ArticleBMC evolutionary biology2020
The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin.
Article in BMC evolutionary biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pooled it
- Structural-functional analyses of the huntingtin/HAP40 complex inJournal of biomolecular structure & dynamics · 2026Article
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- Tailoring treatments: pharmacogenomics in the management of neurodegenerative diseases.Acta neurologica Belgica · 2026Review
- Pathogenic Proteins Through the Lens of NMR Spectroscopy: Structural and Functional Insights into Disease.Cell biochemistry and biophysics · 2025Review
- Diversity and structural-functional insights of alpha-solenoid proteins.Protein science : a publication of the Protein Society · 2024Review
- ProteinCoLoc streamlines Bayesian analysis of colocalization in microscopic images.Scientific reports · 2024Article
- Delineation of functional subdomains of Huntingtin protein and their interaction with HAP40.Structure (London, England : 1993) · 2023Article
- Huntingtin and Its Partner Huntingtin-Associated Protein 40: Structural and Functional Considerations in Health and Disease.Journal of Huntington's disease · 2022Review
- Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1.Communications biology · 2021Article
- Huntingtin Ubiquitination Mechanisms and Novel Possible Therapies to Decrease the Toxic Effects of Mutated Huntingtin.Journal of personalized medicine · 2021Review
- The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin.International journal of molecular sciences · 2021Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington's disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT.
resultsWe found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such as Capsaspora owczarzaki and the amoebozoan Dictyostelium discoideum, but both proteins are absent from fungi. Outside unikonts, a few species, such as the free-living amoeboflagellate Naegleria gruberi, contain putative HTT and HAP40 orthologs. Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs).
conclusionOur results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction.
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