TEK [The Human Chemical-Genetic Interaction Map Project]

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======= TEK =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TEK
  * **<color #00a2e8>Official Name</color>**: TEK receptor tyrosine kinase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7010|7010]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q02763|Q02763]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TEK&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TEK|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600221|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post- natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1. {ECO:0000269|PubMed:12816861, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:18366015, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:20651738, ECO:0000269|PubMed:9204896}.

<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|
|Ig Tie2 1|
|fn3|
|Pkinase Tyr|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|Tie signaling pathway|
|heart trabecula formation|
|definitive hemopoiesis|
|glomerulus vasculature development|
|positive regulation of actin cytoskeleton reorganization|
|renal system vasculature development|
|kidney vasculature development|
|trabecula formation|
|endothelial cell proliferation|
|regulation of establishment or maintenance of cell polarity|
|positive regulation of focal adhesion assembly|
|endochondral ossification|
|replacement ossification|
|negative regulation of endothelial cell apoptotic process|
|positive regulation of adherens junction organization|
|growth factor binding|
|positive regulation of phosphatidylinositol 3-kinase activity|
|heart trabecula morphogenesis|
|positive regulation of cell junction assembly|
|basal plasma membrane|
|positive regulation of lipid kinase activity|
|regulation of vascular permeability|
|regulation of actin cytoskeleton reorganization|
|negative regulation of epithelial cell apoptotic process|
|trabecula morphogenesis|
|positive regulation of phospholipid metabolic process|
|regulation of endothelial cell apoptotic process|
|positive regulation of cell-matrix adhesion|
|glomerulus development|
|substrate adhesion-dependent cell spreading|
|regulation of phosphatidylinositol 3-kinase activity|
|transmembrane receptor protein tyrosine kinase activity|
|sprouting angiogenesis|
|regulation of focal adhesion assembly|
|regulation of cell-substrate junction assembly|
|regulation of lipid kinase activity|
|microvillus|
|regulation of adherens junction organization|
|stress fiber|
|endochondral bone morphogenesis|
|response to estrogen|
|regulation of epithelial cell apoptotic process|
|actin filament|
|regulation of phospholipid metabolic process|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|epithelial cell proliferation|
|protein tyrosine kinase activity|
|regulation of cell junction assembly|
|positive regulation of endothelial cell proliferation|
|positive regulation of endothelial cell migration|
|response to cAMP|
|negative regulation of angiogenesis|
|negative regulation of blood vessel morphogenesis|
|bone morphogenesis|
|regulation of cell-matrix adhesion|
|negative regulation of vasculature development|
|regulation of phosphatidylinositol 3-kinase signaling|
|positive regulation of cell-substrate adhesion|
|nephron development|
|cardiac chamber morphogenesis|
|regulation of endothelial cell proliferation|
|response to organophosphorus|
|negative regulation of inflammatory response|
|positive regulation of epithelial cell migration|
|positive regulation of lipid metabolic process|
|peptidyl-tyrosine phosphorylation|
|peptidyl-tyrosine modification|
|response to purine-containing compound|
|regulation of endothelial cell migration|
|microtubule organizing center|
|positive regulation of angiogenesis|
|positive regulation of protein kinase B signaling|
|vascular process in circulatory system|
|cardiac chamber development|
|cell-cell junction|
|positive regulation of vasculature development|
|cell-substrate adhesion|
|positive regulation of epithelial cell proliferation|
|protein autophosphorylation|
|basolateral plasma membrane|
|bone development|
|receptor complex|
|signaling receptor activity|
|negative regulation of defense response|
|regulation of cell-substrate adhesion|
|positive regulation of ERK1 and ERK2 cascade|
|regulation of protein kinase B signaling|
|positive regulation of cytoskeleton organization|
|regulation of epithelial cell migration|
|membrane raft|
|protein kinase activity|
|skeletal system morphogenesis|
|heart morphogenesis|
|ossification|
|kidney development|
|renal system development|
|regulation of angiogenesis|
|regulation of ERK1 and ERK2 cascade|
|angiogenesis|
|apical plasma membrane|
|urogenital system development|
|regulation of vasculature development|
|regulation of epithelial cell proliferation|
|regulation of inflammatory response|
|response to hypoxia|
|regulation of actin cytoskeleton organization|
|response to decreased oxygen levels|
|negative regulation of response to external stimulus|
|MAPK cascade|
|leukocyte migration|
|response to oxygen levels|
|regulation of actin filament-based process|
|blood circulation|
|response to peptide hormone|
|signal transduction by protein phosphorylation|
|circulatory system process|
|regulation of lipid metabolic process|
|positive regulation of cell adhesion|
|blood vessel morphogenesis|
|focal adhesion|
|response to peptide|
|blood vessel development|
|skeletal system development|
|positive regulation of cell migration|
|vasculature development|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|cardiovascular system development|
|protein complex oligomerization|
|positive regulation of cellular component biogenesis|
|positive regulation of cell motility|
|heart development|
|positive regulation of cellular component movement|
|regulation of cytoskeleton organization|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|cell population proliferation|
|hemopoiesis|
|cell morphogenesis involved in differentiation|
|positive regulation of kinase activity|
|hematopoietic or lymphoid organ development|
|cell surface|
|positive regulation of organelle organization|
|immune system development|
|tube morphogenesis|
|positive regulation of transferase activity|
|regulation of cell adhesion|
|enzyme linked receptor protein signaling pathway|
|cell morphogenesis|
|regulation of MAPK cascade|
|regulation of defense response|
|cellular component morphogenesis|
|tube development|
|regulation of cell migration|
|circulatory system development|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|anatomical structure formation involved in morphogenesis|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|response to organic cyclic compound|
|cell adhesion|
|biological adhesion|
|negative regulation of developmental process|
|animal organ morphogenesis|
|regulation of cellular component biogenesis|
|cell migration|
|protein phosphorylation|
|regulation of transferase activity|
|regulation of locomotion|
|regulation of cellular component movement|
|negative regulation of cell death|
|response to organonitrogen compound|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|cell motility|
|localization of cell|
|response to nitrogen compound|
|regulation of response to external stimulus|
|cell-cell signaling|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|response to abiotic stimulus|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|phosphorylation|
|regulation of organelle organization|
|locomotion|
|positive regulation of developmental process|
|integral component of plasma membrane|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|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|
|cell development|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|extracellular region|
|system 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:exp510|Nicotine 3000μM R08 exp510]]|-1.76|
|[[:results:exp260|ABT-702 0.1μM R06 exp260]]|1.7|
|[[:results:exp410|THZ531 0.11 to 0.125μM on day4 R07 exp410]]|1.76|
</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>**: 7033
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -6.6 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TEK Expression in NALM6 Cells: -6.6'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>