NTRK1 - High affinity nerve growth factor receptor - human protein (Function)
 
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NTRK1 »  High affinity nerve growth factor receptor
 
Gene name:  NTRK1
Entry whose protein(s) existence is based on evidence at protein level
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1 202 4
GENE REF ISO

Function

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Overview 
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.  
6
  • CuratedUniProtKB
Isoform  TrkA-III   Is resistant to NGF, 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.  
6
  • CuratedUniProtKB
Isoform  TrkA-III   Promotes angiogenesis and has oncogenic activity when overexpressed.  
6
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Ephrin receptor bindingdefinition[GO:0046875] silver  
  • IEAOrtholog Compara
Isoforms  TrkA-II , TrkA-I and Iso 3 but not isoform  TrkA-III   Nerve growth factor bindingdefinition[GO:0048406]  
2
  • IDAUniProtKB
Nerve growth factor receptor activitydefinition[GO:0010465]  
1
  • IDAUniProtKB
Neurotrophin bindingdefinition[GO:0043121]  
1
  • TASPINC
Neurotrophin p75 receptor bindingdefinition[GO:0005166] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
4
  • IPIIntAct
  • IPIUniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
1
  • IDAUniProtKB
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • IDAUniProtKB
GO biological process 
Agingdefinition[GO:0007568] silver  
  • IEAOrtholog Compara
Axon guidancedefinition[GO:0007411] silver  
  • IEAOrtholog Compara
Axonogenesis involved in innervationdefinition[GO:0060385]  
  • ISSOrtholog Curator
B cell differentiationdefinition[GO:0030183] silver  
  • IEAOrtholog Compara
Cellular response to nerve growth factor stimulusdefinition[GO:1990090]  
  • ISSOrtholog Curator
Cellular response to nicotinedefinition[GO:0071316] silver  
  • IEAOrtholog Compara
Detection of mechanical stimulus involved in sensory perception of paindefinition[GO:0050966] silver  
  • IEAOrtholog Compara
Detection of temperature stimulus involved in sensory perception of paindefinition[GO:0050965] silver  
  • IEAOrtholog Compara
Developmental programmed cell deathdefinition[GO:0010623]  
  • ISSOrtholog Curator
Learning or memorydefinition[GO:0007611] silver  
  • IEAOrtholog Compara
Mechanoreceptor differentiationdefinition[GO:0042490] silver  
  • IEAOrtholog Compara
Not Isoform  TrkA-III   Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • IDAUniProtKB
Negative regulation of neuron apoptotic processdefinition[GO:0043524]  
  • ISSOrtholog Curator
Nerve growth factor signaling pathwaydefinition[GO:0038180] silver  
  • IEAOrtholog Compara
Neurotrophin TRK receptor signaling pathwaydefinition[GO:0048011]  
1
  • IDAUniProtKB
Olfactory nerve developmentdefinition[GO:0021553] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • IDAGOC
  • IEAEC 2 GO
  • IEAUniProtKB KW
  • IEAOrtholog Compara
  • IEAInterPro 2 GO
Isoform  TrkA-III   Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • IDAUniProtKB
Not Isoform  TrkA-III   Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • IDAUniProtKB
Not Isoform  TrkA-III   Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • IDAUniProtKB
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • IDAUniProtKB
Positive regulation of programmed cell deathdefinition[GO:0043068]  
  • ISSOrtholog Curator
Not Isoform  TrkA-III   Positive regulation of Ras GTPase activitydefinition[GO:0032320]  
1
  • IDAUniProtKB
Not Isoform  TrkA-III   Positive regulation of Ras protein signal transductiondefinition[GO:0046579]  
1
  • IDAUniProtKB
Positive regulation of synaptic transmission, glutamatergicdefinition[GO:0051968] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Response to activitydefinition[GO:0014823] silver  
  • IEAOrtholog Compara
Response to axon injurydefinition[GO:0048678] silver  
  • IEAOrtholog Compara
Response to drugdefinition[GO:0042493] silver  
  • IEAOrtholog Compara
Response to electrical stimulusdefinition[GO:0051602] silver  
  • IEAOrtholog Compara
Response to ethanoldefinition[GO:0045471] silver  
  • IEAOrtholog Compara
Response to hydrostatic pressuredefinition[GO:0051599] silver  
  • IEAOrtholog Compara
Response to nutrient levelsdefinition[GO:0031667] silver  
  • IEAOrtholog Compara
Response to radiationdefinition[GO:0009314] silver  
  • IEAOrtholog Compara
Sertoli cell developmentdefinition[GO:0060009] silver  
  • IEAOrtholog Compara
Sympathetic nervous system developmentdefinition[GO:0048485]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
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).  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Apoptosis  hsa04210+4914  
Endocytosis  hsa04144+4914  
MAPK signaling pathway  hsa04010+4914  
Neurotrophin signaling pathway  hsa04722+4914  
Pathways in cancer  hsa05200+4914  
Thyroid cancer  hsa05216+4914  
According to Reactome, this protein belongs to the following pathways:
ARMS-mediated activation  REACT_12002  
Frs2-mediated activation  REACT_12076  
NGF-independant TRKA activation  REACT_11046  
PI3K/AKT activation  REACT_12464  
PLC-gamma1 signalling  REACT_12079  
Retrograde neurotrophin signalling  REACT_12435  
Signalling to p38 via RIT and RIN  REACT_12077  
Signalling to RAS  REACT_12033  
Signalling to STAT3  REACT_12049  
TRKA activation by NGF  REACT_11060  
Note 
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.  
  • CuratedUniProtKB
 

Keywords

Biological process 
Differentiation  definition   [KW-0221]
Neurogenesis  definition   [KW-0524]
Molecular function 
Developmental protein  definition   [KW-0217]
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GenomeRNAi: 4914
PRO: PR:P04629
Chemistry
GuidetoPHARMACOLOGY: 1817