Homo sapiens Protein: NTRK1 | |||||||||||||||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-245933.6 | ||||||||||||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||||||||||
Gene Symbol | NTRK1 | ||||||||||||||||||||||||||||||||||||||||||||||||
Protein Name | neurotrophic tyrosine kinase, receptor, type 1 | ||||||||||||||||||||||||||||||||||||||||||||||||
Synonyms | MTC; p140-TrkA; TRK; Trk-A; TRK1; TRKA; | ||||||||||||||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000376120 | ||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-103632 (NTRK1) | ||||||||||||||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||||||||||||||
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.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. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. | ||||||||||||||||||||||||||||||||||||||||||||||||
Subcellular Localization | Cell membrane {ECO:0000269PubMed:15488758}; Single-pass type I membrane protein {ECO:0000269PubMed:15488758}. Early endosome membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Late endosome membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Note=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 (By similarity). {ECO:0000250}. | ||||||||||||||||||||||||||||||||||||||||||||||||
Disease Associations | Congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]: Characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II. {ECO:0000269PubMed:10090906, ECO:0000269PubMed:10233776, ECO:0000269PubMed:10330344, ECO:0000269PubMed:10567924, ECO:0000269PubMed:10861667, ECO:0000269PubMed:10982191, ECO:0000269PubMed:11310631, ECO:0000269PubMed:22302274, ECO:0000269PubMed:8696348}. Note=The disease is caused by mutations affecting the gene represented in this entry.Thyroid papillary carcinoma (TPC) [MIM:188550]: A common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving NTRK1 are found in thyroid papillary carcinomas. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1; 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. | ||||||||||||||||||||||||||||||||||||||||||||||||
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. {ECO:0000269PubMed:15488758, ECO:0000269PubMed:8325889}. | ||||||||||||||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 65 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||||||||||||||
InterPro |
IPR000483
Cysteine-rich flanking region, C-terminal IPR000719 Protein kinase domain IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain IPR007110 Immunoglobulin-like domain IPR011009 Protein kinase-like domain IPR020461 Tyrosine-protein kinase, neurotrophic receptor, type 1 IPR020635 Tyrosine-protein kinase, catalytic domain IPR020777 Tyrosine-protein kinase, neurotrophic receptor |
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PFAM |
PF01463
PF00069 PF07714 |
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PRINTS |
PR00109
PR01940 PR01939 |
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PIRSF | |||||||||||||||||||||||||||||||||||||||||||||||||
SMART |
SM00082
SM00220 SM00219 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||||||||||||||
SwissProt | P04629 | ||||||||||||||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P04629 | ||||||||||||||||||||||||||||||||||||||||||||||||
TrEMBL | |||||||||||||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||||||||||
Entrez Gene | 4914 | ||||||||||||||||||||||||||||||||||||||||||||||||
UniGene | Hs.406293 | ||||||||||||||||||||||||||||||||||||||||||||||||
RefSeq | NP_001007793 | ||||||||||||||||||||||||||||||||||||||||||||||||
HUGO | HGNC:8031 | ||||||||||||||||||||||||||||||||||||||||||||||||
OMIM | 191315 | ||||||||||||||||||||||||||||||||||||||||||||||||
CCDS | CCDS30890 | ||||||||||||||||||||||||||||||||||||||||||||||||
HPRD | 01869 | ||||||||||||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||||||||||||
EMBL | AB019488 AK312704 AL158169 AY321513 BC062580 BC136554 BC144239 DB265639 M23102 X03541 X06704 X62947 X85960 | ||||||||||||||||||||||||||||||||||||||||||||||||
GenPept | AAA36770 AAH62580 AAI36555 AAI44240 AAP88292 BAA34355 BAG35582 CAA27243 CAA29888 CAA44719 CAA59936 CAH70010 | ||||||||||||||||||||||||||||||||||||||||||||||||