InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Stk4

Summary

InnateDB Protein

IDBP-212021.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Stk4

Protein Name

serine/threonine kinase 4

Synonyms

AI447339; AU020804; Kas-2; Mst1; Ysk3;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000018353

InnateDB Gene

IDBG-212019 (Stk4)

Protein Structure

UniProt Annotation

Function

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Note=The caspase-cleaved form cycles between nucleus and cytoplasm. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 31 interaction(s) predicted by orthology.

Experimentally validated
Total	9 [view]
Protein-Protein	9 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	31 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004702	receptor signaling protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0043539	protein serine/threonine kinase activator activity
GO:0046983	protein dimerization activity

Biological Process

GO:0000902	cell morphogenesis
GO:0001569	patterning of blood vessels
GO:0001841	neural tube formation
GO:0003157	endocardium development
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0007417	central nervous system development
GO:0008285	negative regulation of cell proliferation
GO:0018105	peptidyl-serine phosphorylation
GO:0023014	signal transduction by phosphorylation
GO:0030216	keratinocyte differentiation
GO:0035329	hippo signaling
GO:0035556	intracellular signal transduction
GO:0043065	positive regulation of apoptotic process
GO:0046621	negative regulation of organ growth
GO:0046777	protein autophosphorylation
GO:0060215	primitive hemopoiesis
GO:0060706	cell differentiation involved in embryonic placenta development
GO:0071902	positive regulation of protein serine/threonine kinase activity
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:0097284	hepatocyte apoptotic process
GO:1902043	positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

MGI:1929004

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011524 SARAH domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR024205 Mst1 SARAH domain

PFAM

PF00069
PF07714
PF11629

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt