Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene.^[3] 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.

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TPM1
Identifiers
Aliases	TPM1, C15orf13, CMD1Y, CMH3, HTM-alpha, LVNC9, TMSA, HEL-S-265, tropomyosin 1 (alpha), tropomyosin 1
External IDs	OMIM: 191010 HomoloGene: 121635 GeneCards: TPM1
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q22.2 Start 63,042,632 bp[1] End 63,071,915 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle atrium seminal vesicula saphenous vein smooth muscle tissue biceps brachii popliteal artery right coronary artery pancreatic ductal cell myometrium n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cytoskeletal protein binding structural constituent of cytoskeleton protein binding 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 sarcomere stress fiber ruffle membrane bleb cytoskeleton cytosol actin filament actin cytoskeleton myofibril filamentous actin Biological process regulation of muscle contraction muscle contraction regulation of heart contraction positive regulation of ATP-dependent activity negative regulation of vascular associated smooth muscle cell migration negative regulation of vascular associated smooth muscle cell proliferation ruffle organization wound healing cellular response to reactive oxygen species negative regulation of cell migration cytoskeleton organization regulation of cell shape muscle filament sliding sarcomere organization positive regulation of stress fiber assembly positive regulation of cell adhesion actin filament organization in utero embryonic development positive regulation of heart rate by epinephrine ventricular cardiac muscle tissue morphogenesis cardiac muscle contraction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7168 n/a Ensembl ENSG00000140416 n/a UniProt P09493 n/a RefSeq (mRNA) NM_000366 NM_001018004 NM_001018005 NM_001018006 NM_001018007 NM_001018008 NM_001018020 NM_001301244 NM_001301289 NM_001330344 NM_001330346 NM_001330351 NM_001365776 NM_001365777 NM_001365778 NM_001365779 NM_001365780 NM_001365781 NM_001365782 n/a RefSeq (protein) NP_000357 NP_001018004 NP_001018005 NP_001018006 NP_001018007 NP_001018008 NP_001018020 NP_001288173 NP_001288218 NP_001317273 NP_001317275 NP_001317280 NP_001352705 NP_001352706 NP_001352707 NP_001352708 NP_001352709 NP_001352710 NP_001352711 NP_001018006.1 n/a Location (UCSC) Chr 15: 63.04 – 63.07 Mb n/a PubMed search [2] n/a
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Tm is a 32.7 kDa protein composed of 284 amino acids.^[4] 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.^[5] 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.^[6]

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,^[7] 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.

Mutations in TPM1 have been associated with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy (LVNC). HCM mutations tend to cluster around the N-terminal region and a primary actin binding region known as period 5.^[8]