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TPR (Translocated promoter region)

Identity

Other namesTumor potentiating region
HGNC TPR
Location 1q25
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
HGNCTPR   12017
Entrez_GeneTPR  7175  translocated promoter region (to activated MET oncogene)
Cards
AtlasTPRID282
GeneCardsTPR
EnsemblTPR [Search_View]   ENSG00000047410 [Gene_View]
GenatlasTPR
GeneLynxTPR
eGenomeTPR
euGene7175
Genomic and cartography
GoldenPathTPR  -  1q25   chr1:184547409-184611080 -  1q25   [Description]    (hg18-Mar_2006)
EnsemblTPR - 1q25 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneTPR
Gene and transcription
GenbankAA688415 [ ENTREZ ]
GenbankAK023111 [ ENTREZ ]
GenbankAK309473 [ ENTREZ ]
GenbankBC016514 [ ENTREZ ]
GenbankBC025177 [ ENTREZ ]
RefSeqNM_003292 [ SRS ]    NM_003292 [ ENTREZ ]
RefSeqAC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeqAC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeqNC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeqNG_008248 [ SRS ]    NG_008248 [ ENTREZ ]
RefSeqNT_004487 [ SRS ]    NT_004487 [ ENTREZ ]
RefSeqNW_001838533 [ SRS ]    NW_001838533 [ ENTREZ ]
RefSeqNW_926128 [ SRS ]    NW_926128 [ ENTREZ ]
AceViewTPR AceView - NCBI
UnigeneHs.279640 [ SRS ]    Hs.279640 [ NCBI ]     HS279640 [ spliceNest ]
Fast-db17654 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtP12270 [ SRS]    P12270 [ EXPASY ]     P12270 [ INTERPRO ]     P12270 [ UNIPROT ]
InterproIPR015866 Ser-tRNA-synth_IIa_N [ SRS ]    IPR015866 Ser-tRNA-synth_IIa_N [ EBI ]
InterproIPR012929 TPR_MLP1_2 [ SRS ]    IPR012929 TPR_MLP1_2 [ EBI ]
CluSTrP12270
PfamPF07926 TPR_MLP1_2 [ SRS ]    PF07926 TPR_MLP1_2 [ Sanger ]    pfam07926 [ NCBI-CDD ]
BlocksP12270
HPRD08927
Protein Interaction databases
DIPP12270
IntActP12270
Polymorphism : SNP, mutations, diseases
OMIM189940    [ map ]   
GENECLINICS189940
SNPTPR [dbSNP-NCBI]  
SNPNM_003292 [SNP-NCI]  
SNPTPR [GeneSNPs - Utah]  TPR] [HGBASE - SRS]
HAPMAPTPR [HAPMAP]  
COSMICTPR [Somatic mutation (COSMIC-CGP-Sanger)]  
TICdbTPR [Translocation breakpoints In Cancer]  
HGMDTPR
General knowledge
Family BrowserTPR [UCSC Family Browser]
SOURCENM_003292
SMDHs.279640
SAGEHs.279640
GOnucleotide binding [Amigo]  nucleotide binding
GOserine-tRNA ligase activity [Amigo]  serine-tRNA ligase activity
GOATP binding [Amigo]  ATP binding
GOnucleus [Amigo]  nucleus
GOnuclear pore [Amigo]  nuclear pore
GOnucleoplasm [Amigo]  nucleoplasm
GOcytoplasm [Amigo]  cytoplasm
GOtranslation [Amigo]  translation
GOseryl-tRNA aminoacylation [Amigo]  seryl-tRNA aminoacylation
GOprotein import into nucleus [Amigo]  protein import into nucleus
GOprotein transport [Amigo]  protein transport
GOmembrane [Amigo]  membrane
GOnuclear membrane [Amigo]  nuclear membrane
GOmRNA transport [Amigo]  mRNA transport
GOintracellular protein transport across a membrane [Amigo]  intracellular protein transport across a membrane
PubGeneTPR
TreeFamTPR
CTD7175 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeTPR Related clones (RZPD - Berlin)
PubMed
PubMed28 Pubmed reference(s) in LocusLink

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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Aug 11 21:18:14 2008


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