STK4 (serine/threonine kinase 4)
2005-11-01 Jonathan Chernoff   AffiliationFox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA
Identity
HGNC
LOCATION
20q13.12
LOCUSID
ALIAS
KRS2,MST1,YSK3
FUSION GENES
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.
Proteins

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
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12757711 | 2003 | Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. | Cheung WL et al |
| 7665586 | 1995 | Cloning and characterization of a human protein kinase with homology to Ste20. | Creasy CL et al |
| 9545236 | 1998 | Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. | Graves JD et al |
| 11805089 | 2002 | Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST). | Lee KK et al |
| 15994916 | 2005 | Mammalian sterile 20-like kinases in tumor suppression: an emerging pathway. | O'Neill EE et al |
| 15109305 | 2004 | Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. | Praskova M et al |
| 8816758 | 1996 | Newly 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
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38443598 | 2024 | The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress. | 1 |
| 38842136 | 2024 | MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway. | 1 |
| 38443598 | 2024 | The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress. | 1 |
| 38842136 | 2024 | MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway. | 1 |
| 36394186 | 2023 | Hematopoietic stem cell transplantation in serine/threonine kinase 4 (STK4) deficiency: Report of two cases and literature review. | 3 |
| 36495715 | 2023 | Mammalian 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 |
| 37137439 | 2023 | MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target. | 2 |
| 37870765 | 2023 | STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma. | 2 |
| 37890777 | 2023 | Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions. | 0 |
| 36394186 | 2023 | Hematopoietic stem cell transplantation in serine/threonine kinase 4 (STK4) deficiency: Report of two cases and literature review. | 3 |
| 36495715 | 2023 | Mammalian 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 |
| 37137439 | 2023 | MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target. | 2 |
| 37870765 | 2023 | STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma. | 2 |
| 37890777 | 2023 | Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions. | 0 |
| 34450249 | 2022 | Non-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/stk4
