TPM1

Protein identityUniProt · HPA

UniProt accession

P09493

Gene

TPM1

Ensembl

ENSG00000140416

Chromosome

15

Canonical length

284 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Actin filaments,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene is a member of the tropomyosin 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. Tropomyosin is composed of two alpha-helical chains arranged as a coiled-coil. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. The encoded protein is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle, where it also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In smooth muscle and non-muscle cells, alternatively spliced transcript variants encoding a range of isoforms have been described. Mutations in this gene are associated with type 3 familial hypertrophic cardiomyopathy and dilated cardiomyopathy 1Y. [provided by RefSeq, Jun 2022]

Canonical amino-acid sequenceUniProt

284 residues, UniProt reviewed canonical sequence.

>P09493|TPM1
     1  MDAIKKKMQM LKLDKENALD RAEQAEADKK AAEDRSKQLE DELVSLQKKL KGTEDELDKY
    61  SEALKDAQEK LELAEKKATD AEADVASLNR RIQLVEEELD RAQERLATAL QKLEEAEKAA
   121  DESERGMKVI ESRAQKDEEK MEIQEIQLKE AKHIAEDADR KYEEVARKLV IIESDLERAE
   181  ERAELSEGKC AELEEELKTV TNNLKSLEAQ AEKYSQKEDR YEEEIKVLSD KLKEAETRAE
   241  FAERSVTKLE KSIDDLEDEL YAQKLKYKAI SEELDHALND MTSI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPM1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.49

Highest tissue expression

11,881 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TPM1.

Disease | AllUniProt

Conditions TPM1 is implicated in, by any mechanism.

• Cardiomyopathy, familial hypertrophic, 3 (CMH3) MIM:115196
• Cardiomyopathy, dilated, 1Y (CMD1Y) MIM:611878
• Left ventricular non-compaction 9 (LVNC9) MIM:611878

Disease | GeneticClinVar

54 pathogenic / likely-pathogenic of 1,072 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypertrophic cardiomyopathy
• Dilated cardiomyopathy 1Y
• Hypertrophic cardiomyopathy 3
• Primary dilated cardiomyopathy
• Cardiovascular phenotype

ReferencesPubMed · IEDB

Publications for TPM1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.78

gnomAD pLI

0

gnomAD missense Z

2.87

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin filament organization
• cardiac muscle contraction
• cellular response to reactive oxygen species
• cytoskeleton organization
• muscle filament sliding
• negative regulation of cell migration
• negative regulation of vascular associated smooth muscle cell migration
• negative regulation of vascular associated smooth muscle cell proliferation
• positive regulation of cell adhesion
• positive regulation of stress fiber assembly
• regulation of cell shape
• regulation of heart contraction
• regulation of muscle contraction
• ruffle organization
• sarcomere organization
• ventricular cardiac muscle tissue morphogenesis
• wound healing
• positive regulation of heart rate by epinephrine

Molecular functions

• actin binding
• actin filament binding
• cytoskeletal protein binding
• identical protein binding
• protein heterodimerization activity
• protein homodimerization activity
• structural constituent of cytoskeleton
• structural constituent of muscle

Cellular components

• actin cytoskeleton
• actin filament
• bleb
• cytoskeleton
• cytosol
• muscle thin filament tropomyosin
• ruffle membrane
• sarcomere
• stress fiber

Protein domainsUniProt · Pfam · InterPro

• Tropomyosin
• Tropomyosin

KeywordsUniProt

• Acetylation
• Actin-binding
• Cardiomyopathy
• Coiled coil
• Cytoplasm
• Cytoskeleton
• Muscle protein
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of TPM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HRG
• KXD1
• MAD1L1
• SYCE1
• TNNT1
• TPM2