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STK4 (serine/threonine kinase 4)

Identity

Other namesMST1
KRS2
HGNC (Hugo) STK4
LocusID (NCBI) 6789
Location 20q13.12
Location_base_pair Starts at 43595120 and ends at 43708593 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order centromere - YWHAB - TOMM34 - STK4 - MATN4 - RBPSUHL - telomere
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).

External links

Nomenclature
HGNC (Hugo)STK4   11408
Cards
AtlasSTK4ID42440ch20q11
Entrez_Gene (NCBI)STK4  6789  serine/threonine kinase 4
GeneCards (Weizmann)STK4
Ensembl (Hinxton)ENSG00000101109 [Gene_View]  chr20:43595120-43708593 [Contig_View]  STK4 [Vega]
ICGC DataPortalENSG00000101109
cBioPortalSTK4
AceView (NCBI)STK4
Genatlas (Paris)STK4
WikiGenes6789
SOURCE (Princeton)NM_006282
Genomic and cartography
GoldenPath (UCSC)STK4  -  20q13.12   chr20:43595120-43708593 +  20q11.2-q13.2   [Description]    (hg19-Feb_2009)
EnsemblSTK4 - 20q11.2-q13.2 [CytoView]
Mapping of homologs : NCBISTK4 [Mapview]
OMIM604965   614868   
Gene and transcription
Genbank (Entrez)AB209315 AK027088 AK225326 AK309169 AK315238
RefSeq transcript (Entrez)NM_006282
RefSeq genomic (Entrez)AC_000152 NC_000020 NC_018931 NG_032172 NT_011362 NW_001838666 NW_004929418
Consensus coding sequences : CCDS (NCBI)STK4
Cluster EST : UnigeneHs.472838 [ NCBI ]
CGAP (NCI)Hs.472838
Alternative Splicing : Fast-db (Paris)GSHG0018776
Alternative Splicing GalleryENSG00000101109
Gene ExpressionSTK4 [ NCBI-GEO ]     STK4 [ SEEK ]   STK4 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13043 (Uniprot)
NextProtQ13043  [Medical]
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 ]   
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    SARAH (PS50951)   
Domains : Interpro (EBI)Kinase-like_dom [organisation]   Mst1_SARAH_domain [organisation]   Prot_kinase_dom [organisation]   Protein_kinase_ATP_BS [organisation]   SARAH_dom [organisation]   Ser/Thr_dual-sp_kinase_dom [organisation]  
Related proteins : CluSTrQ13043
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)Q13043
PDB (SRS)2JO8    3COM    4NR2   
PDB (PDBSum)2JO8    3COM    4NR2   
PDB (IMB)2JO8    3COM    4NR2   
PDB (RSDB)2JO8    3COM    4NR2   
Human Protein AtlasENSG00000101109 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ13043
HPRD05395
IPIIPI00011488   IPI00645585   IPI01015033   IPI00385784   
Protein Interaction databases
DIP (DOE-UCLA)Q13043
IntAct (EBI)Q13043
FunCoupENSG00000101109
BioGRIDSTK4
InParanoidQ13043
Interologous Interaction database Q13043
IntegromeDBSTK4
STRING (EMBL)STK4
Ontologies - Pathways
Ontology : AmiGOmagnesium ion binding  cell morphogenesis  patterning of blood vessels  neural tube formation  endocardium development  protein serine/threonine kinase activity  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 phosphorylation  keratinocyte differentiation  hippo signaling  hippo signaling  intracellular signal transduction  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  protein serine/threonine kinase activator activity  negative regulation of organ growth  protein autophosphorylation  protein dimerization activity  primitive hemopoiesis  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  endocardium development  protein serine/threonine kinase activity  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 phosphorylation  keratinocyte differentiation  hippo signaling  hippo signaling  intracellular signal transduction  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  protein serine/threonine kinase activator activity  negative regulation of organ growth  protein autophosphorylation  protein dimerization activity  primitive hemopoiesis  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   
Protein Interaction DatabaseSTK4
Wikipedia pathwaysSTK4
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)STK4
snp3D : Map Gene to Disease6789
SNP (GeneSNP Utah)STK4
SNP : HGBaseSTK4
Genetic variants : HAPMAPSTK4
Exome VariantSTK4
1000_GenomesSTK4 
ICGC programENSG00000101109 
Somatic Mutations in Cancer : COSMICSTK4 
CONAN: Copy Number AnalysisSTK4 
Mutations and Diseases : HGMDSTK4
Genomic VariantsSTK4  STK4 [DGVbeta]
dbVarSTK4
ClinVarSTK4
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM604965    614868   
MedgenSTK4
GENETestsSTK4
Disease Genetic AssociationSTK4
Huge Navigator STK4 [HugePedia]  STK4 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSTK4
Homology/Alignments : Family Browser (UCSC)STK4
Phylogenetic Trees/Animal Genes : TreeFamSTK4
Chemical/Protein Interactions : CTD6789
Chemical/Pharm GKB GenePA36215
Clinical trialSTK4
Cancer Resource (Charite)ENSG00000101109
Other databases
Probes
Litterature
PubMed80 Pubmed reference(s) in Entrez
CoreMineSTK4
iHOPSTK4
OncoSearchSTK4

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
 
REVIEW articlesautomatic search in PubMed
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Contributor(s)

Written11-2005Jonathan Chernoff
Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/STK4ID42440ch20q11.html

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indexed on : Sat Jul 26 15:16:00 CEST 2014

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