Version 5.4
Bos taurus Protein: STK4
Summary
InnateDB Protein IDBP-695344.2
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol STK4
Protein Name Serine/threonine-protein kinase 4
Synonyms
Species Bos taurus
Ensembl Protein ENSBTAP00000004221
InnateDB Gene IDBG-642847 (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 0 experimentally validated interaction(s) in this database.
They are also associated with 36 interaction(s) predicted by orthology.
Predicted by orthology
Total 36 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 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:0016301 kinase activity
GO:0016740 transferase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0046872 metal ion binding
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:0016310 phosphorylation
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: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
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 Q5E9L6
PhosphoSite PhosphoSite-
TrEMBL
UniProt Splice Variant
Entrez Gene 514886
UniGene Bt.59649
RefSeq NP_001015602
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL BC112753 BT020904
GenPept AAI12754 AAX08921

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

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Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca