Affinage

PRR16

Protein Largen · UniProt Q569H4

Round 2 corrected
Length
304 aa
Mass
32.8 kDa
Annotated
2026-04-28
35 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRR16 (Largen) is a regulator of mammalian cell size that acts independently of mTOR and Hippo signalling by selectively stimulating translation of mRNAs encoding mitochondrial-function proteins, thereby increasing mitochondrial mass and ATP production (PMID:24656129). PRR16 also promotes epithelial–mesenchymal transition (EMT) by physically binding ABI2 and relieving its inhibition of ABL1 kinase, leading to ABL1 activation (Y412 phosphorylation) and enhanced cell migration and invasion (PMID:35719027).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2014 High

    The mechanism by which mammalian cells control their size outside the canonical mTOR and Hippo pathways was unknown; a genetic screen identified PRR16 (Largen) as a cell-size regulator that preferentially stimulates translation of mitochondrial-function mRNAs, increasing mitochondrial mass and ATP production.

    Evidence Genetic screen for cell-size genes, overexpression in human cells, in vitro translation assays, conditional transgenic mouse, mitochondrial mass/ATP assays

    PMID:24656129

    Open questions at the time
    • The direct RNA-binding or ribosome-recruitment mechanism by which Largen selects specific mRNA subsets for translational stimulation is unresolved
    • No structural information for Largen or its translational regulatory domain exists
    • Whether Largen-dependent cell-size control operates equivalently across different tissues in vivo remains untested beyond the transgenic model
  2. 2022 Medium

    Whether PRR16 had roles beyond cell-size control was unclear; PRR16 was shown to bind ABI2 and relieve its inhibition of ABL1 kinase, activating ABL1 and inducing EMT-associated migration and invasion in breast cancer cells.

    Evidence Co-immunoprecipitation, overexpression and siRNA knockdown in MCF7 cells, ABL1 Y412 phosphorylation assay, migration/invasion assays

    PMID:35719027

    Open questions at the time
    • The PRR16–ABI2 interaction has been demonstrated by Co-IP in a single study and lacks independent replication or structural mapping of the binding interface
    • Whether the translational and EMT-promoting functions of PRR16 are mechanistically coupled or represent independent activities is unknown
    • In vivo relevance of the PRR16–ABI2–ABL1 axis in tumour progression has not been tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular basis by which PRR16 selectively enhances translation of specific mRNA subsets, and whether its translational and EMT-promoting functions converge on a shared mechanism, remain open questions.
  • No RNA-binding domain or ribosome-interaction surface has been identified in PRR16
  • No proteome-wide or ribosome-profiling study has validated the translational selectivity in an independent system
  • Relationship between mitochondrial biogenesis function and ABI2/ABL1-mediated EMT induction is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2
Pathway
R-HSA-392499 Metabolism of proteins 1
Partners
ABI2ABL1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 PRR16 (named Largen) was identified as a regulator of mammalian cell size: overexpression increased cell size in human cells and in conditional transgenic mice, independently of mTOR and Hippo signalling pathways. Mechanistically, Largen preferentially stimulates the translation of specific subsets of mRNAs, including those encoding mitochondrial function proteins, leading to increased mitochondrial mass and greater ATP production. Genetic screen for cell-size-controlling genes; overexpression in human cells; in vitro translation assays; conditional transgenic mouse analysis; mitochondrial mass and ATP production assays Molecular Cell High 24656129
2022 PRR16/Largen induces epithelial-mesenchymal transition (EMT) by physically binding to ABI2 (Abl interactor 2), thereby interfering with ABI2's inhibitory role on ABL1 kinase. PRR16 overexpression increased phosphorylation of ABL1 at Y412 (activation), enhanced migration and invasion in MCF7 breast cancer cells, and gene silencing of ABI2 phenocopied PRR16 overexpression by also inducing EMT and ABL1 activation. Co-immunoprecipitation/binding partner screen; gene overexpression and siRNA knockdown; ABL1 phosphorylation assay (Y412); migration and invasion assays in MCF7 cells Biomolecules & Therapeutics Medium 35719027

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2005 Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS medicine 332 15971941
2011 Protein interactome reveals converging molecular pathways among autism disorders. Science translational medicine 180 21653829
2011 Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of biological chemistry 131 21832049
2009 Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays. Molecular systems biology 129 19953087
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2013 Maternal preconception body mass index and offspring cord blood DNA methylation: exploration of early life origins of disease. Environmental and molecular mutagenesis 99 24243566
2008 Human fetal placental endothelial cells have a mature arterial and a juvenile venous phenotype with adipogenic and osteogenic differentiation potential. Differentiation; research in biological diversity 94 18673379
2013 A genome-wide association study (GWAS) for bronchopulmonary dysplasia. Pediatrics 93 23897914
2020 Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index. Cancer medicine 81 32311840
2012 Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. Human genetics 66 22610502
2018 An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders. Nature genetics 61 29892012
2023 Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders. Nature human behaviour 38 37945807
2012 Protein phosphatase 1α interacting proteins in the human brain. Omics : a journal of integrative biology 35 22321011
2022 Quantitative fragmentomics allow affinity mapping of interactomes. Nature communications 33 36115835
2018 Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins. Proteomics 31 29513927
2020 SUMOylation of DDX39A Alters Binding and Export of Antiviral Transcripts to Control Innate Immunity. Journal of immunology (Baltimore, Md. : 1950) 27 32393512
2014 Largen: a molecular regulator of mammalian cell size control. Molecular cell 27 24656129
2010 Identification of substrates of SMURF1 ubiquitin ligase activity utilizing protein microarrays. Assay and drug development technologies 24 20804422
2023 Sequential genome-wide CRISPR-Cas9 screens identify genes regulating cell-surface expression of tetraspanins. Cell reports 20 36724073
2019 [Novel Genes Associated with the Development of Carotid Paragangliomas]. Molekuliarnaia biologiia 15 31397435
2012 Protein phosphatase 1γ isoforms linked interactions in the brain. Journal of molecular neuroscience : MN 15 23080069
2016 Characterization and Genetic Analyses of New Genes Coding for NOD2 Interacting Proteins. PloS one 14 27812135
2014 Genome-wide association studies and heritability estimates of body mass index related phenotypes in Bangladeshi adults. PloS one 13 25133637
2022 PRR16/Largen Induces Epithelial-Mesenchymal Transition through the Interaction with ABI2 Leading to the Activation of ABL1 Kinase. Biomolecules & therapeutics 9 35719027
2023 Epigenetic transgenerational effects of PM2.5 collected from southern Taiwan on sperm functions and DNA methylation in mouse offspring. Ecotoxicology and environmental safety 8 38091677
2025 EndoMAP.v1 charts the structural landscape of human early endosome complexes. Nature 6 40437099
2022 Genetic and genomic analysis of oxygen consumption in mice. Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 3 35608337