serine/threonine protein kinase 24; mammalian STE20-like protein kinase 3; MST-3; STE20-like kinase MST3; contains: serine/threonine protein kinase 24 36kDa subunit MST3/N, serine/threonine protein kinase 24 12kDa subunit MST3/C (STK24, MST3)

Function: - serine/threonine protein kinase - phosphorylateds both Ser & Thr - promotes apoptosis in response to stress stimuli & caspase activation - mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8-MAPK9), JUN & p38 (MAPK11, MAPK12, MAPK13 & MAPK14) during oxidative stress - role in a staurosporine-induced caspase-independent apoptosis by regulating the nuclear translocation of AIFM1 & ENDOG & the DNAse activity associated with ENDOG - phosphorylates STK38L on Thr-442 & stimulates its kinase activity - regulates cellular migration with alteration of PTPN12 activity & PXN phosphorylation: - phosphorylates PTPN12 & inhibits its activity - may regulate PXN phosphorylation through PTPN12 - may act as a key regulator of axon regeneration in the optic nerve & radial nerve - proteolytically processed by caspases during apoptosis - proteolytic cleavage results in kinase activation, nuclear translocation of the truncated form (MST3/N) & induction of apoptosis - isoform B is activated by phosphorylation by PKA - oxidative stress induces phosphorylation - activated by autophosphorylation at Thr-190 - Thr-190 phosphorylation is essential for function - Mn+2, Mg⁺² & cobalt-dependent autophosphorylation is mainly on Thr - Zn⁺²-dependent autophosphorylation is on both Ser & Thr Cofactor: Mg⁺², Mn+2, cobalt & Zn⁺² Kinetic parameters: - KM=12.8 uM for Mn+2 - KM=34.9 uM for cobalt ions - KM=22.7 uM for Mg⁺² - KM=4.1 uM for Zn⁺² - Vmax=2623.1 pmol/min/mg enzyme for Mn+2 - Vmax=1746.1 pmol/min/mg enzyme for cobalt ions - Vmax=129.1 pmol/min/mg enzyme for Mg⁺² - Vmax=22.3 pmol/min/mg enzyme for Zn⁺² Structure: - monomer - belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily - contains 1 protein kinase domain Compartment: -cytoplasm, nucleus, membrane - the truncated form (MST3/N) translocates to the nucleus - co-localizes with STK38L in the membrane Alternative splicing: named isoforms=2 Expression: - isoform A is ubiquitous - isoform B is expressed in brain - high expression in hippocampus & cerebral cortex

Properties

SIZE: entity length = 443 aa MW = 49 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: Thr phosphorylation site {T18} kinase domain SITE: 36-286 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 42-50 ATP-binding site NAME: ATP-binding site SITE: 65-65 ATP-binding site NAME: ATP-binding site SITE: 112-114 aspartate residue {D156} Mg+2-binding site SITE: 161-161 Mg+2-binding site SITE: 174-174 Thr phosphorylation site {T190} nuclear translocation signal {278-292} Ser phosphorylation site {S311} Ser phosphorylation site {S315} Ser phosphorylation site {S316} Ser phosphorylation site {S317} Ser phosphorylation site {S320} proteolytic site {325-326} nuclear export signal {335-386}

Database Correlations

OMIM 604984 UniProt Q9Y6E0 Pfam PF00069 Entrez Gene 8428 Kegg hsa:8428 ENZYME 2.7.11.1

References

UniProt :accession Q9Y6E0