TPM1

Tropomyosin 1 (alpha)
PDB rendering based on 1c1g.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1c1g​, 1ic2​, 1mv4​, 2g9j​, 2tma​
Identifiers
Symbols	TPM1 ; C15orf13; CMD1Y; CMH3; HTM-alpha; LVNC9; TMSA
External IDs	OMIM: 191010 MGI: 98809 HomoloGene: 121635 GeneCards: TPM1 Gene
Gene ontology Molecular function • actin binding • structural constituent of cytoskeleton • protein binding • cytoskeletal protein binding • structural constituent of muscle Cellular component • stress fiber • cytosol • cytoskeleton • muscle thin filament tropomyosin • sarcomere • filamentous actin • bleb • ruffle membrane Biological process • in utero embryonic development • positive regulation of heart rate by epinephrine • movement of cell or subcellular component • muscle contraction • regulation of muscle contraction • cytoskeleton organization • regulation of heart contraction • muscle filament sliding • negative regulation of cell migration • ruffle organization • positive regulation of ATPase activity • cellular response to reactive oxygen species • wound healing • sarcomere organization • positive regulation of cell adhesion • positive regulation of stress fiber assembly • ventricular cardiac muscle tissue morphogenesis • cardiac muscle contraction Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7168	22003
Ensembl	ENSG00000140416	ENSMUSG00000032366
UniProt	P09493	Q545Y3
RefSeq (mRNA)	NM_000366	NM_024427
RefSeq (protein)	NP_000357	NP_077745
Location (UCSC)	Chr 15: 63.04 – 63.07 Mb	Chr 9: 66.82 – 66.85 Mb
PubMed search

Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene.^[1] This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells.

Structure

Tm is a 32.7 kDa protein composed of 284 amino acids.^[2] Tm 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.^[3] It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. Human striated muscles express protein from the TPM1 (α-Tm), TPM2 (β-Tm) and TPM3 (γ-Tm) genes, with α-Tm being the predominant isoform in striated muscle. In human cardiac muscle the ratio of α-Tm to β-Tm is roughly 5:1.^[4]

Function

Tm functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. Tm molecules are arranged head-to-tail along the actin thin filament, and are a key component in cooperative activation of muscle. A three state model has been proposed by McKillop and Geeves,^[5] which describes the positions of Tm during a cardiac cycle. The blocked (B) state occurs in diastole when intracellular calcium is low and Tm blocks the myosin binding site on actin. The closed (C) state is when Tm is positioned on the inner groove of actin; in this state myosin is in a "cocked" position where heads are weakly bound and not generating force. The myosin binding (M) state is when Tm is further displaced from actin by myosin crossbridges that are strongly-bound and actively generating force. In addition to actin, Tm binds troponin T (TnT). TnT tethers the region of head-to-tail overlap of subsequent Tm molecules to actin.

Clinical Significance

Mutations in TPM1 have been associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy. HCM mutations tend to cluster around the N-terminal region and a primary actin binding region known as period 5.^[6]

References

1. Mogensen J, Kruse TA, Borglum AD (Jun 1999). "Refined localization of the human alpha-tropomyosin gene (TPM1) by genetic mapping". Cytogenet Cell Genet 84 (1-2): 35–6. doi:10.1159/000015207. PMID 10343096.
2. http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P09493. Missing or empty |title= (help)
3. Brown, J. H.; Kim, K. H.; Jun, G; Greenfield, N. J.; Dominguez, R; Volkmann, N; Hitchcock-Degregori, S. E.; Cohen, C (2001). "Deciphering the design of the tropomyosin molecule". Proceedings of the National Academy of Sciences 98 (15): 8496–501. doi:10.1073/pnas.131219198. PMC 37464. PMID 11438684.
4. Yin, Z; Ren, J; Guo, W (2015). "Sarcomeric protein isoform transitions in cardiac muscle: A journey to heart failure". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1852 (1): 47–52. doi:10.1016/j.bbadis.2014.11.003. PMC 4268308. PMID 25446994.
5. McKillop, D. F.; Geeves, M. A. (1993). "Regulation of the interaction between actin and myosin subfragment 1: Evidence for three states of the thin filament". Biophysical Journal 65 (2): 693–701. doi:10.1016/S0006-3495(93)81110-X. PMC 1225772. PMID 8218897.
6. Tardiff, J. C. (2011). "Thin filament mutations: Developing an integrative approach to a complex disorder". Circulation Research 108 (6): 765–82. doi:10.1161/CIRCRESAHA.110.224170. PMC 3075069. PMID 21415410.

Further reading

• Lees-Miller JP, Helfman DM (1992). "The molecular basis for tropomyosin isoform diversity.". BioEssays 13 (9): 429–37. doi:10.1002/bies.950130902. PMID 1796905.
• Balvay L, Fiszman MY (1995). "[Analysis of the diversity of tropomyosin isoforms]". C. R. Seances Soc. Biol. Fil. 188 (5-6): 527–40. PMID 7780795.
• Gunning P, Weinberger R, Jeffrey P (1997). "Actin and tropomyosin isoforms in morphogenesis.". Anat. Embryol. 195 (4): 311–5. doi:10.1007/s004290050050. PMID 9108196.
• Perry SV (2002). "Vertebrate tropomyosin: distribution, properties and function.". J. Muscle Res. Cell. Motil. 22 (1): 5–49. doi:10.1023/A:1010303732441. PMID 11563548.
• Perry SV (2004). "What is the role of tropomyosin in the regulation of muscle contraction?". J. Muscle Res. Cell. Motil. 24 (8): 593–6. doi:10.1023/B:JURE.0000009811.95652.68. PMID 14870975.
• Jääskeläinen P, Miettinen R, Kärkkäinen P, et al. (2004). "Genetics of hypertrophic cardiomyopathy in eastern Finland: few founder mutations with benign or intermediary phenotypes.". Ann. Med. 36 (1): 23–32. doi:10.1080/07853890310017161. PMID 15000344.
• Mak A, Smillie LB, Bárány M (1978). "Specific phosphorylation at serine-283 of alpha tropomyosin from frog skeletal and rabbit skeletal and cardiac muscle.". Proc. Natl. Acad. Sci. U.S.A. 75 (8): 3588–92. doi:10.1073/pnas.75.8.3588. PMC 392830. PMID 278975.
• Höner B, Shoeman RL, Traub P (1992). "Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease.". Cell Biol. Int. Rep. 16 (7): 603–12. doi:10.1016/S0309-1651(06)80002-0. PMID 1516138.
• Chevray PM, Nathans D (1992). "Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun.". Proc. Natl. Acad. Sci. U.S.A. 89 (13): 5789–93. doi:10.1073/pnas.89.13.5789. PMC 402103. PMID 1631061.
• Shoeman RL, Kesselmier C, Mothes E, et al. (1991). "Non-viral cellular substrates for human immunodeficiency virus type 1 protease.". FEBS Lett. 278 (2): 199–203. doi:10.1016/0014-5793(91)80116-K. PMID 1991513.
• Cho YJ, Liu J, Hitchcock-DeGregori SE (1990). "The amino terminus of muscle tropomyosin is a major determinant for function.". J. Biol. Chem. 265 (1): 538–45. PMID 2136742.
• Colote S, Widada JS, Ferraz C, et al. (1988). "Evolution of tropomyosin functional domains: differential splicing and genomic constraints.". J. Mol. Evol. 27 (3): 228–35. doi:10.1007/BF02100079. PMID 3138425.
• Lin CS, Leavitt J (1988). "Cloning and characterization of a cDNA encoding transformation-sensitive tropomyosin isoform 3 from tumorigenic human fibroblasts.". Mol. Cell. Biol. 8 (1): 160–8. PMC 363096. PMID 3336357.
• MacLeod AR, Gooding C (1988). "Human hTM alpha gene: expression in muscle and nonmuscle tissue.". Mol. Cell. Biol. 8 (1): 433–40. PMC 363144. PMID 3336363.
• Mische SM, Manjula BN, Fischetti VA (1987). "Relation of streptococcal M protein with human and rabbit tropomyosin: the complete amino acid sequence of human cardiac alpha tropomyosin, a highly conserved contractile protein.". Biochem. Biophys. Res. Commun. 142 (3): 813–8. doi:10.1016/0006-291X(87)91486-0. PMID 3548719.
• Heeley DH, Golosinska K, Smillie LB (1987). "The effects of troponin T fragments T1 and T2 on the binding of nonpolymerizable tropomyosin to F-actin in the presence and absence of troponin I and troponin C.". J. Biol. Chem. 262 (21): 9971–8. PMID 3611073.
• Brown HR, Schachat FH (1985). "Renaturation of skeletal muscle tropomyosin: implications for in vivo assembly.". Proc. Natl. Acad. Sci. U.S.A. 82 (8): 2359–63. doi:10.1073/pnas.82.8.2359. PMC 397557. PMID 3857586.
• Tanokura M, Ohtsuki I (1984). "Interactions among chymotryptic troponin T subfragments, tropomyosin, troponin I and troponin C.". J. Biochem. 95 (5): 1417–21. PMID 6746613.
• Pearlstone JR, Smillie LB (1983). "Effects of troponin-I plus-C on the binding of troponin-T and its fragments to alpha-tropomyosin. Ca2+ sensitivity and cooperativity.". J. Biol. Chem. 258 (4): 2534–42. PMID 6822572.

External links

• Mass spectrometry characterization of human TPM1 at COPaKB ^[1]
• GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview

1. Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.