Serine/threonine-protein kinase 24 (STK24)

The protein contains 443 amino acids for an estimated molecular weight of 49308 Da.

 

Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Regulates also cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve. (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 83%
Model score: 99
MODL_MODELLER-9.18

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs55953606
dbSNP:rs55897869

The reference OMIM entry for this protein is 604984

Serine/threonine protein kinase 24; stk24
Mammalian sterile 20-like 3; mst3 mammalian sterile 20-like 3, isoform b, included; mst3b, included

DESCRIPTION

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; 300142) contain a C-terminal catalytic domain and an N-terminal regulatory domain that has a CDC42 (116952)-binding domain. In contrast, members of the GCK subfamily (see MAP4K2; 603166), 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 (Zhou et al., 2000).

CLONING

Using PCR with degenerate primers based on conserved regions of the kinase domains of STE20 and p65 PAK (PAK2; 605022), Schinkmann and Blenis (1997) obtained a fragment from a HeLa cell cDNA library. By screening T cell and HeLa cell cDNA libraries using the fragment as the probe, they isolated a cDNA encoding STK24, which they termed MST3. Sequence analysis showed that the predicted 431-amino acid STK24 protein contains an N-terminal kinase domain and a C-terminal regulatory domain. STK24 shares 69% amino acid identity with STK25 (602255) and is a member of the GCK subfamily of STE20-like proteins. Northern blot analysis revealed ubiquitous expression of a 2.0-kb STK24 transcript, with highest levels detected in heart, skeletal muscle, and pancreas. Western blot analysis detected a 52-kD STK24 protein in all cell lines tested. By searching an EST database using the conserved catalytic domain of STE20 as the probe, Zhou et al. (2000) identified an STK24 isoform that they called MST3B. The sequence of MST3B is identical after nucleotide 223 to the MST3 sequence reported by Schinkmann and Blenis (1997). MST3B encodes a predicted 443-amino acid protein. RT-PCR and Northern blot analyses revealed that expression of the 2.5-kb MST3B transcript is restricted to brain; Western blot analysis confirmed the brain-specific expression. In situ hybridization analysis showed that MST3B is widely expressed in different brain regions, with high levels in hippocampus, cerebral cortex, and hypothalamus, and moderate levels in geniculate nucleus and thalamic nucleus. Reduced MST3B expression was observed in cerebellum. By analyzing the subcellular localization of truncated MST3 proteins in transfected HeLa cells, Lee et al. (2004) identified a nuclear localization signal at the C terminus of the kinase domain and a nuclear export signal in the C-terminal regulatory domain.

GENE FUNCTION

By in vitro kinase assays, Schinkmann and Blenis (1997) demonstrated that STK24 readily phosphorylates MBP (159430), histone H3, and itself but not histones H1, H2, and H4 (see 142711), casein (see 115450), or phosvitin (CSNK2B; 115441); phosphorylation occurs with manganese as the cofactor. Immunofluorescence microscopy showed that STK24 is expressed in the cytoplasm. By functional analyses, Zhou et al. (2000) demonstrated that MST3 but not MST3B phosphorylates and activates p42 MAPK (MAPK1; 176948)/p44 MAPK (MAPK3; 601795) but not MAPK14 (602896) or JNK (see MAPK8; 601158). Mutational analysis indicated that protein kinase A (see 176911) phosphorylation of thr18 at the N terminus of MST3B negatively regulates its ability to phosphorylate and activate MAPK3. The purine nucleoside inosine stimulates axon outgrowth in certain types of neurons in culture and in vi ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604984 was added.