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Details on Person UniProt:Q15831 STK11

Class:Id	ReferenceGeneProduct:65200
_chainChangeLog	chain:1-430 added on Fri February 6 2015;propeptide:431-433 added on Fri February 6 2015
_displayName	UniProt:Q15831 STK11
_timestamp	2025-02-21 19:12:57
chain	chain:1-430 propeptide:431-433
checksum	6DF4C37AB7A89569
comment	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. 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).FUNCTION Has a role in spermiogenesis.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR 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.SUBUNIT 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.INTERACTION 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. PTEN promotes cytoplasmic localization.SUBCELLULAR LOCATION Predominantly nuclear, but translocates to the cytoplasm in response to metformin or peroxynitrite treatment.ALTERNATIVE PRODUCTS Ubiquitously expressed. Strongest expression in testis and fetal liver.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).PTM Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE 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.SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.CAUTION Its phosphorylation by PKC/PRKCZ at Ser-428 is reported to promote peroxynitrite-induced nuclear export of STK11, leading to PTEN activation and subsequent inhibition of PI3K/AKT signaling and induction of apoptosis in vein endothelial cells (PubMed:18321849). However this paper was withdrawn by the authors due to concerns of image duplication in the figures. Its phosphorylation by PKC/PRKCZ has been confirmed in other studies (PubMed:18854309, PubMed:23612973).ONLINE INFORMATION PJS entry
description	recommendedName: fullName evidence="42"Serine/threonine-protein kinase STK11 ecNumber evidence="16"2.7.11.1 alternativeName: Liver kinase B1 shortName: LKB1 shortName: hLKB1 alternativeName: Renal carcinoma antigen NY-REN-19
geneName	STK11 LKB1 PJS
identifier	Q15831
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Apoptosis ATP-binding Autophagy Cell cycle Cytoplasm Differentiation Disease variant DNA damage Kinase Lipoprotein Magnesium Manganese Membrane Metal-binding Methylation Mitochondrion Nucleotide-binding Nucleus Palmitate Phosphoprotein Prenylation Proteomics identification Reference proteome Serine/threonine-protein kinase Spermatogenesis Transferase Tumor suppressor
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
name	STK11
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8988692] ENSEMBL:ENSG00000118046 STK11 [Homo sapiens]
secondaryIdentifier	STK11_HUMAN B2RBX7 E7EW76
sequenceLength	433
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8970749] UniProt:Q15831-1 STK11 [Homo sapiens] [ReferenceIsoform:8970750] UniProt:Q15831-2 STK11 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:164119] STK11 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:380954] STK11 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9984930] Ac-K48,8K-STK11 [nucleoplasm] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:9984933] N6-acetyl-L-lysine at 48 [ModifiedResidue:9984934] N6-acetyl-L-lysine at unknown position
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