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Reviewed, UniProtKB/Swiss-Prot Q15831 (STK11_HUMAN)

Last modified November 25, 2008. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Serine/threonine-protein kinase 11
    EC=2.7.11.1
Alternative name(s):
    Serine/threonine-protein kinase LKB1
    Renal carcinoma antigen NY-REN-19
Gene names
Name: STK11
Synonyms: LKB1, PJS
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length433 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Essential role in G1 cell cycle arrest. Phosphorylates and activates members of the AMPK-related subfamily of protein kinases. Tumor suppressor.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium or Manganese.

Enzyme regulation

Activated by binding of a complex consisting of CAB39 and STRAD or CAB39 and ALS2CR2.

Subunit structure

Found in a ternary complex composed of SMAD4, STK11 and STK11IP. Interacts with SMAD4 and STK11IP.

Subcellular location

Nucleus. Cytoplasm. Note= Relocates to the cytoplasm when bound to CAB39 and STRAD or CAB39 and ALS2CR2.

Tissue specificity

Ubiquitously expressed. Strongest expression in testis and fetal liver.

Post-translational modification

Phosphorylated by a cAMP-dependent protein kinase By similarity.

Involvement in disease

Defects in STK11 are a cause of Peutz-Jeghers syndrome (PJS) [MIM:175200]. PJS is a rare hereditary disease in which there is predisposition to benign and malignant tumors of many organ systems. PJS is 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.

Defects in STK11 have been associated with testicular tumors [MIM:273300]. It includes germ cell tumor (GCT) or testicular germ cell tumor (TGCT).

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 433433Serine/threonine-protein kinase 11
PRO_0000086699

Regions

Domain49 – 309261Protein kinase
Nucleotide binding55 – 639ATP By similarity

Sites

Active site1761Proton acceptor
Binding site781ATP By similarity

Amino acid modifications

Modified residue311Phosphoserine By similarity
Modified residue3361Phosphothreonine; by autocatalysis
Modified residue3631Phosphothreonine; by autocatalysis
Modified residue4281Phosphoserine; by PKA Potential

Natural variations

Natural variant491Y → D in melanoma; sporadic malignant; somatic mutation.
VAR_033138
Natural variant671L → P in PJS.
VAR_006202
Natural variant871R → K in a metastatic melanoma sample; somatic mutation.
VAR_041139
Natural variant1351G → R in melanoma; sporadic malignant; somatic mutation.
VAR_033139
Natural variant162 – 1643DGL → NDM in PJS.
VAR_007920
Natural variant1631G → D in testicular tumors; a tumor with seminoma and teratoma components; associated with severely impaired but detectable kinase activity; somatic mutation.
VAR_033140
Natural variant1941D → N in PJS.
VAR_007921
Natural variant1941D → Y in melanoma; sporadic malignant; somatic mutation.
VAR_033141
Natural variant2391W → C in PJS; late onset suggests reduced penetrance.
VAR_033142
Natural variant2471Missing in PJS.
VAR_006203
Natural variant2971R → K in PJS.
VAR_007922
Natural variant303 – 3064IRQH → N in PJS.
VAR_033143
Natural variant3151P → S in PJS; pathogenicity uncertain.
VAR_033144

Experimental info

Mutagenesis1761D → Y: Loss of kinase activity
Mutagenesis1941D → A: Loss of kinase activity

Sequences

Sequence LengthMass (Da)Tools
Q15831-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6DF4C37AB7A89569

FASTA43348,636
        10         20         30         40         50         60 
MEVVDPQQLG MFTEGELMSV GMDTFIHRID STEVIYQPRR KRAKLIGKYL MGDLLGEGSY 

        70         80         90        100        110        120 
GKVKEVLDSE TLCRRAVKIL KKKKLRRIPN GEANVKKEIQ LLRRLRHKNV IQLVDVLYNE 

       130        140        150        160        170        180 
EKQKMYMVME YCVCGMQEML DSVPEKRFPV CQAHGYFCQL IDGLEYLHSQ GIVHKDIKPG 

       190        200        210        220        230        240 
NLLLTTGGTL KISDLGVAEA LHPFAADDTC RTSQGSPAFQ PPEIANGLDT FSGFKVDIWS 

       250        260        270        280        290        300 
AGVTLYNITT GLYPFEGDNI YKLFENIGKG SYAIPGDCGP PLSDLLKGML EYEPAKRFSI 

       310        320        330        340        350        360 
RQIRQHSWFR KKHPPAEAPV PIPPSPDTKD RWRSMTVVPY LEDLHGADED EDLFDIEDDI 

       370        380        390        400        410        420 
IYTQDFTVPG QVPEEEASHN GQRRGLPKAV CMNGTEAAQL STKSRAEGRA PNPARKACSA 

       430 
SSKIRRLSAC KQQ 

« Hide

References

« Hide 'large scale' references
[1]Nezu J.
Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase."
Jenne D.E., Reimann H., Nezu J., Friedl W., Loff S., Jeschke R., Mueller O., Back W., Zimmer M.
Nat. Genet. 18:38-43(1998) [PubMed: 9425897] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer."
Bignell G.R., Barfoot R., Seal S., Collins N., Warren W., Stratton M.R.
Cancer Res. 58:1384-1386(1998) [PubMed: 9537235] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung and Uterus.
[5]"Antigens recognized by autologous antibody in patients with renal-cell carcinoma."
Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J.
Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract]
Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN.
Tissue: Renal cell carcinoma.
[6]"LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1."
Smith D.P., Rayter S.I., Niederlander C., Spicer J., Jones C.M., Ashworth A.
Hum. Mol. Genet. 10:2869-2877(2001) [PubMed: 11741830] [Abstract]
Cited for: IDENTIFICATION IN A TERNARY COMPLEX COMPOSED OF SMAD4 AND STK11IP, INTERACTS WITH SMAD4 AND STK11IP.
[7]"Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD."
Baas A.F., Boudeau J., Sapkota G.P., Smit L., Medema R., Morrice N.A., Alessi D.R., Clevers H.C.
EMBO J. 22:3062-3072(2003) [PubMed: 12805220] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STRAD, AUTOPHOSPHORYLATION AT THR-336 AND THR-363, MUTAGENESIS OF ASP-176.
[8]"MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm."
Boudeau J., Baas A.F., Deak M., Morrice N.A., Kieloch A., Schutkowski M., Prescott A.R., Clevers H.C., Alessi D.R.
EMBO J. 22:5102-5114(2003) [PubMed: 14517248] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-194, INTERACTION WITH STRAD AND CAB39.
[9]"Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors."
Avizienyte E., Roth S., Loukola A., Hemminki A., Lothe R.A., Stenwig A.E., Fossaa S.D., Salovaara R., Aaltonen L.A.
Cancer Res. 58:2087-2090(1998) [PubMed: 9605748] [Abstract]
Cited for: VARIANT TESTICULAR TUMORS ASP-163.
[10]"Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome."
Nakagawa H., Koyama K., Miyoshi Y., Ando H., Baba S., Watatani M., Yasutomi M., Matsuura N., Monden M., Nakamura Y.
Hum. Genet. 103:168-172(1998) [PubMed: 9760200] [Abstract]
Cited for: VARIANT PJS ASN-247 DEL.
[11]"A serine/threonine kinase gene defective in Peutz-Jeghers syndrome."
Hemminki A., Markie D., Tomlinson I., Avizienyte E., Roth S., Loukola A., Bignell G., Warren W., Aminoff M., Hoeglund P., Jaervinen H., Kristo P., Pelin K., Ridanpaeae M., Salovaara R., Toro T., Bodmer W., Olschwang S. expand/collapse author list , Olsen A.S., Stratton M.R., de la Chapelle A., Aaltonen L.A.
Nature 391:184-187(1998) [PubMed: 9428765] [Abstract]
Cited for: VARIANTS PJS PRO-67 AND 303-ILE--GLN-306 DELINS ASN.
[12]"Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families."
Westerman A.M., Entius M.M., Boor P.P.C., Koole R., de Baar E., Offerhaus G.J.A., Lubinski J., Lindhout D., Halley D.J.J., de Rooij F.W.M., Wilson J.H.P.
Hum. Mutat. 13:476-481(1999) [PubMed: 10408777] [Abstract]
Cited for: VARIANTS PJS 162-ASN--MET-164; ASN-194 AND LYS-297.
[13]"Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer."
Ylikorkala A., Avizienyte E., Tomlinson I.P., Tiainen M., Roth S., Loukola A., Hemminki A., Johansson M., Sistonen P., Markie D., Neale K., Phillips R., Zauber P., Twama T., Sampson J., Jaervinen H., Maekelae T.P., Aaltonen L.A.
Hum. Mol. Genet. 8:45-51(1999) [PubMed: 9887330] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT TESTICULAR TUMORS ASP-163.
[14]"Somatic mutations in the Peutz-Jeghers (LKB1/STKII) gene in sporadic malignant melanomas."
Rowan A., Bataille V., MacKie R., Healy E., Bicknell D., Bodmer W., Tomlinson I.
J. Invest. Dermatol. 112:509-511(1999) [PubMed: 10201537] [Abstract]
Cited for: VARIANTS MELANOMA ASP-49 AND ARG-135.
[15]"Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma."
Guldberg P., thor Straten P., Ahrenkiel V., Seremet T., Kirkin A.F., Zeuthen J.
Oncogene 18:1777-1780(1999) [PubMed: 10208439] [Abstract]
Cited for: VARIANT MELANOMA TYR-194.
[16]"Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients."
Scott R.J., Crooks R., Meldrum C.J., Thomas L., Smith C.J.A., Mowat D., McPhillips M., Spigelman A.D.
Clin. Genet. 62:282-287(2002) [PubMed: 12372054] [Abstract]
Cited for: VARIANTS PJS CYS-239 AND SER-315.
[17]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-87.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF035625 mRNA. Translation: AAC39527.1.
U63333 mRNA. Translation: AAB05809.1.
AF032984 Genomic DNA. Translation: AAB97833.1.
AF055327 expand/collapse EMBL AC list , AF055320, AF055321, AF055322, AF055323, AF055324, AF055325, AF055326 Genomic DNA. Translation: AAC15742.1.
BC007981 mRNA. Translation: AAH07981.1.
BC019334 mRNA. Translation: AAH19334.1.
RefSeqNP_000446.1.
UniGeneHs.515005

3D structure databases

HSSPHSSP built from PDB template 1H0V based on UniProtKB P24941.
ModBaseSearch...

Protein-protein interaction databases

IntActQ15831.

PTM databases

PhosphoSiteQ15831.

Genome annotation databases

EnsemblENSG00000118046. Homo sapiens. [Contig view]
GeneID6794.
KEGGhsa:6794.

Organism-specific databases

H-InvDBHIX0014573.
HGNCHGNC:11389. STK11.
HPACAB016231.
HPA017254.
MIM175200. phenotype.
273300. phenotype.
602216. gene.
Orphanet2869. Peutz-Jeghers syndrome.
842. Testicular seminoma.
PharmGKBPA36198.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ15831.
HOVERGENQ15831.

Enzyme and pathway databases

ReactomeREACT_1505. Integration of energy metabolism.

Gene expression databases

ArrayExpressQ15831.
CleanExHS_STK11.
GermOnlineENSG00000118046. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
IPR015735. STK11.
[Graphical view]
PANTHERPTHR22982:SF41. STK11. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio26541.
SOURCESearch...

Entry information

Entry nameSTK11_HUMAN
AccessionPrimary (citable) accession number: Q15831
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 25, 2008
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents