Affinage

LRATD1

Protein LRATD1 · UniProt Q96KN4

Length
292 aa
Mass
32.5 kDa
Annotated
2026-06-10
15 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRATD1 (FAM84A) is a cytoplasmic, membrane-proximal protein that influences cell motility and Wnt/β-catenin-dependent tumor cell behavior (PMID:16820875, PMID:41390849). It localizes to subcellular membrane regions lacking cell–cell attachment and to the cytoplasm of hepatocytes, and its overexpression increases cell migration in fibroblast and hepatocyte models; phosphorylation of serine 38 is associated with cell morphology changes (PMID:16820875, PMID:21424122). In colorectal cancer stem cells, FAM84A physically binds β-catenin and promotes its ubiquitination and degradation, restraining β-catenin-driven self-renewal (PMID:41390849), whereas in papillary thyroid carcinoma FAM84A promotes epithelial–mesenchymal transition and activates Wnt/β-catenin signaling (PMID:33751775), indicating context-dependent effects on this pathway. FAM84A expression is controlled at multiple levels: transcriptionally by the nuclear receptor CAR (PMID:21424122), post-transcriptionally through ALKBH5-mediated m6A demethylation that triggers mRNA decay (PMID:41390849), and through direct targeting by miR-874-3p and miR-215 (PMID:33751775, PMID:32561231). Beyond these findings, the precise biochemical activity of the LRATD1 protein has not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2006 Medium

    Established the first functional readout for FAM84A by linking its membrane-proximal localization and serine-38 phosphorylation to cell motility and morphology, framing it as a regulator of cell migration.

    Evidence Immunocytochemical localization and exogenous overexpression motility assay in NIH3T3 cells, with site-specific phosphorylation analysis

    PMID:16820875

    Open questions at the time
    • Molecular mechanism by which FAM84A increases motility not defined
    • Kinase responsible for serine-38 phosphorylation unknown
    • No direct binding partners identified
  2. 2011 Medium

    Identified an upstream transcriptional driver of FAM84A by showing the nuclear xenobiotic receptor CAR activates its promoter, placing FAM84A downstream of CAR signaling in liver.

    Evidence CAR-driven promoter reporter assay, Western blot, IHC, and overexpression migration assay in HepG2 cells and mouse liver

    PMID:21424122

    Open questions at the time
    • Functional consequence of CAR-induced FAM84A in liver tumorigenesis not resolved
    • Reason serine-38 is unphosphorylated in liver versus other contexts unexplained
  3. 2020 Medium

    Extended post-transcriptional control of FAM84A by validating miR-215 as a direct repressor, indicating miRNA regulation of FAM84A across tissues.

    Evidence Dual-luciferase reporter assay with miR-215 and FAM84A 3'UTR in rooster testis cells

    PMID:32561231

    Open questions at the time
    • Single reporter method without downstream functional consequence
    • Physiological context of miR-215–FAM84A axis in mammals not established
  4. 2021 Medium

    Connected FAM84A to Wnt/β-catenin signaling and EMT in cancer and added miR-874-3p as a direct upstream repressor, defining a tumor-promoting role in thyroid carcinoma.

    Evidence miR-874-3p target validation plus FAM84A knockdown with EMT and Wnt/β-catenin readouts in vitro and in xenografts

    PMID:33751775

    Open questions at the time
    • Mechanism by which FAM84A activates Wnt/β-catenin here not biochemically defined
    • Apparent opposite effect on β-catenin versus colorectal CSC context unreconciled
  5. 2021 Low

    Nominated LRATD1 as an N-myristoylation substrate of NMT1/NMT2, hinting at a lipid-modification mechanism for its membrane association.

    Evidence Interactome data mining using NMT1/2 binding as a substrate proxy, framed by in vitro NMT assays

    PMID:34956690

    Open questions at the time
    • No direct in vitro myristoylation assay performed on LRATD1 itself
    • Functional impact of myristoylation on LRATD1 localization or activity untested
  6. 2025 High

    Defined a direct molecular mechanism: FAM84A binds β-catenin and drives its ubiquitination and degradation, with ALKBH5-mediated m6A demethylation controlling FAM84A abundance, establishing FAM84A as a tumor suppressor in colorectal cancer stem cells.

    Evidence Integrated RNA-seq/MeRIP-seq/Ribo-seq, Co-IP, β-catenin ubiquitination assay, and ALKBH5 knockin/knockout mouse models

    PMID:41390849

    Open questions at the time
    • Whether FAM84A acts as or recruits an E3 ligase for β-catenin not resolved
    • Structural basis of the FAM84A–β-catenin interaction unknown
    • Reconciliation with FAM84A activating Wnt/β-catenin in other tumors unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intrinsic biochemical activity of the LRATD1 protein and how it switches between suppressing and activating Wnt/β-catenin signaling in different cancers remain unresolved.
  • No defined catalytic or molecular function for the LRATD1 protein
  • Determinants of context-dependent β-catenin regulation unknown
  • Direct test of NMT-mediated myristoylation and its consequences lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 2
Partners
CTNNB1

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 FAM84A (LRATD1) protein localizes to the subcellular membrane region, specifically in areas lacking attachment with neighboring cells, and exogenous FAM84A expression increases cell motility in NIH3T3 cells. Phosphorylation of serine 38 of FAM84A was found to be associated with cell morphology changes. Immunocytochemical staining for localization; exogenous overexpression in NIH3T3 cells with motility assay; site-specific phosphorylation analysis International journal of oncology Medium 16820875
2011 FAM84A expression is regulated by the nuclear xenobiotic receptor CAR (constitutive androstane receptor): CAR activates the FAM84A promoter (reporter assay), PB treatment induces FAM84A protein in mouse liver, and FAM84A protein in liver/liver tumors is NOT phosphorylated at serine 38. Immunohistochemistry showed cytoplasmic localization of FAM84A protein in hepatocytes. Exogenous overexpression of FAM84A in HepG2 cells resulted in increased cell migration. HepG2 cell-based reporter assay for CAR-driven promoter activation; Western blotting for protein expression and serine-38 phosphorylation status; immunohistochemistry for subcellular localization; overexpression migration assay in HepG2 cells International journal of oncology Medium 21424122
2021 LRATD1 is a substrate of human N-myristoyltransferases NMT1 and NMT2, identified by mining available interactome data (protein–protein interaction with NMT1/2 as proxy for substrate relationship), consistent with the principle that binding affinity to the enzyme predicts substrate specificity. Interactome data mining to identify NMT1/2-interacting proteins as substrates; in vitro NMT enzymatic assays establishing binding-affinity-based substrate identification framework ACS catalysis Low 34956690
2021 FAM84A expression is negatively regulated by miR-874-3p (direct target validated), and FAM84A promotes epithelial-mesenchymal transition (EMT) and activates the Wnt/β-catenin signaling pathway in papillary thyroid carcinoma cells; knockdown of FAM84A inhibited tumor development in vitro and in vivo. miR-874-3p target validation (implied luciferase/functional assay); FAM84A knockdown with EMT marker analysis and Wnt/β-catenin pathway readouts in vitro and in vivo xenograft Molecular oncology Medium 33751775
2025 FAM84A represses colorectal cancer stem cells (CSCs) by physically interacting with β-catenin and promoting β-catenin ubiquitination and degradation. ALKBH5 (m6A eraser) demethylates m6A-modified FAM84A mRNA, causing FAM84A mRNA decay and reduced FAM84A protein expression, thereby relieving FAM84A-mediated suppression of CSC self-renewal. Integrated RNA-seq, MeRIP-seq, and Ribo-seq to identify FAM84A as ALKBH5 target; co-immunoprecipitation/interaction assay for FAM84A–β-catenin binding; ubiquitination assay for β-catenin degradation; ALKBH5 knockin/knockout mouse models with FAM84A pathway validation Nature communications High 41390849
2020 miR-215 directly negatively regulates FAM84A expression, validated by dual-luciferase reporter system in rooster testis cells. Dual-luciferase reporter assay with miR-215 and FAM84A 3'UTR Reproductive biology Medium 32561231

Source papers

Stage 0 corpus · 15 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 DNA methylation mediates the association between breastfeeding and early-life growth trajectories. Clinical epigenetics 37 34937578
2010 Identification of a novel autoantigen in inflammatory bowel disease by protein microarray. Inflammatory bowel diseases 34 21560193
2021 Binding Affinity Determines Substrate Specificity and Enables Discovery of Substrates for N-Myristoyltransferases. ACS catalysis 28 34956690
2020 Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity. PloS one 28 32881863
2006 A gene encoding a family with sequence similarity 84, member A (FAM84A) enhanced migration of human colon cancer cells. International journal of oncology 24 16820875
2016 Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons. Neural plasticity 21 28116168
2012 A de novo 4.4-Mb microdeletion in 2p24.3 → p24.2 in a girl with bilateral hearing impairment, microcephaly, digit abnormalities and Feingold syndrome. European journal of medical genetics 16 22842076
2011 Nuclear receptor CAR-regulated expression of the FAM84A gene during the development of mouse liver tumors. International journal of oncology 15 21424122
2021 The direct miR-874-3p-target FAM84A promotes tumor development in papillary thyroid cancer. Molecular oncology 13 33751775
2023 Epigenome-wide association study identifies novel genes associated with ischemic stroke. Clinical epigenetics 12 37370144
2020 An integrated analysis of testis miRNA and mRNA transcriptome reveals important functional miRNA-targets in reproduction traits of roosters. Reproductive biology 9 32561231
2012 Genome-wide linkage and positional association study of blood pressure response to dietary sodium intervention: the GenSalt Study. American journal of epidemiology 9 22865701
2023 Genetic parameters estimation and genome molecular marker identification for gestation length in pigs. Frontiers in genetics 8 36685960
2022 Genome-wide Scan of Dental Fear and Anxiety Nominates Novel Genes. Journal of dental research 5 35771046
2025 Targeting of the m6A eraser ALKBH5 suppresses stemness and chemoresistance of colorectal cancer. Nature communications 2 41390849

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