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
384435982024The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.1
388421362024MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway.1
384435982024The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.1
388421362024MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway.1
363941862023Hematopoietic stem cell transplantation in serine/threonine kinase 4 (STK4) deficiency: Report of two cases and literature review.3
364957152023Mammalian STE20-like kinase-1/2 are activated in human platelets stimulated by collagen or thrombin and play a vital role in collagen-activated platelets.0
371374392023MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target.2
378707652023STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.2
378907772023Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions.0
363941862023Hematopoietic stem cell transplantation in serine/threonine kinase 4 (STK4) deficiency: Report of two cases and literature review.3
364957152023Mammalian STE20-like kinase-1/2 are activated in human platelets stimulated by collagen or thrombin and play a vital role in collagen-activated platelets.0
371374392023MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target.2
378707652023STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.2
378907772023Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions.0
344502492022Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer.9

Citation

Jonathan Chernoff

STK4 (serine/threonine kinase 4)

Atlas Genet Cytogenet Oncol Haematol. 2005-11-01

Online version: http://atlasgeneticsoncology.org/gene/42440/favicon/deep-insight-explorer/