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Protein

Serine/threonine-protein kinase STK11

Gene

STK11

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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). 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).11 Publications
Isoform 2: Has a role in spermiogenesis.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Enzyme regulationi

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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei78 – 781ATPCurated
Active sitei176 – 1761Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi55 – 639ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • p53 binding Source: UniProtKB
  • protein kinase activator activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Autophagy, Cell cycle, Differentiation, DNA damage, Spermatogenesis

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-163680. AMPK inhibits chREBP transcriptional activation activity.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ15831.
SIGNORiQ15831.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase STK11 (EC:2.7.11.1)
Alternative name(s):
Liver kinase B1
Short name:
LKB1
Short name:
hLKB1
Renal carcinoma antigen NY-REN-19
Gene namesi
Name:STK11
Synonyms:LKB1, PJS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:11389. STK11.

Subcellular locationi

  • Nucleus
  • Cytoplasm
  • Membrane By similarity
  • 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.By similarity
Isoform 2 :
  • Nucleus 1 Publication
  • Cytoplasm 1 Publication

  • Note: Predominantly nuclear, but translocates to the cytoplasm in response to metformin or peroxynitrite treatment.

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
  • TCR signalosome Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Peutz-Jeghers syndrome (PJS)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer.
See also OMIM:175200
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti16 – 161E → G in PJS. 1 Publication
VAR_065628
Natural varianti50 – 534Missing in PJS. 1 Publication
VAR_071057
Natural varianti67 – 671L → P in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 2 Publications
Corresponds to variant rs137853077 [ dbSNP | Ensembl ].
VAR_006202
Natural varianti162 – 1643DGL → NDM in PJS.
VAR_007920
Natural varianti176 – 1761D → N in PJS; loss of kinase activity, leading to greatly reduced autophosphorylation; fails to phosphorylate PTEN in vitro; no significant effect on nucleocytoplasmic localization. 2 Publications
Corresponds to variant rs730881979 [ dbSNP | Ensembl ].
VAR_071058
Natural varianti194 – 1941D → N in PJS. 1 Publication
Corresponds to variant rs121913315 [ dbSNP | Ensembl ].
VAR_007921
Natural varianti239 – 2391W → C in PJS; late onset suggests reduced penetrance. 1 Publication
Corresponds to variant rs137853082 [ dbSNP | Ensembl ].
VAR_033142
Natural varianti247 – 2471Missing in PJS. 1 Publication
VAR_006203
Natural varianti297 – 2971R → K in PJS. 1 Publication
VAR_007922
Natural varianti303 – 3064IRQH → N in PJS.
VAR_033143
Natural varianti308 – 3081W → C in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 1 Publication
VAR_071059
Natural varianti315 – 3151P → S in PJS; pathogenicity uncertain; no effect heterotrimeric complex assembly with STRADA and CAB39. 2 Publications
Corresponds to variant rs786202431 [ dbSNP | Ensembl ].
VAR_033144
Testicular germ cell tumor (TGCT)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA 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.
See also OMIM:273300
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti163 – 1631G → D in TGCT; a tumor with seminoma and teratoma components; associated with severely impaired but detectable kinase activity; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39; predominantly nuclear localization. 3 Publications
Corresponds to variant rs137853078 [ dbSNP | Ensembl ].
VAR_033140

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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi44 – 441K → R: No effect on kinase activity. 1 Publication
Mutagenesisi48 – 481K → Q: No effect on basal nucleocytoplasmic localization, but fails to translocate to the cytoplasm when coexpressed with SIRT1. 1 Publication
Mutagenesisi48 – 481K → R: Enhanced phosphorylation at Thr-336 and Ser-428, enhanced cytoplasmic localization and increased kinase activity. 1 Publication
Mutagenesisi74 – 741R → A: Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-204. 1 Publication
Mutagenesisi78 – 781K → I: Loss of kinase activity, leading to greatly reduced autophosphorylation. 2 Publications
Mutagenesisi78 – 781K → M: Loss of kinase activity, leading to reduced autophosphorylation and acting as a dominant-negative mutant. 2 Publications
Mutagenesisi96 – 961K → R: No effect on kinase activity. 1 Publication
Mutagenesisi97 – 971K → R: No effect on kinase activity. 1 Publication
Mutagenesisi189 – 1891T → A: Reduced phosphorylation. 1 Publication
Mutagenesisi194 – 1941D → A: Loss of kinase activity. 3 Publications
Mutagenesisi204 – 2041F → A: No effect. Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-74. 1 Publication
Mutagenesisi428 – 4281S → A or E: No effect on kinase activity. 2 Publications
Mutagenesisi428 – 4281S → A: Inhibits peroxynitrite-induced nuclear export of STK11, and consequent PTEN phosphorylation and inhibition of PI3K/Akt signaling. 2 Publications

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

MalaCardsiSTK11.
MIMi175200. phenotype.
273300. phenotype.
Orphaneti2869. Peutz-Jeghers syndrome.
PharmGKBiPA36198.

Chemistry

ChEMBLiCHEMBL5606.
GuidetoPHARMACOLOGYi2212.

Polymorphism and mutation databases

BioMutaiSTK11.
DMDMi3024670.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 430430Serine/threonine-protein kinase STK11PRO_0000086699Add
BLAST
Propeptidei431 – 4333Removed in mature formBy similarityPRO_0000422300

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei31 – 311PhosphoserineCombined sources
Modified residuei44 – 441N6-acetyllysine1 Publication
Modified residuei48 – 481N6-acetyllysine1 Publication
Modified residuei96 – 961N6-acetyllysine1 Publication
Modified residuei97 – 971N6-acetyllysine1 Publication
Modified residuei189 – 1891Phosphothreonine; by autocatalysis1 Publication
Modified residuei296 – 2961N6-acetyllysine1 Publication
Modified residuei311 – 3111N6-acetyllysine1 Publication
Modified residuei325 – 3251PhosphoserineBy similarity
Modified residuei336 – 3361Phosphothreonine; by autocatalysis1 Publication
Modified residuei363 – 3631Phosphothreonine; by ATM and autocatalysis1 Publication
Modified residuei401 – 4011PhosphoserineCombined sources
Modified residuei416 – 4161N6-acetyllysine1 Publication
Lipidationi418 – 4181S-palmitoyl cysteineBy similarity
Modified residuei423 – 4231N6-acetyllysine1 Publication
Modified residuei428 – 4281Phosphoserine; by autocatalysis, PKA, PKC/PRKCZ and RPS6KA12 Publications
Modified residuei430 – 4301Cysteine methyl esterBy similarity
Lipidationi430 – 4301S-farnesyl cysteineBy similarity
Modified residuei431 – 4311N6-acetyllysine1 Publication

Post-translational modificationi

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-428 promotes peroxynitrite-induced nuclear export of STK11, leading to PTEN activation and subsequent inhibition of AKT signaling. 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).By similarity4 Publications
Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.1 Publication

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Palmitate, Phosphoprotein, Prenylation

Proteomic databases

EPDiQ15831.
MaxQBiQ15831.
PaxDbiQ15831.
PeptideAtlasiQ15831.
PRIDEiQ15831.

PTM databases

iPTMnetiQ15831.
PhosphoSiteiQ15831.

Expressioni

Tissue specificityi

Ubiquitously expressed. Strongest expression in testis and fetal liver.

Gene expression databases

BgeeiENSG00000118046.
CleanExiHS_STK11.
ExpressionAtlasiQ15831. baseline and differential.
GenevisibleiQ15831. HS.

Organism-specific databases

HPAiCAB016231.
CAB022105.
HPA017254.

Interactioni

Subunit structurei

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.11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CAB39Q9Y3767EBI-306838,EBI-306905
CDC37Q165433EBI-306838,EBI-295634
COPS4Q9BT782EBI-306838,EBI-742413
FKBP5Q134514EBI-306838,EBI-306914
HSP90AA1P079002EBI-306838,EBI-296047
HSP90AB1P082383EBI-306838,EBI-352572
MARK4Q96L342EBI-306838,EBI-302319
STRADAQ7RTN612EBI-306838,EBI-1109114
STRADBQ9C0K76EBI-306838,EBI-306893
TNIP2Q8NFZ55EBI-306838,EBI-359372
WDR6Q9NNW53EBI-306838,EBI-1568315
YWHAZP631046EBI-306838,EBI-347088

GO - Molecular functioni

  • p53 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112670. 91 interactions.
DIPiDIP-31317N.
IntActiQ15831. 108 interactions.
MINTiMINT-204048.
STRINGi9606.ENSP00000324856.

Chemistry

BindingDBiQ15831.

Structurei

Secondary structure

1
433
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi54 – 574Combined sources
Beta strandi62 – 687Combined sources
Turni69 – 713Combined sources
Beta strandi74 – 807Combined sources
Helixi82 – 876Combined sources
Helixi91 – 10212Combined sources
Beta strandi113 – 1186Combined sources
Beta strandi125 – 1306Combined sources
Beta strandi133 – 1353Combined sources
Helixi136 – 1427Combined sources
Helixi150 – 16920Combined sources
Helixi179 – 1813Combined sources
Beta strandi182 – 1843Combined sources
Beta strandi190 – 1923Combined sources
Helixi217 – 2193Combined sources
Helixi222 – 2254Combined sources
Beta strandi231 – 2333Combined sources
Helixi234 – 25017Combined sources
Helixi260 – 26910Combined sources
Beta strandi276 – 2783Combined sources
Helixi280 – 28910Combined sources
Turni294 – 2963Combined sources
Helixi300 – 3056Combined sources
Helixi307 – 3104Combined sources
Helixi334 – 3363Combined sources
Helixi339 – 3413Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WTKX-ray2.65C/F43-347[»]
4ZDRX-ray2.90A/B333-340[»]
ProteinModelPortaliQ15831.
SMRiQ15831. Positions 22-369.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15831.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini49 – 309261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni45 – 9046Sufficient for interaction with SIRT1Add
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063214.
HOGENOMiHOG000007002.
HOVERGENiHBG054467.
InParanoidiQ15831.
KOiK07298.
OMAiQQLGMFT.
OrthoDBiEOG091G0BNP.
PhylomeDBiQ15831.
TreeFamiTF105322.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15831-1) [UniParc]FASTAAdd to basket
Also known as: LKB1(L)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEVVDPQQLG MFTEGELMSV GMDTFIHRID STEVIYQPRR KRAKLIGKYL
60 70 80 90 100
MGDLLGEGSY GKVKEVLDSE TLCRRAVKIL KKKKLRRIPN GEANVKKEIQ
110 120 130 140 150
LLRRLRHKNV IQLVDVLYNE EKQKMYMVME YCVCGMQEML DSVPEKRFPV
160 170 180 190 200
CQAHGYFCQL IDGLEYLHSQ GIVHKDIKPG NLLLTTGGTL KISDLGVAEA
210 220 230 240 250
LHPFAADDTC RTSQGSPAFQ PPEIANGLDT FSGFKVDIWS AGVTLYNITT
260 270 280 290 300
GLYPFEGDNI YKLFENIGKG SYAIPGDCGP PLSDLLKGML EYEPAKRFSI
310 320 330 340 350
RQIRQHSWFR KKHPPAEAPV PIPPSPDTKD RWRSMTVVPY LEDLHGADED
360 370 380 390 400
EDLFDIEDDI IYTQDFTVPG QVPEEEASHN GQRRGLPKAV CMNGTEAAQL
410 420 430
STKSRAEGRA PNPARKACSA SSKIRRLSAC KQQ
Length:433
Mass (Da):48,636
Last modified:November 1, 1996 - v1
Checksum:i6DF4C37AB7A89569
GO
Isoform 2 (identifier: Q15831-2) [UniParc]FASTAAdd to basket
Also known as: LKB1(S)

The sequence of this isoform differs from the canonical sequence as follows:
     371-433: QVPEEEASHN...IRRLSACKQQ → GEEASEAGLRAERGLQKSEGSDLSGEEASRPAPQ

Note: Phosphorylated by PKC/PRKCZ on Ser-399.
Show »
Length:404
Mass (Da):45,387
Checksum:i6E4F3920F8F873DD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti14 – 141E → K in cervical cancer; somatic mutation. 1 Publication
VAR_065627
Natural varianti16 – 161E → G in PJS. 1 Publication
VAR_065628
Natural varianti49 – 491Y → D in melanoma; sporadic malignant; somatic mutation. 1 Publication
Corresponds to variant rs137853080 [ dbSNP | Ensembl ].
VAR_033138
Natural varianti50 – 534Missing in PJS. 1 Publication
VAR_071057
Natural varianti66 – 661V → M in cervical carcinoma; somatic mutation. 2 Publications
VAR_065629
Natural varianti67 – 671L → P in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 2 Publications
Corresponds to variant rs137853077 [ dbSNP | Ensembl ].
VAR_006202
Natural varianti86 – 861R → G in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065630
Natural varianti87 – 871R → K in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_041139
Natural varianti123 – 1231Q → R in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
Corresponds to variant rs764449808 [ dbSNP | Ensembl ].
VAR_065631
Natural varianti135 – 1351G → R in melanoma; sporadic malignant; somatic mutation. 1 Publication
Corresponds to variant rs137853081 [ dbSNP | Ensembl ].
VAR_033139
Natural varianti157 – 1571F → S in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065632
Natural varianti160 – 1601L → P in cervical cancer; somatic mutation. 1 Publication
VAR_065633
Natural varianti162 – 1643DGL → NDM in PJS.
VAR_007920
Natural varianti163 – 1631G → D in TGCT; a tumor with seminoma and teratoma components; associated with severely impaired but detectable kinase activity; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39; predominantly nuclear localization. 3 Publications
Corresponds to variant rs137853078 [ dbSNP | Ensembl ].
VAR_033140
Natural varianti170 – 1701Q → P in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065634
Natural varianti171 – 1711G → S in colorectal cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 2 Publications
VAR_065635
Natural varianti174 – 1741H → R in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065636
Natural varianti176 – 1761D → N in PJS; loss of kinase activity, leading to greatly reduced autophosphorylation; fails to phosphorylate PTEN in vitro; no significant effect on nucleocytoplasmic localization. 2 Publications
Corresponds to variant rs730881979 [ dbSNP | Ensembl ].
VAR_071058
Natural varianti176 – 1761D → Y in sporadic cancer; somatic mutation; Loss of kinase activity. 2 Publications
VAR_065637
Natural varianti177 – 1771I → N in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065638
Natural varianti181 – 1811N → E in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39; requires 2 nucleotide substitutions. 1 Publication
VAR_065639
Natural varianti194 – 1941D → N in PJS. 1 Publication
Corresponds to variant rs121913315 [ dbSNP | Ensembl ].
VAR_007921
Natural varianti194 – 1941D → V in lung cancer; somatic mutation. 1 Publication
VAR_065640
Natural varianti194 – 1941D → Y in melanoma; sporadic malignant; somatic mutation. 1 Publication
Corresponds to variant rs121913315 [ dbSNP | Ensembl ].
VAR_033141
Natural varianti199 – 1991E → K in colorectal cancer; somatic mutation; impaired kinase activity. 1 Publication
VAR_065641
Natural varianti199 – 1991E → Q in sporadic cancer; somatic mutation; does not affect kinase activity. 1 Publication
VAR_065642
Natural varianti205 – 2051A → T in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
Corresponds to variant rs730881981 [ dbSNP | Ensembl ].
VAR_065643
Natural varianti208 – 2081D → N in colorectal cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065644
Natural varianti215 – 2151G → D in colorectal cancer; somatic mutation. 1 Publication
VAR_065645
Natural varianti216 – 2161S → F in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065646
Natural varianti223 – 2231E → V in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065647
Natural varianti230 – 2301T → P in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065648
Natural varianti231 – 2311F → L in cervical cancer; somatic mutation. 1 Publication
VAR_065649
Natural varianti232 – 2321S → P in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065650
Natural varianti239 – 2391W → C in PJS; late onset suggests reduced penetrance. 1 Publication
Corresponds to variant rs137853082 [ dbSNP | Ensembl ].
VAR_033142
Natural varianti245 – 2451L → R in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065651
Natural varianti247 – 2471Missing in PJS. 1 Publication
VAR_006203
Natural varianti250 – 2501T → P in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065652
Natural varianti272 – 2721Y → H in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065653
Natural varianti277 – 2771D → Y in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065654
Natural varianti281 – 2811P → L in ovarian carcinoma; somatic mutation. 1 Publication
Corresponds to variant rs121913322 [ dbSNP | Ensembl ].
VAR_065655
Natural varianti285 – 2851L → Q in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065656
Natural varianti297 – 2971R → K in PJS. 1 Publication
VAR_007922
Natural varianti303 – 3064IRQH → N in PJS.
VAR_033143
Natural varianti308 – 3081W → C in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 1 Publication
VAR_071059
Natural varianti314 – 3141P → H in colorectal cancer; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
VAR_065657
Natural varianti315 – 3151P → S in PJS; pathogenicity uncertain; no effect heterotrimeric complex assembly with STRADA and CAB39. 2 Publications
Corresponds to variant rs786202431 [ dbSNP | Ensembl ].
VAR_033144
Natural varianti324 – 3241P → L in gastric carcinoma; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication
Corresponds to variant rs367807476 [ dbSNP | Ensembl ].
VAR_065658
Natural varianti354 – 3541F → L in colorectal cancer; somatic mutation. 1 Publication
Corresponds to variant rs59912467 [ dbSNP | Ensembl ].
VAR_065659
Natural varianti367 – 3671T → M in colorectal cancer; somatic mutation. 1 Publication
Corresponds to variant rs587782835 [ dbSNP | Ensembl ].
VAR_065660

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei371 – 43363QVPEE…ACKQQ → GEEASEAGLRAERGLQKSEG SDLSGEEASRPAPQ in isoform 2. CuratedVSP_041746Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63333 mRNA. Translation: AAB05809.1.
AF035625 mRNA. Translation: AAC39527.1.
AF032984 Genomic DNA. Translation: AAB97833.1.
AF055327
, AF055320, AF055321, AF055322, AF055323, AF055324, AF055325, AF055326 Genomic DNA. Translation: AAC15742.1.
AK314858 mRNA. Translation: BAG37374.1.
AC011544 Genomic DNA. No translation available.
AC004221 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69540.1.
BC007981 mRNA. Translation: AAH07981.1.
BC019334 mRNA. Translation: AAH19334.1.
CCDSiCCDS45896.1. [Q15831-1]
RefSeqiNP_000446.1. NM_000455.4. [Q15831-1]
XP_005259675.1. XM_005259618.3. [Q15831-2]
UniGeneiHs.515005.

Genome annotation databases

EnsembliENST00000326873; ENSP00000324856; ENSG00000118046. [Q15831-1]
GeneIDi6794.
KEGGihsa:6794.
UCSCiuc002lrl.2. human. [Q15831-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

PJS entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63333 mRNA. Translation: AAB05809.1.
AF035625 mRNA. Translation: AAC39527.1.
AF032984 Genomic DNA. Translation: AAB97833.1.
AF055327
, AF055320, AF055321, AF055322, AF055323, AF055324, AF055325, AF055326 Genomic DNA. Translation: AAC15742.1.
AK314858 mRNA. Translation: BAG37374.1.
AC011544 Genomic DNA. No translation available.
AC004221 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69540.1.
BC007981 mRNA. Translation: AAH07981.1.
BC019334 mRNA. Translation: AAH19334.1.
CCDSiCCDS45896.1. [Q15831-1]
RefSeqiNP_000446.1. NM_000455.4. [Q15831-1]
XP_005259675.1. XM_005259618.3. [Q15831-2]
UniGeneiHs.515005.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WTKX-ray2.65C/F43-347[»]
4ZDRX-ray2.90A/B333-340[»]
ProteinModelPortaliQ15831.
SMRiQ15831. Positions 22-369.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112670. 91 interactions.
DIPiDIP-31317N.
IntActiQ15831. 108 interactions.
MINTiMINT-204048.
STRINGi9606.ENSP00000324856.

Chemistry

BindingDBiQ15831.
ChEMBLiCHEMBL5606.
GuidetoPHARMACOLOGYi2212.

PTM databases

iPTMnetiQ15831.
PhosphoSiteiQ15831.

Polymorphism and mutation databases

BioMutaiSTK11.
DMDMi3024670.

Proteomic databases

EPDiQ15831.
MaxQBiQ15831.
PaxDbiQ15831.
PeptideAtlasiQ15831.
PRIDEiQ15831.

Protocols and materials databases

DNASUi6794.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000326873; ENSP00000324856; ENSG00000118046. [Q15831-1]
GeneIDi6794.
KEGGihsa:6794.
UCSCiuc002lrl.2. human. [Q15831-1]

Organism-specific databases

CTDi6794.
GeneCardsiSTK11.
GeneReviewsiSTK11.
HGNCiHGNC:11389. STK11.
HPAiCAB016231.
CAB022105.
HPA017254.
MalaCardsiSTK11.
MIMi175200. phenotype.
273300. phenotype.
602216. gene.
neXtProtiNX_Q15831.
Orphaneti2869. Peutz-Jeghers syndrome.
PharmGKBiPA36198.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063214.
HOGENOMiHOG000007002.
HOVERGENiHBG054467.
InParanoidiQ15831.
KOiK07298.
OMAiQQLGMFT.
OrthoDBiEOG091G0BNP.
PhylomeDBiQ15831.
TreeFamiTF105322.

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-163680. AMPK inhibits chREBP transcriptional activation activity.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ15831.
SIGNORiQ15831.

Miscellaneous databases

ChiTaRSiSTK11. human.
EvolutionaryTraceiQ15831.
GeneWikiiSTK11.
GenomeRNAii6794.
PROiQ15831.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118046.
CleanExiHS_STK11.
ExpressionAtlasiQ15831. baseline and differential.
GenevisibleiQ15831. HS.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSTK11_HUMAN
AccessioniPrimary (citable) accession number: Q15831
Secondary accession number(s): B2RBX7, E7EW76
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: September 7, 2016
This is version 184 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.