STK24
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3A7F, 3A7G, 3A7H, 3A7I, 3A7J, 3CKW, 3CKX, 3ZHP, 4O27, 4QML, 4QMM, 4QMN, 4QMO, 4QMP, 4QMQ, 4QMS, 4QMT, 4QMU, 4QMV, 4QMW, 4QMX, 4QMY, 4QMZ, 4QO9, 4U8Z, 4W8D, 4W8E, 4QNA
Identifiers
Aliases	STK24, HEL-S-95, MST3, MST3B, STE20, STK3, serine/threonine kinase 24
External IDs	OMIM: 604984 MGI: 2385007 HomoloGene: 20793 GeneCards: STK24
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q32.2 Start 98,445,185 bp[1] End 98,577,940 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 E5|14 64.95 cM Start 121,523,755 bp[2] End 121,617,423 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte amniotic fluid pancreatic ductal cell retinal pigment epithelium endothelial cell hair follicle palpebral conjunctiva germinal epithelium jejunal mucosa human penis Top expressed in blood ascending aorta aortic valve cumulus cell molar lip conjunctival fornix Paneth cell submandibular gland belly cord More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding metal ion binding kinase activity protein binding ATP binding protein kinase activity protein serine/threonine kinase activity cadherin binding MAP kinase kinase kinase kinase activity Cellular component membrane nucleoplasm nucleolus extracellular exosome nucleus cytosol cytoplasm Golgi apparatus Biological process intrinsic apoptotic signaling pathway in response to oxidative stress regulation of axon regeneration phosphorylation negative regulation of cell migration response to hydrogen peroxide signal transduction apoptotic process protein phosphorylation execution phase of apoptosis cellular response to starvation protein autophosphorylation MAPK cascade regulation of mitotic cell cycle stress-activated protein kinase signaling cascade regulation of apoptotic process neuron projection morphogenesis activation of protein kinase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8428 223255 Ensembl ENSG00000102572 ENSMUSG00000063410 UniProt Q9Y6E0 Q5JV99 Q99KH8 RefSeq (mRNA) NM_001032296 NM_001286649 NM_003576 NM_145465 RefSeq (protein) NP_001027467 NP_001273578 NP_003567 NP_663440 Location (UCSC) Chr 13: 98.45 – 98.58 Mb Chr 14: 121.52 – 121.62 Mb PubMed search [3] [4]
Wikidata
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Serine/threonine-protein kinase 24 is an enzyme that in humans is encoded by the STK24 gene^[5][6][7] located in the chromosome 13, band q32.2. It is also known as Mammalian STE20-like protein kinase 3 (MST-3).^[8] The protein is 443 amino acids long and its mass is 49 kDa.^[8]

Classification and discovery

The yeast 'Sterile 20' gene (STE20) functions upstream of the mitogen-activated protein kinase (MAPK) cascade. In mammals, protein kinases related to STE20 can be divided into 2 subfamilies based on their structure and regulation. Members of the PAK subfamily (see PAK3) contain a C-terminal catalytic domain and an N-terminal regulatory domain that has a CDC42-binding domain. In contrast, members of the GCK subfamily (MAP4K2), also called the Sps1 subfamily, have an N-terminal catalytic domain and a C-terminal regulatory domain without a CDC42-binding domain. STK24 belongs to the GCK subfamily of STE20-like kinases.^[6][7]

The sterile 20 protein was first found in yeast.^[9] The MST-20 related kinases family is growing, having 28 members divided into two groups - p21-activated kinase and germinal center kinase (GCK) families.^[10] STK24 belongs to the germinal center kinase (GCK) III subfamily of sterile 20 kinases.

Function

Kinases of GCKIII subfamily are involved in regulation of multiple functions of the cells^[10] and interaction with programmed cell death 10 (CCM3).^[11] CCM is a pathological vascular situation that, influencing the blood vessels in central nervous system (CNS), may cause stroke, seizure and even cerebral hemorrhage.^[12] It has been shown that STK24 and STK25 operate in the same cardiovascular development pathway with CCM3. According to the results of the experiment by Zhang et al.,^[12] lack of STK24 has no effect on the amount of neutrophils or leucocytes, as well as it does not affect the chemotaxis of neutrophils.^[12] Zhang et al. also the interaction between STK24 and CCM. Using tandem affinity purification with mass spectrometry, they found that CCM3 is the main protein that binds to STK24 in HEK293 cells.^[12]

STK24 operates on serine and threonine residues and, as a response to oxidative stress and caspase activity, develops cell death.^[8]

STK24 is activated by autophosphorylation at Thr-190 and phosphorylation at this site is essential for its function. Phosphorylation by protein kinase A activates the isoform B of STK24.^[8]

The mutagenesis of four residues in STK24 have been carried out. In position 18, the replacement of threonine (T) with alanine (A) causes the reduction of phosphorylation by PKA.^[6] the modification in positions 65, where lysine (K) is replaced with A, and the position 190, where T is replaced with A, affects the activity and autophosphorylation.^[10] In residue 321, the change of aspartic acid (D) to Asparagine (N) reveals as loss of proteolytic cleavage by caspases.^[10] Those residues may play an important role apoptotic signal transduction.^[10]

Structure and tissue distribution

STK24 has two subunits, 36kDa N-terminal subunit and 12 kDa C-terminal subunit.^[8] In the cells, STK24 is located in nucleus and less in cytoplasm and membrane. There are two isoforms of the protein, isoform A is ubiquitous and is expressed in 237 organs, isoform B is expressed in brain hippocampus and cerebral cortex.^[8]

Interactions

STK24 has been shown to interact with PDCD10,^[13][14][15] TRAF3IP3,^[15] STRN3,^[14][15] MOBKL3,^[14][15] STRN,^[14][15] SLMAP,^[14][15] PPP2R1A,^[14][15] CTTNBP2NL,^[15] FAM40A^[14][15] and STRN4.^[14][15]

References

Further reading