======= STK4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: STK4
  * **<color #00a2e8>Official Name</color>**: serine/threonine kinase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6789|6789]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q13043|Q13043]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=STK4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20STK4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/604965|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase|
|Pkinase Tyr|
|Mst1 SARAH|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of cell differentiation involved in embryonic placenta development|
|primitive hemopoiesis|
|positive regulation of vascular associated smooth muscle cell apoptotic process|
|regulation of vascular associated smooth muscle cell apoptotic process|
|hepatocyte apoptotic process|
|endocardium development|
|positive regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|positive regulation of smooth muscle cell apoptotic process|
|embryonic hemopoiesis|
|regulation of smooth muscle cell apoptotic process|
|cell differentiation involved in embryonic placenta development|
|hippo signaling|
|epithelial cell apoptotic process|
|positive regulation of muscle cell apoptotic process|
|branching involved in blood vessel morphogenesis|
|protein serine/threonine kinase activator activity|
|negative regulation of organ growth|
|positive regulation of extrinsic apoptotic signaling pathway|
|regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|positive regulation of fat cell differentiation|
|regulation of muscle cell apoptotic process|
|embryonic placenta development|
|positive regulation of protein binding|
|regulation of organ growth|
|positive regulation of peptidyl-serine phosphorylation|
|negative regulation of developmental growth|
|neural tube formation|
|regulation of fat cell differentiation|
|embryonic epithelial tube formation|
|regulation of embryonic development|
|branching morphogenesis of an epithelial tube|
|epithelial tube formation|
|regulation of peptidyl-serine phosphorylation|
|stress-activated protein kinase signaling cascade|
|morphogenesis of embryonic epithelium|
|tube formation|
|placenta development|
|regulation of extrinsic apoptotic signaling pathway|
|protein dimerization activity|
|morphogenesis of a branching epithelium|
|neural tube development|
|regulation of reproductive process|
|morphogenesis of a branching structure|
|positive regulation of apoptotic signaling pathway|
|negative regulation of canonical Wnt signaling pathway|
|peptidyl-serine phosphorylation|
|positive regulation of binding|
|protein stabilization|
|protein autophosphorylation|
|peptidyl-serine modification|
|negative regulation of Wnt signaling pathway|
|magnesium ion binding|
|regulation of protein binding|
|protein kinase activity|
|negative regulation of growth|
|keratinocyte differentiation|
|regulation of canonical Wnt signaling pathway|
|nuclear body|
|regulation of protein stability|
|epithelial tube morphogenesis|
|epidermal cell differentiation|
|angiogenesis|
|activation of protein kinase activity|
|regulation of developmental growth|
|transcription factor binding|
|positive regulation of protein serine/threonine kinase activity|
|regulation of Wnt signaling pathway|
|protein serine/threonine kinase activity|
|in utero embryonic development|
|regulation of binding|
|skin development|
|signal transduction by protein phosphorylation|
|regulation of apoptotic signaling pathway|
|blood vessel morphogenesis|
|epidermis development|
|reproductive structure development|
|reproductive system development|
|morphogenesis of an epithelium|
|embryonic organ development|
|blood vessel development|
|vasculature development|
|regulation of protein serine/threonine kinase activity|
|cardiovascular system development|
|heart development|
|positive regulation of protein kinase activity|
|hemopoiesis|
|tissue morphogenesis|
|embryonic morphogenesis|
|positive regulation of kinase activity|
|protein-containing complex|
|hematopoietic or lymphoid organ development|
|chordate embryonic development|
|positive regulation of apoptotic process|
|immune system development|
|positive regulation of programmed cell death|
|embryo development ending in birth or egg hatching|
|tube morphogenesis|
|positive regulation of transferase activity|
|developmental process involved in reproduction|
|regulation of growth|
|negative regulation of cell population proliferation|
|epithelial cell differentiation|
|positive regulation of cell death|
|cell morphogenesis|
|regulation of protein kinase activity|
|cellular component morphogenesis|
|tube development|
|circulatory system development|
|regulation of kinase activity|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|apoptotic process|
|negative regulation of developmental process|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|embryo development|
|central nervous system development|
|positive regulation of protein phosphorylation|
|programmed cell death|
|positive regulation of phosphorylation|
|identical protein binding|
|cell death|
|epithelium development|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of multicellular organismal process|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|phosphorylation|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|regulation of apoptotic process|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of protein modification process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp141|Nifurtimox 1μM R03 exp141]]|-1.88|
|[[:results:exp275|Citral 75μM R06 exp275]]|-1.75|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 17388
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.98 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='STK4 Expression in NALM6 Cells: 6.98'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>