serine/threonine protein kinase 3; mammalian STE20-like protein kinase 2; MST-2; STE20-like kinase MST2; serine/threonine protein kinase Krs-1 (STK3, MST2)

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 which plays a role in organ size control & tumor suppression - phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, & cell migration. - MST1/MST2 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), & to inhibit tumor formation - phosphorylates NKX2-1 - inhibited by the C-terminal non-catalytic region - activated by caspase-cleavage - full activation also requires homodimerization & autophosphorylation of Thr-180; both are inhibited by the proto-oncogene product RAF1 - interacts with NORE1, which inhibits autoactivation (putative) - interacts with & stabilizes SAV1 - interacts with RAF1, which prevents dimerization & phosphorylation - interacts with RASSF1, which leads to enzyme activation Cofactor: Mg⁺² Structure: - homodimerization is 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 (putative), nucleus - caspase-cleaved form cycles between nucleus & cytoplasm (putative) Expression: - expressed at high levels in adult kidney, skeletal & placenta tissues - expressed at very low levels in adult heart, lung & brain

Properties

SIZE: entity length = 491 aa MW = 56 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl Ser phosphorylation site {S15} kinase domain SITE: 27-278 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 33-41 ATP-binding site NAME: ATP-binding site SITE: 56-56 aspartate residue {D146} Thr phosphorylation site {T180} coiled coil {287-328} MOTIF: glutamate-rich region {308-314} MOTIF: glutamate residue (SEVERAL) Ser phosphorylation site {S316} Ser phosphorylation site {S323} Thr phosphorylation site {T325} Thr phosphorylation site {T336} glutamate-rich region {370-375} MOTIF: glutamate residue (SEVERAL) Thr phosphorylation site {T384} Ser phosphorylation site {S385} Ser phosphorylation site {S392} SARAH {437-484} MOTIF: coiled coil {442-475} Ser phosphorylation site {S444}

Database Correlations

OMIM 605030 UniProt Q13188 Pfam PF00069 Entrez Gene 6788 Kegg hsa:6788 ENZYME 2.7.11.1

References

UniProt :accession Q13188