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TPR (Translocated promoter region)

Identity

Other namesTumor potentiating region
HGNC (Hugo) TPR
LocusID (NCBI) 7175
Location 1q25
Location_base_pair Starts at 186280786 and ends at 186344457 bp from pter ( according to hg19-Feb_2009)  [Mapping]
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

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

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.

External links

Nomenclature
HGNC (Hugo)TPR   12017
Entrez_Gene (NCBI)TPR  7175  translocated promoter region, nuclear basket protein
Cards
AtlasTPRID282
GeneCards (Weizmann)TPR
Ensembl (Hinxton)ENSG00000047410 [Gene_View]  chr1:186280786-186344457 [Contig_View]  TPR [Vega]
AceView (NCBI)TPR
Genatlas (Paris)TPR
euGene (Indiana)7175
SOURCE (Stanford)NM_003292
Genomic and cartography
GoldenPath (UCSC)TPR  -  1q25   chr1:186280786-186344457 -  1q25   [Description]    (hg19-Feb_2009)
EnsemblTPR - 1q25 [CytoView]
Mapping of homologs : NCBITPR [Mapview]
OMIM189940   
Gene and transcription
Genbank (Entrez)AA688415 AK023111 AK309473 BC016514 BC025177
RefSeq transcript (SRS)NM_003292
RefSeq transcript (Entrez)NM_003292
RefSeq genomic (SRS)AC_000133 NC_000001 NG_008248 NG_023284 NT_004487 NW_001838533
RefSeq genomic (Entrez)AC_000133 NC_000001 NG_008248 NG_023284 NT_004487 NW_001838533
Consensus coding sequences : CCDS (NCBI)TPR
Cluster EST : UnigeneHs.279640 [ SRS ] Hs.279640 [ NCBI ]
Alternative Splicing : Fast-db (Paris)17654
Alternative Splicing GalleryENSG00000047410
Gene ExpressionTPR [ NCBI-GEO ]   TPR [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP12270 (SRS) P12270 (Uniprot)
With graphics : InterProP12270
Splice isoforms : SwissVarP12270(Swissvar)
Domains : Interpro (SRS)Prefoldin    Ser-tRNA-synth_IIa_N    TPR_MLP1_2   
Domains : Interpro (EBI)Prefoldin    Ser-tRNA-synth_IIa_N    TPR_MLP1_2   
Related proteins : CluSTrP12270
Domain families : Pfam (SRS)TPR_MLP1_2 (PF07926)   
Domain families : Pfam (Sanger)TPR_MLP1_2 (PF07926)   
Domain families : Pfam (NCBI)pfam07926   
Blocks (Seattle)P12270
Human Protein AtlasENSG00000047410
HPRD08927
IPIIPI00742682   IPI00514531   
Protein Interaction databases
DIP (DOE-UCLA)P12270
IntAct (EBI)P12270
FunCoupENSG00000047410
REACTOMETPR
BioGRIDTPR
InParanoidP12270
Interologous Interaction database P12270
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TPR
SNP (GeneSNP Utah)TPR
SNP : HGBaseTPR
Genetic variants : HAPMAPTPR
Cancer Gene: CensusTPR 
Somatic Mutations in Cancer : COSMICTPR 
CONAN: Copy Number AnalysisTPR 
Translocation Breakpoints in Cancer : TICdbTPR 
Mutations and Diseases : HGMDTPR
OMIM189940   
GENETests189940   
Disease Genetic AssociationTPR
Huge Navigator TPR [HugePedia]  TPR [HugeCancerGEM]
Genomic VariantsTPR
snp3D : Map Gene to Disease7175
General knowledge
Homologs : HomoloGeneTPR
Homology/Alignments : Family Browser (UCSC)TPR
Phylogenetic Trees/Animal Genes : TreeFamTPR
Chemical/Protein Interactions : CTD7175
Chemical/Pharm GKB GenePA36696
Clinical trialTPR
Cancer Resource (Charite)ENSG00000047410
Ontology : AmiGOnucleotide binding  kinetochore  condensed chromosome kinetochore  serine-tRNA ligase activity  protein binding  ATP binding  nucleus  nuclear envelope  nuclear pore  nucleoplasm  chromosome  cytoplasm  carbohydrate metabolic process  seryl-tRNA aminoacylation  protein import into nucleus  mitotic cell cycle spindle assembly checkpoint  hexose transport  regulation of glucose transport  protein transport  glucose transport  membrane  viral reproduction  cytokine-mediated signaling pathway  nuclear membrane  small molecule metabolic process  mRNA transport  transmembrane transport  
Ontology : EGO-EBInucleotide binding  kinetochore  condensed chromosome kinetochore  serine-tRNA ligase activity  protein binding  ATP binding  nucleus  nuclear envelope  nuclear pore  nucleoplasm  chromosome  cytoplasm  carbohydrate metabolic process  seryl-tRNA aminoacylation  protein import into nucleus  mitotic cell cycle spindle assembly checkpoint  hexose transport  regulation of glucose transport  protein transport  glucose transport  membrane  viral reproduction  cytokine-mediated signaling pathway  nuclear membrane  small molecule metabolic process  mRNA transport  transmembrane transport  
Other databases
Probes
Probes : ImagenesTPR Related clones (RZPD - Berlin)
Litterature
PubMed49 Pubmed reference(s) in Entrez
PubGeneTPR
iHOPTPR

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, Bayerdrffer 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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2002Brigitte David-Watine

Citation

This paper should be referenced as such :
David-Watine B . TPR (Translocated promoter region). Atlas Genet Cytogenet Oncol Haematol. March 2002 .
URL : http://AtlasGeneticsOncology.org/Genes/TPRID282.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37866/1/03-2002-TPRID282.pdf   [ Bibliographic record ]

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indexed on : Sat Apr 28 15:09:09 CEST 2012

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