STK4 - Serine/threonine-protein kinase 4 - human protein (Function)
 
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STK4 »  Serine/threonine-protein kinase 4   [ EC 2.7.11.1 ]
 
Protein also known as:  Mammalian STE20-like protein kinase 1 (MST-1). Cleaved into:  Serine/threonine-protein kinase 4 18kDa subunit; Serine/threonine-protein kinase 4 37kDa subunit.
Gene name:  STK4
Entry whose protein(s) existence is based on evidence at protein level
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1 99 2
GENE REF ISO

Function

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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 (By similarity). 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.  
16
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
Identical protein bindingdefinition[GO:0042802]  
2
  • IPIIntAct
Magnesium ion bindingdefinition[GO:0000287]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
18
  • IPIIntAct
  • IPIUniProtKB
Protein dimerization activitydefinition[GO:0046983]  
1
  • IDAUniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
1
  • IDAMGI
Protein serine/threonine kinase activator activitydefinition[GO:0043539]  
1
  • TASBHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
8
  • IDAUniProtKB
  • IDAMGI
Transcription factor bindingdefinition[GO:0008134]  
1
  • IPIUniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
1
  • IDAUniProtKB
Cell differentiation involved in embryonic placenta developmentdefinition[GO:0060706] silver  
  • IEAOrtholog Compara
Cell morphogenesisdefinition[GO:0000902]  
1
  • IDAMGI
Central nervous system developmentdefinition[GO:0007417] silver  
  • IEAOrtholog Compara
Endocardium developmentdefinition[GO:0003157] silver  
  • IEAOrtholog Compara
Hepatocyte apoptotic processdefinition[GO:0097284] silver  
  • IEAOrtholog Compara
Hippo signalingdefinition[GO:0035329]  
2
  • IDABHF-UCL
  • TASUniProtKB
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAUniProtKB
Keratinocyte differentiationdefinition[GO:0030216] silver  
  • IEAOrtholog Compara
Negative regulation of canonical Wnt signaling pathwaydefinition[GO:0090090]  
1
  • IMPBHF-UCL
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
  • IEAOrtholog Compara
Negative regulation of organ growthdefinition[GO:0046621] silver  
  • IEAOrtholog Compara
Neural tube formationdefinition[GO:0001841] silver  
  • IEAOrtholog Compara
Patterning of blood vesselsdefinition[GO:0001569] silver  
  • IEAOrtholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDAUniProtKB
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • IDAUniProtKB
Positive regulation of extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:1902043] silver  
  • IEAOrtholog Compara
Positive regulation of protein serine/threonine kinase activitydefinition[GO:0071902]  
1
  • TASGOC
Primitive hemopoiesisdefinition[GO:0060215] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAMGI
Protein phosphorylationdefinition[GO:0006468]  
3
  • IDAUniProtKB
  • IDAMGI
Signal transductiondefinition[GO:0007165]  
2
  • 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-183. Activated by RASSF1 which acts by preventing its dephosphorylation.  
3
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
MAPK signaling pathway  hsa04010+6789  
Non-small cell lung cancer  hsa05223+6789  
Pathways in cancer  hsa05200+6789  
According to Reactome, this protein belongs to the following pathway:
Signaling by Hippo  REACT_118607  
 

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: STK4
GenomeRNAi: 6789
PRO: PR:Q13043
Chemistry
GuidetoPHARMACOLOGY: 2225