======= NTRK1 =======
== Gene Information ==
* **Official Symbol**: NTRK1
* **Official Name**: neurotrophic receptor tyrosine kinase 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4914|4914]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P04629|P04629]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=NTRK1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NTRK1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/191315|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008].
* **UniProt Summary**: Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:17196528). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras- PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.
|Pkinase Tyr|
|Pkinase|
|neurotrophin p75 receptor binding|
|behavioral response to chemical pain|
|nerve growth factor receptor activity|
|behavioral response to formalin induced pain|
|olfactory nerve development|
|neurotrophin receptor activity|
|neurotrophin binding|
|nerve growth factor binding|
|response to hydrostatic pressure|
|axonogenesis involved in innervation|
|GPI-linked ephrin receptor activity|
|cellular response to nicotine|
|programmed cell death involved in cell development|
|nerve growth factor signaling pathway|
|detection of mechanical stimulus involved in sensory perception of pain|
|Sertoli cell development|
|behavioral response to pain|
|detection of temperature stimulus involved in sensory perception of pain|
|response to water|
|detection of temperature stimulus involved in sensory perception|
|chemosensory behavior|
|detection of temperature stimulus|
|Sertoli cell differentiation|
|neurotrophin TRK receptor signaling pathway|
|sympathetic nervous system development|
|sensory perception of temperature stimulus|
|innervation|
|neurotrophin signaling pathway|
|detection of mechanical stimulus involved in sensory perception|
|response to pain|
|peptidyl-tyrosine autophosphorylation|
|positive regulation of synaptic transmission, glutamatergic|
|cellular response to amyloid-beta|
|response to electrical stimulus|
|detection of mechanical stimulus|
|autonomic nervous system development|
|cellular response to nerve growth factor stimulus|
|response to axon injury|
|response to amyloid-beta|
|response to nicotine|
|cranial nerve development|
|response to nerve growth factor|
|activation of MAPKK activity|
|transmembrane receptor protein tyrosine kinase activity|
|mechanoreceptor differentiation|
|positive regulation of Ras protein signal transduction|
|positive regulation of synapse assembly|
|multicellular organismal response to stress|
|regulation of synaptic transmission, glutamatergic|
|phosphatidylinositol-mediated signaling|
|positive regulation of small GTPase mediated signal transduction|
|sensory perception of pain|
|inositol lipid-mediated signaling|
|nerve development|
|recycling endosome membrane|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|ephrin receptor signaling pathway|
|protein tyrosine kinase activity|
|kinase binding|
|regulation of synapse assembly|
|B cell differentiation|
|late endosome membrane|
|detection of external stimulus|
|regulation of phosphatidylinositol 3-kinase signaling|
|detection of abiotic stimulus|
|late endosome|
|male gonad development|
|development of primary male sexual characteristics|
|circadian rhythm|
|peptidyl-tyrosine phosphorylation|
|negative regulation of neuron apoptotic process|
|peptidyl-tyrosine modification|
|positive regulation of synaptic transmission|
|early endosome membrane|
|positive regulation of NF-kappaB transcription factor activity|
|B cell activation|
|male sex differentiation|
|sensory perception of mechanical stimulus|
|response to temperature stimulus|
|epithelial cell development|
|protein autophosphorylation|
|receptor complex|
|negative regulation of neuron death|
|regulation of neuron apoptotic process|
|gonad development|
|positive regulation of ERK1 and ERK2 cascade|
|endosome membrane|
|response to mechanical stimulus|
|cellular response to toxic substance|
|development of primary sexual characteristics|
|regulation of synapse organization|
|regulation of synapse structure or activity|
|lymphocyte differentiation|
|regulation of Ras protein signal transduction|
|early endosome|
|learning or memory|
|axon guidance|
|positive regulation of DNA-binding transcription factor activity|
|neuron projection guidance|
|positive regulation of MAP kinase activity|
|sex differentiation|
|rhythmic process|
|aging|
|positive regulation of neuron projection development|
|regulation of ERK1 and ERK2 cascade|
|axon|
|cognition|
|regulation of neuron death|
|cellular response to peptide|
|activation of protein kinase activity|
|leukocyte differentiation|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|regulation of small GTPase mediated signal transduction|
|response to acid chemical|
|positive regulation of neuron differentiation|
|neuronal cell body|
|axonogenesis|
|positive regulation of cell projection organization|
|lymphocyte activation|
|cellular response to drug|
|axon development|
|positive regulation of GTPase activity|
|dendrite|
|reproductive structure development|
|regulation of DNA-binding transcription factor activity|
|reproductive system development|
|cell morphogenesis involved in neuron differentiation|
|response to radiation|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|positive regulation of neurogenesis|
|response to peptide|
|neuron projection morphogenesis|
|regulation of GTPase activity|
|plasma membrane bounded cell projection morphogenesis|
|cell projection morphogenesis|
|regulation of neuron projection development|
|response to nutrient levels|
|cellular response to growth factor stimulus|
|response to toxic substance|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|cell part morphogenesis|
|regulation of protein serine/threonine kinase activity|
|positive regulation of cellular component biogenesis|
|response to growth factor|
|response to extracellular stimulus|
|response to inorganic substance|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cell development|
|positive regulation of MAPK cascade|
|detection of stimulus involved in sensory perception|
|chemotaxis|
|taxis|
|hemopoiesis|
|cell morphogenesis involved in differentiation|
|behavior|
|response to wounding|
|positive regulation of kinase activity|
|protein-containing complex|
|cellular response to organonitrogen compound|
|hematopoietic or lymphoid organ development|
|cell surface|
|Golgi membrane|
|immune system development|
|positive regulation of programmed cell death|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|neuron projection development|
|developmental process involved in reproduction|
|negative regulation of cell population proliferation|
|epithelial cell differentiation|
|detection of stimulus|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|regulation of cell projection organization|
|enzyme linked receptor protein signaling pathway|
|cell morphogenesis|
|regulation of MAPK cascade|
|positive regulation of hydrolase activity|
|regulation of protein kinase activity|
|neuron development|
|regulation of neurogenesis|
|cellular component morphogenesis|
|regulation of kinase activity|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|regulation of nervous system development|
|leukocyte activation|
|regulation of cell development|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|sensory perception|
|protein phosphorylation|
|regulation of transferase activity|
|negative regulation of cell death|
|response to organonitrogen compound|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|response to drug|
|positive regulation of intracellular signal transduction|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|cell activation|
|response to nitrogen compound|
|cell death|
|epithelium development|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|response to abiotic stimulus|
|cell projection organization|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|phosphorylation|
|locomotion|
|positive regulation of developmental process|
|nervous system process|
|integral component of plasma membrane|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|ATP binding|
|generation of neurons|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|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|
|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 intracellular signal transduction|
|regulation of protein modification process|
|system process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp261|ABT-702 5μM R06 exp261]]|-2.15|
|[[:results:exp520|Rucaparib 6.5μM R08 exp520]]|-1.89|
|[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|-1.74|
No correlation found to any other genes in chemogenomics.
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|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 6892
* **Expression level (log2 read counts)**: -1.43
{{:chemogenomics:nalm6 dist.png?nolink |}}