Human Gene TPM3 (uc001fec.2) Description and Page Index
  Description: Homo sapiens tropomyosin 3 (TPM3), transcript variant 1, mRNA.
RefSeq Summary (NM_152263): This gene encodes a member of the tropomyosin family of actin-binding proteins. Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. Mutations in this gene result in autosomal dominant nemaline myopathy and other muscle disorders. This locus is involved in translocations with other loci, including anaplastic lymphoma receptor tyrosine kinase (ALK) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), which result in the formation of fusion proteins that act as oncogenes. There are numerous pseudogenes for this gene on different chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013].
Transcript (Including UTRs)
   Position: hg19 chr1:154,134,289-154,164,611 Size: 30,323 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr1:154,140,413-154,164,494 Size: 24,082 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:154,134,289-154,164,611)mRNA (may differ from genome)Protein (285 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: TPM3_HUMAN
DESCRIPTION: RecName: Full=Tropomyosin alpha-3 chain; AltName: Full=Gamma-tropomyosin; AltName: Full=Tropomyosin-3; AltName: Full=Tropomyosin-5; Short=hTM5;
FUNCTION: Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.
SUBUNIT: Heterodimer of an alpha and a beta chain. Binds to TMOD1.
INTERACTION: Q14240:EIF4A2; NbExp=1; IntAct=EBI-355607, EBI-73473; P23508:MCC; NbExp=1; IntAct=EBI-355607, EBI-307531;
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
DOMAIN: The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven- residues periodicity.
DISEASE: Defects in TPM3 are the cause of nemaline myopathy type 1 (NEM1) [MIM:609284]. A form of nemaline myopathy with autosomal dominant or recessive inheritance. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-or rod-like structures in muscle fibers on histologic examination. Autosomal dominant nemaline myopathy type 1 is characterized by a moderate phenotype with onset between birth and early second decade of life. Weakness is diffuse and symmetric with slow progression often with need for a wheelchair in adulthood. The autosomal recessive form has onset at birth with moderate-to-severe hypotonia and diffuse weakness. In the most severe cases, death can occur before 2 years. Less severe cases have delayed major motor milestones, and these patients may walk, but often need a wheelchair before 10 years.
DISEASE: Defects in TPM3 are a cause of thyroid papillary carcinoma (TPC) [MIM:188550]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TPM3 is found in thyroid papillary carcinomas. A rearrangement with NTRK1 generates the TRK fusion transcript by fusing the amino end of isoform 2 of TPM3 to the 3'-end of NTRK1.
SIMILARITY: Belongs to the tropomyosin family.
SEQUENCE CAUTION: Sequence=AAH08407.1; Type=Erroneous initiation; Sequence=AAH08425.1; Type=Erroneous initiation; Sequence=CAA27798.1; Type=Erroneous initiation;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TPM3ID225.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TPM3";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TPM3
CDC HuGE Published Literature: TPM3
Positive Disease Associations: nemaline myopathy
Related Studies:
  1. nemaline myopathy
    Wattanasirichaigoon, D. et al. 2002, Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy, Neurology. 2002 Aug;59(4):613-7. [PubMed 12196661]
    A single compound heterozygous patient was identified carrying one mutation that converts the stop codon to a serine and a second splicing mutation that is predicted to prevent inclusion of skeletal muscle exon IX. TPM3 mutations are a rare cause of NM, probably accounting for less than 3% of cases. The severity of cases with TPM3 mutations may vary from severe infantile to late childhood onset, slowly progressive forms.

-  MalaCards Disease Associations
  MalaCards Gene Search: TPM3
Diseases sorted by gene-association score: myopathy, congenital, with fiber-type disproportion* (1231), nemaline myopathy 1, autosomal dominant or recessive* (1200), congenital fiber-type disproportion* (877), tpm3-related nemaline myopathy* (500), cap myopathy* (389), intermediate congenital nemaline myopathy* (350), congenital generalized hypercontractile muscle stiffness syndrome* (350), childhood-onset nemaline myopathy* (247), inflammatory myofibroblastic tumor* (179), nemaline myopathy* (172), tpm3-related congenital fiber-type disproportion* (100), childhood kidney cell carcinoma (15), muscle disorders (13), chronic eosinophilic leukemia (10), congenital structural myopathy (9), myopathy (9), pediatric fibrosarcoma (7), mesenchymal cell neoplasm (7), lymphatic system cancer (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 365.92 RPKM in Muscle - Skeletal
Total median expression: 1687.92 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -30.90117-0.264 Picture PostScript Text
3' UTR -2588.916124-0.423 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000533 - Tropomyosin

Pfam Domains:
PF00261 - Tropomyosin
PF12718 - Tropomyosin like
PF16526 - C-terminal leucine zipper domain of cyclic nucleotide-gated channels

ModBase Predicted Comparative 3D Structure on P06753
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
   FlyBaseWormBase 
   Protein SequenceProtein Sequence 
   AlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003674 molecular_function
GO:0003779 actin binding
GO:0005515 protein binding
GO:0008307 structural constituent of muscle
GO:0051015 actin filament binding

Biological Process:
GO:0006936 muscle contraction
GO:0007015 actin filament organization
GO:0030049 muscle filament sliding

Cellular Component:
GO:0001725 stress fiber
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005862 muscle thin filament tropomyosin
GO:0005884 actin filament
GO:0015629 actin cytoskeleton
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK056889 - Homo sapiens cDNA FLJ32327 fis, clone PROST2004416, moderately similar to TROPOMYOSIN 5, CYTOSKELETAL TYPE.
AB062125 - Homo sapiens OK/SW-cl.5 mRNA for cytoskeletal tropomyosin TM30, complete cds.
AK125367 - Homo sapiens cDNA FLJ43377 fis, clone OCBBF2001961, moderately similar to TROPOMYOSIN 5, CYTOSKELETAL TYPE.
X04588 - Human 2.5 kb mRNA for cytoskeletal tropomyosin TM30(nm).
AK092712 - Homo sapiens cDNA FLJ35393 fis, clone SKNSH2000971, highly similar to TROPOMYOSIN, CYTOSKELETAL TYPE.
AX747685 - Sequence 1210 from Patent EP1308459.
BC000771 - Homo sapiens tropomyosin 3, mRNA (cDNA clone MGC:3261 IMAGE:3506357), complete cds.
BC072428 - Homo sapiens tropomyosin 3, mRNA (cDNA clone MGC:87759 IMAGE:6472532), complete cds.
AK026559 - Homo sapiens cDNA: FLJ22906 fis, clone KAT05659, highly similar to HSTROPCR Human 2.5 kb mRNA for cytoskeletal tropomyosin TM30(nm).
AK123571 - Homo sapiens cDNA FLJ41577 fis, clone CTONG2019579.
AK056921 - Homo sapiens cDNA FLJ32359 fis, clone PROST2008516, highly similar to TROPOMYOSIN, CYTOSKELETAL TYPE.
BX648485 - Homo sapiens mRNA; cDNA DKFZp686J1372 (from clone DKFZp686J1372).
FJ224335 - Homo sapiens epididymis luminal protein 189 (HEL-189) mRNA, complete cds.
GQ891304 - Homo sapiens clone HEL-S-27a epididymis secretory sperm binding protein mRNA, complete cds.
BC015403 - Homo sapiens tropomyosin 3, mRNA (cDNA clone MGC:21936 IMAGE:4389911), complete cds.
BC017195 - Homo sapiens cDNA clone IMAGE:3138799, containing frame-shift errors.
AK298678 - Homo sapiens cDNA FLJ50612 complete cds, highly similar to Rattus norvegicus tropomyosin 3, gamma (Tpm3), transcript variant 2, mRNA.
AK308007 - Homo sapiens cDNA, FLJ97955.
AK301674 - Homo sapiens cDNA FLJ50720 complete cds, highly similar to Homo sapiens tropomyosin 3 (TPM3), transcript variant 2, mRNA.
AK315504 - Homo sapiens cDNA, FLJ96568, highly similar to Homo sapiens tropomyosin 3 (TPM3), mRNA.
KJ905944 - Synthetic construct Homo sapiens clone ccsbBroadEn_15614 TPM3 gene, encodes complete protein.
KU178368 - Homo sapiens tropomyosin 3 isoform 1 (TPM3) mRNA, partial cds.
KU178369 - Homo sapiens tropomyosin 3 isoform 2 (TPM3) mRNA, complete cds, alternatively spliced.
KU178370 - Homo sapiens tropomyosin 3 isoform 3 (TPM3) mRNA, partial cds.
AB529194 - Synthetic construct DNA, clone: pF1KB5272, Homo sapiens TPM3 gene for tropomyosin 3, without stop codon, in Flexi system.
AY004867 - Homo sapiens tropomyosin isoform mRNA, complete cds.
AK056997 - Homo sapiens cDNA FLJ32435 fis, clone SKMUS2001287, highly similar to Tropomyosin alpha-3 chain.
AK092690 - Homo sapiens cDNA FLJ35371 fis, clone SKMUS2001740, highly similar to TROPOMYOSIN ALPHA CHAIN, SKELETAL MUSCLE TYPE.
AX747672 - Sequence 1197 from Patent EP1308459.
EU668324 - Homo sapiens epididymis secretory sperm binding protein Li 82p (HEL-S-82p) mRNA, complete cds.
X04201 - Human skeletal muscle 1.3 kb mRNA for tropomyosin.
BC008407 - Homo sapiens tropomyosin 3, mRNA (cDNA clone MGC:14532 IMAGE:4245271), complete cds.
BC008425 - Homo sapiens tropomyosin 3, mRNA (cDNA clone MGC:14582 IMAGE:4246114), complete cds.
BC062740 - Homo sapiens tropomyosin 3, mRNA (cDNA clone MGC:72094 IMAGE:4271142), complete cds.
BC050470 - Homo sapiens, clone IMAGE:6200207, mRNA.
JD019965 - Sequence 989 from Patent EP1572962.
JD032940 - Sequence 13964 from Patent EP1572962.
JD070382 - Sequence 51406 from Patent EP1572962.
JD070383 - Sequence 51407 from Patent EP1572962.
JD514161 - Sequence 495185 from Patent EP1572962.
JD514162 - Sequence 495186 from Patent EP1572962.
JD151014 - Sequence 132038 from Patent EP1572962.
JD107953 - Sequence 88977 from Patent EP1572962.
JD515271 - Sequence 496295 from Patent EP1572962.
JD431721 - Sequence 412745 from Patent EP1572962.
JD165861 - Sequence 146885 from Patent EP1572962.
JD441768 - Sequence 422792 from Patent EP1572962.
JD329856 - Sequence 310880 from Patent EP1572962.
JD111221 - Sequence 92245 from Patent EP1572962.
JD120502 - Sequence 101526 from Patent EP1572962.
JD131319 - Sequence 112343 from Patent EP1572962.
JD071472 - Sequence 52496 from Patent EP1572962.
JD094474 - Sequence 75498 from Patent EP1572962.
KY806113 - Homo sapiens tropomyosin 3 nu (TPM3nu) mRNA, complete cds.
KJ901804 - Synthetic construct Homo sapiens clone ccsbBroadEn_11198 TPM3 gene, encodes complete protein.
AF474157 - Homo sapiens TPMsk3 (TPM3) mRNA, partial cds.
KJ892309 - Synthetic construct Homo sapiens clone ccsbBroadEn_01703 TPM3 gene, encodes complete protein.
KR710204 - Synthetic construct Homo sapiens clone CCSBHm_00010339 TPM3 (TPM3) mRNA, encodes complete protein.
KR710205 - Synthetic construct Homo sapiens clone CCSBHm_00010341 TPM3 (TPM3) mRNA, encodes complete protein.
KR710206 - Synthetic construct Homo sapiens clone CCSBHm_00010342 TPM3 (TPM3) mRNA, encodes complete protein.
KR710207 - Synthetic construct Homo sapiens clone CCSBHm_00010346 TPM3 (TPM3) mRNA, encodes complete protein.
M12128 - Human cytoskeletal tropomyosin isoform (2.5 kb) mRNA, 3' end.
JD207136 - Sequence 188160 from Patent EP1572962.
JD332957 - Sequence 313981 from Patent EP1572962.
JD375366 - Sequence 356390 from Patent EP1572962.
JD335978 - Sequence 317002 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04260 - Cardiac muscle contraction
hsa05200 - Pathways in cancer
hsa05216 - Thyroid cancer
hsa05410 - Hypertrophic cardiomyopathy (HCM)
hsa05414 - Dilated cardiomyopathy

Reactome (by CSHL, EBI, and GO)

Protein P06753 (Reactome details) participates in the following event(s):

R-HSA-445705 Release Of ADP From Myosin
R-HSA-445699 ATP Hydrolysis By Myosin
R-HSA-445700 Myosin Binds ATP
R-HSA-445704 Calcium Binds Caldesmon
R-HSA-390597 Release Of ADP From Myosin
R-HSA-390593 ATP Hydrolysis By Myosin
R-HSA-390598 Myosin Binds ATP
R-HSA-390595 Calcium Binds Troponin-C
R-HSA-445355 Smooth Muscle Contraction
R-HSA-390522 Striated Muscle Contraction
R-HSA-397014 Muscle contraction

-  Other Names for This Gene
  Alternate Gene Symbols: D3DV71, NM_152263, NP_689476, P06753, P12324, Q2QD06, Q5VU71, Q969Q2, Q9NQH8, TPM3_HUMAN, uc001fec.1
UCSC ID: uc001fec.2
RefSeq Accession: NM_152263
Protein: P06753 (aka TPM3_HUMAN)
CCDS: CCDS41403.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_152263.3
exon count: 10CDS single in 3' UTR: no RNA size: 7109
ORF size: 858CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1908.50frame shift in genome: no % Coverage: 99.86
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.