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TPR (Translocated promoter region)

Written2002-03Brigitte 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

(Note : for Links provided by Atlas : click)

Identity

Other namesTumor potentiating region
HGNC (Hugo) TPR
LocusID (NCBI) 7175
Atlas_Id 282
Location 1q31.1  [Link to chromosome band 1q31]
Location_base_pair Starts at 186280786 and ends at 186344457 bp from pter ( according to hg19-Feb_2009)  [Mapping TPR.png]
Local_order The 3' coding end of Tpr overlaps with the 3' no-coding region of the PRG4 (Proteoglycan 4) gene (or MGCSF for megacaryocyte stimulating factor) which is involved in the Camptodactyly-arthropathy-coxa vara-pericarditis syndrom
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
NTRK1 (1q23.1) / TPR (1q31.1)TPM3 (1q21.3) / TPR (1q31.1)TPR (1q31.1) / ALK (2p23.2)
TPR (1q31.1) / FGFR1 (8p11.23)TPR (1q31.1) / MET (7q31.2)TPR (1q31.1) / NTRK1 (1q23.1)
Note see also The nuclear pore complex: structure and function

DNA/RNA

Description 51-52 exons spanning about 63 kb
Transcription in a telomeric to centromeric direction. 10kb mRNA.

Protein

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

Note
Entity 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/Mutated Gene 5' TPR- 3'MET 5 kb mRNA
Abnormal 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 humanpapillary thyroid carcinomas with TPR- NTRK1 hybrid gene
Hybrid/Mutated 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.
Abnormal 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 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

Rat c-raf oncogene activation by a rearrangement that produces a fused protein.
Ishikawa F, Takaku F, Nagao M, Sugimura T
Molecular and cellular biology. 1987 ; 7 (3) : 1226-1232.
PMID 3550433
 
Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases.
Gonzatti-Haces M, Seth A, Park M, Copeland T, Oroszlan S, Vande Woude GF
Proceedings of the National Academy of Sciences of the United States of America. 1988 ; 85 (1) : 21-25.
PMID 3277171
 
The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions.
Soman NR, Correa P, Ruiz BA, Wogan GN
Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (11) : 4892-4896.
PMID 2052572
 
Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes.
Greco A, Miranda C, Pagliardini S, Fusetti L, Bongarzone I, Pierotti MA
Genes, chromosomes & cancer. 1997 ; 19 (2) : 112-123.
PMID 9172002
 
Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export.
Bangs P, Burke B, Powers C, Craig R, Purohit A, Doxsey S
The Journal of cell biology. 1998 ; 143 (7) : 1801-1812.
PMID 9864356
 
Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives.
Yu J, Miehlke S, Ebert MP, Hoffmann J, Breidert M, Alpen B, Starzynska T, Stolte Prof M, Malfertheiner P, Bayerdörffer E
Cancer. 2000 ; 88 (8) : 1801-1806.
PMID 10760755
 
Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export.
Frosst P, Guan T, Subauste C, Hahn K, Gerace L
The Journal of cell biology. 2002 ; 156 (4) : 617-630.
PMID 11839768
 

Citation

This paper should be referenced as such :
David-Watine, B
TPR (translocated promoter region)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):197-198.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TPRID282.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 0 ]
  Thyroid: Papillary carcinoma/Adenocarcinoma

External links

Nomenclature
HGNC (Hugo)TPR   12017
Cards
AtlasTPRID282
Entrez_Gene (NCBI)TPR  7175  translocated promoter region, nuclear basket protein
Aliases
GeneCards (Weizmann)TPR
Ensembl hg19 (Hinxton)ENSG00000047410 [Gene_View]  chr1:186280786-186344457 [Contig_View]  TPR [Vega]
Ensembl hg38 (Hinxton)ENSG00000047410 [Gene_View]  chr1:186280786-186344457 [Contig_View]  TPR [Vega]
ICGC DataPortalENSG00000047410
TCGA cBioPortalTPR
AceView (NCBI)TPR
Genatlas (Paris)TPR
WikiGenes7175
SOURCE (Princeton)TPR
Genomic and cartography
GoldenPath hg19 (UCSC)TPR  -     chr1:186280786-186344457 -  1q25   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TPR  -     1q25   [Description]    (hg38-Dec_2013)
EnsemblTPR - 1q25 [CytoView hg19]  TPR - 1q25 [CytoView hg38]
Mapping of homologs : NCBITPR [Mapview hg19]  TPR [Mapview hg38]
OMIM189940   
Gene and transcription
Genbank (Entrez)AA688415 AK023111 AK309473 BC016514 BC025177
RefSeq transcript (Entrez)NM_003292
RefSeq genomic (Entrez)NC_000001 NC_018912 NG_023284 NT_004487 NW_004929293
Consensus coding sequences : CCDS (NCBI)TPR
Cluster EST : UnigeneHs.279640 [ NCBI ]
CGAP (NCI)Hs.279640
Alternative Splicing GalleryENSG00000047410
Gene ExpressionTPR [ NCBI-GEO ]   TPR [ EBI - ARRAY_EXPRESS ]   TPR [ SEEK ]   TPR [ MEM ]
Gene Expression Viewer (FireBrowse)TPR [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7175
GTEX Portal (Tissue expression)TPR
Protein : pattern, domain, 3D structure
UniProt/SwissProtP12270 (Uniprot)
NextProtP12270  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP12270
Splice isoforms : SwissVarP12270 (Swissvar)
PhosPhoSitePlusP12270
Domains : Interpro (EBI)Ser-tRNA-synth_1_N    TPR/MLP1   
Domain families : Pfam (Sanger)TPR_MLP1_2 (PF07926)   
Domain families : Pfam (NCBI)pfam07926   
DMDM Disease mutations7175
Blocks (Seattle)TPR
SuperfamilyP12270
Human Protein AtlasENSG00000047410
Peptide AtlasP12270
HPRD08927
IPIIPI00742682   IPI00514531   
Protein Interaction databases
DIP (DOE-UCLA)P12270
IntAct (EBI)P12270
FunCoupENSG00000047410
BioGRIDTPR
STRING (EMBL)TPR
ZODIACTPR
Ontologies - Pathways
QuickGOP12270
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  MAPK import into nucleus  kinetochore  kinetochore  kinetochore  molecular_function  chromatin binding  mRNA binding  transporter activity  nucleocytoplasmic transporter activity  protein binding  cellular_component  nucleus  nuclear envelope  nuclear pore  nucleoplasm  cytoplasm  cytoplasmic dynein complex  RNA import into nucleus  RNA export from nucleus  mRNA export from nucleus  tRNA export from nucleus  protein import into nucleus  protein import into nucleus  protein export from nucleus  nuclear pore organization  nuclear pore organization  mitotic nuclear division  mitotic nuclear envelope disassembly  mitotic spindle assembly checkpoint  biological_process  regulation of mRNA export from nucleus  regulation of glucose transport  regulation of mitotic sister chromatid separation  tubulin binding  viral process  protein sumoylation  viral transcription  extrinsic component of membrane  gene silencing by RNA  heat shock protein binding  positive regulation of heterochromatin assembly  regulation of protein stability  nuclear membrane  mRNA export from nucleus in response to heat stress  nuclear periphery  cellular response to heat  cellular response to interferon-alpha  regulation of protein import into nucleus  positive regulation of protein import into nucleus  nuclear inclusion body  protein homodimerization activity  protein anchor  nuclear matrix organization  nuclear pore nuclear basket  poly(A) RNA binding  negative regulation of translational initiation  regulation of protein export from nucleus  positive regulation of protein export from nucleus  negative regulation of RNA export from nucleus  negative regulation of RNA export from nucleus  mitogen-activated protein kinase binding  nuclear pore complex assembly  cell division  dynein complex binding  response to epidermal growth factor  mitotic spindle  intracellular transport of virus  positive regulation of mitotic cell cycle spindle assembly checkpoint  positive regulation of intracellular protein transport  regulation of cellular response to heat  regulation of mitotic spindle assembly  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  MAPK import into nucleus  kinetochore  kinetochore  kinetochore  molecular_function  chromatin binding  mRNA binding  transporter activity  nucleocytoplasmic transporter activity  protein binding  cellular_component  nucleus  nuclear envelope  nuclear pore  nucleoplasm  cytoplasm  cytoplasmic dynein complex  RNA import into nucleus  RNA export from nucleus  mRNA export from nucleus  tRNA export from nucleus  protein import into nucleus  protein import into nucleus  protein export from nucleus  nuclear pore organization  nuclear pore organization  mitotic nuclear division  mitotic nuclear envelope disassembly  mitotic spindle assembly checkpoint  biological_process  regulation of mRNA export from nucleus  regulation of glucose transport  regulation of mitotic sister chromatid separation  tubulin binding  viral process  protein sumoylation  viral transcription  extrinsic component of membrane  gene silencing by RNA  heat shock protein binding  positive regulation of heterochromatin assembly  regulation of protein stability  nuclear membrane  mRNA export from nucleus in response to heat stress  nuclear periphery  cellular response to heat  cellular response to interferon-alpha  regulation of protein import into nucleus  positive regulation of protein import into nucleus  nuclear inclusion body  protein homodimerization activity  protein anchor  nuclear matrix organization  nuclear pore nuclear basket  poly(A) RNA binding  negative regulation of translational initiation  regulation of protein export from nucleus  positive regulation of protein export from nucleus  negative regulation of RNA export from nucleus  negative regulation of RNA export from nucleus  mitogen-activated protein kinase binding  nuclear pore complex assembly  cell division  dynein complex binding  response to epidermal growth factor  mitotic spindle  intracellular transport of virus  positive regulation of mitotic cell cycle spindle assembly checkpoint  positive regulation of intracellular protein transport  regulation of cellular response to heat  regulation of mitotic spindle assembly  
Pathways : KEGGRNA transport    Pathways in cancer    Thyroid cancer   
REACTOMEP12270 [protein]
REACTOME PathwaysR-HSA-5578749 Transcriptional regulation by small RNAs [pathway]
REACTOME PathwaysR-HSA-165054 Rev-mediated nuclear export of HIV RNA [pathway]
REACTOME PathwaysR-HSA-180910 Vpr-mediated nuclear import of PICs [pathway]
REACTOME PathwaysR-HSA-1169408 ISG15 antiviral mechanism [pathway]
REACTOME PathwaysR-HSA-180746 Nuclear import of Rev protein [pathway]
REACTOME PathwaysR-HSA-165054 Rev-mediated nuclear export of HIV RNA [pathway]
REACTOME PathwaysR-HSA-168325 Viral Messenger RNA Synthesis [pathway]
REACTOME PathwaysR-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein [pathway]
REACTOME PathwaysR-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly [pathway]
REACTOME PathwaysR-HSA-3371453 Regulation of HSF1-mediated heat shock response [pathway]
REACTOME PathwaysR-HSA-3108214 SUMOylation of DNA damage response and repair proteins [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkTPR
Wikipedia pathwaysTPR
Orthology - Evolution
OrthoDB7175
GeneTree (enSembl)ENSG00000047410
Phylogenetic Trees/Animal Genes : TreeFamTPR
Homologs : HomoloGeneTPR
Homology/Alignments : Family Browser (UCSC)TPR
Gene fusions - Rearrangements
Fusion : MitelmanTPM3/TPR [1q21.3/1q31.1]  [inv(1)(q21q31)]  
Fusion : MitelmanTPR/ALK [1q31.1/2p23.2]  [t(1;2)(q31;p23)]  
Fusion : MitelmanTPR/FGFR1 [1q31.1/8p11.23]  [t(1;8)(q31;p11)]  
Fusion : MitelmanTPR/NTRK1 [1q31.1/1q23.1]  [inv(1)(q23q31)]  
Fusion : TICdbTPR [1q31.1]  -  NTRK1 [1q23.1]
Polymorphisms : SNP, variants
NCBI Variation ViewerTPR [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TPR
dbVarTPR
ClinVarTPR
1000_GenomesTPR 
Exome Variant ServerTPR
ExAC (Exome Aggregation Consortium)TPR (select the gene name)
Genetic variants : HAPMAP7175
Genomic Variants (DGV)TPR [DGVbeta]
Mutations
ICGC Data PortalTPR 
TCGA Data PortalTPR 
Broad Tumor PortalTPR
OASIS PortalTPR [ Somatic mutations - Copy number]
Cancer Gene: CensusTPR 
Somatic Mutations in Cancer : COSMICTPR 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TPR
DgiDB (Drug Gene Interaction Database)TPR
DoCM (Curated mutations)TPR (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TPR (select a term)
intoGenTPR
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)1:186280786-186344457  ENSG00000047410
CONAN: Copy Number AnalysisTPR 
Mutations and Diseases : HGMDTPR
OMIM189940   
MedgenTPR
Genetic Testing Registry TPR
NextProtP12270 [Medical]
TSGene7175
GENETestsTPR
Huge Navigator TPR [HugePedia]
snp3D : Map Gene to Disease7175
BioCentury BCIQTPR
ClinGenTPR
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7175
Chemical/Pharm GKB GenePA36696
Clinical trialTPR
Miscellaneous
canSAR (ICR)TPR (select the gene name)
Probes
Litterature
PubMed88 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTPR
EVEXTPR
GoPubMedTPR
iHOPTPR
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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