ArticleTraffic (Copenhagen, Denmark)2021
Sequence-based features that are determinant for tail-anchored membrane protein sorting in eukaryotes.
Article in Traffic (Copenhagen, Denmark), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- GET3 regulates apoptosis via tail-anchoring of MCL1.Cell death and differentiation · 2026Article
- ALS mutations disrupt self-association between the ubiquilin STI1 hydrophobic groove and internal placeholder sequences.The EMBO journal · 2026Article
- Degradation Determinants Are Abundant in Human Noncanonical Proteins and Minor Annotated Isoforms.Genome biology and evolution · 2026Article
- Legionella effector LpPIP recruits protein phosphatase 1 to the mitochondria to induce dephosphorylation of outer membrane proteins.PLoS biology · 2025Article
- A dual role of the conserved PEX19 helix in safeguarding peroxisomal membrane proteins.iScience · 2024Article
- A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.The Journal of cell biology · 2023Article
- Structures of Get3d reveal a distinct architecture associated with the emergence of photosynthesis.The Journal of biological chemistry · 2023Article
- The Endoplasmic Reticulum and the Fidelity of Nascent Protein Localization.Cold Spring Harbor perspectives in biology · 2023Review
- Role of Hsp70 in Post-Translational Protein Targeting: Tail-Anchored Membrane Proteins and Beyond.International journal of molecular sciences · 2023Review
- ATP13A1 prevents ERAD of folding-competent mislocalized and misoriented proteins.Molecular cell · 2022Article
- MTCH2 is a mitochondrial outer membrane protein insertase.Science (New York, N.Y.) · 2022Article
- CAMLG-CDG: a novel congenital disorder of glycosylation linked to defective membrane trafficking.Human molecular genetics · 2022Article
- Structurally derived universal mechanism for the catalytic cycle of the tail-anchored targeting factor Get3.Nature structural & molecular biology · 2022Article
- The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The correct targeting and insertion of tail-anchored (TA) integral membrane proteins is critical for cellular homeostasis. TA proteins are defined by a hydrophobic transmembrane domain (TMD) at their C-terminus and are targeted to either the ER or mitochondria. Derived from experimental measurements of a few TA proteins, there has been little examination of the TMD features that determine localization. As a result, the localization of many TA proteins are misclassified by the simple heuristic of overall hydrophobicity. Because ER-directed TMDs favor arrangement of hydrophobic residues to one side, we sought to explore the role of geometric hydrophobic properties. By curating TA proteins with experimentally determined localizations and assessing hypotheses for recognition, we bioinformatically and experimentally verify that a hydrophobic face is the most accurate singular metric for separating ER and mitochondria-destined yeast TA proteins. A metric focusing on an 11 residue segment of the TMD performs well when classifying human TA proteins. The most inclusive predictor uses both hydrophobicity and C-terminal charge in tandem. This work provides context for previous observations and opens the door for more detailed mechanistic experiments to determine the molecular factors driving this recognition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.