InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: STK3

Summary

InnateDB Protein

IDBP-374220.4

Last Modified

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

Gene Symbol

STK3

Protein Name

serine/threonine kinase 3

Synonyms

KRS1; MST2;

Species

Homo sapiens

Ensembl Protein

ENSP00000390500

InnateDB Gene

IDBG-30072 (STK3)

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 NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38. {ECO:0000250, ECO:0000269PubMed:15688006, ECO:0000269PubMed:16930133, ECO:0000269PubMed:18328708, ECO:0000269PubMed:18362890, ECO:0000269PubMed:19525978, ECO:0000269PubMed:20212043, ECO:0000269PubMed:21076410, ECO:0000269PubMed:21104395, ECO:0000269PubMed:8566796, ECO:0000269PubMed:8816758}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Note=The caspase-cleaved form cycles between nucleus and cytoplasm (By similarity). Phosphorylation at Thr-117 leads to inhibition of nuclear translocation. {ECO:0000250, ECO:0000269PubMed:19525978}.

Disease Associations

Tissue Specificity

Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues. {ECO:0000269PubMed:8566796}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 119 experimentally validated interaction(s) in this database.

Experimentally validated
Total	119 [view]
Protein-Protein	118 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

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:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0043539	protein serine/threonine kinase activator activity
GO:0046983	protein dimerization activity

Biological Process

GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0023014	signal transduction by phosphorylation
GO:0035329	hippo signaling
GO:0035556	intracellular signal transduction
GO:0043065	positive regulation of apoptotic process
GO:0071902	positive regulation of protein serine/threonine kinase activity
GO:0090090	negative regulation of canonical Wnt signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol

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