NTRK1 - High affinity nerve growth factor receptor - human protein (Function)
 
Home Recent activites arrow-down favorite My favorites arrow-down favorite My labels arrow-down Downloads
Protein
Gene
References

 
NTRK1 »  High affinity nerve growth factor receptor   [ EC 2.7.10.1 ]
 
Protein also known as:  Neurotrophic tyrosine kinase receptor type 1.
Gene name:  NTRK1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 212 4
GENE REF ISO

Function

 show evidences
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.  
1
  • UniProtKB
Isoform  TrkA-III   Promotes angiogenesis and has oncogenic activity when overexpressed.  
1
  • UniProtKB
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.  
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Ephrin receptor bindingdefinition[GO:0046875] silver  
1
  • Ortholog Compara
Isoforms  TrkA-II , TrkA-I and Iso 3 but not isoform  TrkA-III   Nerve growth factor bindingdefinition[GO:0048406]  
2
  • UniProtKB
Nerve growth factor receptor activitydefinition[GO:0010465]  
1
  • UniProtKB
Neurotrophin bindingdefinition[GO:0043121]  
1
  • PINC
Neurotrophin p75 receptor bindingdefinition[GO:0005166] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
7
  • IntAct
  • UniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
1
  • UniProtKB
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • UniProtKB
GO biological process 
Agingdefinition[GO:0007568] silver  
1
  • Ortholog Compara
Axon guidancedefinition[GO:0007411] silver  
1
  • Ortholog Compara
Axonogenesis involved in innervationdefinition[GO:0060385]  
1
  • Ortholog Curator
B cell differentiationdefinition[GO:0030183] silver  
1
  • Ortholog Compara
Cellular response to nerve growth factor stimulusdefinition[GO:1990090]  
1
  • Ortholog Curator
Cellular response to nicotinedefinition[GO:0071316] silver  
1
  • Ortholog Compara
Circadian rhythmdefinition[GO:0007623] silver  
1
  • Ortholog Compara
Detection of mechanical stimulus involved in sensory perception of paindefinition[GO:0050966] silver  
1
  • Ortholog Compara
Detection of temperature stimulus involved in sensory perception of paindefinition[GO:0050965] silver  
1
  • Ortholog Compara
Developmental programmed cell deathdefinition[GO:0010623]  
1
  • Ortholog Curator
Learning or memorydefinition[GO:0007611] silver  
1
  • Ortholog Compara
Mechanoreceptor differentiationdefinition[GO:0042490] silver  
1
  • Ortholog Compara
Not Isoform  TrkA-III   Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • UniProtKB
Negative regulation of neuron apoptotic processdefinition[GO:0043524]  
1
  • Ortholog Curator
Nerve growth factor signaling pathwaydefinition[GO:0038180] silver  
1
  • Ortholog Compara
Neurotrophin TRK receptor signaling pathwaydefinition[GO:0048011]  
1
  • UniProtKB
Olfactory nerve developmentdefinition[GO:0021553] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
4
  • GOC
  • EC 2 GO
  • UniProtKB KW
  • InterPro 2 GO
Isoform  TrkA-III   Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • UniProtKB
Not Isoform  TrkA-III   Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • UniProtKB
Not Isoform  TrkA-III   Positive regulation of GTPase activitydefinition[GO:0043547]  
1
  • UniProtKB
Not Isoform  TrkA-III   Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • UniProtKB
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • UniProtKB
Positive regulation of programmed cell deathdefinition[GO:0043068]  
1
  • Ortholog Curator
Not Isoform  TrkA-III   Positive regulation of Ras protein signal transductiondefinition[GO:0046579]  
1
  • UniProtKB
Positive regulation of synaptic transmission, glutamatergicdefinition[GO:0051968] silver  
1
  • Ortholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
1
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Response to activitydefinition[GO:0014823] silver  
1
  • Ortholog Compara
Response to axon injurydefinition[GO:0048678] silver  
1
  • Ortholog Compara
Response to drugdefinition[GO:0042493] silver  
1
  • Ortholog Compara
Response to electrical stimulusdefinition[GO:0051602] silver  
1
  • Ortholog Compara
Response to ethanoldefinition[GO:0045471] silver  
1
  • Ortholog Compara
Response to hydrostatic pressuredefinition[GO:0051599] silver  
1
  • Ortholog Compara
Response to nutrient levelsdefinition[GO:0031667] silver  
1
  • Ortholog Compara
Response to radiationdefinition[GO:0009314] silver  
1
  • Ortholog Compara
Sertoli cell developmentdefinition[GO:0060009] silver  
1
  • Ortholog Compara
Sympathetic nervous system developmentdefinition[GO:0048485]  
1
  • Ortholog 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.  
2
  • PROSITE-ProRule
  • UniProtKB
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
  • UniProtKB
 
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.  
1
  • UniProtKB
 

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