UniProt functional annotation for Q9Y6E0



	UniProt functional annotation for Q9Y6E0

UniProt code: Q9Y6E0.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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. {ECO:0000269|PubMed:16314523, ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:19604147, ECO:0000269|PubMed:19782762, ECO:0000269|PubMed:19855390, ECO:0000269|PubMed:27807006}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:15917084}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:15917084}; Name=Co(2+); Xref=ChEBI:CHEBI:48828; Evidence={ECO:0000269|PubMed:15917084}; Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:15917084};

Biophysicochemical properties: Kinetic parameters: KM=12.8 uM for manganese ions {ECO:0000269|PubMed:15917084}; KM=34.9 uM for cobalt ions {ECO:0000269|PubMed:15917084}; KM=22.7 uM for magnesium ions {ECO:0000269|PubMed:15917084}; KM=4.1 uM for zinc ions {ECO:0000269|PubMed:15917084}; Vmax=2623.1 pmol/min/mg enzyme for manganese ions {ECO:0000269|PubMed:15917084}; Vmax=1746.1 pmol/min/mg enzyme for cobalt ions {ECO:0000269|PubMed:15917084}; Vmax=129.1 pmol/min/mg enzyme for magnesium ions {ECO:0000269|PubMed:15917084}; Vmax=22.3 pmol/min/mg enzyme for zinc ions {ECO:0000269|PubMed:15917084};

Subunit: Monomer (PubMed:20124694). Interacts with CTTNBP2NL (PubMed:18782753). Interacts with RIPOR1 (via C-terminus); this interaction occurs in a PDCD10-dependent and Rho-independent manner (PubMed:27807006). Interacts with PDCD10; this interaction is required for the association of STK24 with RIPOR1 (PubMed:27807006). {ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:20124694, ECO:0000269|PubMed:27807006}.

Subcellular location: Cytoplasm. Nucleus. Membrane. Note=The truncated form (MST3/N) translocates to the nucleus. Colocalizes with STK38L in the membrane.

Tissue specificity: Isoform A is ubiquitous. Isoform B is expressed in brain with high expression in hippocampus and cerebral cortex.

Ptm: Proteolytically processed by caspases during apoptosis. Proteolytic cleavage results in kinase activation, nuclear translocation of the truncated form (MST3/N) and the induction of apoptosis. {ECO:0000269|PubMed:12107159}.

Ptm: Isoform B is activated by phosphorylation by PKA. Oxidative stress induces phosphorylation. Activated by autophosphorylation at Thr-190 and phosphorylation at this site is essential for its function. Manganese, magnesium and cobalt-dependent autophosphorylation is mainly on threonine residues while zinc-dependent autophosphorylation is on both serine and threonine residues. {ECO:0000269|PubMed:10644707, ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:19604147, ECO:0000269|PubMed:20124694}.

Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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. {ECO:0000269\|PubMed:16314523, ECO:0000269\|PubMed:17046825, ECO:0000269\|PubMed:19604147, ECO:0000269\|PubMed:19782762, ECO:0000269\|PubMed:19855390, ECO:0000269\|PubMed:27807006}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:15917084}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:15917084}; Name=Co(2+); Xref=ChEBI:CHEBI:48828; Evidence={ECO:0000269\|PubMed:15917084}; Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269\|PubMed:15917084};
Biophysicochemical properties:		Kinetic parameters: KM=12.8 uM for manganese ions {ECO:0000269\|PubMed:15917084}; KM=34.9 uM for cobalt ions {ECO:0000269\|PubMed:15917084}; KM=22.7 uM for magnesium ions {ECO:0000269\|PubMed:15917084}; KM=4.1 uM for zinc ions {ECO:0000269\|PubMed:15917084}; Vmax=2623.1 pmol/min/mg enzyme for manganese ions {ECO:0000269\|PubMed:15917084}; Vmax=1746.1 pmol/min/mg enzyme for cobalt ions {ECO:0000269\|PubMed:15917084}; Vmax=129.1 pmol/min/mg enzyme for magnesium ions {ECO:0000269\|PubMed:15917084}; Vmax=22.3 pmol/min/mg enzyme for zinc ions {ECO:0000269\|PubMed:15917084};
Subunit:		Monomer (PubMed:20124694). Interacts with CTTNBP2NL (PubMed:18782753). Interacts with RIPOR1 (via C-terminus); this interaction occurs in a PDCD10-dependent and Rho-independent manner (PubMed:27807006). Interacts with PDCD10; this interaction is required for the association of STK24 with RIPOR1 (PubMed:27807006). {ECO:0000269\|PubMed:18782753, ECO:0000269\|PubMed:20124694, ECO:0000269\|PubMed:27807006}.
Subcellular location:		Cytoplasm. Nucleus. Membrane. Note=The truncated form (MST3/N) translocates to the nucleus. Colocalizes with STK38L in the membrane.
Tissue specificity:		Isoform A is ubiquitous. Isoform B is expressed in brain with high expression in hippocampus and cerebral cortex.
Ptm:		Proteolytically processed by caspases during apoptosis. Proteolytic cleavage results in kinase activation, nuclear translocation of the truncated form (MST3/N) and the induction of apoptosis. {ECO:0000269\|PubMed:12107159}.
Ptm:		Isoform B is activated by phosphorylation by PKA. Oxidative stress induces phosphorylation. Activated by autophosphorylation at Thr-190 and phosphorylation at this site is essential for its function. Manganese, magnesium and cobalt-dependent autophosphorylation is mainly on threonine residues while zinc-dependent autophosphorylation is on both serine and threonine residues. {ECO:0000269\|PubMed:10644707, ECO:0000269\|PubMed:17046825, ECO:0000269\|PubMed:19604147, ECO:0000269\|PubMed:20124694}.
Similarity:		Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. {ECO:0000305}.