Tclin NTRK1 High affinity nerve growth factor receptor

Protein Summary

Description

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, PubMed:27445338). 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. Isoform TrkA-III: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. 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 Accession IDs

• P04629
• B2R6T5
• B7ZM34
• P08119
• Q15655
• Q15656
• Q5D056
• Q5VZS2
• Q7Z5C3
• Q9UIU7

Gene Name

• NTRK1

Ensembl ID

• ENST00000368196
• ENSP00000357179
• ENSG00000198400
• ENST00000392302
• ENSP00000376120
• ENST00000524377
• ENSP00000431418

Symbol

• MTC
• TRK
• TRKA
• MTC
• TRK
• TRK1
• TRKA
• Trk-A
• p140-TrkA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	1
protein domain	1
hub protein	0.99
biological term	0.96

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Trk Family / High Affinity Nerve Growth Factor Receptor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2428.95   (req: < 5)

Gene RIFs: 273   (req: <= 3)

Antibodies: 1414   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2428.95   (req: >= 5)

Gene RIFs: 273   (req: > 3)

Antibodies: 1414   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 58

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1271

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 7