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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

Alias_namesNEM1
Alias_symbol (synonym)TRK
Other alias
HGNC (Hugo) TPM3
LocusID (NCBI) 7170
Atlas_Id 225
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 154155304 and ends at 154183249 bp from pter ( according to hg19-Feb_2009)  [Mapping TPM3.png]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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)

Leukemias AnaplLargeCelLymphID2103 t0102ID1168 t0105q22q33ID1115 TL_t0101q21q23ID2534 TL_t0105q21q32ID1455
TL_t0105q21q32ID3271 TL_t0109q21p24ID2852 TL_t0109q21p24ID3270


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 10 ]

Solid Tumors ALKrenalCellCarcID6279 MyofibroID5073 PapilThyroidCarID5053 softissuTumID5042 t0102ID5129
TranslocLungAdenocarcID6751 TT_inv01q21q23ID5451 TT_inv01q21q31ID100055 TT_inv01q21q31ID6619 TT_t0106q21q22ID6761


External links

Nomenclature
HGNC (Hugo)TPM3   12012
LRG (Locus Reference Genomic)LRG_681
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; TPM3nu; TPMsk3; TRK; hscp30
GeneCards (Weizmann)TPM3
Ensembl hg19 (Hinxton)ENSG00000143549 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000143549 [Gene_View]  ENSG00000143549 [Sequence]  chr1:154155304-154183249 [Contig_View]  TPM3 [Vega]
ICGC DataPortalENSG00000143549
TCGA cBioPortalTPM3
AceView (NCBI)TPM3
Genatlas (Paris)TPM3
WikiGenes7170
SOURCE (Princeton)TPM3
Genetics Home Reference (NIH)TPM3
Genomic and cartography
GoldenPath hg38 (UCSC)TPM3  -     chr1:154155304-154183249 -  1q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TPM3  -     1q21.3   [Description]    (hg19-Feb_2009)
GoldenPathTPM3 - 1q21.3 [CytoView hg19]  TPM3 - 1q21.3 [CytoView hg38]
ImmunoBaseENSG00000143549
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_001349679 NM_001364679 NM_001364680 NM_001364681 NM_001364682 NM_001364683 NM_152263 NM_153649
RefSeq genomic (Entrez)
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]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7170
GTEX Portal (Tissue expression)TPM3
Human Protein AtlasENSG00000143549-TPM3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP06753   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP06753  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP06753
Splice isoforms : SwissVarP06753
PhosPhoSitePlusP06753
Domaine pattern : Prosite (Expaxy)TROPOMYOSIN (PS00326)   
Domains : Interpro (EBI)Tropomyosin   
Domain families : Pfam (Sanger)Tropomyosin (PF00261)   
Domain families : Pfam (NCBI)pfam00261   
Conserved Domain (NCBI)TPM3
DMDM Disease mutations7170
Blocks (Seattle)TPM3
SuperfamilyP06753
Human Protein Atlas [tissue]ENSG00000143549-TPM3 [tissue]
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  protein binding  cytosol  cytosol  cytoskeleton  cytoskeleton  muscle thin filament tropomyosin  actin filament  muscle contraction  actin filament organization  actin cytoskeleton  muscle filament sliding  actin filament binding  extracellular exosome  
Ontology : EGO-EBIstress fiber  molecular_function  protein binding  cytosol  cytosol  cytoskeleton  cytoskeleton  muscle thin filament tropomyosin  actin filament  muscle contraction  actin filament organization  actin cytoskeleton  muscle filament sliding  actin filament binding  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-445355 [pathway]   
NDEx NetworkTPM3
Atlas of Cancer Signalling NetworkTPM3
Wikipedia pathwaysTPM3
Orthology - Evolution
OrthoDB7170
GeneTree (enSembl)ENSG00000143549
Phylogenetic Trees/Animal Genes : TreeFamTPM3
HOGENOMP06753
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 : COSMICNTRK1 [1q23.1]  -  TPM3 [1q21.3]  [fusion_1321]  [fusion_1322]  [fusion_1332]  
Fusion : COSMICTPM3 [1q21.3]  -  ALK [2p23.2]  [fusion_439]  [fusion_440]  [fusion_443]  
Fusion : COSMICTPM3 [1q21.3]  -  NTRK1 [1q23.1]  [fusion_1318]  [fusion_1319]  [fusion_1320]  [fusion_1329]  [fusion_1330]  
Fusion : COSMICTPM3 [1q21.3]  -  ROS1 [6q22.1]  [fusion_1273]  [fusion_1274]  [fusion_1663]  [fusion_1664]  
Fusion PortalTPM3 1q21.3 NTRK1 1q23.1 THCA
Fusion : TICdbTPM3 [1q21.3]  -  ALK [2p23.2]
Fusion : TICdbTPM3 [1q21.3]  -  PDGFRB [5q32]
Fusion : FusionGDB10959    25215    30977    33059    33626    36387    39230    39231    39232    39233    39234    39235    39236    39237   
Fusion : Fusion_HubADAR--TPM3    ALK--TPM3    BSG--TPM3    C20ORF166--TPM3    CAP2--TPM3    CFLAR--TPM3    CLIP1--TPM3    COA1--TPM3    COX20--TPM3    CSGALNACT1--TPM3    EEF1A1--TPM3    FHL1--TPM3    GRK5--TPM3    HBB--TPM3    IL6R--TPM3   
JA040723--TPM3    MTERFD2--TPM3    MYBPC1--TPM3    MYL2--TPM3    NTRK1--TPM3    NUP210L--TPM3    PCBD2--TPM3    PDE4DIP--TPM3    PDGFRB--TPM3    RERE--TPM3    RNF44--TPM3    ROS1--TPM3    RP11-297L17.6--TPM3    RP11-618N24.1--TPM3    RP5-857K21.7--TPM3   
SEC24D--TPM3    SH3BGRL3--TPM3    TNNI1--TPM3    TPM2--TPM3    TPM3--ACTN2    TPM3--ADAR    TPM3--ALDOA    TPM3--ALK    TPM3--BAIAP2    TPM3--C1ORF43    TPM3--CA3    TPM3--CASQ1    TPM3--CDC42BPB    TPM3--CDC42SE1    TPM3--CELF1   
TPM3--DES    TPM3--FAM192A    TPM3--GLUL    TPM3--GNL2    TPM3--IFRD1    TPM3--MAP4K1    TPM3--MB    TPM3--MYBPC1    TPM3--MYH1    TPM3--MYH7    TPM3--MYL2    TPM3--MYOT    TPM3--NBPF10    TPM3--NEB    TPM3--NPTN   
TPM3--NRAP    TPM3--NSL1    TPM3--NTRK1    TPM3--NTRK1_ENST00000392302    TPM3--PDGFRB    TPM3--RCN3    TPM3--ROS1    TPM3--RXRA    TPM3--RYR1    TPM3--SEC24D    TPM3--SLC19A2    TPM3--SMR3B    TPM3--SRSF11    TPM3--TECRL    TPM3--TNNC1   
TPM3--TNNI1    TPM3--TNNT1    TPM3--TPM3P1    TPM3--TPR    TPM3--TRKA    TPM3--TSC22D1    TPM3--TTN    TPM3--UBE2D2    TPM3--UBE2R2    TPM3--WIPF3    TPM3--WNK1    TPM4--TPM3    TTN--TPM3    VCL--TPM3   
Fusion : QuiverTPM3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTPM3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TPM3
dbVarTPM3
ClinVarTPM3
1000_GenomesTPM3 
Exome Variant ServerTPM3
ExAC (Exome Aggregation Consortium)ENSG00000143549
GNOMAD BrowserENSG00000143549
Varsome BrowserTPM3
Genetic variants : HAPMAP7170
Genomic Variants (DGV)TPM3 [DGVbeta]
DECIPHERTPM3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTPM3 
Mutations
ICGC Data PortalTPM3 
TCGA Data PortalTPM3 
Broad Tumor PortalTPM3
OASIS PortalTPM3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTPM3  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTPM3
Mutations and Diseases : HGMDTPM3
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
NCG5 (London)TPM3
Cancer3DTPM3(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM191030    255310    609284   
Orphanet17907    17909    493    18017    17949   
DisGeNETTPM3
MedgenTPM3
Genetic Testing Registry TPM3
NextProtP06753 [Medical]
TSGene7170
GENETestsTPM3
Target ValidationTPM3
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)
DataMed IndexTPM3
Probes
Litterature
PubMed162 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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indexed on : Mon Aug 12 15:18:41 CEST 2019

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