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Details on Person UniProt:Q3UFB7 Ntrk1
| Class:Id | ReferenceGeneProduct:198282 |
|---|---|
| _chainChangeLog | signal peptide:1-33 added on Sat February 7 2015;chain:34-799 added on Sat February 7 2015 |
| _displayName | UniProt:Q3UFB7 Ntrk1 |
| _timestamp | 2025-02-21 20:12:15 |
| chain | signal peptide:1-33 chain:34-799 |
| checksum | 1A37F76A63564603 |
| comment | FUNCTION 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, it 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. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. 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.CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY REGULATION The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. Regulated by NGFR.SUBUNIT Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a nerve growth factor (NGF)-dependent manner. Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation. Interacts with SQSTM1; bridges NTRK1 to NGFR. Forms a ternary complex with NGFR and KIDINS220; this complex is affected by the expression levels of KIDINS220 and an increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1. Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation. Interacts (phosphorylated) with SH2B1 and SH2B2. Interacts with GRB2. Interacts with PIK3R1. Interacts with FRS2. Interacts with SORT1; may regulate NTRK1 anterograde axonal transport (By similarity). Interacts with SH2D1A; regulates NTRK1 (PubMed:16223723). Interacts with NRADD. Interacts with RAB7A. Interacts with PTPRS (By similarity). Interacts with USP36; USP36 does not deubiquitinate NTRK1 (By similarity). Interacts with GGA3 (By similarity). Interacts with TSPAN1; this interaction promotes NTRK1 stability (By similarity).SUBCELLULAR LOCATION Internalized to endosomes upon binding of NGF or NTF3 and further transported to the cell body via a retrograde axonal transport. Localized at cell membrane and early endosomes before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late endosomes.DEVELOPMENTAL STAGE First detected at 13.5 dpc, a time coinciding with the requirement of sympathetic neurons for NGF.INDUCTION Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain.DOMAIN The transmembrane domain mediates interaction with KIDINS220.DOMAIN The extracellular domain mediates interaction with NGFR.PTM Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-499 mediates interaction and phosphorylation of SHC1.PTM N-glycosylated.PTM Ubiquitinated (PubMed:16113645). Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads to degradation (By similarity). Ubiquitination regulates the internalization of the receptor (PubMed:16113645).DISRUPTION PHENOTYPE Mice die early after birth due to severe sensory and sympathetic neuropathies characterized by extensive neuronal cell loss in trigeminal, sympathetic and dorsal root ganglia, as well as a decrease in the cholinergic basal forebrain projections to the hippocampus and cortex. There are for instance 35% fewer cells by 17.5 dpc in the superior cervical ganglion, a major component of the sympathetic system.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.SEQUENCE CAUTION Truncated N-terminus. |
| created | [InstanceEdit:198310] 2007-07-10 08:01:55 |
| description | recommendedName: High affinity nerve growth factor receptor ecNumber: 2.7.10.1 alternativeName: Neurotrophic tyrosine kinase receptor type 1 |
| geneName | Ntrk1 |
| identifier | Q3UFB7 |
| isSequenceChanged | FALSE |
| keyword | ATP-binding Cell membrane Developmental protein Differentiation Disulfide bond Endosome Glycoprotein Immunoglobulin domain Kinase Leucine-rich repeat Membrane Neurogenesis Nucleotide-binding Phosphoprotein Receptor Reference proteome Repeat Signal Transferase Transmembrane Transmembrane helix Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9607352] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | Ntrk1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | NTRK1_MOUSE |
| sequenceLength | 799 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:198277] Phospho-NTRK1 [plasma membrane] [Mus musculus] [EntityWithAccessionedSequence:198318] High affinity nerve growth factor receptor [plasma membrane] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:198261] O4'-phospho-L-tyrosine at 794 [ModifiedResidue:198271] O4'-phospho-L-tyrosine at 679 [ModifiedResidue:198293] O4'-phospho-L-tyrosine at 683 [ModifiedResidue:198296] O4'-phospho-L-tyrosine at 499 [ModifiedResidue:198302] O4'-phospho-L-tyrosine at 684 |
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No pathways have been reviewed or authored by UniProt:Q3UFB7 Ntrk1 (198282)
