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STK4 (serine/threonine kinase 4)

Identity

Other namesMST1
KRS2
Hugo STK4
Location 20q11.2-q13.2
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
HugoSTK4
GDBSTK4
Entrez_GeneSTK4  6789  serine/threonine kinase 4
Cards
AtlasSTK4ID42440ch20q11
GeneCardsSTK4
EnsemblSTK4 [Search_View]   ENSG00000101109 [Gene_View]
GenatlasSTK4
GeneLynxSTK4
eGenomeSTK4
euGene6789
Genomic and cartography
GoldenPathSTK4  -     chr20:43028534-43142005 +  20q11.2-q13.2   [Description]    (hg18-Mar_2006)
EnsemblSTK4 - 20q11.2-q13.2 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneSTK4
Gene and transcription
GenbankAB209315 [ ENTREZ ]
GenbankAK027088 [ ENTREZ ]
GenbankAL597960 [ ENTREZ ]
GenbankBC005231 [ ENTREZ ]
GenbankBC015332 [ ENTREZ ]
RefSeqNM_006282 [ SRS ]    NM_006282 [ ENTREZ ]
RefSeqAC_000063 [ SRS ]    AC_000063 [ ENTREZ ]
RefSeqNC_000020 [ SRS ]    NC_000020 [ ENTREZ ]
RefSeqNT_011362 [ SRS ]    NT_011362 [ ENTREZ ]
RefSeqNW_927339 [ SRS ]    NW_927339 [ ENTREZ ]
AceViewSTK4 AceView - NCBI
UnigeneHs.472838 [ SRS ]    Hs.472838 [ NCBI ]     HS472838 [ spliceNest ]
Fast-db11933 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ13043 [ SRS]    Q13043 [ EXPASY ]     Q13043 [ INTERPRO ]
PrositePS00107 PROTEIN_KINASE_ATP [ SRS ]    PS00107 PROTEIN_KINASE_ATP [ Expasy ]
PrositePS50011 PROTEIN_KINASE_DOM [ SRS ]    PS50011 PROTEIN_KINASE_DOM [ Expasy ]
PrositePS00108 PROTEIN_KINASE_ST [ SRS ]    PS00108 PROTEIN_KINASE_ST [ Expasy ]
PrositePS50951 SARAH [ SRS ]    PS50951 SARAH [ Expasy ]
InterproIPR000719 Prot_kinase_core [ SRS ]    IPR000719 Prot_kinase_core [ EBI ]
InterproIPR011524 SARAH [ SRS ]    IPR011524 SARAH [ EBI ]
InterproIPR008271 Ser_thr_pkin_AS [ SRS ]    IPR008271 Ser_thr_pkin_AS [ EBI ]
InterproIPR002290 Ser_thr_pkinase [ SRS ]    IPR002290 Ser_thr_pkinase [ EBI ]
CluSTrQ13043
PfamPF00069 Pkinase [ SRS ]    PF00069 Pkinase [ Sanger ]    pfam00069 [ NCBI-CDD ]
SmartSM00220 S_TKc [EMBL]
ProdomPD000001 Prot_kinase[INRA-Toulouse]
ProdomQ13043 STK4_HUMAN [ Domain structure ]   Q13043 STK4_HUMAN  [ sequences sharing at least 1 domain ]
BlocksQ13043
PDB2JO8 [ SRS ]    2JO8 [ PdbSum ],   2JO8 [ IMB ]   2JO8 [ RSDB ]
HPRD05395
Protein Interaction databases
DIPQ13043
IntActQ13043
Polymorphism : SNP, mutations, diseases
OMIM604965    [ map ]   
GENECLINICS604965
SNPSTK4 [dbSNP-NCBI]  
SNPNM_006282 [SNP-NCI]  
SNPSTK4 [GeneSNPs - Utah]  STK4] [HGBASE - SRS]
HAPMAPSTK4 [HAPMAP]  
COSMICSTK4 [Somatic mutation (COSMIC-CGP-Sanger)]  
HGMDSTK4
General knowledge
Family BrowserSTK4 [UCSC Family Browser]
SOURCENM_006282
SMDHs.472838
SAGEHs.472838
Enzyme2.7.11.1 [ Enzyme-SRS ]   2.7.11.1 [ Brenda-SRS ]   2.7.11.1 [ KEGG ]   2.7.11.1 [ WIT ]
GOnucleotide binding [Amigo]  nucleotide binding
GOmagnesium ion binding [Amigo]  magnesium ion binding
GOcell morphogenesis [Amigo]  cell morphogenesis
GOprotein serine/threonine kinase activity [Amigo]  protein serine/threonine kinase activity
GOprotein-tyrosine kinase activity [Amigo]  protein-tyrosine kinase activity
GOATP binding [Amigo]  ATP binding
GOATP binding [Amigo]  ATP binding
GOnucleus [Amigo]  nucleus
GOcytoplasm [Amigo]  cytoplasm
GOprotein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GOapoptosis [Amigo]  apoptosis
GOsignal transduction [Amigo]  signal transduction
GOcell surface receptor linked signal transduction [Amigo]  cell surface receptor linked signal transduction
GOprotein kinase cascade [Amigo]  protein kinase cascade
GOtranscription factor binding [Amigo]  transcription factor binding
GOtransferase activity [Amigo]  transferase activity
GOpeptidyl-serine phosphorylation [Amigo]  peptidyl-serine phosphorylation
GOprotein homodimerization activity [Amigo]  protein homodimerization activity
GOpositive regulation of apoptosis [Amigo]  positive regulation of apoptosis
GOprotein amino acid autophosphorylation [Amigo]  protein amino acid autophosphorylation
KEGGMAPK signaling pathway
PubGeneSTK4
TreeFamSTK4
CTD6789 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeSTK4 Related clones (RZPD - Berlin)
PubMed
PubMed35 Pubmed reference(s) in LocusLink

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
Last year publicationsautomatic 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. November 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/STK4ID42440ch20q11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:27:21 2008


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