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TPM2
Identifiers
Aliases	TPM2, AMCD1, DA1, DA2B, HEL-S-273, NEM4, TMSB, tropomyosin 2 (beta), tropomyosin 2, DA2B4
External IDs	OMIM: 190990; MGI: 98810; HomoloGene: 134045; GeneCards: TPM2; OMA:TPM2 - orthologs
Gene location (Human) Chr. Chromosome 9 (human) Band 9p13.3 Start 35,681,992 bp End 35,690,056 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4|4 A5 Start 43,514,711 bp End 43,523,765 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in saphenous vein popliteal artery tibial arteries Skeletal muscle tissue of rectus abdominis muscle of thigh gastric mucosa right coronary artery ascending aorta Skeletal muscle tissue of biceps brachii Descending thoracic aorta Top expressed in intercostal muscle tunica media of zone of aorta ascending aorta ankle sternocleidomastoid muscle soleus muscle muscle of thigh temporal muscle digastric muscle triceps brachii muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function actin binding structural constituent of muscle identical protein binding protein homodimerization activity protein heterodimerization activity actin filament binding Cellular component cytoplasm muscle thin filament tropomyosin cytosol cytoskeleton actin filament actin cytoskeleton Biological process regulation of ATP-dependent activity muscle filament sliding muscle contraction actin filament organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7169 22004 Ensembl ENSG00000198467 ENSMUSG00000028464 UniProt P07951 P58774 RefSeq (mRNA) NM_001145822 NM_001301226 NM_001301227 NM_003289 NM_213674 NM_001277875 NM_001277876 NM_009416 RefSeq (protein) NP_001288155 NP_001288156 NP_003280 NP_998839 NP_001264804 NP_001264805 NP_033442 Location (UCSC) Chr 9: 35.68 – 35.69 Mb Chr 4: 43.51 – 43.52 Mb PubMed search
Wikidata
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β-Tropomyosin, also known as tropomyosin beta chain is a protein that in humans is encoded by the TPM2 gene. β-tropomyosin is striated muscle-specific coiled coil dimer that functions to stabilize actin filaments and regulate muscle contraction.

Structure

β-tropomyosin is roughly 32 kDa in molecular weight (284 amino acids), but multiple splice variants exist. Tropomysin is a flexible protein homodimer or heterodimer composed of two alpha-helical chains, which adopt a bent coiled coil conformation to wrap around the seven actin molecules in a functional unit of muscle. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. Tropomyosin dimers are composed of varying combinations of tropomyosin isoforms; human striated muscles express protein from the TPM1 (α-tropoomyosin), TPM2 (β-tropomyosin) and TPM3 (γ-tropomyosin) genes, with α-tropomyosin being the predominant isoform in striated muscle. Fast skeletal muscle and cardiac muscle contain more αα-homodimers, and slow skeletal muscle contains more ββ-homodimers. In human cardiac muscle the ratio of α-tropomyosin to β-tropomyosin is roughly 5:1. It has been shown that different combinations of tropomyosin isoforms bind troponin T with differing affinities, demonstrating that isoform combinations are used to impart a specific functional impact.

Function

β-tropomyosin functions in association with α-tropomyosin and the troponin complex—composed of troponin I, troponin C and troponin T—to modulated the actin and myosin interaction. In diastole, the tropomyosin-troponin complex inhibits this interaction, and during systole the rise in intracellular calcium from sarcoplasmic reticulum binds to troponin C and induces a conformational change in the troponin-tropomyosin complex that disinhibits the actomyosin ATPase and permits contraction.

Specific functional insights into the function of the β-tropomyosin isoform have come from studies employing transgenesis. A study overexpressing β-tropomyosin in adult cardiac muscle evoked a 34-fold increase in expression of β-tropomyosin, resulting in preferential formation of the αβ-tropomyosin heterodimer. Transgenic hearts showed a significant delay in relaxation time as well as a decrease in the maximum rate of left ventricular relaxation. A more aggressive overexpression of β-tropomyosin (to over 75% of total tropomyosin) in the heart causes death of mice 10–14 days old, along with cardiac abnormalities, suggesting that the normal distribution of tropomyosin isoforms is critical to normal cardiac function.

In a disease model of cardiac hypertrophy, β-tropomyosin was shown to be reexpressed within two days following induction of pressure overload.

Studies from mice, which express 98% α-tropomyosin, have shown that α-tropomyosin can be phosphorylated at Serine-283, which is one amino acid away from the C-terminus. β-tropomyosin also has a Serine residue at position 283, thus, it is likely that β-tropomyosin is also phosphorylated. Mouse transgenic studies in which the phosphorylation site in α-tropomyosin is mutated to Alanine have shown that phosphorylation may function to modulate tropomyosin polymerization, head-to-tail interactions between adjacent tropomyosin molecules, cooperativity, myosin ATPase activity, and the cardiac response to stress.

Clinical significance

A decrease in β-tropomyosin in patients with heart failure was demonstrated, as failing ventricles expressed solely α-tropomyosin.

Heterozygous mutations in TPM2 have been identified in patients with congenital cap myopathy, a rare disorder defined by cap-like structures in muscle fiber periphery.

Mutations in TPM2 have also been associated with nemaline myopathy, a rare disorder characterized by muscle weakness and nemaline bodies,

as well as distal arthrogryposis.

The muscle weakness observed in these patients may be due to a change in mutated TPM2 affinity for actin or decreased calcium-induced activation of contractility. Moreover, studies unveiled alterations in cross-bridge attachment and detachment rates, as well as changes in ATPase rates.

Interactions

TPM2 has been shown to interact with:

• RRAD,
• PDLIM7,
• TNNT3, and
• TPM1.

References

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Further reading

• Gunning P, Weinberger R, Jeffrey P (Apr 1997). "Actin and tropomyosin isoforms in morphogenesis". Anatomy and Embryology. 195 (4): 311–5. doi:10.1007/s004290050050. PMID 9108196. S2CID 9692297.
• Holtzer ME, Kidd SG, Crimmins DL, Holtzer A (Mar 1992). "Beta beta homodimers exist in native rabbit skeletal muscle tropomyosin and increase after denaturation-renaturation". Protein Science. 1 (3): 335–41. doi:10.1002/pro.5560010305. PMC 2142203. PMID 1304342.
• Höner B, Shoeman RL, Traub P (Jul 1992). "Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease". Cell Biology International Reports. 16 (7): 603–12. doi:10.1016/S0309-1651(06)80002-0. PMID 1516138.
• Chevray PM, Nathans D (Jul 1992). "Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun". Proceedings of the National Academy of Sciences of the United States of America. 89 (13): 5789–93. Bibcode:1992PNAS...89.5789C. doi:10.1073/pnas.89.13.5789. PMC 402103. PMID 1631061.
• Prasad GL, Meissner S, Sheer DG, Cooper HL (Jun 1991). "A cDNA encoding a muscle-type tropomyosin cloned from a human epithelial cell line: identity with human fibroblast tropomyosin TM1". Biochemical and Biophysical Research Communications. 177 (3): 1068–75. doi:10.1016/0006-291X(91)90647-P. PMID 2059197.
• Libri D, Mouly V, Lemonnier M, Fiszman MY (Feb 1990). "A nonmuscle tropomyosin is encoded by the smooth/skeletal beta-tropomyosin gene and its RNA is transcribed from an internal promoter". The Journal of Biological Chemistry. 265 (6): 3471–3. doi:10.1016/S0021-9258(19)39791-1. PMID 2303454.
• Widada JS, Ferraz C, Capony JP, Liautard JP (Apr 1988). "Complete nucleotide sequence of the adult skeletal isoform of human skeletal muscle beta-tropomyosin". Nucleic Acids Research. 16 (7): 3109. doi:10.1093/nar/16.7.3109. PMC 336462. PMID 3368322.
• MacLeod AR, Houlker C, Reinach FC, Smillie LB, Talbot K, Modi G, Walsh FS (Dec 1985). "A muscle-type tropomyosin in human fibroblasts: evidence for expression by an alternative RNA splicing mechanism". Proceedings of the National Academy of Sciences of the United States of America. 82 (23): 7835–9. Bibcode:1985PNAS...82.7835M. doi:10.1073/pnas.82.23.7835. PMC 390864. PMID 3865200.
• Gimona M, Watakabe A, Helfman DM (Oct 1995). "Specificity of dimer formation in tropomyosins: influence of alternatively spliced exons on homodimer and heterodimer assembly". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9776–80. Bibcode:1995PNAS...92.9776G. doi:10.1073/pnas.92.21.9776. PMC 40885. PMID 7568216.
• Bamshad M, Watkins WS, Zenger RK, Bohnsack JF, Carey JC, Otterud B, Krakowiak PA, Robertson M, Jorde LB (Dec 1994). "A gene for distal arthrogryposis type I maps to the pericentromeric region of chromosome 9". American Journal of Human Genetics. 55 (6): 1153–8. PMC 1918435. PMID 7977374.
• Takenaga K, Nakamura Y, Sakiyama S, Hasegawa Y, Sato K, Endo H (Mar 1994). "Binding of pEL98 protein, an S100-related calcium-binding protein, to nonmuscle tropomyosin". The Journal of Cell Biology. 124 (5): 757–68. doi:10.1083/jcb.124.5.757. PMC 2119958. PMID 8120097.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Shoeman RL, Sachse C, Höner B, Mothes E, Kaufmann M, Traub P (Jan 1993). "Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, desmin, myosin, and tropomyosin". The American Journal of Pathology. 142 (1): 221–30. PMC 1886840. PMID 8424456.
• Tiso N, Rampoldi L, Pallavicini A, Zimbello R, Pandolfo D, Valle G, Lanfranchi G, Danieli GA (Jan 1997). "Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast". Biochemical and Biophysical Research Communications. 230 (2): 347–50. doi:10.1006/bbrc.1996.5958. hdl:11577/2466889. PMID 9016781.
• Gimona M, Lando Z, Dolginov Y, Vandekerckhove J, Kobayashi R, Sobieszek A, Helfman DM (Mar 1997). "Ca2+-dependent interaction of S100A2 with muscle and nonmuscle tropomyosins". Journal of Cell Science. 110 (5): 611–21. doi:10.1242/jcs.110.5.611. PMID 9092943.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.

External links

• GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy

• Genes on human chromosome 9