Rasmus Hartmann-Petersen

Review from Fia B. Larsen in @rhp-lab.bsky.social with everything you always wanted to know about proteasomal control of transcription factors (but were afraid to ask about)

Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.
doi.org/10.1007/s000...

Happy to share our newest preprint on Parkin missense variants in work led by Erna Sol &
@vvouts.bsky.social in @rhp-lab.bsky.social

Using a multiplexed assay we determined the effects of 9,212 out of 9,300 single amino acid substitutions and nonsense Parkin variants. 1/n

doi.org/10.64898/202...

We map the effects of >99% Parkin (PRKN) missense variants on mitophagy. The landscape separates benign & pathogenic variants, reveals misfolded variants induce mitophagy and flags hypomorphic alleles for rescue. Collab w. @lindorfflarsen.bsky.social. Work led by Erna Sol & @vvouts.bsky.social.

A near-complete map of human cytosolic degrons and their relevance for disease

We measured degron potency of >200,000 30-residue tiles from >5,000 human proteins, and trained a model to predict degrons from sequence

Led by @vvouts.bsky.social in @rhp-lab.bsky.social

doi.org/10.1126/scia...

Now on bioRxiv: genome‑wide CRISPR KO reveals BAG6 (chaperone) and RNF126 (E3) as core PQC for non‑native missense proteins. VAMP seq. shows >1000 Parkin variants are BAG6 targets, including known pathogenic variants. Work led by Line Pedersen. Collab with @lindorfflarsen.bsky.social

BAG6 and RNF126 are broadly involved in protein quality control of non-native missense protein variants https://www.biorxiv.org/content/10.64898/2026.02.04.703735v1

Second preprint of the year in which @sarahgersing.bsky.social from @rhp-lab.bsky.social mapped the effects of >7500 variants in glucokinase (GCK) on the interaction with the glucokinase regulatory protein so that we now have a 3D GCK scan (abundance, interaction, activity)

doi.org/10.64898/202...

New preprint!
Led by @sarahgersing.bsky.social we map how 7,500+ variants in glucokinase (GCK) affect binding to GKRP and disentangle this from stability.
We now have activity, abundance, and interaction scores for 7,128 GCK variants - a resource for understanding phenotypes and glucose homeostasis.

The proteasome-substrate-shuttle protein UBQLN2 contains—like other quality control system proteins—a long region devoid of lysine (a lysine desert)

Martin Grønbæk-Thygesen (from @rhp-lab.bsky.social) et al show that introducing K here causes ubiquitylation and degradation

doi.org/10.1101/2025...

Martin Grønbæk-Thygesen in @rhp-lab.bsky.social measured abundance and toxicity (both independently of function) of missense variants in aspartoacylase, and found that a subset of the low-abundance variants were toxic, induced a stress response which correlated with toxicity

doi.org/10.1038/s414...

I thought science hinged on prestige. Moving abroad made me reassess my priorities In Denmark, this Ph.D. student fell in love with an egalitarian society that values work-life balance

I’m biased 🇩🇰, but this is quite nice to read:

I thought science hinged on prestige. Moving abroad made me reassess my priorities

www.science.org/content/arti...

We are back with an exciting seminar on September 8 at 3pm CEST! We’ll hear from Prof. Birthe Kragelund and Maximilian Vieler (@uu.se).

Register to attend:
tinyurl.com/PMCseminar2

Recordings of previous seminars: www.youtube.com/@PMCModularity

PhD scholarship in Machine Learning for Molecules - DTU Chemistry Advance large scale data generation for chemical and biological AI in a 3 year PhD. Work on the frontier of active learning, and develop novel probabilistic machine learning techniques for experiment ...

I'm looking for my first PhD student! We will push the frontiers of probabilistic machine learning for the molecular sciences, and study how to design new algorithms that exploit the unique properties of molecular systems to learn about the world.

efzu.fa.em2.oraclecloud.com/hcmUI/Candid...

Curiosity underlies a breakthrough in rare disease We must recognise and protect the pipelines that lead from research to real-world benefit

Both translational and fundamental curiosity-driven research are needed to fuel the incredible progress we're seeing in genomic medicine; an important message in this article and and some lovely quotes from @sarahlwynn.bsky.social
www.ft.com/content/25dd...

@lindorfflarsen.bsky.social at #VariantEffect25

Comprehensive degron mapping in human transcription factors Gene expression is regulated by the targeted degradation of transcription factors through the ubiquitin-proteasome system. Transcription factors destined for degradation are recognized by E3 ubiquitin...

With the @lindorfflarsen.bsky.social group we present our map of degrons in all human transcription factors, incl. examples of constitutive degrons in exposed regions & buried degrons that are exposed upon mutation. In addition, we show that most TADs overlap with degrons. Work led by Fia Larsen.

A complete map of human cytosolic degrons and their relevance for disease Degrons are short protein segments that target proteins for degradation via the ubiquitin-proteasome system and thus ensure timely removal of signaling proteins and clearance of misfolded proteins fro...

In collaboration with the @lindorfflarsen.bsky.social group we release our map of degrons in >5,000 human cytosolic proteins with >99% coverage. A machine learning model trained on the data identifies missense variants forming degrons in exposed & disordered regions. Work led by @vvouts.bsky.social.

We are looking for a PhD student with interest in protein biochemistry on a really cool project “Cooperation of deubiquitinating enzymes and VCP/p97 in cellular stress responses”. Build your own reactions! fully funded. apply with code 193-25. #ubiquitin

... wait! There's more great Review content!
☘️ mechanisms of #SAM homeostasis (Ben Tu et al)
☘️ glucose sensing by #glucokinase and how disease variants impact its function @sarahgersing.bsky.social @lindorfflarsen.bsky.social @rhp-lab.bsky.social

Now online - the Review "#Glucokinase: from allosteric glucose sensing to disease variants" from @sarahgersing.bsky.social, Torben Hansen, @lindorfflarsen.bsky.social, and @rhp-lab.bsky.social.

#GlucoseHomeostasis #GlucoseSensor #GCKMODY #CooperativeKinetics

authors.elsevier.com/a/1kN5M3S6Gf...

Happy to share our review, 'Glucokinase: from allosteric glucose sensing to disease variants', published in @cp-trendsbiochem.bsky.social, which explores the fascinating enzyme glucokinase. authors.elsevier.com/a/1kN5M3S6Gf...

Systematic characterization of indel variants using a yeast-based protein folding sensor Larsen-Ledet et al. developed a yeast-based protein folding sensor to determine the effects of indel variants in DHFR. Using a saturated indel library, it was found that most indels are not tolerated. Several are temperature sensitive and folding is rescued by methotrexate. Rosetta and AlphaFold2 predictions correlate with the observed effects.

In our new paper we characterize the effects of indel variants on protein folding and stability using a new yeast-based protein folding sensor. The work was led by Sven Larsen-Ledet and supported by the @novo-nordisk.bsky.social.
Link to paper: www.cell.com/structure/fu...