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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)DescriptionActionsGraphical viewLength
Binding sitei78ATPCurated1
Active sitei176Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi55 – 63ATPPROSITE-ProRule annotation9

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

BioCyciZFISH:HS04187-MONOMER.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06562816E → G in PJS. 1 Publication1
Natural variantiVAR_07105750 – 53Missing in PJS. 1 Publication4
Natural variantiVAR_00620267L → P in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 2 PublicationsCorresponds to variant rs137853077dbSNPEnsembl.1
Natural variantiVAR_007920162 – 164DGL → NDM in PJS. 3
Natural variantiVAR_071058176D → 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 PublicationsCorresponds to variant rs730881979dbSNPEnsembl.1
Natural variantiVAR_007921194D → N in PJS. 1 PublicationCorresponds to variant rs121913315dbSNPEnsembl.1
Natural variantiVAR_033142239W → C in PJS; late onset suggests reduced penetrance. 1 PublicationCorresponds to variant rs137853082dbSNPEnsembl.1
Natural variantiVAR_006203247Missing in PJS. 1 Publication1
Natural variantiVAR_007922297R → K in PJS. 1 Publication1
Natural variantiVAR_033143303 – 306IRQH → N in PJS. 4
Natural variantiVAR_071059308W → C in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 1 Publication1
Natural variantiVAR_033144315P → S in PJS; pathogenicity uncertain; no effect heterotrimeric complex assembly with STRADA and CAB39. 2 PublicationsCorresponds to variant rs786202431dbSNPEnsembl.1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_033140163G → 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 PublicationsCorresponds to variant rs137853078dbSNPEnsembl.1

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)DescriptionActionsGraphical viewLength
Mutagenesisi44K → R: No effect on kinase activity. 1 Publication1
Mutagenesisi48K → Q: No effect on basal nucleocytoplasmic localization, but fails to translocate to the cytoplasm when coexpressed with SIRT1. 1 Publication1
Mutagenesisi48K → R: Enhanced phosphorylation at Thr-336 and Ser-428, enhanced cytoplasmic localization and increased kinase activity. 1 Publication1
Mutagenesisi74R → A: Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-204. 1 Publication1
Mutagenesisi78K → I: Loss of kinase activity, leading to greatly reduced autophosphorylation. 2 Publications1
Mutagenesisi78K → M: Loss of kinase activity, leading to reduced autophosphorylation and acting as a dominant-negative mutant. 2 Publications1
Mutagenesisi96K → R: No effect on kinase activity. 1 Publication1
Mutagenesisi97K → R: No effect on kinase activity. 1 Publication1
Mutagenesisi189T → A: Reduced phosphorylation. 1 Publication1
Mutagenesisi194D → A: Loss of kinase activity. 3 Publications1
Mutagenesisi204F → A: No effect. Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-74. 1 Publication1
Mutagenesisi428S → A or E: No effect on kinase activity. 2 Publications1
Mutagenesisi428S → A: Inhibits peroxynitrite-induced nuclear export of STK11, and consequent PTEN phosphorylation and inhibition of PI3K/Akt signaling. 2 Publications1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi6794.
MalaCardsiSTK11.
MIMi175200. phenotype.
273300. phenotype.
OpenTargetsiENSG00000118046.
Orphaneti2869. Peutz-Jeghers syndrome.
PharmGKBiPA36198.

Chemistry databases

ChEMBLiCHEMBL5606.
GuidetoPHARMACOLOGYi2212.

Polymorphism and mutation databases

BioMutaiSTK11.
DMDMi3024670.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866991 – 430Serine/threonine-protein kinase STK11Add BLAST430
PropeptideiPRO_0000422300431 – 433Removed in mature formBy similarity3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei31PhosphoserineCombined sources1
Modified residuei44N6-acetyllysine1 Publication1
Modified residuei48N6-acetyllysine1 Publication1
Modified residuei96N6-acetyllysine1 Publication1
Modified residuei97N6-acetyllysine1 Publication1
Modified residuei189Phosphothreonine; by autocatalysis1 Publication1
Modified residuei296N6-acetyllysine1 Publication1
Modified residuei311N6-acetyllysine1 Publication1
Modified residuei325PhosphoserineBy similarity1
Modified residuei336Phosphothreonine; by autocatalysis1 Publication1
Modified residuei363Phosphothreonine; by ATM and autocatalysis1 Publication1
Modified residuei401PhosphoserineCombined sources1
Modified residuei416N6-acetyllysine1 Publication1
Lipidationi418S-palmitoyl cysteineBy similarity1
Modified residuei423N6-acetyllysine1 Publication1
Modified residuei428Phosphoserine; by autocatalysis, PKA, PKC/PRKCZ and RPS6KA12 Publications1
Modified residuei430Cysteine methyl esterBy similarity1
Lipidationi430S-farnesyl cysteineBy similarity1
Modified residuei431N6-acetyllysine1 Publication1

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.
PhosphoSitePlusiQ15831.

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 interactors.
DIPiDIP-31317N.
IntActiQ15831. 108 interactors.
MINTiMINT-204048.
STRINGi9606.ENSP00000324856.

Chemistry databases

BindingDBiQ15831.

Structurei

Secondary structure

1433
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi54 – 57Combined sources4
Beta strandi62 – 68Combined sources7
Turni69 – 71Combined sources3
Beta strandi74 – 80Combined sources7
Helixi82 – 87Combined sources6
Helixi91 – 102Combined sources12
Beta strandi113 – 118Combined sources6
Beta strandi125 – 130Combined sources6
Beta strandi133 – 135Combined sources3
Helixi136 – 142Combined sources7
Helixi150 – 169Combined sources20
Helixi179 – 181Combined sources3
Beta strandi182 – 184Combined sources3
Beta strandi190 – 192Combined sources3
Helixi217 – 219Combined sources3
Helixi222 – 225Combined sources4
Beta strandi231 – 233Combined sources3
Helixi234 – 250Combined sources17
Helixi260 – 269Combined sources10
Beta strandi276 – 278Combined sources3
Helixi280 – 289Combined sources10
Turni294 – 296Combined sources3
Helixi300 – 305Combined sources6
Helixi307 – 310Combined sources4
Helixi334 – 336Combined sources3
Helixi339 – 341Combined sources3

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ15831.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini49 – 309Protein kinasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni45 – 90Sufficient for interaction with SIRT11 PublicationAdd BLAST46

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06562714E → K in cervical cancer; somatic mutation. 1 Publication1
Natural variantiVAR_06562816E → G in PJS. 1 Publication1
Natural variantiVAR_03313849Y → D in melanoma; sporadic malignant; somatic mutation. 1 PublicationCorresponds to variant rs137853080dbSNPEnsembl.1
Natural variantiVAR_07105750 – 53Missing in PJS. 1 Publication4
Natural variantiVAR_06562966V → M in cervical carcinoma; somatic mutation. 2 Publications1
Natural variantiVAR_00620267L → P in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 2 PublicationsCorresponds to variant rs137853077dbSNPEnsembl.1
Natural variantiVAR_06563086R → G in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_04113987R → K in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_065631123Q → R in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 PublicationCorresponds to variant rs764449808dbSNPEnsembl.1
Natural variantiVAR_033139135G → R in melanoma; sporadic malignant; somatic mutation. 1 PublicationCorresponds to variant rs137853081dbSNPEnsembl.1
Natural variantiVAR_065632157F → S in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065633160L → P in cervical cancer; somatic mutation. 1 Publication1
Natural variantiVAR_007920162 – 164DGL → NDM in PJS. 3
Natural variantiVAR_033140163G → 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 PublicationsCorresponds to variant rs137853078dbSNPEnsembl.1
Natural variantiVAR_065634170Q → P in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065635171G → S in colorectal cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 2 Publications1
Natural variantiVAR_065636174H → R in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_071058176D → 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 PublicationsCorresponds to variant rs730881979dbSNPEnsembl.1
Natural variantiVAR_065637176D → Y in sporadic cancer; somatic mutation; Loss of kinase activity. 2 Publications1
Natural variantiVAR_065638177I → N in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065639181N → E in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_007921194D → N in PJS. 1 PublicationCorresponds to variant rs121913315dbSNPEnsembl.1
Natural variantiVAR_065640194D → V in lung cancer; somatic mutation. 1 PublicationCorresponds to variant rs121913316dbSNPEnsembl.1
Natural variantiVAR_033141194D → Y in melanoma; sporadic malignant; somatic mutation. 1 PublicationCorresponds to variant rs121913315dbSNPEnsembl.1
Natural variantiVAR_065641199E → K in colorectal cancer; somatic mutation; impaired kinase activity. 1 PublicationCorresponds to variant rs121913317dbSNPEnsembl.1
Natural variantiVAR_065642199E → Q in sporadic cancer; somatic mutation; does not affect kinase activity. 1 Publication1
Natural variantiVAR_065643205A → T in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 PublicationCorresponds to variant rs730881981dbSNPEnsembl.1
Natural variantiVAR_065644208D → N in colorectal cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065645215G → D in colorectal cancer; somatic mutation. 1 Publication1
Natural variantiVAR_065646216S → F in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065647223E → V in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065648230T → P in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065649231F → L in cervical cancer; somatic mutation. 1 Publication1
Natural variantiVAR_065650232S → P in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_033142239W → C in PJS; late onset suggests reduced penetrance. 1 PublicationCorresponds to variant rs137853082dbSNPEnsembl.1
Natural variantiVAR_065651245L → R in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_006203247Missing in PJS. 1 Publication1
Natural variantiVAR_065652250T → P in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065653272Y → H in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065654277D → Y in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_065655281P → L in ovarian carcinoma; somatic mutation. 1 PublicationCorresponds to variant rs121913322dbSNPEnsembl.1
Natural variantiVAR_065656285L → Q in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_007922297R → K in PJS. 1 Publication1
Natural variantiVAR_033143303 – 306IRQH → N in PJS. 4
Natural variantiVAR_071059308W → C in PJS; abolishes kinase activity, leading to loss of autophosphorylation. 1 Publication1
Natural variantiVAR_065657314P → H in colorectal cancer; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 Publication1
Natural variantiVAR_033144315P → S in PJS; pathogenicity uncertain; no effect heterotrimeric complex assembly with STRADA and CAB39. 2 PublicationsCorresponds to variant rs786202431dbSNPEnsembl.1
Natural variantiVAR_065658324P → L in gastric carcinoma; no effect heterotrimeric complex assembly with STRADA and CAB39. 1 PublicationCorresponds to variant rs367807476dbSNPEnsembl.1
Natural variantiVAR_065659354F → L in colorectal cancer; somatic mutation. 1 PublicationCorresponds to variant rs59912467dbSNPEnsembl.1
Natural variantiVAR_065660367T → M in colorectal cancer; somatic mutation. 1 PublicationCorresponds to variant rs587782835dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041746371 – 433QVPEE…ACKQQ → GEEASEAGLRAERGLQKSEG SDLSGEEASRPAPQ in isoform 2. CuratedAdd BLAST63

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WTKX-ray2.65C/F43-347[»]
4ZDRX-ray2.90A/B333-340[»]
ProteinModelPortaliQ15831.
SMRiQ15831.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiQ15831.
ChEMBLiCHEMBL5606.
GuidetoPHARMACOLOGYi2212.

PTM databases

iPTMnetiQ15831.
PhosphoSitePlusiQ15831.

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.
DisGeNETi6794.
GeneCardsiSTK11.
GeneReviewsiSTK11.
HGNCiHGNC:11389. STK11.
HPAiCAB016231.
CAB022105.
HPA017254.
MalaCardsiSTK11.
MIMi175200. phenotype.
273300. phenotype.
602216. gene.
neXtProtiNX_Q15831.
OpenTargetsiENSG00000118046.
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

BioCyciZFISH:HS04187-MONOMER.
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: November 30, 2016
This is version 187 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.