Serine/threonine-protein kinase 11 - Homo sapiens (Human)

Contribute

Send feedback

Reviewed, UniProtKB/Swiss-Prot Q15831 (STK11_HUMAN)

Last modified November 25, 2008. Version 99. 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

Hide | Top

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length	433 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

Hide | Top

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.

Hide | Top

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell cycle arrest Ref.7 Inferred from direct assay. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Ref.7 Ref.11 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.7 Inferred from direct assay. Source: UniProtKB nucleus Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.7 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.7 Inferred from direct assay. Source: UniProtKB manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.7 Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Ref.7 Ref.11 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Hide | Top

Binary interactions

With	Entry	#Exp.	IntAct
STRAD	Q7RTN6	3	EBI-306838,EBI-1109114
TNIP2	Q8NFZ5	4	EBI-306838,EBI-359372
WDR6	Q9NNW5	1	EBI-306838,EBI-1568315

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 433

433

Serine/threonine-protein kinase 11

PRO_0000086699

Regions

Domain

49 – 309

261

Protein kinase

Nucleotide binding

55 – 63

ATP By similarity

Sites

Active site

176

Proton acceptor

Binding site

ATP By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

336

Phosphothreonine; by autocatalysis

Modified residue

363

Phosphothreonine; by autocatalysis

Modified residue

428

Phosphoserine; by PKA Potential

Natural variations

Natural variant

Y → D in melanoma; sporadic malignant; somatic mutation.

VAR_033138

Natural variant

L → P in PJS.

VAR_006202

Natural variant

R → K in a metastatic melanoma sample; somatic mutation.

VAR_041139

Natural variant

135

G → R in melanoma; sporadic malignant; somatic mutation.

VAR_033139

Natural variant

162 – 164

DGL → NDM in PJS.

VAR_007920

Natural variant

163

G → D in testicular tumors; a tumor with seminoma and teratoma components; associated with severely impaired but detectable kinase activity; somatic mutation.

VAR_033140

Natural variant

194

D → N in PJS.

VAR_007921

Natural variant

194

D → Y in melanoma; sporadic malignant; somatic mutation.

VAR_033141

Natural variant

239

W → C in PJS; late onset suggests reduced penetrance.

VAR_033142

Natural variant

247

Missing in PJS.

VAR_006203

Natural variant

297

R → K in PJS.

VAR_007922

Natural variant

303 – 306

IRQH → N in PJS.

VAR_033143

Natural variant

315

P → S in PJS; pathogenicity uncertain.

VAR_033144

Experimental info

Mutagenesis

176

D → Y: Loss of kinase activity

Mutagenesis

194

D → A: Loss of kinase activity

Hide | Top

Sequences

Sequence

Length

Mass (Da)

Tools

Q15831-1 [UniParc].

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

FASTA

433

48,636

        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

Hide | Top

References

	« Hide 'large scale' referencesShow '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. 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. Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-87.
+	Additional computationally mapped references.

Hide | Top

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Wikipedia

PJS entry

Hide | Top

Cross-references

Sequence databases
	AF035625 mRNA. Translation: AAC39527.1. U63333 mRNA. Translation: AAB05809.1. AF032984 Genomic DNA. Translation: AAB97833.1. AF055327 AF055326 Genomic DNA. Translation: AAC15742.1. BC007981 mRNA. Translation: AAH07981.1. BC019334 mRNA. Translation: AAH19334.1.
RefSeq	NP_000446.1.
UniGene	Hs.515005
3D structure databases
HSSP	HSSP built from PDB template 1H0V based on UniProtKB P24941.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15831.
PTM databases
PhosphoSite	Q15831.
Genome annotation databases
Ensembl	ENSG00000118046. Homo sapiens. [Contig view]
GeneID	6794.
KEGG	hsa:6794.
Organism-specific databases
H-InvDB	HIX0014573.
HGNC	HGNC:11389. STK11.
HPA	CAB016231. HPA017254.
MIM	175200. phenotype. 273300. phenotype. 602216. gene.
Orphanet	2869. Peutz-Jeghers syndrome. 842. Testicular seminoma.
PharmGKB	PA36198.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q15831.
HOVERGEN	Q15831.
Enzyme and pathway databases
Reactome	REACT_1505. Integration of energy metabolism.
Gene expression databases
ArrayExpress	Q15831.
CleanEx	HS_STK11.
GermOnline	ENSG00000118046. Homo sapiens.
Family and domain databases
InterPro	IPR000719. 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]
PANTHER	PTHR22982:SF41. STK11. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	26541.
SOURCE	Search...

Hide | Top

Entry information

Entry name

STK11_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Hide | Top

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

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents