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Details on Person UniProt:P04629-1 NTRK1
| Class:Id | ReferenceIsoform:66431 |
|---|---|
| _chainChangeLog | signal peptide:1-32 added on Fri February 6 2015;chain:33-796 added on Fri February 6 2015 |
| _displayName | UniProt:P04629-1 NTRK1 |
| _timestamp | 2025-02-21 20:12:15 |
| chain | signal peptide:1-32 chain:33-796 |
| checksum | 6C15C721E336B601 |
| 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 (PubMed:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). 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.FUNCTION 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.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 (By similarity). Regulated by NGFR (By similarity).SUBUNIT Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer (PubMed:10490030, PubMed:1281417, PubMed:17196528). Interacts with SQSTM1; bridges NTRK1 to NGFR (PubMed:11244088). 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 (By similarity). Interacts with SH2D1A; regulates NTRK1 (By similarity). Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation (PubMed:15488758, PubMed:8155326). Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation (PubMed:15488758, PubMed:7510697). Interacts (phosphorylated) with SH2B1 and SH2B2 (By similarity). Interacts with GRB2 (PubMed:15488758). Interacts with PIK3R1 (PubMed:15488758). Interacts with FRS2 (PubMed:15488758). Interacts with SORT1; may regulate NTRK1 anterograde axonal transport (PubMed:21102451). Interacts with RAB7A (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 (By similarity). Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation (By similarity). Interacts with PTPRS (By similarity). Interacts with USP36; USP36 does not deubiquitinate NTRK1 (PubMed:27445338). Interacts with GGA3 (PubMed:26446845). Interacts with TSPAN1; this interaction promotes NTRK1 stability (By similarity).INTERACTION Rapidly internalized after NGF binding (PubMed:1281417). 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.ALTERNATIVE PRODUCTS TrkA-I and TrkA-II isoforms have similar biological properties but are differentially expressed.TISSUE SPECIFICITY Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors.INDUCTION Isoform TrkA-III is up-regulated upon hypoxia in cells normally expressing it.DOMAIN The transmembrane domain mediates interaction with KIDINS220.DOMAIN The extracellular domain mediates interaction with NGFR.PTM Ligand-mediated autophosphorylation (PubMed:1281417, PubMed:15488758, PubMed:27676246, PubMed:28177573, PubMed:2927393, PubMed:7510697, PubMed:8155326, PubMed:8325889). Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1 (PubMed:15488758, PubMed:7510697, PubMed:8155326, PubMed:8325889).PTM N-glycosylated (PubMed:2927393). Isoform TrkA-I and isoform TrkA-II are N-glycosylated.PTM Ubiquitinated (PubMed:27445338). Undergoes polyubiquitination upon activation; regulated by NGFR (PubMed:27445338). Ubiquitination by NEDD4L leads to degradation (PubMed:27445338). Ubiquitination regulates the internalization of the receptor (By similarity).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Chromosomal aberrations involving NTRK1 are found in papillary thyroid carcinomas (PTCs) (PubMed:1532241, PubMed:2869410, PubMed:7565764). Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1 (PubMed:7565764). A rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1 (PubMed:2869410). An intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein (PubMed:1532241).MISCELLANEOUS Trk also stands for tropomyosin-related kinase since it was first isolated as an oncogenic protein which was the result of a fusion between the tropomyosin gene TPM3 and NTRK1.MISCELLANEOUS Major isoform.MISCELLANEOUS Has enhanced responsiveness to NTF3 neurotrophin.MISCELLANEOUS Constitutively active. Does not bind NGF and does not interact with GRB2 and FRS2.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.SEQUENCE CAUTION Truncated C-terminus.SEQUENCE CAUTION Contaminating sequence. Sequence of unknown origin in the N-terminal part.SEQUENCE CAUTION Contaminating sequence. Sequence of unknown origin in the N-terminal part.SEQUENCE CAUTION Contaminating sequence. Sequence of unknown origin in the N-terminal part.SEQUENCE CAUTION Contaminating sequence. Sequence of unknown origin in the N-terminal part. |
| description | recommendedName: High affinity nerve growth factor receptor ecNumber evidence="20 37"2.7.10.1 alternativeName: Neurotrophic tyrosine kinase receptor type 1 alternativeName: TRK1-transforming tyrosine kinase protein alternativeName: Tropomyosin-related kinase A alternativeName: Tyrosine kinase receptor alternativeName: Tyrosine kinase receptor A shortName: Trk-A alternativeName: fullName evidence="45"gp140trk alternativeName: p140-TrkA |
| geneName | NTRK1 MTC TRK TRKA |
| identifier | P04629 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing ATP-binding Cell membrane Chromosomal rearrangement Developmental protein Differentiation Disease variant Disulfide bond Endosome Glycoprotein Immunoglobulin domain Kinase Leucine-rich repeat Membrane Neurogenesis Nucleotide-binding Phosphoprotein Proteomics identification Proto-oncogene Receptor Reference proteome Repeat Signal Transferase Transmembrane Transmembrane helix Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | NTRK1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990285] ENSEMBL:ENSG00000198400 NTRK1 [Homo sapiens] |
| secondaryIdentifier | NTRK1_HUMAN B2R6T5 B7ZM34 P08119 Q15655 Q15656 Q5D056 Q5VZS2 Q7Z5C3 Q9UIU7 |
| sequenceLength | 796 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P04629-1 |
| (referenceEntity) | [EntityWithAccessionedSequence:162555] NTRK-1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:187672] NTRK1-1 [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:190064] p-5Y-NTRK1-1 [endosome membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P04629-1 NTRK1 (66431)
