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STK4 (serine/threonine kinase 4)

Written2005-11Jonathan Chernoff
Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA

(Note : for Links provided by Atlas : click)

Identity

Other namesMST1
KRS2
HGNC (Hugo) STK4
LocusID (NCBI) 6789
Atlas_Id 42440
Location 20q13.12  [Link to chromosome band 20q13]
Location_base_pair Starts at 43595120 and ends at 43708593 bp from pter ( according to hg19-Feb_2009)  [Mapping STK4.png]
Local_order centromere - YWHAB - TOMM34 - STK4 - MATN4 - RBPSUHL - telomere
Fusion genes
(updated 2016)
AD_1 () / STK4 (20q13.12)CARD14 (17q25.3) / STK4 (20q13.12)HECTD1 (14q12) / STK4 (20q13.12)
RPS25 (11q23.3) / STK4 (20q13.12)STK4 (20q13.12) / TSHZ2 (20q13.2)
Note STK4 encodes a serine/threonine specific protein kinase that is a member of the GC kinase branch of the STE20 family. STK4 plays a role in apoptosis and may have tumor suppressor function.

DNA/RNA

 
  The alignment of STK4 mRNA to its genomic sequence
Description The STK4 gene contains 11 exons. The sizes of the exons 1-11 are 68, 81, 129, 115, 165, 168, 138, 129, 192, 154, and 585 bps. Exon 1 contains the 5' untranslated region and the translation initation ATG, and a few additional codons. Exon 11 contains the stop codon and the 3' untranslated region. Other features of the STK4 gene, such as promoters or enhancer elements, have not been described.
Transcription A 7 kb transcript is detected in many tissues with highest steady state levels in the thymus amd bone marrow. The predominant human STK4 mRNA encodes an open reading frame of 1883 bases, resulting in a predicted proteins of 487 amino acids.

Protein

 
  Structure of STK4 protein. The catalytic (protein kinase) domain occupies the N-terminal half of STK4. The regulatory domain inhibits kinase activity and also contains a dimerization motif. A caspase-sensitive cleavage site is located between these two domains.
Description STK4 is a member of the GC kinase group of the STE20 family of serine/threonine protein kinases. STK4 homodimerizes through a C-terminal motif, and removal of the C terminus results in marked activation of the kinase. STK4 is cleaved by caspases during apotosis, releasing an active 34 kD kinase fragment. STK4 associates with the WW-domain protein Salvadore, which may link STK4 to the LATS tumor suppressor pathway.
Expression Widely expressed in both embryonic and adult tissues.
Localisation Nucleus and cytoplasm. In the nucleus, STK4 phosphorylates Histone 2B at Ser 14, a modification associated with chromosome condensation in apoptotic cells.
Function STK4 plays a role in promoting apotosis, in particular, in chromosome condensation during programmed cell death. STK4 is cleaved by caspase 3 during apoptosis, releasing the highly active N-terminal kinase domain. This active protein promotes apoptosis by activating JNK and also by further caspase activation. STK4, and/or the highly related protein , may act as tumor suppressors, acting downstream of Raf.
Homology STK3 (a.k.a. MST2, KRS1).

Bibliography

Cloning and characterization of a human protein kinase with homology to Ste20.
Creasy CL, Chernoff J
The Journal of biological chemistry. 1995 ; 270 (37) : 21695-21700.
PMID 7665586
 
Newly identified stress-responsive protein kinases, Krs-1 and Krs-2.
Taylor LK, Wang HC, Erikson RL
Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (19) : 10099-10104.
PMID 8816758
 
Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.
Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA, Krebs EG
The EMBO journal. 1998 ; 17 (8) : 2224-2234.
PMID 9545236
 
Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST).
Lee KK, Yonehara S
The Journal of biological chemistry. 2002 ; 277 (14) : 12351-12358.
PMID 11805089
 
Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase.
Cheung WL, Ajiro K, Samejima K, Kloc M, Cheung P, Mizzen CA, Beeser A, Etkin LD, Chernoff J, Earnshaw WC, Allis CD
Cell. 2003 ; 113 (4) : 507-517.
PMID 12757711
 
Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase.
Cheung WL, Ajiro K, Samejima K, Kloc M, Cheung P, Mizzen CA, Beeser A, Etkin LD, Chernoff J, Earnshaw WC, Allis CD
Cell. 2003 ; 113 (4) : 507-517.
PMID 12757711
 
Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.
Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J
The Biochemical journal. 2004 ; 381 (Pt 2) : 453-462.
PMID 15109305
 
Mammalian sterile 20-like kinases in tumor suppression: an emerging pathway.
O'Neill EE, Matallanas D, Kolch W
Cancer research. 2005 ; 65 (13) : 5485-5487.
PMID 15994916
 

Citation

This paper should be referenced as such :
Chernoff, J
STK4 (serine/threonine kinase 4)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):103-104.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/STK4ID42440ch20q11.html


External links

Nomenclature
HGNC (Hugo)STK4   11408
Cards
AtlasSTK4ID42440ch20q11
Entrez_Gene (NCBI)STK4  6789  serine/threonine kinase 4
AliasesKRS2; MST1; TIIAC; YSK3
GeneCards (Weizmann)STK4
Ensembl hg19 (Hinxton)ENSG00000101109 [Gene_View]  chr20:43595120-43708593 [Contig_View]  STK4 [Vega]
Ensembl hg38 (Hinxton)ENSG00000101109 [Gene_View]  chr20:43595120-43708593 [Contig_View]  STK4 [Vega]
ICGC DataPortalENSG00000101109
TCGA cBioPortalSTK4
AceView (NCBI)STK4
Genatlas (Paris)STK4
WikiGenes6789
SOURCE (Princeton)STK4
Genomic and cartography
GoldenPath hg19 (UCSC)STK4  -     chr20:43595120-43708593 +  20q11.2-q13.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)STK4  -     20q11.2-q13.2   [Description]    (hg38-Dec_2013)
EnsemblSTK4 - 20q11.2-q13.2 [CytoView hg19]  STK4 - 20q11.2-q13.2 [CytoView hg38]
Mapping of homologs : NCBISTK4 [Mapview hg19]  STK4 [Mapview hg38]
OMIM604965   614868   
Gene and transcription
Genbank (Entrez)AB209315 AK027088 AK225326 AK309169 AK315238
RefSeq transcript (Entrez)NM_006282
RefSeq genomic (Entrez)NC_000020 NC_018931 NG_032172 NT_011362 NW_004929418
Consensus coding sequences : CCDS (NCBI)STK4
Cluster EST : UnigeneHs.472838 [ NCBI ]
CGAP (NCI)Hs.472838
Alternative Splicing GalleryENSG00000101109
Gene ExpressionSTK4 [ NCBI-GEO ]   STK4 [ EBI - ARRAY_EXPRESS ]   STK4 [ SEEK ]   STK4 [ MEM ]
Gene Expression Viewer (FireBrowse)STK4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6789
GTEX Portal (Tissue expression)STK4
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13043 (Uniprot)
NextProtQ13043  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13043
Splice isoforms : SwissVarQ13043 (Swissvar)
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusQ13043
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    SARAH (PS50951)   
Domains : Interpro (EBI)Kinase-like_dom    Mst1_SARAH_domain    Prot_kinase_dom    Protein_kinase_ATP_BS    SARAH_dom    Ser/Thr_dual-sp_kinase   
Domain families : Pfam (Sanger)Mst1_SARAH (PF11629)    Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam11629    pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
DMDM Disease mutations6789
Blocks (Seattle)STK4
PDB (SRS)2JO8    3COM    4NR2    4OH8   
PDB (PDBSum)2JO8    3COM    4NR2    4OH8   
PDB (IMB)2JO8    3COM    4NR2    4OH8   
PDB (RSDB)2JO8    3COM    4NR2    4OH8   
Structural Biology KnowledgeBase2JO8    3COM    4NR2    4OH8   
SCOP (Structural Classification of Proteins)2JO8    3COM    4NR2    4OH8   
CATH (Classification of proteins structures)2JO8    3COM    4NR2    4OH8   
SuperfamilyQ13043
Human Protein AtlasENSG00000101109
Peptide AtlasQ13043
HPRD05395
IPIIPI00011488   IPI00645585   IPI01015033   IPI00385784   
Protein Interaction databases
DIP (DOE-UCLA)Q13043
IntAct (EBI)Q13043
FunCoupENSG00000101109
BioGRIDSTK4
STRING (EMBL)STK4
ZODIACSTK4
Ontologies - Pathways
QuickGOQ13043
Ontology : AmiGOmagnesium ion binding  cell morphogenesis  patterning of blood vessels  neural tube formation  positive regulation of protein phosphorylation  endocardium development  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  cytoplasm  cytosol  protein phosphorylation  apoptotic process  signal transduction  central nervous system development  transcription factor binding  negative regulation of cell proliferation  peptidyl-serine phosphorylation  signal transduction by protein phosphorylation  keratinocyte differentiation  positive regulation of protein binding  positive regulation of peptidyl-serine phosphorylation  hippo signaling  hippo signaling  intracellular signal transduction  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  protein complex  protein serine/threonine kinase activator activity  positive regulation of fat cell differentiation  negative regulation of organ growth  protein autophosphorylation  protein dimerization activity  protein stabilization  primitive hemopoiesis  cell differentiation involved in embryonic placenta development  regulation of cell differentiation involved in embryonic placenta development  positive regulation of protein serine/threonine kinase activity  negative regulation of canonical Wnt signaling pathway  hepatocyte apoptotic process  positive regulation of extrinsic apoptotic signaling pathway via death domain receptors  
Ontology : EGO-EBImagnesium ion binding  cell morphogenesis  patterning of blood vessels  neural tube formation  positive regulation of protein phosphorylation  endocardium development  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  cytoplasm  cytosol  protein phosphorylation  apoptotic process  signal transduction  central nervous system development  transcription factor binding  negative regulation of cell proliferation  peptidyl-serine phosphorylation  signal transduction by protein phosphorylation  keratinocyte differentiation  positive regulation of protein binding  positive regulation of peptidyl-serine phosphorylation  hippo signaling  hippo signaling  intracellular signal transduction  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  protein complex  protein serine/threonine kinase activator activity  positive regulation of fat cell differentiation  negative regulation of organ growth  protein autophosphorylation  protein dimerization activity  protein stabilization  primitive hemopoiesis  cell differentiation involved in embryonic placenta development  regulation of cell differentiation involved in embryonic placenta development  positive regulation of protein serine/threonine kinase activity  negative regulation of canonical Wnt signaling pathway  hepatocyte apoptotic process  positive regulation of extrinsic apoptotic signaling pathway via death domain receptors  
Pathways : KEGGMAPK signaling pathway    Ras signaling pathway    FoxO signaling pathway    Pathways in cancer    Non-small cell lung cancer   
REACTOMEQ13043 [protein]
REACTOME PathwaysR-HSA-2028269 Signaling by Hippo [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkSTK4
Wikipedia pathwaysSTK4
Orthology - Evolution
OrthoDB6789
GeneTree (enSembl)ENSG00000101109
Phylogenetic Trees/Animal Genes : TreeFamSTK4
Homologs : HomoloGeneSTK4
Homology/Alignments : Family Browser (UCSC)STK4
Gene fusions - Rearrangements
Fusion : MitelmanSTK4/TSHZ2 [20q13.12/20q13.2]  
Fusion: TCGASTK4 20q13.12 TSHZ2 20q13.2 BRCA
Fusion Cancer (Beijing)AD_1 [STK4]  -  20q13.12 [FUSC000468]
Polymorphisms : SNP, variants
NCBI Variation ViewerSTK4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)STK4
dbVarSTK4
ClinVarSTK4
1000_GenomesSTK4 
Exome Variant ServerSTK4
ExAC (Exome Aggregation Consortium)STK4 (select the gene name)
Genetic variants : HAPMAP6789
Genomic Variants (DGV)STK4 [DGVbeta]
Mutations
ICGC Data PortalSTK4 
TCGA Data PortalSTK4 
Broad Tumor PortalSTK4
OASIS PortalSTK4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSTK4 
intOGen PortalSTK4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
BioMutasearch STK4
DgiDB (Drug Gene Interaction Database)STK4
DoCM (Curated mutations)STK4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)STK4 (select a term)
intoGenSTK4
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)20:43595120-43708593  ENSG00000101109
CONAN: Copy Number AnalysisSTK4 
Mutations and Diseases : HGMDSTK4
OMIM604965    614868   
MedgenSTK4
Genetic Testing Registry STK4
NextProtQ13043 [Medical]
TSGene6789
GENETestsSTK4
Huge Navigator STK4 [HugePedia]
snp3D : Map Gene to Disease6789
BioCentury BCIQSTK4
ClinGenSTK4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6789
Chemical/Pharm GKB GenePA36215
Clinical trialSTK4
Miscellaneous
canSAR (ICR)STK4 (select the gene name)
Probes
Litterature
PubMed99 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSTK4
EVEXSTK4
GoPubMedSTK4
iHOPSTK4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Sat Jun 11 13:05:05 CEST 2016

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