TPM4

Protein identityUniProt · HPA

UniProt accession

P67936

Gene

TPM4

Ensembl

ENSG00000167460

Chromosome

19

Canonical length

248 aa

Protein class

Cancer-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 involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosins are dimers of coiled-coil proteins that polymerize end-to-end along the major groove in most actin filaments. They provide stability to the filaments and regulate access of other actin-binding proteins. In muscle cells, they regulate muscle contraction by controlling the binding of myosin heads to the actin filament. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

Canonical amino-acid sequenceUniProt

248 residues, UniProt reviewed canonical sequence.

>P67936|TPM4
     1  MAGLNSLEAV KRKIQALQQQ ADEAEDRAQG LQRELDGERE RREKAEGDVA ALNRRIQLVE
    61  EELDRAQERL ATALQKLEEA EKAADESERG MKVIENRAMK DEEKMEIQEM QLKEAKHIAE
   121  EADRKYEEVA RKLVILEGEL ERAEERAEVS ELKCGDLEEE LKNVTNNLKS LEAASEKYSE
   181  KEDKYEEEIK LLSDKLKEAE TRAEFAERTV AKLEKTIDDL EEKLAQAKEE NVGLHQTLDQ
   241  TLNELNCI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPM4 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

523 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TPM4.

Disease | AllUniProt

Conditions TPM4 is implicated in, by any mechanism.

• Bleeding disorder, platelet-type, 25 (BDPLT25) MIM:620486

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 61 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Bleeding disorder, platelet-type, 25

ReferencesPubMed · IEDB

Publications for TPM4 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)

0.51

gnomAD pLI

0.39

gnomAD missense Z

0.95

DepMap mean gene effect

-0.22

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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
• osteoblast differentiation
• platelet formation

Molecular functions

• actin filament binding
• calcium ion binding
• identical protein binding
• protein heterodimerization activity
• protein homodimerization activity
• structural constituent of muscle

Cellular components

• actin filament
• cortical cytoskeleton
• cytoskeleton
• cytosol
• extracellular exosome
• focal adhesion
• membrane
• muscle thin filament tropomyosin
• podosome
• stress fiber

Protein domainsUniProt · Pfam · InterPro

• Tropomyosin
• DNA repair protein XRCC4-like, C-terminal
• Tropomyosin

KeywordsUniProt

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

InteractionsUniProt · HPA

Protein binding partners of TPM4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TPM3