ALK [The Human Chemical-Genetic Interaction Map Project]

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======= ALK =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ALK
  * **<color #00a2e8>Official Name</color>**: ALK 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=238|238]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9UM73|Q9UM73]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ALK&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ALK|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/105590|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y- x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK. {ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:15908427, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988}.

<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'>
|Gly rich|
|Pkinase Tyr|
|MAM|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|response to environmental enrichment|
|swimming behavior|
|NF-kappaB-inducing kinase activity|
|regulation of dopamine receptor signaling pathway|
|regulation of cellular response to drug|
|transmembrane receptor protein tyrosine kinase activity|
|positive regulation of dendrite development|
|NIK/NF-kappaB signaling|
|hippocampus development|
|protein tyrosine kinase activity|
|regulation of response to drug|
|limbic system development|
|peptidyl-tyrosine phosphorylation|
|adult behavior|
|peptidyl-tyrosine modification|
|regulation of dendrite development|
|positive regulation of NF-kappaB transcription factor activity|
|activation of MAPK activity|
|pallium development|
|protein autophosphorylation|
|locomotory behavior|
|receptor complex|
|telencephalon development|
|positive regulation of MAP kinase activity|
|positive regulation of DNA-binding transcription factor activity|
|positive regulation of neuron projection development|
|activation of protein kinase activity|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|positive regulation of neuron differentiation|
|positive regulation of cell projection organization|
|forebrain development|
|regulation of DNA-binding transcription factor activity|
|positive regulation of neurogenesis|
|regulation of neuron projection development|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cell development|
|positive regulation of MAPK cascade|
|cell population proliferation|
|behavior|
|positive regulation of kinase activity|
|protein-containing complex|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|regulation of plasma membrane bounded cell projection organization|
|regulation of cell projection organization|
|enzyme linked receptor protein signaling pathway|
|brain development|
|regulation of MAPK cascade|
|head development|
|regulation of protein kinase activity|
|neuron development|
|regulation of neurogenesis|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|regulation of nervous system development|
|regulation of cell development|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|central nervous system development|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|positive regulation of phosphorylation|
|identical protein binding|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|phosphorylation|
|positive regulation of developmental process|
|integral component of plasma membrane|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|generation of neurons|
|regulation of apoptotic process|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|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|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|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:exp528|TGF-beta1 44ng/ml R08 exp528]]|-2.03|
|[[:results:exp282|Fluvastatin 2.2μM R06 exp282]]|-1.99|
|[[:results:exp472|CI-1040 9.5μM R08 exp472]]|-1.95|
|[[:results:exp405|Tenofovir 10μM R07 exp405]]|-1.92|
|[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|-1.84|
|[[:results:exp40|2-Methoxyestradiol 0.2μM R01 exp40]]|-1.79|
</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: 1/739
^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>**: 7525
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -5.01 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ALK Expression in NALM6 Cells: -5.01'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>