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TPR (Translocated promoter region)

Identity

Other namesTumor potentiating region
HGNC (Hugo) TPR
Location 1q25
Location_base_pair Starts at 184547409 and ends at 184611080 bp from pter ( according to hg18-Mar_2006)  [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

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 (to activated MET oncogene)
Cards
AtlasTPRID282
GeneCards (Weizmann)TPR
Ensembl (Hinxton)ENSG00000047410 [Gene_View]  TPR [Vega]
AceView (NCBI)TPR
Genatlas (Paris)TPR
euGene (Indiana)7175
SOURCE (Stanford)NM_003292
Gene Expression (Array Express) ENSG00000047410
Genomic and cartography
GoldenPath (UCSC)TPR  -  1q25   chr1:184547409-184611080 -  1q25   [Description]    (hg18-Mar_2006)
EnsemblTPR - 1q25 [CytoView]
Mapping of homologs : NCBITPR [Mapview]
OMIM189940   
Gene and transcription
Gene : Genbank (Entrez)AA688415 AK023111 AK309473 BC016514 BC025177
Reference sequence (RefSeq transcript) :SRSNM_003292
Reference transcript : EntrezNM_003292
RefSeq genomic : SRSAC_000044 AC_000133 NC_000001 NT_004487 NW_001838533 NW_926128
RefSeq genomic : EntrezAC_000044 AC_000133 NC_000001 NT_004487 NW_001838533 NW_926128
Consensus coding sequences : CCDS NCBITPR
Cluster EST : UnigeneHs.279640 [ SRS ] Hs.279640 [ NCBI ]
Alternative Splicing : Fast-db (Paris)17654
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP12270 (SRS) P12270 (Expasy) P12270 (Uniprot)
With graphics : InterProP12270
Splice isoforms : VarSplice FASTAP12270(VarSplice FASTA)
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 SRSTPR_MLP1_2 (PF07926)   
Domain families : Pfam SangerTPR_MLP1_2 (PF07926)   
Domain families : Pfam NCBIpfam07926   
Blocks (Seattle)P12270
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD08927
Protein Interaction databases
DIP (DOE-UCLA)P12270
IntAct (EBI)P12270
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBITPR
SNP : GeneSNP UtahTPR
SNP : HGBaseTPR
Genetic variants : HAPMAPTPR
Cancer Gene: CensusTPR 
Somatic Mutations in Cancer : COSMICTPR 
Translocation Breakpoints in Cancer : TICdbTPR 
Mutations and Diseases : HGMDTPR
Hereditary diseases : OMIM189940   
Hereditary diseases : GENETests189940   
Diseases : Genetic AssociationTPR
General knowledge
Homologs : HomoloGeneTPR
Homology/Alignments : Family Browser UCSCTPR
Phylogenetic Trees/Animal Genes : TreeFamTPR
Chemical/Protein Interactions : CTD7175
Keywords Ontology : AmiGOnucleotide binding  kinetochore  serine-tRNA ligase activity  protein binding  ATP binding  nucleus  nuclear pore  nucleoplasm  cytoplasm  translation  seryl-tRNA aminoacylation  protein import into nucleus  mitotic cell cycle spindle assembly checkpoint  protein transport  membrane  mRNA transport  transmembrane transport  
Keywords Ontology : EGO-EBInucleotide binding  kinetochore  serine-tRNA ligase activity  protein binding  ATP binding  nucleus  nuclear pore  nucleoplasm  cytoplasm  translation  seryl-tRNA aminoacylation  protein import into nucleus  mitotic cell cycle spindle assembly checkpoint  protein transport  membrane  mRNA transport  transmembrane transport  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesTPR Related clones (RZPD - Berlin)
Literature
PubMed30 Pubmed reference(s) in Entrez
PubGeneTPR

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
 
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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

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indexed on : Sat Feb 27 10:53:40 CET 2010

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