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
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:
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.
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.
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.
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
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.