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serine/threonine protein kinase 4; mammalian STE20-like protein kinase 1; MST-1; STE20-like kinase MST1; serine/threonine protein kinase Krs-2 (STK4 MST1)
Function:
- stress-activated, pro-apoptotic kinase
- following caspase-cleavage, enters the nucleus & induces chromatin condensation followed by internucleosomal DNA fragmentation
- component of the Hippo signaling pathway
- phosphorylates Ser-14 of histone H2B (H2BS14ph) during apoptosis
- phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation & cell death initiation
- inhibited by the C-terminal non-catalytic region
- activated by caspase-cleavage
- full activation also requires homodimerization & autophosphorylation of Thr-183
- autophosphorylated on Ser & Thr
- interacts with NORE1, which inhibits autoactivation
- interacts with & stabilizes SAV1
- interacts with RASSF1, which leads to enzyme activation
Cofactor: Mg+2
Structure:
- homodimer mediated via the coiled-coil region
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily
- contains 1 protein kinase domain
- contains 1 SARAH domain
Compartment:
- cytoplasm, nucleus
- the caspase-cleaved form cycles between the nucleus & cytoplasm
Alternative splicing: named isoforms=2
Expression: ubiquitously expressed
General
serine/threonine kinase
Properties
SIZE: entity length = 487 aa
MW = 56 kD
COMPARTMENT: cytoplasm
cell nucleus
STATE: active state
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
Thr phosphorylation site {T3}
kinase domain
SITE: 30-281
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 36-44
Ser phosphorylation site {S40}
Tyr phosphorylation site {Y41}
ATP-binding site
NAME: ATP-binding site
SITE: 59-59
aspartate residue {D149}
Thr phosphorylation site {T175}
Thr phosphorylation site {T177}
Thr phosphorylation site {T183}
Ser phosphorylation site {S265}
coiled coil {290-310}
Ser phosphorylation site {S320}
proteolytic site {326-327}
MOTIF: Ser phosphorylation site {S327}
Thr phosphorylation site {T329}
Thr phosphorylation site {T340}
proteolytic site {349-350}
Thr phosphorylation site {T353}
Thr phosphorylation site {T360}
Thr phosphorylation site {T367}
glutamate-rich region {373-378}
MOTIF: glutamate residue (SEVERAL)
Thr phosphorylation site {T380}
Thr phosphorylation site {T387}
Ser phosphorylation site {S394}
Ser phosphorylation site {S410}
Ser phosphorylation site {S414}
Ser phosphorylation site {S422}
SARAH {433-480}
MOTIF: Tyr phosphorylation site {Y433}
Ser phosphorylation site {S438}
Database Correlations
OMIM 604965
UniProt Q13043
PFAM correlations
Entrez Gene 6789
Kegg hsa:6789
ENZYME 2.7.11.1
References
- UniProt :accession Q13043
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/STK4ID42440ch20q11.html