q9WTK7}. 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) (PubMed:18854309). Translocates to the mitochondrion during apoptosis. PTEN promotes cytoplasmic localization (PubMed:11430832). Translocates to late endosomes in response to calorie restriction (By similarity). {ECO:0000250|UniProtKB:Q9WTK7, ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:18854309}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:23612973}. Cytoplasm {ECO:0000269|PubMed:23612973}. Note=Predominantly nuclear, but translocates to the cytoplasm in response to metformin or peroxynitrite treatment. {ECO:0000269|PubMed:23612973}.
uniprot
proteins