Affinage

LIAT1

Protein LIAT1 · UniProt Q6ZQX7

Length
453 aa
Mass
49.7 kDa
Annotated
2026-06-10
5 papers in source corpus 3 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIAT1 (Ligand of Ate1) is an intrinsically disordered protein that functions as a positive regulator of the Arg/N-degron pathway by directly binding the arginyltransferase Ate1 and stimulating its N-terminal arginylation activity (PMID:25369936). Binding occurs through a conserved ~30-residue region of LIAT1 and shows preference for specific Ate1 isoforms (PMID:25369936). Its N-terminal half is an intrinsically disordered region containing a low-complexity poly-K segment that targets LIAT1 to the nucleolus and supports liquid-liquid phase separation there (PMID:33443146). Nucleolar targeting is controlled by Jmjd6, whose lysyl-hydroxylase activity modifies LIAT1 in a poly-K-dependent manner and inhibits its nucleolar localization (PMID:33443146). Beyond these activities and an in vitro capacity to bind tRNA-Arg (PMID:39081859), no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2014 Medium

    Established LIAT1's defining molecular partnership by showing it directly binds the arginyltransferase Ate1 through a discrete conserved region, defining LIAT1 as an Ate1-interacting factor.

    Evidence Binding assays with isoform-specific affinity measurement and deletion/domain mapping

    PMID:25369936

    Open questions at the time
    • Structural basis of the Ate1 interaction unresolved
    • Functional consequence of isoform preference in cells not established
  2. 2014 Medium

    Answered whether LIAT1 merely binds or actively modulates Ate1 by demonstrating it stimulates arginylation, placing LIAT1 as a positive regulator of the Arg/N-degron pathway.

    Evidence In vitro arginylation assay on a model substrate

    PMID:25369936

    Open questions at the time
    • No endogenous substrate dependence shown in cells
    • Mechanism of stimulation (allosteric vs substrate presentation) unknown
  3. 2020 Medium

    Defined the subcellular logic of LIAT1 by mapping its IDR poly-K region as a nucleolar-targeting and phase-separation determinant, linking it to nucleolar condensate biology.

    Evidence BiFC, immunocytochemistry, and domain deletion analysis

    PMID:33443146

    Open questions at the time
    • Functional role of LIAT1 within the nucleolus not defined
    • Relationship between nucleolar LLPS and Ate1 regulation unclear
  4. 2020 Medium

    Identified a regulatory input controlling LIAT1 localization by showing Jmjd6 lysyl-hydroxylation of the poly-K region inhibits nucleolar targeting.

    Evidence Immunocytochemistry, BiFC, and Jmjd6 inhibitor/knockout experiments

    PMID:33443146

    Open questions at the time
    • Specific hydroxylated residues not mapped
    • Physiological trigger for Jmjd6 modification of LIAT1 unknown
  5. 2024 Low

    Raised an RNA-binding dimension for LIAT1 by demonstrating in vitro binding to tRNA-Arg.

    Evidence In vitro RNA-protein binding assay with recombinant LIAT1 and in vitro-transcribed tRNA-Arg

    PMID:39081859

    Open questions at the time
    • Single in vitro binding assay without mutagenesis or functional consequence
    • Specificity versus other tRNAs not established
    • Connection to arginylation (tRNA-Arg is the arginyl donor) not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The integrated cellular function of LIAT1 — how Ate1 stimulation, nucleolar phase separation, Jmjd6 regulation, and tRNA-Arg binding combine into one physiological role — remains unresolved.
  • No organismal or knockout phenotype reported
  • No endogenous arginylation substrate linked to LIAT1
  • Whether nucleolar LIAT1 and Ate1-regulatory LIAT1 are the same functional pool is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0003723 RNA binding 1
Localization
GO:0005730 nucleolus 2
Pathway
R-HSA-392499 Metabolism of proteins 1
Partners
ATE1JMJD6

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 LIAT1 (Ligand of Ate1) directly binds the arginyltransferase Ate1, with higher affinity for Ate1 isoforms 1A7A and 1B7A; a conserved ~30-residue region of LIAT1 is required for this binding. Protein interaction studies (binding assays), isoform-specific affinity measurements, deletion/domain mapping Proceedings of the National Academy of Sciences of the United States of America Medium 25369936
2014 LIAT1 stimulates the in vitro N-terminal arginylation of a model substrate by Ate1, indicating a positive regulatory role in the N-end rule/Arg/N-degron pathway. In vitro arginylation assay Proceedings of the National Academy of Sciences of the United States of America Medium 25369936
2020 LIAT1's N-terminal half is an intrinsically disordered region (IDR) containing a low-complexity poly-K region that targets LIAT1 to the nucleolus and facilitates liquid-liquid phase separation (LLPS) there. Bimolecular fluorescence complementation, immunocytochemistry, domain deletion analysis Proceedings of the National Academy of Sciences of the United States of America Medium 33443146
2020 Jumonji Domain Containing 6 (Jmjd6) modifies LIAT1 via its lysyl-hydroxylase activity in a manner requiring the LIAT1 poly-K region, and this modification inhibits LIAT1 nucleolar targeting. Immunocytochemistry, bimolecular fluorescence complementation, Jmjd6 inhibitor/knockout experiments Proceedings of the National Academy of Sciences of the United States of America Medium 33443146
2024 Recombinant mouse LIAT1 directly binds human tRNA-Arg in vitro, identifying LIAT1 as an RNA-binding protein. In vitro RNA-protein binding assay with recombinant LIAT1 and in vitro-transcribed tRNA-Arg microPublication biology Low 39081859

Source papers

Stage 0 corpus · 5 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats. Proceedings of the National Academy of Sciences of the United States of America 20 25369936
2020 The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6. Proceedings of the National Academy of Sciences of the United States of America 6 33443146
2024 tRNA Arg binds in vitro TDP-43 RNA recognition motifs and ligand of Ate1 protein LIAT1. microPublication biology 3 39081859
2017 Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study. Human genomics 3 28865488
2025 Erratum: Corrigendum: tRNA Arg binds in vitro TDP-43 RNA recognition motifs and ligand of Ate1 protein LIAT1. microPublication biology 0 39897169

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