TPM3

Protein identityUniProt · HPA

UniProt accession

P06753

Gene

TPM3

Ensembl

ENSG00000143549

Chromosome

1

Canonical length

285 aa

Protein class

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

Subcellular location

Actin filaments,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the tropomyosin family of actin-binding proteins. Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. Mutations in this gene result in autosomal dominant nemaline myopathy and other muscle disorders. This locus is involved in translocations with other loci, including anaplastic lymphoma receptor tyrosine kinase (ALK) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), which result in the formation of fusion proteins that act as oncogenes. There are numerous pseudogenes for this gene on different chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

Canonical amino-acid sequenceUniProt

285 residues, UniProt reviewed canonical sequence.

>P06753|TPM3
     1  MMEAIKKKMQ MLKLDKENAL DRAEQAEAEQ KQAEERSKQL EDELAAMQKK LKGTEDELDK
    61  YSEALKDAQE KLELAEKKAA DAEAEVASLN RRIQLVEEEL DRAQERLATA LQKLEEAEKA
   121  ADESERGMKV IENRALKDEE KMELQEIQLK EAKHIAEEAD RKYEEVARKL VIIEGDLERT
   181  EERAELAESK CSELEEELKN VTNNLKSLEA QAEKYSQKED KYEEEIKILT DKLKEAETRA
   241  EFAERSVAKL EKTIDDLEDE LYAQKLKYKA ISEELDHALN DMTSI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPM3 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)

0.5

Highest tissue expression

8,345 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TPM3.

Disease | AllUniProt

Conditions TPM3 is implicated in, by any mechanism.

• Congenital myopathy 4A, autosomal dominant (CMYO4A) MIM:255310
• Congenital myopathy 4B, autosomal recessive (CMYO4B) MIM:609284

Disease | GeneticClinVar

36 pathogenic / likely-pathogenic of 433 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital myopathy 4B, autosomal recessive
• Congenital myopathy with fiber type disproportion
• Congenital myopathy 4A, autosomal dominant
• See cases
• TPM3-related core myopathy

Disease | ImmuneIEDB

Conditions an epitope on TPM3 was assayed in.

• shrimp allergy B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against TPM3 are reported. Each links to that disease's full target list.

• Colitis, Ulcerative 4

ReferencesPubMed · IEDB

Publications for TPM3 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

0.69

gnomAD pLI

0.01

gnomAD missense Z

2.35

DepMap mean gene effect

-0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin filament organization
• muscle contraction

Molecular functions

• actin filament binding

Cellular components

• actin cytoskeleton
• actin filament
• cytoskeleton
• cytosol
• extracellular exosome
• mitochondrion
• muscle thin filament tropomyosin
• stress fiber

Protein domainsUniProt · Pfam · InterPro

• Tropomyosin
• Tropomyosin

KeywordsUniProt

• Acetylation
• Actin-binding
• Chromosomal rearrangement
• Coiled coil
• Cytoplasm
• Cytoskeleton
• Muscle protein
• Nemaline myopathy
• Phosphoprotein
• Proto-oncogene

InteractionsUniProt · HPA

Protein binding partners of TPM3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TMOD1
• TNNT1
• CAVIN3
• KXD1
• PSMC5
• TFPT
• TPM4