TPR (Translocated promoter region)
2002-03-01 Brigitte David-Watine AffiliationUnité de Biologie Cellulaire du Noyau, CNRS URA 2582, Département de Biologie Cellulaire et Infection, Institut Pasteur, 25, Rue du Docteur Roux, 75724 Paris Cedex 15, France
Identity
HGNC
LOCATION
1q31.1
IMAGE
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
-
FUSION GENES
DNA/RNA
Description
51-52 exons spanning about 63 kb
Transcription
in a telomeric to centromeric direction. 10kb mRNA.
Proteins
Description
2349 amino acids, 267 kDa. The protein contains extensive coilecoiled domains and an acidic globular C-terminus, and is phosphorylated.
Expression
widespread, if not ubiquitous; highest in testis, thymus, spleen and brain, lower levels in heart, liver and kidney.
Localisation
nucleoplasmic side of the nucleopore and discrete foci in the nuclear interior, binds to the nucleoporin Nup98.
Function
still controversial, part of a filamentous intranuclear network, role in nuclear protein and/or polyA+RNA export.
Homology
yeast Mlp1 and Mlp2, drosophila Bx34 , xenopus Tpr.
Mutations
Note
Tpr was first described as a fusion partner with the MET oncogene (7q) in a cell line rendered tumorigenic with the direct acting carcinogen N-methyl-N-prime-nitrosoguanidine (MNNG). Then, this Tpr-MET rearrangement was also described in gastric cancers and a TRK-Tpr fusion was found in thyroid cancers. Fusions with at least one other proto-oncogene have since been described.
Implicated in
Disease
the TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions
Hybrid gene
5 TPR- 3MET 5 kb mRNA
Fusion protein
65 kDa, The fusion protein contains the constitutive promoter and first 424 coding nucleotides (142 amino acids) of Tpr, and the the tyrosine kinase domain of the c-met protooncogene.
Oncogenesis
transgenic expression of TPR-MET oncogene leads to development of mammary hyperplasia and tumors.
Hybrid gene
TRK-T1 (TPR-NTRK1): 598 nucleotides of the TPR gene 5 end are fused to 1148 bp of the TRK proto-oncogene which contain the TRK tyrosine kinase domain. TRK-T2 : 3073 nucleotides of Tpr 5 end fused to 1412 nucleotides of TRK . There is another hybrid gene between TPR and NTRK1 named TRK-T4. Arise by paracentric inversions on chromosome 1.
Fusion protein
55 kDa for the TRK-T1 fusion protein.
Oncogenesis
TRK-T1 induces neoplastic transformation of thyroid epithelium in transgenic mice expressing the hybrid gene.
Entity name
rat induced tumors (adenocarcinomas and fibroblastomas). with Tpr-raf
Breakpoints
Note
All TRK breakpoints fall within a 2,9 kb genomic region of NTRK1. In the Tpr locus, the TRK-T1 and TRK-T2 break points are at least 11 kb apart, indicating the absence of a region prone to rearrangements.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9864356 | 1998 | Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export. | Bangs P et al |
| 11839768 | 2002 | Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export. | Frosst P et al |
| 3277171 | 1988 | Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. | Gonzatti-Haces M et al |
| 9172002 | 1997 | Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes. | Greco A et al |
| 3550433 | 1987 | Rat c-raf oncogene activation by a rearrangement that produces a fused protein. | Ishikawa F et al |
| 2052572 | 1991 | The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. | Soman NR et al |
| 10760755 | 2000 | Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives. | Yu J et al |
Other Information
Locus ID:
NCBI: 7175
MIM: 189940
HGNC: 12017
Ensembl: ENSG00000047410
Variants:
dbSNP: 7175
ClinVar: 7175
TCGA: ENSG00000047410
COSMIC: TPR
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000047410 | ENST00000367478 | P12270 |
| ENSG00000047410 | ENST00000451586 | Q5SWX9 |
| ENSG00000047410 | ENST00000613151 | P12270 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37643197 | 2023 | Identification of MKI67, TPR , and TCHH Mutations as Prognostic Biomarkers for Patients With Defective Mismatch Repair Colon Cancer Stage II/III. | 1 |
| 37643197 | 2023 | Identification of MKI67, TPR , and TCHH Mutations as Prognostic Biomarkers for Patients With Defective Mismatch Repair Colon Cancer Stage II/III. | 1 |
| 32207633 | 2021 | Nucleoporin TPR (translocated promoter region, nuclear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma. | 25 |
| 33307343 | 2021 | Cancer-related SRCAP and TPR mutations in colon cancers. | 6 |
| 34168151 | 2021 | The human nucleoporin Tpr protects cells from RNA-mediated replication stress. | 16 |
| 34440706 | 2021 | ZC3HC1 Is a Novel Inherent Component of the Nuclear Basket, Resident in a State of Reciprocal Dependence with TPR. | 10 |
| 34793452 | 2021 | Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells. | 9 |
| 32207633 | 2021 | Nucleoporin TPR (translocated promoter region, nuclear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma. | 25 |
| 33307343 | 2021 | Cancer-related SRCAP and TPR mutations in colon cancers. | 6 |
| 34168151 | 2021 | The human nucleoporin Tpr protects cells from RNA-mediated replication stress. | 16 |
| 34440706 | 2021 | ZC3HC1 Is a Novel Inherent Component of the Nuclear Basket, Resident in a State of Reciprocal Dependence with TPR. | 10 |
| 34793452 | 2021 | Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells. | 9 |
| 33091126 | 2020 | TPR is required for the efficient nuclear export of mRNAs and lncRNAs from short and intron-poor genes. | 26 |
| 33091126 | 2020 | TPR is required for the efficient nuclear export of mRNAs and lncRNAs from short and intron-poor genes. | 26 |
| 30692205 | 2019 | Nuclear pore density controls heterochromatin reorganization during senescence. | 40 |
Citation
Brigitte David-Watine
TPR (Translocated promoter region)
Atlas Genet Cytogenet Oncol Haematol. 2002-03-01
Online version: http://atlasgeneticsoncology.org/gene/282/tpr-(translocated-promoter-region)
