Protein:NTRK1 |
Protein Summary |
 Gene summary |
| Gene name: NTRK1 | ASpdb.0 ID: 4914 | Gene | Gene symbol | NTRK1 | Gene ID | 4914 |
| Gene name | neurotrophic receptor tyrosine kinase 1 |
| Synonyms | MTC|TRK|TRK1|TRKA|Trk-A|p140-TrkA |
| Cytomap | 1q23.1 |
| Type of gene | protein-coding |
| Description | high affinity nerve growth factor receptorOncogene TRKTRK1-transforming tyrosine kinase proteingp140trkneurotrophic tyrosine kinase, receptor, type 1tropomyosin receptor kinase Atropomyosin-related kinase Atyrosine kinase receptor A |
| Modification date | 20240411 |
| UniProtAcc | P04629 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | NTRK1 | GO:0004713 | protein tyrosine kinase activity | 2927393 |
| Gene | NTRK1 | GO:0004714 | transmembrane receptor protein tyrosine kinase activity | 15488758 |
| Gene | NTRK1 | GO:0005886 | plasma membrane | 1281417|2927393|15488758 |
| Gene | NTRK1 | GO:0006468 | protein phosphorylation | 15488758 |
| Gene | NTRK1 | GO:0008285 | negative regulation of cell population proliferation | 15488758 |
| Gene | NTRK1 | GO:0010465 | nerve growth factor receptor activity | 15488758 |
| Gene | NTRK1 | GO:0010976 | positive regulation of neuron projection development | 15488758 |
| Gene | NTRK1 | GO:0018108 | peptidyl-tyrosine phosphorylation | 2927393 |
| Gene | NTRK1 | GO:0042803 | protein homodimerization activity | 1281417|17196528 |
| Gene | NTRK1 | GO:0043235 | receptor complex | 23382219 |
| Gene | NTRK1 | GO:0043547 | positive regulation of GTPase activity | 15488758 |
| Gene | NTRK1 | GO:0046579 | positive regulation of Ras protein signal transduction | 15488758 |
| Gene | NTRK1 | GO:0046777 | protein autophosphorylation | 15488758 |
| Gene | NTRK1 | GO:0048011 | neurotrophin TRK receptor signaling pathway | 15488758 |
| Gene | NTRK1 | GO:0048406 | nerve growth factor binding | 1281417|15488758|17196528 |
| Gene | NTRK1 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 15488758 |
| Gene | NTRK1 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 15488758 |
| Gene | NTRK1 | GO:1904646 | cellular response to amyloid-beta | 11927634 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P04629-1 | P04629-1_2ifg_A.pdb | 2IFG | X-ray | 3.4 | A | 36 | 382 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P04629 | NTRK1 | P04629-1 | P04629-2 | 796 | 790 | 393 | 398 | Deletion | none | none | 392 | 392 |
| P04629 | NTRK1 | P04629-1 | P04629-4 | 796 | 698 | 192 | 284 | Substitution | GVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSF | V | 192 | 192 |
| P04629 | NTRK1 | P04629-1 | P04629-4 | 796 | 698 | 393 | 398 | Deletion | none | none | 300 | 300 |
| Multiple sequence alignment of our canonical and alternatively spliced NTRK1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of NTRK1 |
| UniProt-id | ENSG | ENST | ENSP |
| P04629-1 | ENSG00000198400.14 | ENST00000524377.7 | ENSP00000431418.1 |
| P04629-2 | ENSG00000198400.14 | ENST00000368196.7 | ENSP00000357179.3 |
| UniProt-id | NM ID | NP ID |
| P04629-1 | NM_002529.3 | NP_002520.2 |
| P04629-2 | NM_001012331.1 | NP_001012331.1 |
| Amino acid sequences of our canonical and alternatively spliced NTRK1 |
| accession_id | Protein sequence |
| P04629-1 | MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGL GELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ GPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAEND VGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYT LLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGI NRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKML VAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAV ASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEI |
| P04629-2 | MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGL GELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ GPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAEND VGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYT LLAANPFGQASASIMAAFMDNPFEFNPEDPIPDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVL APEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKAL KEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAA GMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQ |
| P04629-4 | MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGL GELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ GPLAHMPNASCVPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLL AANPFGQASASIMAAFMDNPFEFNPEDPIPDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAP EDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKE ASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGM VYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPW |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| NTRK1 (go to UniProt):P04629 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P04629 | Topological domain | 33 | 423 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=393;End=398 |
| P04629 | Topological domain | 33 | 423 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=192;End=284 |
| P04629 | Topological domain | 33 | 423 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=393;End=398 |
| P04629 | Domain | 148 | 193 | Note=LRRCT | Type=Substitution;Start=192;End=284 |
| P04629 | Domain | 194 | 283 | Note=Ig-like C2-type 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00114 | Type=Substitution;Start=192;End=284 |
Gene Isoform Structures and Expression Levels for NTRK1 |
| Gene structures of our canonical and alternative spliced genes of NTRK1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P04629-1 |
| 3D view using mol* of P04629-2 |
| 3D view using mol* of P04629-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P04629-1 |
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| pLDDT distribution across the protein length of P04629-2 |
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| pLDDT distribution across the protein length of P04629-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P04629-1 |
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| Ramachandran plot of P04629-2 |
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| Ramachandran plot of P04629-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P04629-1 | 1.072 | 336 | 1.086 | 760.088 | 0.434 | 0.802 | 1.114 | 1.448 | 1.028 | 1.409 | 1.138 | 458,459,460,461,462,463,464,465,466,467,468,469,47 0,471,472,473,474,490,492,493,494,495,496,497,498, 500,520,521,544,546,547,548,550,552,553,555,556,55 7,559,560,562,563,564,566,567,572,573,575,589,641, 646,648,649,666,667,668,669,687,702,704 |
| P04629-2 | 1.029 | 172 | 1.049 | 680.512 | 0.63 | 0.736 | 0.891 | 0.585 | 1.021 | 0.573 | 1.058 | 484,485,486,487,490,491,515,538,540,541,542,547,55 0,551,553,554,557,558,561,566,567,581,583,635,639, 640,641,642,643,644,649,660,661,662,663,664,667,67 4,682,696,697,698 |
| P04629-4 | 1.112 | 158 | 1.094 | 362.208 | 0.406 | 0.865 | 1.201 | 1.044 | 1.12 | 0.932 | 1.44 | 262,293,295,296,297,298,299,417,418,419,420,444,49 2,493,494,495,496,497,498,501,502,504,505,513,556, 557,559,571,572,573,574,576,577 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P04629-1_P04629-1_2ifg_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P04629-1_2ifg_A_P04629-2.pdb |
| 3D view using mol* of P04629-1_2ifg_A_P04629-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P04629-1_P04629-2.pdb |
| 3D view using mol* of P04629-1_P04629-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P04629-1_vs_P04629-2.png |
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| ./stats/secondary_structure/figure/P04629-1_vs_P04629-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P04629-1_vs_P04629-2.png |
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| ./stats/relative_asa/P04629-1_vs_P04629-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to NTRK1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P04629 | NTRK1 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P04629 | NTRK1 | DB15822 | Pralsetinib | approved, investigational | inhibitor |
| P04629 | NTRK1 | DB00321 | Amitriptyline | approved | agonist, activator |
| P04629 | NTRK1 | DB14723 | Larotrectinib | approved, investigational | inhibitor |
| P04629 | NTRK1 | DB11986 | Entrectinib | approved, investigational | inhibitor |
| P04629 | NTRK1 | DB08896 | Regorafenib | approved | inhibitor |
| P04629 | NTRK1 | DB16826 | Repotrectinib | approved, investigational | inhibitor |
| P04629 | NTRK1 | DB13926 | Cenegermin | approved, investigational | stimulator |
| P04629 | NTRK1 | DB00619 | Imatinib | approved | antagonist |
Related Diseases to NTRK1 |
| Previous studies relating to the alternative splicing of NTRK1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| NTRK1 | 7565764 | The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. | Oncogenic rearrangements of the NTRK1 gene (also designated TRKA), encoding one of the receptors for the nerve growth factor, are frequently detected in thyroid carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end sequences belonging to different genes. In previously reported studies we have demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR, both localized similarly to the receptor tyrosine kinase, on the q arm of chromosome 1. Here we report the characterization of a novel NTRK1-derived thyroid oncogene, named TRK-T3. A cDNA clone, capable of transforming activity, was isolated from a transformant cell line. Sequence analysis revealed that TRK-T3 contains 1,412 nucleotides of NTRK1 preceded by 598 nucleotides belonging to a novel gene that we have named TFG (TRK-fused gene). The TRK-T3 amino acid sequence displays, within the TFG region, a coiled-coil motif that could endow the oncoprotein with the capability to form complexes. The TRK-T3 oncogene encodes a 68-kDa cytoplasmic protein reacting with NTRK1-specific antibodies. By sedimentation gradient experiments the TRK-T3 oncoprotein was shown to form, in vivo, multimeric complexes, most likely trimers or tetramers. The TFG gene is ubiquitously expressed and is located on chromosome 3. The breakpoint producing the TRK-T3 oncogene occurs within exons of both the TFG gene and the NTRK1 gene and produces a chimeric exon that undergoes alternative splicing. Molecular analysis of the NTRK1 rearranged fragments indicated that the chromosomal rearrangement is reciprocal and balanced and involves loss of a few nucleotides of germ line sequences. | D002277 | Carcinoma |
| NTRK1 | 7565764 | The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. | Oncogenic rearrangements of the NTRK1 gene (also designated TRKA), encoding one of the receptors for the nerve growth factor, are frequently detected in thyroid carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end sequences belonging to different genes. In previously reported studies we have demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR, both localized similarly to the receptor tyrosine kinase, on the q arm of chromosome 1. Here we report the characterization of a novel NTRK1-derived thyroid oncogene, named TRK-T3. A cDNA clone, capable of transforming activity, was isolated from a transformant cell line. Sequence analysis revealed that TRK-T3 contains 1,412 nucleotides of NTRK1 preceded by 598 nucleotides belonging to a novel gene that we have named TFG (TRK-fused gene). The TRK-T3 amino acid sequence displays, within the TFG region, a coiled-coil motif that could endow the oncoprotein with the capability to form complexes. The TRK-T3 oncogene encodes a 68-kDa cytoplasmic protein reacting with NTRK1-specific antibodies. By sedimentation gradient experiments the TRK-T3 oncoprotein was shown to form, in vivo, multimeric complexes, most likely trimers or tetramers. The TFG gene is ubiquitously expressed and is located on chromosome 3. The breakpoint producing the TRK-T3 oncogene occurs within exons of both the TFG gene and the NTRK1 gene and produces a chimeric exon that undergoes alternative splicing. Molecular analysis of the NTRK1 rearranged fragments indicated that the chromosomal rearrangement is reciprocal and balanced and involves loss of a few nucleotides of germ line sequences. | D002869 | Chromosome Aberrations |
| NTRK1 | 7565764 | The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. | Oncogenic rearrangements of the NTRK1 gene (also designated TRKA), encoding one of the receptors for the nerve growth factor, are frequently detected in thyroid carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end sequences belonging to different genes. In previously reported studies we have demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR, both localized similarly to the receptor tyrosine kinase, on the q arm of chromosome 1. Here we report the characterization of a novel NTRK1-derived thyroid oncogene, named TRK-T3. A cDNA clone, capable of transforming activity, was isolated from a transformant cell line. Sequence analysis revealed that TRK-T3 contains 1,412 nucleotides of NTRK1 preceded by 598 nucleotides belonging to a novel gene that we have named TFG (TRK-fused gene). The TRK-T3 amino acid sequence displays, within the TFG region, a coiled-coil motif that could endow the oncoprotein with the capability to form complexes. The TRK-T3 oncogene encodes a 68-kDa cytoplasmic protein reacting with NTRK1-specific antibodies. By sedimentation gradient experiments the TRK-T3 oncoprotein was shown to form, in vivo, multimeric complexes, most likely trimers or tetramers. The TFG gene is ubiquitously expressed and is located on chromosome 3. The breakpoint producing the TRK-T3 oncogene occurs within exons of both the TFG gene and the NTRK1 gene and produces a chimeric exon that undergoes alternative splicing. Molecular analysis of the NTRK1 rearranged fragments indicated that the chromosomal rearrangement is reciprocal and balanced and involves loss of a few nucleotides of germ line sequences. | D025063 | Chromosome Disorders |
| NTRK1 | 7565764 | The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. | Oncogenic rearrangements of the NTRK1 gene (also designated TRKA), encoding one of the receptors for the nerve growth factor, are frequently detected in thyroid carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end sequences belonging to different genes. In previously reported studies we have demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR, both localized similarly to the receptor tyrosine kinase, on the q arm of chromosome 1. Here we report the characterization of a novel NTRK1-derived thyroid oncogene, named TRK-T3. A cDNA clone, capable of transforming activity, was isolated from a transformant cell line. Sequence analysis revealed that TRK-T3 contains 1,412 nucleotides of NTRK1 preceded by 598 nucleotides belonging to a novel gene that we have named TFG (TRK-fused gene). The TRK-T3 amino acid sequence displays, within the TFG region, a coiled-coil motif that could endow the oncoprotein with the capability to form complexes. The TRK-T3 oncogene encodes a 68-kDa cytoplasmic protein reacting with NTRK1-specific antibodies. By sedimentation gradient experiments the TRK-T3 oncoprotein was shown to form, in vivo, multimeric complexes, most likely trimers or tetramers. The TFG gene is ubiquitously expressed and is located on chromosome 3. The breakpoint producing the TRK-T3 oncogene occurs within exons of both the TFG gene and the NTRK1 gene and produces a chimeric exon that undergoes alternative splicing. Molecular analysis of the NTRK1 rearranged fragments indicated that the chromosomal rearrangement is reciprocal and balanced and involves loss of a few nucleotides of germ line sequences. | D013964 | Thyroid Neoplasms |
| NTRK1 | 7565764 | The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. | Oncogenic rearrangements of the NTRK1 gene (also designated TRKA), encoding one of the receptors for the nerve growth factor, are frequently detected in thyroid carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end sequences belonging to different genes. In previously reported studies we have demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR, both localized similarly to the receptor tyrosine kinase, on the q arm of chromosome 1. Here we report the characterization of a novel NTRK1-derived thyroid oncogene, named TRK-T3. A cDNA clone, capable of transforming activity, was isolated from a transformant cell line. Sequence analysis revealed that TRK-T3 contains 1,412 nucleotides of NTRK1 preceded by 598 nucleotides belonging to a novel gene that we have named TFG (TRK-fused gene). The TRK-T3 amino acid sequence displays, within the TFG region, a coiled-coil motif that could endow the oncoprotein with the capability to form complexes. The TRK-T3 oncogene encodes a 68-kDa cytoplasmic protein reacting with NTRK1-specific antibodies. By sedimentation gradient experiments the TRK-T3 oncoprotein was shown to form, in vivo, multimeric complexes, most likely trimers or tetramers. The TFG gene is ubiquitously expressed and is located on chromosome 3. The breakpoint producing the TRK-T3 oncogene occurs within exons of both the TFG gene and the NTRK1 gene and produces a chimeric exon that undergoes alternative splicing. Molecular analysis of the NTRK1 rearranged fragments indicated that the chromosomal rearrangement is reciprocal and balanced and involves loss of a few nucleotides of germ line sequences. | D014178 | Translocation, Genetic |
| NTRK1 | 19564412 | The alternative TrkAIII splice variant targets the centrosome and promotes genetic instability. | "The hypoxia-regulated alternative TrkAIII splice variant expressed by human neuroblastomas exhibits oncogenic potential, driven by in-frame exon 6 and 7 alternative splicing, leading to omission of the receptor extracellular immunoglobulin C(1) domain and several N-glycosylation sites. Here, we show that the TrkAIII oncogene promotes genetic instability by interacting with and exhibiting catalytic activity at the centrosome. This function depends upon intracellular TrkAIII accumulation and spontaneous interphase-restricted activation, in cytoplasmic tyrosine kinase (tk) domain orientation, predominantly within structures that closely associate with the fully assembled endoplasmic reticulum intermediate compartment and Golgi network. This facilitates TrkAIII tk-mediated binding of gamma-tubulin, which is regulated by endogenous protein tyrosine phosphatases and geldanamycin-sensitive interaction with Hsp90, paving the way for TrkAIII recruitment to the centrosome. At the centrosome, TrkAIII differentially phosphorylates several centrosome-associated components, increases centrosome interaction with polo kinase 4, and decreases centrosome interaction with separase, the net results of which are centrosome amplification and increased genetic instability. The data characterize TrkAIII as a novel internal membrane-associated centrosome kinase, unveiling an important alternative mechanism to ""classical"" cell surface oncogenic receptor tk signaling through which stress-regulated alternative TrkAIII splicing influences the oncogenic process." | D042822 | Genomic Instability |
| NTRK1 | 19564412 | The alternative TrkAIII splice variant targets the centrosome and promotes genetic instability. | "The hypoxia-regulated alternative TrkAIII splice variant expressed by human neuroblastomas exhibits oncogenic potential, driven by in-frame exon 6 and 7 alternative splicing, leading to omission of the receptor extracellular immunoglobulin C(1) domain and several N-glycosylation sites. Here, we show that the TrkAIII oncogene promotes genetic instability by interacting with and exhibiting catalytic activity at the centrosome. This function depends upon intracellular TrkAIII accumulation and spontaneous interphase-restricted activation, in cytoplasmic tyrosine kinase (tk) domain orientation, predominantly within structures that closely associate with the fully assembled endoplasmic reticulum intermediate compartment and Golgi network. This facilitates TrkAIII tk-mediated binding of gamma-tubulin, which is regulated by endogenous protein tyrosine phosphatases and geldanamycin-sensitive interaction with Hsp90, paving the way for TrkAIII recruitment to the centrosome. At the centrosome, TrkAIII differentially phosphorylates several centrosome-associated components, increases centrosome interaction with polo kinase 4, and decreases centrosome interaction with separase, the net results of which are centrosome amplification and increased genetic instability. The data characterize TrkAIII as a novel internal membrane-associated centrosome kinase, unveiling an important alternative mechanism to ""classical"" cell surface oncogenic receptor tk signaling through which stress-regulated alternative TrkAIII splicing influences the oncogenic process." | D009447 | Neuroblastoma |
Clinically important variants in NTRK1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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