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TPM3 (tropomyosin 3)

Written2001-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

Other namesNEM1
HGNC (Hugo) TPM3
LocusID (NCBI) 7170
Atlas_Id 225
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 154127780 and ends at 154155725 bp from pter ( according to hg19-Feb_2009)  [Mapping TPM3.png]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
ALK (2p23.2) / TPM3 (1q21.3)B4GALT3 (1q23.3) / TPM3 (1q21.3)EEF1A1 (6q13) / TPM3 (1q21.3)
JAK2 (9p24.1) / TPM3 (1q21.3)MTERF4 (2q37.3) / TPM3 (1q21.3)NTRK1 (1q23.1) / TPM3 (1q21.3)
SEC24D (4q26) / TPM3 (1q21.3)SH3BGRL3 (1p36.11) / TPM3 (1q21.3)TPM2 (9p13.3) / TPM3 (1q21.3)
TPM3 (1q21.3) / ALK (2p23.2)TPM3 (1q21.3) / C1orf43 (1q21.3)TPM3 (1q21.3) / JAK2 (9p24.1)
TPM3 (1q21.3) / NTRK1 (1q23.1)TPM3 (1q21.3) / PDGFRB (5q32)TPM3 (1q21.3) / ROS1 (6q22.1)
TPM3 (1q21.3) / SEC24D (4q26)TPM3 (1q21.3) / TPR (1q31.1)

DNA/RNA

Description spans at least 42 kb; 13 exons

Protein

Description by tissue-specific alternate splincing are produced 2 proteins: the tropomyosin alpha chain, skeletal muscle type, made of 284 amino acids (32 kDa), and the cytosqueletal type, made of 248 amino acids (29 kDa). Coiled-coil structure
Function Tropomyosins are actin-binding proteins; component of cytoskeletal microfilaments; tropomyosins mediate the effect of Ca2+ on the myosin-actin interaction In skeletal muscles, but their function in smooth muscles and other tissues is yet unknown
Homology Other tropomyosins: TPM1 (alpha) located in 15q22, TPM2 (beta), located in 9q13, and TPM4 located in 19p13.1

Implicated in

Note
Entity rare cases of ALK+ anaplasic large cell lymphoma (ALCL) with t(1;2)(q25;p23)
Disease ALCL presents as an aggressive lymphoma with systemic signs
Prognosis nonetheless, have a favourable prognosis
Hybrid/Mutated Gene 5' CLTC - 3' ALK
Abnormal Protein 104 kDa ; 221 N-term amino acids from TPM3 fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein.
Oncogenesis TPM3-ALK is contitutively activated
  
Entity cases of Inflammatory myofibroblastic tumors with t(1;2)(q25;p23)
Disease rare soft tissue tumour found in children and young adults
Prognosis good prognosis
Hybrid/Mutated Gene 5' CLTC - 3' ALK
Abnormal Protein 104 kDa ; 221 N-term amino acids from TPM3 fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein.
Oncogenesis TPM3-ALK is contitutively activated
  
Entity papillary thyroid carcinoma
Disease represents about 60% of thyroid cancers; small, undetectable, chromosome 1q inversions have shown to produce a TPM3-NTRK1 hybrid gene in a very few cases of papillary thyroid carcinoma.
Prognosis prognosis of papillary thyroid carcinoma is excellent
Hybrid/Mutated Gene 5' TPM3 - 3' NTRK1
Abnormal Protein 221 N-term amino acids from PM3 fused to the C-term of NTRK1, including its tyrosine kinase domain
  

Breakpoints

 

To be noted

ALK and TPM3 are therefore implicated in both anaplasic large cell lymphoma and inflammatory myofibroblastic tumours; this is a new concept, that 2 different types of tumour may result from the same chromosomal and genes rearrangement.

Bibliography

Deciphering the design of the tropomyosin molecule.
Brown JH, Kim KH, Jun G, Greenfield NJ, Dominguez R, Volkmann N, Hitchcock-DeGregori SE, Cohen C
Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (15) : 8496-8501.
PMID 11438684
 
A sequence analysis of the genomic regions involved in the rearrangements between TPM3 and NTRK1 genes producing TRK oncogenes in papillary thyroid carcinomas.
Butti MG, Bongarzone I, Ferraresi G, Mondellini P, Borrello MG, Pierotti MA
Genomics. 1995 ; 28 (1) : 15-24.
PMID 7590742
 
Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.
Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ
Cancer research. 1999 ; 59 (12) : 2776-2780.
PMID 10383129
 
Aberrant ALK tyrosine kinase signaling. Different cellular lineages, common oncogenic mechanisms.
Ladanyi M
The American journal of pathology. 2000 ; 157 (2) : 341-345.
PMID 10934137
 
A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation.
Lamant L, Dastugue N, Pulford K, Delsol G, Mariamé B
Blood. 1999 ; 93 (9) : 3088-3095.
PMID 10216106
 
TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.
Lawrence B, Perez-Atayde A, Hibbard MK, Rubin BP, Dal Cin P, Pinkus JL, Pinkus GS, Xiao S, Yi ES, Fletcher CD, Fletcher JA
The American journal of pathology. 2000 ; 157 (2) : 377-384.
PMID 10934142
 
Tropomyosin and actin isoforms modulate the localization of tropomyosin strands on actin filaments.
Lehman W, Hatch V, Korman V, Rosol M, Thomas L, Maytum R, Geeves MA, Van Eyk JE, Tobacman LS, Craig R
Journal of molecular biology. 2000 ; 302 (3) : 593-606.
PMID 10986121
 
A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences.
Martin-Zanca D, Hughes SH, Barbacid M
Nature. 1986 ; 319 (6056) : 743-748.
PMID 2869410
 
Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma.
Siebert R, Gesk S, Harder L, Steinemann D, Grote W, Schlegelberger B, Tiemann M, Wlodarska I, Schemmel V
Blood. 1999 ; 94 (10) : 3614-3617.
PMID 10610119
 

Citation

This paper should be referenced as such :
Huret, JL
TPM3 (tropomyosin 3)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):271-272.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TPM3ID225.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  Anaplastic large cell lymphoma (ALCL)
der(5)t(1;5)(q12-q25;q13-q35)
t(1;2)(q25;p23) TPM3/ALK

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
  Soft Tissues: Inflammatory myofibroblastic tumor
Thyroid: Papillary carcinoma/Adenocarcinoma
Soft tissue tumors: an overview
Soft Tissues: Inflammatory myofibroblastic tumor with t(1;2)(q21;p23) TPM3/ALK
Lung: Translocations in Adenocarcinoma

External links

Nomenclature
HGNC (Hugo)TPM3   12012
Cards
AtlasTPM3ID225
Entrez_Gene (NCBI)TPM3  7170  tropomyosin 3
AliasesCAPM1; CFTD; HEL-189; HEL-S-82p; 
NEM1; OK/SW-cl.5; TM-5; TM3; TM30; TM30nm; TM5; TPMsk3; TRK; hscp30
GeneCards (Weizmann)TPM3
Ensembl hg19 (Hinxton)ENSG00000143549 [Gene_View]  chr1:154127780-154155725 [Contig_View]  TPM3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000143549 [Gene_View]  chr1:154127780-154155725 [Contig_View]  TPM3 [Vega]
ICGC DataPortalENSG00000143549
TCGA cBioPortalTPM3
AceView (NCBI)TPM3
Genatlas (Paris)TPM3
WikiGenes7170
SOURCE (Princeton)TPM3
Genomic and cartography
GoldenPath hg19 (UCSC)TPM3  -     chr1:154127780-154155725 -  1q21.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TPM3  -     1q21.2   [Description]    (hg38-Dec_2013)
EnsemblTPM3 - 1q21.2 [CytoView hg19]  TPM3 - 1q21.2 [CytoView hg38]
Mapping of homologs : NCBITPM3 [Mapview hg19]  TPM3 [Mapview hg38]
OMIM191030   255310   609284   
Gene and transcription
Genbank (Entrez)AA429717 AA863064 AB062125 AF474157 AJ573307
RefSeq transcript (Entrez)NM_001043351 NM_001043352 NM_001043353 NM_001278188 NM_001278189 NM_001278190 NM_001278191 NM_152263 NM_153649
RefSeq genomic (Entrez)NC_000001 NC_018912 NG_008621 NT_004487 NW_004929293
Consensus coding sequences : CCDS (NCBI)TPM3
Cluster EST : UnigeneHs.654421 [ NCBI ]
CGAP (NCI)Hs.654421
Alternative Splicing GalleryENSG00000143549
Gene ExpressionTPM3 [ NCBI-GEO ]   TPM3 [ EBI - ARRAY_EXPRESS ]   TPM3 [ SEEK ]   TPM3 [ MEM ]
Gene Expression Viewer (FireBrowse)TPM3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7170
GTEX Portal (Tissue expression)TPM3
Protein : pattern, domain, 3D structure
UniProt/SwissProtP06753 (Uniprot)
NextProtP06753  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP06753
Splice isoforms : SwissVarP06753 (Swissvar)
PhosPhoSitePlusP06753
Domaine pattern : Prosite (Expaxy)TROPOMYOSIN (PS00326)   
Domains : Interpro (EBI)Tropomyosin   
Domain families : Pfam (Sanger)Tropomyosin (PF00261)   
Domain families : Pfam (NCBI)pfam00261   
DMDM Disease mutations7170
Blocks (Seattle)TPM3
SuperfamilyP06753
Human Protein AtlasENSG00000143549
Peptide AtlasP06753
HPRD01840
IPIIPI00218319   IPI00218320   IPI00909961   IPI00640264   IPI01021744   IPI00183968   IPI00642042   IPI00854592   IPI00382894   IPI00479185   IPI00477649   IPI00643370   IPI00967467   IPI00965179   IPI00966330   IPI00966664   
Protein Interaction databases
DIP (DOE-UCLA)P06753
IntAct (EBI)P06753
FunCoupENSG00000143549
BioGRIDTPM3
STRING (EMBL)TPM3
ZODIACTPM3
Ontologies - Pathways
QuickGOP06753
Ontology : AmiGOstress fiber  molecular_function  actin binding  protein binding  cytosol  cytoskeleton  cytoskeleton  muscle thin filament tropomyosin  movement of cell or subcellular component  muscle contraction  muscle filament sliding  extracellular exosome  
Ontology : EGO-EBIstress fiber  molecular_function  actin binding  protein binding  cytosol  cytoskeleton  cytoskeleton  muscle thin filament tropomyosin  movement of cell or subcellular component  muscle contraction  muscle filament sliding  extracellular exosome  
Pathways : KEGGCardiac muscle contraction    Adrenergic signaling in cardiomyocytes    Pathways in cancer    Thyroid cancer    Hypertrophic cardiomyopathy (HCM)    Dilated cardiomyopathy   
REACTOMEP06753 [protein]
REACTOME PathwaysR-HSA-390522 Striated Muscle Contraction [pathway]
REACTOME PathwaysR-HSA-445355 Smooth Muscle Contraction [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkTPM3
Wikipedia pathwaysTPM3
Orthology - Evolution
OrthoDB7170
GeneTree (enSembl)ENSG00000143549
Phylogenetic Trees/Animal Genes : TreeFamTPM3
Homologs : HomoloGeneTPM3
Homology/Alignments : Family Browser (UCSC)TPM3
Gene fusions - Rearrangements
Fusion : MitelmanB4GALT3/TPM3 [1q23.3/1q21.3]  [t(1;1)(q21;q23)]  
Fusion : MitelmanJAK2/TPM3 [9p24.1/1q21.3]  [t(1;9)(q21;p24)]  
Fusion : MitelmanTPM3/ALK [1q21.3/2p23.2]  [t(1;2)(q21;p23)]  
Fusion : MitelmanTPM3/JAK2 [1q21.3/9p24.1]  [t(1;9)(q21;p24)]  
Fusion : MitelmanTPM3/NTRK1 [1q21.3/1q23.1]  [inv(1)(q21q23)]  [t(1;1)(q21;q23)]  
Fusion : MitelmanTPM3/PDGFRB [1q21.3/5q32]  [t(1;5)(q21;q32)]  
Fusion : MitelmanTPM3/ROS1 [1q21.3/6q22.1]  [t(1;6)(q21;q22)]  
Fusion : MitelmanTPM3/TPR [1q21.3/1q31.1]  [inv(1)(q21q31)]  
Fusion : COSMICTPM3 [1q21.3]  -  ROS1 [6q22.1]  [fusion_1273]  [fusion_1274]  [fusion_1663]  [fusion_1664]  
Fusion: TCGATPM3 1q21.3 NTRK1 1q23.1 THCA
Fusion : TICdbTPM3 [1q21.3]  -  ALK [2p23.2]
Fusion : TICdbTPM3 [1q21.3]  -  PDGFRB [5q32]
Polymorphisms : SNP, variants
NCBI Variation ViewerTPM3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TPM3
dbVarTPM3
ClinVarTPM3
1000_GenomesTPM3 
Exome Variant ServerTPM3
ExAC (Exome Aggregation Consortium)TPM3 (select the gene name)
Genetic variants : HAPMAP7170
Genomic Variants (DGV)TPM3 [DGVbeta]
Mutations
ICGC Data PortalTPM3 
TCGA Data PortalTPM3 
Broad Tumor PortalTPM3
OASIS PortalTPM3 [ Somatic mutations - Copy number]
Cancer Gene: CensusTPM3 
Somatic Mutations in Cancer : COSMICTPM3 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)Leiden Muscular Dystrophy pages
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TPM3
DgiDB (Drug Gene Interaction Database)TPM3
DoCM (Curated mutations)TPM3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TPM3 (select a term)
intoGenTPM3
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)1:154127780-154155725  ENSG00000143549
CONAN: Copy Number AnalysisTPM3 
Mutations and Diseases : HGMDTPM3
OMIM191030    255310    609284   
MedgenTPM3
Genetic Testing Registry TPM3
NextProtP06753 [Medical]
TSGene7170
GENETestsTPM3
Huge Navigator TPM3 [HugePedia]
snp3D : Map Gene to Disease7170
BioCentury BCIQTPM3
ClinGenTPM3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7170
Chemical/Pharm GKB GenePA36692
Clinical trialTPM3
Miscellaneous
canSAR (ICR)TPM3 (select the gene name)
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed130 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTPM3
EVEXTPM3
GoPubMedTPM3
iHOPTPM3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Aug 10 18:56:19 CEST 2016

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jlhuret@AtlasGeneticsOncology.org.