STK3 - Serine/threonine-protein kinase 3 - human protein (Function)
 
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STK3 »  Serine/threonine-protein kinase 3   [ EC 2.7.11.1 ]
 
Protein also known as:  Serine/threonine-protein kinase Krs-1. Cleaved into:  Serine/threonine-protein kinase 3 20kDa subunit; Serine/threonine-protein kinase 3 36kDa subunit.
Gene name:  STK3
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 65 2
GENE REF ISO

Function

 show evidences
Overview 
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.  
10
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
Magnesium ion bindingdefinition[GO:0000287]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
15
  • IPIIntAct
  • IPIUniProtKB
Protein dimerization activitydefinition[GO:0046983]  
  • ISSOrtholog Curator
Protein kinase activitydefinition[GO:0004672]  
2
  • TASPINC
Protein serine/threonine kinase activator activitydefinition[GO:0043539]  
1
  • TASBHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
4
  • IDAUniProtKB
Receptor signaling protein serine/threonine kinase activitydefinition[GO:0004702] silver  
  • IBARefGenome
GO biological process 
Apoptotic processdefinition[GO:0006915]  
1
  • TASUniProtKB
Hippo signalingdefinition[GO:0035329]  
2
  • IDABHF-UCL
  • TASUniProtKB
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAUniProtKB
Negative regulation of canonical Wnt signaling pathwaydefinition[GO:0090090]  
1
  • IMPBHF-UCL
Positive regulation of apoptotic processdefinition[GO:0043065]  
  • ISSOrtholog Curator
Positive regulation of protein serine/threonine kinase activitydefinition[GO:0071902]  
1
  • TASGOC
Protein phosphorylationdefinition[GO:0006468]  
3
  • IDAUniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Signal transduction by phosphorylationdefinition[GO:0023014] silver  
  • IBARefGenome
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
  • CuratedUniProtKB
It is regulated in the following manner
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation.  
2
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathway:
MAPK signaling pathway  hsa04010+6788  
According to Reactome, this protein belongs to the following pathway:
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: STK3
GenomeRNAi: 6788
PRO: PR:Q13188
Chemistry
GuidetoPHARMACOLOGY: 2219