Affinage

Showing ARL2BP — BART is a alias.

ARL2BP

ADP-ribosylation factor-like protein 2-binding protein · UniProt Q9Y2Y0

Length
163 aa
Mass
18.8 kDa
Annotated
2026-06-09
20 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARL2BP is a ciliary effector protein that links the small GTPase ARL2 to the structural integrity of microtubule-based cilia and flagella (PMID:23849777, PMID:29718757). It acts as a selective effector of ARL2 rather than ARL3: depletion of ARL2, but not ARL3, displaces ARL2BP from the basal body, establishing that ARL2 recruits or anchors ARL2BP at the base of the cilium, while the disease-associated p.Met45Arg substitution reduces ARL2 binding and abolishes basal-body localization (PMID:23849777). At the photoreceptor basal body and cilium-associated centriole, ARL2BP is required for ciliary doublet microtubule formation and axoneme elongation; its loss produces shortened axonemes, open B-tubule doublets, loss of singlet microtubules, and disorganized outer segments with impaired visual response (PMID:23849777, PMID:29718757). The same activity supports structural maintenance of the sperm flagellum, where loss causes mis-assembled tails and loss of axonemal doublets, and underlies broader ciliopathy phenotypes including situs inversus (PMID:31425546). Through these roles ARL2BP loss of function causes retinitis pigmentosa, situs inversus, and male infertility (PMID:23849777, PMID:29718757, PMID:31425546).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2013 High

    Established that ARL2BP is a basal-body effector whose ciliary localization depends specifically on ARL2, defining the recruitment logic at the cilium base and linking it to human disease.

    Evidence Immunolocalization in mouse retina, selective siRNA depletion of ARL2 vs ARL3, mutant-protein binding assay, and homozygosity mapping/exome sequencing in patients

    PMID:23849777

    Open questions at the time
    • Mechanism by which ARL2-GTP anchors ARL2BP at the basal body not resolved at structural level
    • How basal-body ARL2BP couples to microtubule assembly machinery not defined
  2. 2018 High

    Demonstrated that ARL2BP is required for photoreceptor doublet microtubule formation and axoneme elongation, connecting the basal-body localization to outer-segment morphogenesis and vision.

    Evidence ARL2BP knockout mouse with EM ultrastructure, electroretinography, and immunofluorescence

    PMID:29718757

    Open questions at the time
    • Molecular partners through which ARL2BP promotes B-tubule and singlet microtubule integrity not identified
    • Whether the defect is in microtubule nucleation, stabilization, or transport not distinguished
  3. 2019 High

    Extended ARL2BP function to structural maintenance of the sperm flagellum and motile-cilia-dependent processes, showing the cilium/flagellum phenotype is general rather than photoreceptor-specific.

    Evidence Knockout mouse sperm morphology, EM of axonemal doublets, situs/ventricle phenotyping, and primary cilia depolymerization assay in MEFs

    PMID:31425546

    Open questions at the time
    • Mechanism linking ARL2BP to delayed cilia depolymerization unknown
    • Tissue-specific requirements versus a single shared axonemal function not dissected
  4. 2022 Medium

    Confirmed in patient-derived cells that ARL2BP loss reduces ciliary length and proliferation, corroborating a ciliogenesis role in human tissue.

    Evidence Patient-derived fibroblasts with ciliary length and proliferation measurements

    PMID:36507858

    Open questions at the time
    • Single patient, single lab, no mechanistic follow-up
    • Causal link between proliferation defect and ciliary defect not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical mechanism by which ARL2BP, downstream of ARL2, directs doublet microtubule assembly and axoneme integrity remains undefined.
  • No identified molecular effectors or microtubule-associated partners of ARL2BP
  • No structural model of the ARL2-ARL2BP complex at the basal body
  • Whether ARL2BP has intrinsic biochemical activity beyond ARL2 binding is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 1
Localization
GO:0005929 cilium 3 GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
ARL2

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 ARL2BP is an effector protein of the small GTPases ARL2 and ARL3. In mouse retina, ARL2BP localizes to the basal body and cilium-associated centriole of photoreceptors and the periciliary extension of the inner segment. Depletion of ARL2, but not ARL3, caused displacement of ARL2BP from the basal body, establishing that ARL2 is required for recruiting or anchoring ARL2BP at the base of the cilium. The p.Met45Arg mutation reduced binding to ARL2 and caused loss of ARL2BP localization at the basal body in ciliated nasal epithelial cells. Depletion of ARL2BP caused cilia shortening. Homozygosity mapping, exome sequencing, blood RNA splicing analysis, immunolocalization in mouse retina, siRNA depletion in ciliated cells, binding assay with mutant protein American journal of human genetics High 23849777
2018 ARL2BP is necessary for photoreceptor ciliary doublet microtubule formation and axoneme elongation, which is required for outer segment morphogenesis and vision. ARL2BP knockout mice display disorganization of the photoreceptor outer segment with vertically aligned disks, shortened axonemes, open B-tubule doublets, and loss of singlet microtubules, accompanied by an early and progressive reduction in visual response. Knockout mouse model, electron microscopy of ciliary ultrastructure, electroretinography, immunofluorescence Molecular biology of the cell High 29718757
2019 ARL2BP is required for the structural maintenance of cilia and the sperm flagellum. In ARL2BP knockout mice, spermiogenesis is impaired, resulting in abnormally shaped sperm heads, shortened and mis-assembled sperm tails, and loss of axonemal doublets. Additional ciliopathy phenotypes included enlarged brain ventricles and situs inversus. Mouse embryonic fibroblasts from knockout animals showed delayed depolymerization of primary cilia. Knockout mouse model, sperm morphology analysis, electron microscopy, primary cilia depolymerization assay in MEFs PLoS genetics High 31425546
2022 Loss-of-function variant in ARL2BP in patient-derived fibroblasts resulted in reduced cell proliferation and reduced ciliary length, consistent with a role for ARL2BP in ciliogenesis. Patient-derived fibroblast analysis, ciliary length measurement, cell proliferation assay Clinical genetics Medium 36507858

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma. Nature communications 186 26135619
2018 EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma. PLoS pathogens 93 30557400
2013 Mutations in ARL2BP, encoding ADP-ribosylation-factor-like 2 binding protein, cause autosomal-recessive retinitis pigmentosa. American journal of human genetics 59 23849777
2013 EBV-miR-BART1 is involved in regulating metabolism-associated genes in nasopharyngeal carcinoma. Biochemical and biophysical research communications 58 23685147
2016 Epstein-Barr virus mir-bart1-5p detection via nasopharyngeal brush sampling is effective for diagnosing nasopharyngeal carcinoma. Oncotarget 35 26701721
2019 MiR-BART1-5p targets core 2β-1,6-acetylglucosaminyltransferase GCNT3 to inhibit cell proliferation and migration in EBV-associated gastric cancer. Virology 30 32056716
2020 Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2. International journal of biological sciences 28 32025216
2019 Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice. PLoS genetics 24 31425546
2023 Targeting exosomes enveloped EBV-miR-BART1-5p-antagomiRs for NPC therapy through both anti-vasculogenic mimicry and anti-angiogenesis. Cancer medicine 19 37097161
2018 ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure. Molecular biology of the cell 18 29718757
2021 Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3. International journal of molecular sciences 17 34681596
1996 Isolation and characterization of BART-1: A novel balloon angioplasty responsive transcript in rat carotid arteries. DNA and cell biology 13 8639266
2018 Novel homozygous splicing mutations in ARL2BP cause autosomal recessive retinitis pigmentosa. Molecular vision 10 30210231
2017 ARL2BP mutations account for 0.1% of autosomal recessive rod-cone dystrophies with the report of a novel splice variant. Clinical genetics 10 27790702
2023 Effects of Co-Culture EBV-miR-BART1-3p on Proliferation and Invasion of Gastric Cancer Cells Based on Exosomes. Cancers 6 37345178
2021 As Evidence-Based Tumorigenic Role of Epstein-Barr Virus miR-BART1-3p in Neurological Tumors. Asian Pacific journal of cancer prevention : APJCP 5 33507707
2020 Correction: EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma. PLoS pathogens 5 32339206
2023 MiR-BART1-3p and BART18-5p inhibit cell migration, proliferation and activate autophagy in Epstein-Barr virus-associated gastric cancer by targeting erythropoietin-producing human hepatocellular 2. Virus genes 3 37535140
2022 Novel homozygous variant in ARL2BP associated with retinitis pigmentosa, situs inversus, and male infertility in a Chinese patient. Clinical genetics 2 36507858
2024 A novel homozygous splice site variant in ARL2BP causes a syndromic autosomal recessive rod-cone dystrophy with situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts. BMC medical genomics 0 38649918

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