TPM1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0051015 actin filament binding	IBA GO_REF:0000033	ACCEPT	Summary: Core function of all TPM1 isoforms. Tropomyosin binds along the length of actin filaments in both muscle and non-muscle cells. UniProt states that TPM1 binds to actin filaments. This function is conserved across all isoforms - muscle isoforms bind thin filament actin while cytoskeletal isoforms bind stress fiber actin. Reason: Actin filament binding is the fundamental molecular function of all tropomyosins. IBA annotation is appropriate as this function is phylogenetically conserved. Supported by functional studies showing TPM1 binds actin filaments in both muscle and non-muscle contexts [PMID:12686598]. Supporting Evidence: PMID:12686598 tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation PMID:8205619 alpha-tropomyosin and cardiac troponin T as well as beta myosin heavy chain mutations cause the same phenotype, we conclude that FHC is a disease of the sarcomere file:human/TPM1/TPM1-deep-research-falcon.md The target gene TPM1 in Homo sapiens encodes tropomyosin alpha-1 chain, a coiled-coil protein of the tropomyosin family that binds F-actin and specifies functional properties of actin filaments in both sarcomeric thin filaments and specialized non-muscle actin networks.
GO:0007015 actin filament organization	IBA GO_REF:0000033	ACCEPT	Summary: TPM1 plays a role in actin filament organization in both muscle and non-muscle cells. In muscle, it organizes thin filaments; in non-muscle cells, it contributes to stress fiber formation and cytoskeletal organization [PMID:12686598]. Reason: Actin filament organization is a core function of tropomyosins across all isoforms. Muscle isoforms organize thin filaments in sarcomeres; cytoskeletal isoforms stabilize stress fibers in non-muscle cells. IBA annotation is appropriate. Supporting Evidence: PMID:12686598 phosphorylation of tropomyosin-1 downstream of ERK by contributing to formation of actin filaments increases cellular contractility and promotes the formation of focal adhesions PMID:15897890 TGF-beta induction of stress fibers in epithelial cells requires high molecular weight tropomyosins encoded by TPM1 and TPM2 genes
GO:0005884 actin filament	IBA GO_REF:0000033	ACCEPT	Summary: TPM1 localizes to actin filaments in both muscle and non-muscle cells. This cellular component annotation reflects the physical location of tropomyosin bound along actin filaments. Reason: Tropomyosin is an integral component of actin filaments. In muscle cells it forms the thin filament regulatory complex; in non-muscle cells it associates with stress fibers and other actin structures. IBA annotation is appropriate. Supporting Evidence: PMID:12686598 tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation
GO:0060048 cardiac muscle contraction	IBA GO_REF:0000033	ACCEPT	Summary: ISOFORM-SPECIFIC: Cardiac muscle contraction is a function of the striated muscle isoforms (Isoform 1/TPM1alpha and Isoform 6/TPM1kappa). UniProt states Isoform 1 is expressed in cardiac tissues and Isoform 6 is cardiac-specific. Mutations cause cardiomyopathy (CMH3, CMD1Y) [PMID:8205619, PMID:11273725]. Reason: This is a core function for cardiac isoforms. TPM1 plays a central role in calcium-dependent regulation of cardiac muscle contraction via the troponin complex. Mutations affecting this function cause hypertrophic and dilated cardiomyopathy, demonstrating its importance [PMID:8205619]. IBA annotation is appropriate as this function is conserved in striated muscle isoforms. Supporting Evidence: PMID:8205619 We demonstrate that missense mutations (Asp175Asn; Glu180Gly) in the alpha-tropomyosin gene cause familial hypertrophic cardiomyopathy (FHC) PMID:11136687 HCM was linked to the TPM1 gene... The mutation caused a 40% to 50% increase in calcium affinity in regulated thin filament-myosin subfragment-1 (S1) MgATPase assays
GO:0003779 actin binding	IEA GO_REF:0000043	ACCEPT	Summary: Actin binding is the fundamental molecular function of all tropomyosins. This IEA annotation based on UniProt keyword mapping is correct but less specific than GO:0051015 (actin filament binding) which is already annotated via IBA. Reason: While this is a broader parent term of actin filament binding, it is still correct. IEA annotations at a broader level are acceptable alongside more specific experimental annotations. No action needed as the more specific IBA annotation (GO:0051015) captures the precise function. Supporting Evidence: PMID:12686598 tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: TPM1 is a cytoskeletal protein. UniProt subcellular location indicates "Cytoplasm, cytoskeleton" and notes it "Associates with F-actin stress fibers." This is a broad cellular component annotation appropriate for all isoforms. Reason: This is a valid broad localization term. All TPM1 isoforms are components of the cytoskeleton, whether in sarcomeres (muscle isoforms) or stress fibers (non-muscle isoforms). IEA based on UniProt subcellular location is appropriate. Supporting Evidence: PMID:12686598 tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation
GO:0005862 muscle thin filament tropomyosin	IEA GO_REF:0000117	ACCEPT	Summary: ISOFORM-SPECIFIC: This cellular component term is specifically for muscle isoforms (Isoform 1/skeletal, Isoform 2/smooth, Isoform 6/cardiac). The muscle thin filament tropomyosin complex contains tropomyosin bound to actin filaments in sarcomeres. Non-muscle isoforms (e.g., Isoform 3/fibroblast) do not form this specific complex. Reason: This is a core localization for muscle isoforms of TPM1. The annotation is correct for the muscle-expressed isoforms that are integral to the thin filament regulatory complex in sarcomeres [PMID:8205619]. Supporting Evidence: PMID:8205619 FHC is a disease of the sarcomere PMID:11136687 regulated thin filament-myosin subfragment-1 (S1) MgATPase assays
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: High-throughput Y2H interactome study. The term "protein binding" is uninformative and does not indicate specific binding partners or functional context. TPM1 binds actin, troponins, and other muscle/cytoskeletal proteins, but this generic term does not capture those specific interactions. Reason: "Protein binding" (GO:0005515) is an uninformative annotation that does not convey the specific molecular interactions of TPM1 (e.g., actin binding, troponin complex binding). High-throughput interactome studies often generate these generic annotations. More specific MF terms are preferred [PMID:16189514]. Supporting Evidence: PMID:16189514 Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	MARK AS OVER ANNOTATED	Summary: High-throughput Stitch-seq Y2H interactome study. The generic term "protein binding" is uninformative for this well-characterized actin-binding protein. Reason: "Protein binding" (GO:0005515) from high-throughput interactome studies is too generic. TPM1 has specific, well-characterized binding partners (actin, troponins, LMOD2, TMOD1) that are more informative [PMID:21516116]. Supporting Evidence: PMID:21516116 We describe a massively parallel interactome-mapping pipeline, Stitch-seq, that combines PCR stitching with next-generation sequencing and used it to generate a new human interactome dataset
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Large-scale proteome-scale human interactome map study. Generic "protein binding" term is uninformative for TPM1 which has well-characterized specific interactions. Reason: "Protein binding" (GO:0005515) from systematic interactome mapping is too generic. TPM1 has specific, functionally important binding partners that should be annotated instead [PMID:25416956]. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	MARK AS OVER ANNOTATED	Summary: Study on alternative splicing and protein interaction capabilities. Notably relevant for TPM1 which has 10 isoforms with different interaction profiles. However "protein binding" remains uninformative. Reason: While this study is highly relevant to TPM1 isoform biology, showing that alternative isoforms exhibit different interaction profiles, the generic "protein binding" term does not capture the specific binding partners or isoform-specific interactions [PMID:26871637]. Supporting Evidence: PMID:26871637 The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other
GO:0005515 protein binding	IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma...	MARK AS OVER ANNOTATED	Summary: Crosslinking mass spectrometry study of histone interactions in nuclei. TPM1 is a cytoplasmic/cytoskeletal protein; its detection here may be incidental. Generic "protein binding" term is uninformative. Reason: "Protein binding" from crosslinking MS study of nuclear proteins is not informative for TPM1, which is primarily a cytoskeletal protein. The generic term provides no functional insight [PMID:30021884]. Supporting Evidence: PMID:30021884 Here we use crosslinking mass spectrometry (XL-MS) to chart the protein-protein interactions in intact human nuclei
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: BioPlex 3.0 dual proteome-scale network study in 293T and HCT116 cells. While this reveals cell-specific interactome remodeling relevant to TPM1 isoforms, the generic "protein binding" term is uninformative. Reason: "Protein binding" from large-scale AP-MS interactome study does not provide specific information about TPM1's functional binding partners. More specific terms for actin binding, troponin binding etc. are preferred [PMID:33961781]. Supporting Evidence: PMID:33961781 Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Multimodal cell maps study integrating multiple data types for structural and functional genomics. Generic "protein binding" term is uninformative. Reason: "Protein binding" from multimodal cell mapping study does not convey specific information about TPM1's well-characterized binding partners [PMID:40205054]. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics
GO:0005515 protein binding	IPI P09493-10 PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: ISOFORM-SPECIFIC ANNOTATION (P09493-10). Study on macromolecular interaction perturbations in genetic disorders. While highly relevant to understanding how TPM1 mutations affect interactions, "protein binding" is uninformative. Reason: "Protein binding" from edgetic mutation studies is too generic. This study shows disease mutations can perturb specific interactions, but the annotation lacks specificity about which interactions [PMID:25910212]. Supporting Evidence: PMID:25910212 While common variants from healthy individuals rarely affect interactions, two-thirds of disease-associated alleles perturb protein-protein interactions, with half corresponding to "edgetic" alleles affecting only a subset of interactions while leaving most other interactions unperturbed
GO:0005515 protein binding	IPI P09493-10 PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: ISOFORM-SPECIFIC ANNOTATION (P09493-10). HuRI reference human binary protein interactome map. While highly valuable for mapping interactions, the generic "protein binding" term is uninformative for TPM1. Reason: "Protein binding" from the comprehensive HuRI interactome map does not convey specific binding partners. TPM1 has well-characterized interactions with actin, troponins, and other thin filament proteins that are more informative [PMID:32296183]. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'
GO:0042802 identical protein binding	ISS GO_REF:0000024	ACCEPT	Summary: Tropomyosins form coiled-coil dimers (homo- or heterodimers) as their functional unit. UniProt indicates TPM1 forms dimers with itself or other tropomyosin isoforms. This ISS annotation from sequence similarity is consistent with the coiled-coil structure of tropomyosins. Reason: TPM1 forms parallel coiled-coil dimers that bind along actin filaments. This is a fundamental structural property of all tropomyosins. Self-association (homodimerization) is documented in UniProt. ISS annotation based on sequence similarity to characterized orthologs is appropriate.
GO:0042803 protein homodimerization activity	ISS GO_REF:0000024	ACCEPT	Summary: Tropomyosins function as coiled-coil dimers. TPM1 homodimerizes to form the functional unit that binds along actin filaments. This is a core structural property of tropomyosins. Reason: Homodimerization is fundamental to tropomyosin function. Two TPM1 chains form a parallel coiled-coil dimer that spans seven actin subunits. ISS annotation based on sequence similarity is appropriate for this conserved structural property.
GO:0046982 protein heterodimerization activity	ISS GO_REF:0000024	ACCEPT	Summary: TPM1 can form heterodimers with other tropomyosin isoforms (e.g., TPM2, TPM3). UniProt indicates it interacts with self or TPM2. Heterodimer formation provides functional diversity in different tissue contexts. Reason: Heterodimerization with other tropomyosin isoforms is a documented property that provides functional diversity. TPM1 can form dimers with TPM2 and potentially other isoforms. ISS annotation based on sequence similarity is appropriate.
GO:0051015 actin filament binding	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate of the IBA annotation for actin filament binding. This ISS annotation provides additional evidence for this core function from sequence similarity. Reason: Actin filament binding is the fundamental molecular function of TPM1 across all isoforms. This ISS annotation supplements the IBA annotation and is consistent with the conserved function of tropomyosins.
GO:0008360 regulation of cell shape	IMP PMID:21817107 MicroRNA-21 regulates vascular smooth muscle cell function v...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: This annotation relates to the cytoskeletal (non-muscle) function of TPM1 isoforms. The study shows TPM1 affects vascular smooth muscle cell morphology via cytoskeletal remodeling [PMID:21817107]. Reason: Regulation of cell shape is a function of cytoskeletal TPM1 isoforms in non-muscle cells. While important, it is not the core function of the striated muscle isoforms. This is a valid annotation for cytoskeletal isoforms [PMID:21817107]. Supporting Evidence: PMID:21817107 cell proliferation and migration were significantly decreased by
GO:1904706 negative regulation of vascular associated smooth muscle cell proliferation	IMP PMID:21817107 MicroRNA-21 regulates vascular smooth muscle cell function v...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: TPM1 overexpression inhibits vascular smooth muscle cell (VSMC) proliferation. This relates to the cytoskeletal function of TPM1 in regulating cell behavior [PMID:21817107]. Reason: This is a valid functional annotation for cytoskeletal TPM1 isoforms in smooth muscle cells. While biologically relevant, it represents a peripheral function rather than the core sarcomeric function of TPM1 [PMID:21817107]. Supporting Evidence: PMID:21817107 cell proliferation and migration were significantly decreased by
GO:1904753 negative regulation of vascular associated smooth muscle cell migration	IMP PMID:21817107 MicroRNA-21 regulates vascular smooth muscle cell function v...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: TPM1 overexpression inhibits vascular smooth muscle cell (VSMC) migration. This relates to the cytoskeletal function of TPM1 in regulating cell motility [PMID:21817107]. Reason: This is a valid functional annotation for cytoskeletal TPM1 isoforms in smooth muscle cells. While biologically relevant, it represents a peripheral function rather than the core sarcomeric function of TPM1 [PMID:21817107]. Supporting Evidence: PMID:21817107 cell proliferation and migration were significantly decreased by
GO:0005829 cytosol	TAS Reactome:R-HSA-390593	ACCEPT	Summary: Reactome pathway annotation for muscle contraction. TPM1 is a cytosolic/ cytoskeletal protein that associates with actin filaments. Cytosol localization is valid for soluble tropomyosin before assembly. Reason: Cytosol is an appropriate cellular component for TPM1. Prior to incorporation into actin filaments, tropomyosin exists in the cytosol. Reactome pathway annotations for muscle contraction support this localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-390595	ACCEPT	Summary: Duplicate Reactome pathway annotation for cytosol localization in muscle contraction pathway. Reason: Valid cellular component annotation from Reactome muscle contraction pathway. Cytosol localization is appropriate for soluble tropomyosin.
GO:0005829 cytosol	TAS Reactome:R-HSA-390597	ACCEPT	Summary: Duplicate Reactome pathway annotation for cytosol localization. Reason: Valid cellular component annotation from Reactome pathway. Cytosol localization is appropriate for soluble tropomyosin.
GO:0005829 cytosol	TAS Reactome:R-HSA-390598	ACCEPT	Summary: Duplicate Reactome pathway annotation for cytosol localization. Reason: Valid cellular component annotation from Reactome pathway. Cytosol localization is appropriate for soluble tropomyosin.
GO:0005829 cytosol	TAS Reactome:R-HSA-445699	ACCEPT	Summary: Duplicate Reactome pathway annotation for cytosol localization. Reason: Valid cellular component annotation from Reactome pathway. Cytosol localization is appropriate for soluble tropomyosin.
GO:0005829 cytosol	TAS Reactome:R-HSA-445700	ACCEPT	Summary: Duplicate Reactome pathway annotation for cytosol localization. Reason: Valid cellular component annotation from Reactome pathway. Cytosol localization is appropriate for soluble tropomyosin.
GO:0005829 cytosol	TAS Reactome:R-HSA-445704	ACCEPT	Summary: Duplicate Reactome pathway annotation for cytosol localization. Reason: Valid cellular component annotation from Reactome pathway. Cytosol localization is appropriate for soluble tropomyosin.
GO:0005829 cytosol	TAS Reactome:R-HSA-445705	ACCEPT	Summary: Duplicate Reactome pathway annotation for cytosol localization. Reason: Valid cellular component annotation from Reactome pathway. Cytosol localization is appropriate for soluble tropomyosin.
GO:0008092 cytoskeletal protein binding	IPI PMID:17987659 Nebulette interacts with filamin C.	ACCEPT	Summary: TPM1 binds cytoskeletal proteins including nebulette. The study identified tropomyosin-1 as a binding partner of nebulette in a yeast two-hybrid screen [PMID:17987659]. Reason: Cytoskeletal protein binding accurately describes TPM1's interactions with actin filaments and associated regulatory proteins. This is a valid molecular function annotation that is more specific than "protein binding". Supporting Evidence: PMID:17987659 Nebulette interacts with filamin C.
GO:0045214 sarcomere organization	IMP PMID:11273725 Mutations that alter the surface charge of alpha-tropomyosin...	ACCEPT	Summary: ISOFORM-SPECIFIC: Sarcomere organization is a function of muscle isoforms. TPM1 mutations cause disorganized sarcomere structure in cardiomyopathy [PMID:11273725]. Reason: Sarcomere organization is a core function of striated muscle TPM1 isoforms. Mutations affecting this function cause hypertrophic and dilated cardiomyopathy. This is a well-supported experimental annotation [PMID:11273725]. Supporting Evidence: PMID:11273725 Proteins in cardiac myocytes assemble into contractile units known as sarcomeres
GO:0001725 stress fiber	IDA PMID:12686598 Extracellular signal-regulated kinase mediates phosphorylati...	ACCEPT	Summary: ISOFORM-SPECIFIC: TPM1 localizes to stress fibers in non-muscle cells. The study shows TPM1 colocalizes with actin stress fibers upon stimulation [PMID:12686598]. Reason: Stress fiber localization is a valid cellular component annotation for cytoskeletal TPM1 isoforms (e.g., Isoform 3/TM3). IDA evidence from direct observation of colocalization with stress fibers [PMID:12686598]. Supporting Evidence: PMID:12686598 tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation
GO:0003065 positive regulation of heart rate by epinephrine	ISS PMID:17556658 Dilated cardiomyopathy mutant tropomyosin mice develop cardi...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: This relates to cardiac isoforms (TPM1alpha, TPM1kappa) and their role in beta-adrenergic signaling in the heart. Tropomyosin phosphorylation modulates cardiac contractility. Reason: While TPM1 is involved in cardiac muscle contraction, the specific role in epinephrine-mediated heart rate regulation is indirect via modulation of thin filament Ca2+ sensitivity. This is a secondary function rather than a core molecular function. Supporting Evidence: PMID:17556658 2007 Jun 7. Dilated cardiomyopathy mutant tropomyosin mice develop cardiac dysfunction with significantly decreased fractional shortening and myofilament calcium sensitivity.
GO:0003779 actin binding	TAS PMID:12686598 Extracellular signal-regulated kinase mediates phosphorylati...	ACCEPT	Summary: Core function of TPM1. Actin binding is fundamental to all TPM1 isoforms. This TAS annotation based on literature review is consistent with the well-established role of tropomyosin [PMID:12686598]. Reason: Actin binding is the fundamental molecular function of tropomyosin. This annotation supplements the more specific "actin filament binding" term already annotated via IBA [PMID:12686598]. Supporting Evidence: PMID:12686598 tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation
GO:0005200 structural constituent of cytoskeleton	TAS PMID:12686598 Extracellular signal-regulated kinase mediates phosphorylati...	ACCEPT	Summary: TPM1 is a structural component of the actin cytoskeleton in both muscle and non-muscle cells. In muscle cells it forms thin filaments; in non-muscle cells it stabilizes stress fibers [PMID:12686598]. Reason: Structural constituent of cytoskeleton is an accurate molecular function for TPM1. Tropomyosin provides structural stability to actin filaments and is integral to cytoskeletal architecture [PMID:12686598]. Supporting Evidence: PMID:12686598 phosphorylation of tropomyosin-1 downstream of ERK by contributing to formation of actin filaments increases cellular contractility and promotes the formation of focal adhesions
GO:0007010 cytoskeleton organization	TAS PMID:12686598 Extracellular signal-regulated kinase mediates phosphorylati...	ACCEPT	Summary: TPM1 contributes to cytoskeleton organization in both muscle and non-muscle cells. This is closely related to actin filament organization [PMID:12686598]. Reason: Cytoskeleton organization is a core function of TPM1 across all isoforms. In muscle, it organizes sarcomere thin filaments; in non-muscle cells, it contributes to stress fiber organization [PMID:12686598]. Supporting Evidence: PMID:12686598 phosphorylation of tropomyosin-1 downstream of ERK by contributing to formation of actin filaments increases cellular contractility and promotes the formation of focal adhesions
GO:0030049 muscle filament sliding	ISS PMID:11136687 Hypertrophic cardiomyopathy caused by a novel alpha-tropomyo...	ACCEPT	Summary: ISOFORM-SPECIFIC: Muscle filament sliding is a function of striated muscle isoforms. TPM1 regulates the interaction between thin and thick filaments during muscle contraction [PMID:11136687]. Reason: Muscle filament sliding is a core function of muscle TPM1 isoforms. Tropomyosin regulates the actin-myosin interaction that drives filament sliding during contraction. Mutations affecting this cause cardiomyopathy [PMID:11136687]. Supporting Evidence: PMID:11136687 The mutation caused a 40% to 50% increase in calcium affinity in regulated thin filament-myosin subfragment-1 (S1) MgATPase assays
GO:0030336 negative regulation of cell migration	ISS PMID:15897890 Silencing of the Tropomyosin-1 gene by DNA methylation alter...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: Cytoskeletal TPM1 isoforms regulate cell migration. High molecular weight tropomyosins stabilize stress fibers and inhibit cell motility [PMID:15897890]. Reason: Regulation of cell migration is a function of cytoskeletal TPM1 isoforms in non-muscle cells. While valid, this is a peripheral function related to the core actin-binding activity [PMID:15897890]. Supporting Evidence: PMID:15897890 TGF-beta induction of stress fibers in epithelial cells requires high molecular weight tropomyosins encoded by TPM1 and TPM2 genes
GO:0031529 ruffle organization	ISS PMID:15897890 Silencing of the Tropomyosin-1 gene by DNA methylation alter...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: TPM1 affects membrane ruffle organization in non-muscle cells. This relates to cytoskeletal actin dynamics [PMID:15897890]. Reason: Ruffle organization is a function of cytoskeletal TPM1 isoforms in non-muscle cells. This is a peripheral function related to the core actin-organizing activity [PMID:15897890]. Supporting Evidence: PMID:15897890 TGF-beta induction of stress fibers in epithelial cells requires high molecular weight tropomyosins encoded by TPM1 and TPM2 genes
GO:0032059 bleb	IMP PMID:12686598 Extracellular signal-regulated kinase mediates phosphorylati...	KEEP AS NON CORE	Summary: TPM1 localizes to membrane blebs in response to oxidative stress. This relates to cytoskeletal reorganization during stress responses [PMID:12686598]. Reason: Bleb localization is a peripheral cellular component annotation related to stress responses rather than core TPM1 function [PMID:12686598]. Supporting Evidence: PMID:12686598 presence of H(2)O(2) resulted in a quick and intense membrane blebbing
GO:0032587 ruffle membrane	IDA PMID:12686598 Extracellular signal-regulated kinase mediates phosphorylati...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: TPM1 localizes to ruffle membranes in non-muscle cells. This relates to cytoskeletal actin dynamics at the cell periphery [PMID:12686598]. Reason: Ruffle membrane localization is a cellular component for cytoskeletal TPM1 isoforms in non-muscle cells. This is a peripheral localization related to actin dynamics [PMID:12686598]. Supporting Evidence: PMID:12686598 tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation
GO:0034614 cellular response to reactive oxygen species	IEP PMID:12686598 Extracellular signal-regulated kinase mediates phosphorylati...	KEEP AS NON CORE	Summary: TPM1 is phosphorylated in response to oxidative stress via ERK signaling. This leads to cytoskeletal remodeling and affects membrane dynamics [PMID:12686598]. Reason: Response to ROS is a peripheral function related to stress-induced cytoskeletal remodeling. TPM1 phosphorylation downstream of ERK modulates stress fiber formation during oxidative stress [PMID:12686598]. Supporting Evidence: PMID:12686598 phosphorylation of tropomyosin-1 downstream of ERK by contributing to formation of actin filaments increases cellular contractility and promotes the formation of focal adhesions
GO:0042060 wound healing	ISS PMID:17721995 Role of high-molecular weight tropomyosins in TGF-beta-media...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: TPM1 is involved in wound healing through its role in cytoskeletal remodeling and cell migration during tissue repair [PMID:17721995]. Reason: Wound healing is a peripheral function of cytoskeletal TPM1 isoforms related to cell migration and tissue remodeling. While biologically relevant, this is not a core molecular function [PMID:17721995]. Supporting Evidence: PMID:17721995 HMW-tropomyosins are important for TGF-beta-mediated control of cell
GO:0045785 positive regulation of cell adhesion	ISS PMID:17721995 Role of high-molecular weight tropomyosins in TGF-beta-media...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: TPM1 promotes cell adhesion by enhancing actin stress fibers and focal adhesions in non-muscle cells [PMID:17721995]. Reason: Regulation of cell adhesion is a peripheral function of cytoskeletal TPM1 isoforms related to stress fiber stabilization [PMID:17721995]. Supporting Evidence: PMID:17721995 Tropomyosin increased cell adhesion to matrix by enhancing actin fibers and focal adhesions
GO:0051496 positive regulation of stress fiber assembly	ISS PMID:15897890 Silencing of the Tropomyosin-1 gene by DNA methylation alter...	ACCEPT	Summary: ISOFORM-SPECIFIC: TPM1 (HMW tropomyosins) are required for TGF-beta-induced stress fiber assembly in epithelial cells [PMID:15897890]. Reason: Positive regulation of stress fiber assembly is a well-documented function of cytoskeletal TPM1 isoforms. HMW tropomyosins stabilize and promote stress fiber formation [PMID:15897890]. Supporting Evidence: PMID:15897890 TGF-beta induction of stress fibers in epithelial cells requires high molecular weight tropomyosins encoded by TPM1 and TPM2 genes
GO:0055010 ventricular cardiac muscle tissue morphogenesis	IMP PMID:11136687 Hypertrophic cardiomyopathy caused by a novel alpha-tropomyo...	KEEP AS NON CORE	Summary: ISOFORM-SPECIFIC: Cardiac TPM1 isoforms are essential for ventricular morphogenesis. Mutations cause hypertrophic cardiomyopathy with ventricular hypertrophy [PMID:11136687]. Reason: Ventricular morphogenesis is a developmental process that TPM1 mutations affect. While important, this is a downstream consequence of TPM1's role in cardiac muscle function rather than a core molecular function [PMID:11136687]. Supporting Evidence: PMID:11136687 The mutation caused a 40% to 50% increase in calcium affinity in regulated thin filament-myosin subfragment-1 (S1) MgATPase assays
GO:0060048 cardiac muscle contraction	IMP PMID:11136687 Hypertrophic cardiomyopathy caused by a novel alpha-tropomyo...	ACCEPT	Summary: ISOFORM-SPECIFIC: This IMP annotation with experimental evidence complements the IBA annotation for cardiac muscle contraction. TPM1 mutations affect Ca2+ sensitivity and muscle contraction [PMID:11136687]. Reason: Cardiac muscle contraction is a core function of cardiac TPM1 isoforms. This experimental annotation provides direct evidence that TPM1 mutations affect cardiac contractile function [PMID:11136687]. Supporting Evidence: PMID:11136687 The mutation caused a 40% to 50% increase in calcium affinity in regulated thin filament-myosin subfragment-1 (S1) MgATPase assays
GO:0030017 sarcomere	TAS PMID:16754800 Single-gene mutations and increased left ventricular wall th...	ACCEPT	Summary: ISOFORM-SPECIFIC: Sarcomere localization is specific to striated muscle TPM1 isoforms. TPM1 is an integral component of thin filaments in sarcomeres. Reason: Sarcomere is a core cellular component for muscle TPM1 isoforms. Tropomyosin is an integral part of the thin filament in sarcomeric structures. TAS annotation from literature supports this well-established localization. Supporting Evidence: PMID:16754800 Single-gene mutations and increased left ventricular wall thickness in the community: the Framingham Heart Study.
GO:0005856 cytoskeleton	TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied...	ACCEPT	Summary: TPM1 is a cytoskeletal protein identified in proteomic studies of endothelial cells. This annotation complements the IEA cytoskeleton annotation. Reason: Cytoskeleton is a valid cellular component for TPM1. All isoforms are components of the cytoskeleton, whether in sarcomeres or stress fibers. TAS annotation is appropriate. Supporting Evidence: PMID:16130169 Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis.
GO:0005862 muscle thin filament tropomyosin	TAS PMID:8205619 Alpha-tropomyosin and cardiac troponin T mutations cause fam...	ACCEPT	Summary: ISOFORM-SPECIFIC: This TAS annotation complements the IEA annotation for muscle thin filament tropomyosin. TPM1 mutations in this complex cause familial hypertrophic cardiomyopathy [PMID:8205619]. Reason: Muscle thin filament tropomyosin is a core cellular component for muscle TPM1 isoforms. The cited study demonstrates TPM1's role in the thin filament complex and disease consequences of mutations [PMID:8205619]. Supporting Evidence: PMID:8205619 alpha-tropomyosin and cardiac troponin T as well as beta myosin heavy chain mutations cause the same phenotype, we conclude that FHC is a disease of the sarcomere
GO:0006937 regulation of muscle contraction	TAS PMID:3336363 Human hTM alpha gene: expression in muscle and nonmuscle tis...	ACCEPT	Summary: ISOFORM-SPECIFIC: Regulation of muscle contraction is a core function of muscle TPM1 isoforms. The study describes expression of alpha-tropomyosin in muscle and non-muscle tissues. Reason: Regulation of muscle contraction is a core biological process for muscle TPM1 isoforms. Tropomyosin regulates actin-myosin interaction in a Ca2+-dependent manner via the troponin complex. TAS annotation is appropriate. Supporting Evidence: PMID:3336363 Human hTM alpha gene: expression in muscle and nonmuscle tissue.
GO:0008016 regulation of heart contraction	TAS PMID:8205619 Alpha-tropomyosin and cardiac troponin T mutations cause fam...	ACCEPT	Summary: ISOFORM-SPECIFIC: Cardiac TPM1 isoforms regulate heart contraction. Mutations cause familial hypertrophic cardiomyopathy, demonstrating the essential role of TPM1 in cardiac function [PMID:8205619]. Reason: Regulation of heart contraction is a core function of cardiac TPM1 isoforms. Mutations affecting this function cause cardiomyopathy [PMID:8205619]. Supporting Evidence: PMID:8205619 We demonstrate that missense mutations (Asp175Asn; Glu180Gly) in the alpha-tropomyosin gene cause familial hypertrophic cardiomyopathy (FHC)
GO:0008307 structural constituent of muscle	TAS PMID:8205619 Alpha-tropomyosin and cardiac troponin T mutations cause fam...	ACCEPT	Summary: ISOFORM-SPECIFIC: Muscle TPM1 isoforms are structural constituents of muscle thin filaments in sarcomeres [PMID:8205619]. Reason: Structural constituent of muscle is a core molecular function for muscle TPM1 isoforms. TPM1 is an integral structural component of thin filaments in sarcomeres [PMID:8205619]. Supporting Evidence: PMID:8205619 alpha-tropomyosin and cardiac troponin T as well as beta myosin heavy chain mutations cause the same phenotype, we conclude that FHC is a disease of the sarcomere

Gene Description

Existing Annotations Review

Core Functions

Actin filament binding is the fundamental molecular function of all TPM1 isoforms. Tropomyosin dimers bind along the length of actin filaments in both muscle (thin filaments) and non-muscle (stress fibers) cells, stabilizing actin filaments and regulating their interactions with other proteins.

ISOFORM-SPECIFIC (Cardiac isoforms): Cardiac muscle contraction is a core function of striated muscle isoforms (TPM1alpha, TPM1kappa). TPM1 regulates calcium-dependent actin-myosin interaction via the troponin complex. Mutations cause cardiomyopathy (CMH3, CMD1Y).

ISOFORM-SPECIFIC (Cytoskeletal isoforms): Non-muscle TPM1 isoforms (e.g., TM3) bind actin filaments in stress fibers and contribute to cytoskeletal organization, cell shape regulation, and cell motility.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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