TPR (Translocated promoter region)

2002-03-01   Brigitte David-Watine 

Unité 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
Atlas 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

Entity name
gastric cancers with TPR - MET hybrid gene
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.
Entity name
humanpapillary thyroid carcinomas with TPR - NTRK1 hybrid gene
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.

Bibliography

Pubmed IDLast YearTitleAuthors
98643561998Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export.Bangs P et al
118397682002Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export.Frosst P et al
32771711988Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases.Gonzatti-Haces M et al
91720021997Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes.Greco A et al
35504331987Rat c-raf oncogene activation by a rearrangement that produces a fused protein.Ishikawa F et al
20525721991The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions.Soman NR et al
107607552000Frequency 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 IDTranscript IDUniprot
ENSG00000047410ENST00000367478P12270
ENSG00000047410ENST00000451586Q5SWX9
ENSG00000047410ENST00000613151P12270

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Thyroid cancerKEGGko05216
Pathways in cancerKEGGhsa05200
Thyroid cancerKEGGhsa05216
RNA transportKEGGko03013
RNA transportKEGGhsa03013
Nuclear pore complexKEGGhsa_M00427
Nuclear pore complexKEGGM00427
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
SUMOylationREACTOMER-HSA-2990846
SUMO E3 ligases SUMOylate target proteinsREACTOMER-HSA-3108232
SUMOylation of DNA damage response and repair proteinsREACTOMER-HSA-3108214
DiseaseREACTOMER-HSA-1643685
Infectious diseaseREACTOMER-HSA-5663205
HIV InfectionREACTOMER-HSA-162906
HIV Life CycleREACTOMER-HSA-162587
Late Phase of HIV Life CycleREACTOMER-HSA-162599
Rev-mediated nuclear export of HIV RNAREACTOMER-HSA-165054
Host Interactions of HIV factorsREACTOMER-HSA-162909
Interactions of Vpr with host cellular proteinsREACTOMER-HSA-176033
Vpr-mediated nuclear import of PICsREACTOMER-HSA-180910
Interactions of Rev with host cellular proteinsREACTOMER-HSA-177243
Nuclear import of Rev proteinREACTOMER-HSA-180746
Influenza InfectionREACTOMER-HSA-168254
Influenza Life CycleREACTOMER-HSA-168255
Transport of Ribonucleoproteins into the Host NucleusREACTOMER-HSA-168271
Influenza Viral RNA Transcription and ReplicationREACTOMER-HSA-168273
Viral Messenger RNA SynthesisREACTOMER-HSA-168325
Export of Viral Ribonucleoproteins from NucleusREACTOMER-HSA-168274
NEP/NS2 Interacts with the Cellular Export MachineryREACTOMER-HSA-168333
Host Interactions with Influenza FactorsREACTOMER-HSA-168253
NS1 Mediated Effects on Host PathwaysREACTOMER-HSA-168276
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Interferon SignalingREACTOMER-HSA-913531
Antiviral mechanism by IFN-stimulated genesREACTOMER-HSA-1169410
ISG15 antiviral mechanismREACTOMER-HSA-1169408
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
Transport of Mature Transcript to CytoplasmREACTOMER-HSA-72202
Transport of Mature mRNA derived from an Intron-Containing TranscriptREACTOMER-HSA-159236
Transport of Mature mRNAs Derived from Intronless TranscriptsREACTOMER-HSA-159234
Transport of the SLBP Dependant Mature mRNAREACTOMER-HSA-159230
Transport of the SLBP independent Mature mRNAREACTOMER-HSA-159227
Transport of Mature mRNA Derived from an Intronless TranscriptREACTOMER-HSA-159231
Gene Silencing by RNAREACTOMER-HSA-211000
Transcriptional regulation by small RNAsREACTOMER-HSA-5578749
Metabolism of non-coding RNAREACTOMER-HSA-194441
snRNP AssemblyREACTOMER-HSA-191859
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
M PhaseREACTOMER-HSA-68886
Mitotic ProphaseREACTOMER-HSA-68875
Nuclear Envelope BreakdownREACTOMER-HSA-2980766
Nuclear Pore Complex (NPC) DisassemblyREACTOMER-HSA-3301854
Transmembrane transport of small moleculesREACTOMER-HSA-382551
SLC-mediated transmembrane transportREACTOMER-HSA-425407
Hexose transportREACTOMER-HSA-189200
Glucose transportREACTOMER-HSA-70153
Regulation of Glucokinase by Glucokinase Regulatory ProteinREACTOMER-HSA-170822
MetabolismREACTOMER-HSA-1430728
Metabolism of carbohydratesREACTOMER-HSA-71387
Cellular responses to stressREACTOMER-HSA-2262752
Cellular response to heat stressREACTOMER-HSA-3371556
Regulation of HSF1-mediated heat shock responseREACTOMER-HSA-3371453
tRNA processingREACTOMER-HSA-72306
tRNA processing in the nucleusREACTOMER-HSA-6784531
SUMOylation of RNA binding proteinsREACTOMER-HSA-4570464
SUMOylation of DNA replication proteinsREACTOMER-HSA-4615885

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
152292832004Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket.91
189814712008Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint.71
204074192010Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion.67
257441872015Chromatin organization at the nuclear pore favours HIV replication.43
216135322011The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway.33
202374962010New genetic associations detected in a host response study to hepatitis B vaccine.27
243441812013Spindle assembly checkpoint robustness requires Tpr-mediated regulation of Mad1/Mad2 proteostasis.27
236498042013Defective nuclear import of Tpr in Progeria reflects the Ran sensitivity of large cargo transport.25
222538242012Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA.22
119528382002Nucleocytoplasmic transport of proteins and poly(A)+ RNA in reconstituted Tpr-less nuclei in living mammalian cells.19

Citation

Brigitte David-Watine

TPR (Translocated promoter region)

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

Online version: http://atlasgeneticsoncology.org/gene/282/tpr