STK4 (serine/threonine kinase 4)

2005-11-01   Jonathan Chernoff 

Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA

Identity

HGNC
LOCATION
20q13.12
LOCUSID
ALIAS
KRS2,MST1,YSK3
FUSION GENES

DNA/RNA

Atlas Image
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.

Proteins

Atlas Image
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).

Implicated in

Bibliography

Pubmed IDLast YearTitleAuthors
127577112003Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase.Cheung WL et al
76655861995Cloning and characterization of a human protein kinase with homology to Ste20.Creasy CL et al
95452361998Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.Graves JD et al
118050892002Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST).Lee KK et al
159949162005Mammalian sterile 20-like kinases in tumor suppression: an emerging pathway.O'Neill EE et al
151093052004Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.Praskova M et al
88167581996Newly identified stress-responsive protein kinases, Krs-1 and Krs-2.Taylor LK et al

Other Information

Locus ID:

NCBI: 6789
MIM: 604965
HGNC: 11408
Ensembl: ENSG00000101109

Variants:

dbSNP: 6789
ClinVar: 6789
TCGA: ENSG00000101109
COSMIC: STK4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000101109ENST00000372801Q13043
ENSG00000101109ENST00000372806Q13043
ENSG00000101109ENST00000474717A0A087WVN8
ENSG00000101109ENST00000487587A0A087WYT4
ENSG00000101109ENST00000499879F5H5B4

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
Non-small cell lung cancerKEGGko05223
MAPK signaling pathwayKEGGhsa04010
Pathways in cancerKEGGhsa05200
Non-small cell lung cancerKEGGhsa05223
Ras signaling pathwayKEGGhsa04014
FoxO signaling pathwayKEGGhsa04068
Signal TransductionREACTOMER-HSA-162582
Signaling by HippoREACTOMER-HSA-2028269

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
241414212013Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2.168
242551782013Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions.157
248132512014Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers.93
222947322012The phenotype of human STK4 deficiency.91
221741602012MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival.76
190622802008NDR kinase is activated by RASSF1A/MST1 in response to Fas receptor stimulation and promotes apoptosis.73
192211792009Regulation of neuronal cell death by MST1-FOXO1 signaling.66
175389462007Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma.64
246333052014MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes.64
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62

Citation

Jonathan Chernoff

STK4 (serine/threonine kinase 4)

Atlas Genet Cytogenet Oncol Haematol. 2005-11-01

Online version: http://atlasgeneticsoncology.org/gene/42440/stk4id42440ch20q11