Affinage

UVRAG

UV radiation resistance-associated gene protein · UniProt Q9P2Y5

Length
699 aa
Mass
78.2 kDa
Annotated
2026-06-11
71 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UVRAG is the mammalian ortholog of yeast Vps38 and a defining subunit of a distinct class III PI3K complex (Vps34-VPS15-Beclin1-UVRAG, with Bif-1/Endophilin B1), where it positively activates VPS34 lipid kinase activity and acts as a tumor suppressor (PMID:16799551, PMID:17891140, PMID:18843052). UVRAG outcompetes Atg14L for the Beclin1 coiled-coil to form a strengthened, more stable heterodimer, partitioning these mutually exclusive complexes toward separate functions (PMID:22314358, PMID:29866835). The UVRAG complex governs the maturation arm of the pathway: localizing to Rab9/Rab7-positive late endosomes, it recruits the HOPS/class C Vps tethering complex to drive autophagosome and endosome fusion with lysosomes and lysosomal degradation of cargoes such as EGFR (PMID:18612260, PMID:25533187, PMID:29866835), and it also mediates Rab5-associated early endosome formation and growth-factor receptor downregulation (PMID:20643123, PMID:25275521, PMID:25006588). This maturation activity is tightly regulated: mTORC1 phosphorylates UVRAG (at S550/S571) to promote RUBICON association and inhibit maturation under nutrient-rich conditions while also sustaining VPS34 activity for autolysosome reformation (PMID:25533187, PMID:26139536), SMURF1 ubiquitinates UVRAG (K517/K559) to release it from RUBICON and accelerate maturation—an event reversed by the deubiquitinase ZRANB1 and blocked by CSNK1A1 phosphorylation (PMID:30686098). As a PtdIns(3)P-binding protein, UVRAG additionally engages the RINT-1 ER tethering complex to support Golgi-ER retrograde COPI-vesicle transport, dissociating from this tether upon autophagy induction to mobilize Atg9 (PMID:24056303, PMID:30061422), and independently of its PI3KC3-II role it initiates ER-phagy by binding and organizing the cargo receptors FAM134B, ATL3 and RTN3L (PMID:37902287). Beyond membrane trafficking, UVRAG carries autophagy-independent genome-maintenance functions: it activates DNA-PK in nonhomologous end joining, associates with CEP63 to preserve centrosome stability, and binds DDB1 to assemble the CRL4(DDB2) ligase for nucleotide excision repair (PMID:22542840, PMID:27203177). It further mediates SNARE-dependent viral entry (PMID:24550300, PMID:32493822) and BLOC-1-dependent melanogenesis (PMID:30061422). Cancer-derived frameshift truncation acts dominant-negatively to abrogate autophagy, centrosome stability and DNA repair, driving Rac1-mediated metastasis, NLRP3 inflammasome hyperactivation and tumorigenesis (PMID:26234763, PMID:31831743).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    Established UVRAG as a functional component of the autophagy machinery rather than merely a UV-resistance gene, by showing it activates the Beclin1-associated lipid kinase and suppresses tumor growth.

    Evidence Co-IP, knockdown, and in vitro PI3K lipid kinase assay in colon cancer cells

    PMID:16799551

    Open questions at the time
    • Did not resolve how UVRAG enters the complex relative to other regulators
    • Mechanism of tumor suppression beyond autophagy not addressed
  2. 2007 High

    Identified Bif-1/Endophilin B1 as a UVRAG partner that bridges into the Beclin1-VPS34 complex, linking membrane curvature/SH3-BAR domains to PI3KC3 activation and autophagosome formation.

    Evidence Co-IP with domain mapping, siRNA, fluorescence microscopy

    PMID:17891140

    Open questions at the time
    • Did not define stoichiometry of UVRAG-Bif-1-Beclin1 assembly
    • Membrane source of curvature not identified
  3. 2008 High

    Defined UVRAG as the Vps38 ortholog forming a complex mutually exclusive from Atg14, explaining functional division of labor by distinct subcellular localization (late endosomes vs phagophore).

    Evidence Homology analysis, Co-IP, immunofluorescence, siRNA in HeLa

    PMID:18612260 PMID:18843052

    Open questions at the time
    • HOPS/Rab7 recruitment mechanism was single-lab Co-IP at this stage
    • Switch between complexes not mechanistically defined
  4. 2012 High

    Demonstrated UVRAG functions outside autophagy in genome maintenance, directly activating DNA-PK for NHEJ and stabilizing centrosomes via CEP63.

    Evidence Co-IP, in vitro DNA-PK kinase assay, immunofluorescence, genetic instability and irradiation assays

    PMID:22542840

    Open questions at the time
    • Single lab
    • Structural basis of DNA-PK activation not resolved
    • Relationship between repair and trafficking pools of UVRAG unclear
  5. 2012 High

    Resolved the structural basis for complex assembly, showing Atg14L and UVRAG convert a metastable Beclin1 homodimer into stable heterodimers.

    Evidence Crystal structure of Beclin1 coiled-coil, mutagenesis, Co-IP

    PMID:22314358

    Open questions at the time
    • Did not capture full UVRAG-bound complex
    • Cellular triggers of heterodimer switching not defined
  6. 2013 High

    Showed UVRAG is a PtdIns(3)P-binding protein that couples phosphoinositide metabolism to membrane tethering, working through RINT-1 at the ER and switching to autophagosome biogenesis upon induction.

    Evidence PtdIns(3)P binding assay, Co-IP, COPI vesicle and live-cell trafficking assays

    PMID:24056303

    Open questions at the time
    • Signal driving ER-tether dissociation not identified
    • How Atg9 mobilization is mechanistically linked unclear
  7. 2014 High

    Defined nutrient-responsive regulation: mTORC1 phosphorylation of UVRAG toggles between RUBICON-bound (maturation off) and HOPS-bound (maturation on) states and sustains VPS34 activity for lysosome reformation.

    Evidence In vitro mTOR(C1) kinase assays, phosphosite mapping (S550/S571), Co-IP, autophagy flux and EGFR degradation, lysosomal tubulation imaging

    PMID:25533187 PMID:26139536

    Open questions at the time
    • Phosphatase responsible for dephosphorylation not identified
    • Quantitative occupancy of RUBICON vs HOPS states not measured
  8. 2014 High

    Genetically separated UVRAG-complex functions, establishing Beclin1-UVRAG as the endocytic/maturation arm required for receptor degradation and endosome formation in vivo and across species.

    Evidence Conditional knockout mice with lipid kinase and rescue assays; Drosophila loss-of-function epistasis

    PMID:25006588 PMID:25275521

    Open questions at the time
    • Tissue-specific requirements not fully mapped
    • Distinction of early- vs late-endosome roles incomplete
  9. 2014 High

    Revealed a trafficking-dependent role in pathogen entry, with UVRAG coordinating C-Vps tethering and SNARE assembly to deliver virions through the endolysosomal system.

    Evidence Co-IP, siRNA, viral entry assays, SNARE complex reconstitution

    PMID:24550300

    Open questions at the time
    • Generalizability across virus families addressed only later
    • Direct vs indirect SNARE engagement not fully resolved
  10. 2016 High

    Extended UVRAG genome-maintenance roles to nucleotide excision repair, showing it promotes CRL4(DDB2) ligase assembly and XPC handover at photolesions.

    Evidence Co-IP, localization to photolesions, NER activity assays, siRNA, Drosophila model

    PMID:27203177

    Open questions at the time
    • How UVRAG is recruited to DNA damage sites unclear
    • Relationship to its lipid-kinase complex not addressed
  11. 2018 High

    Provided atomic-resolution rationale for why UVRAG outcompetes Atg14L for Beclin1, linking interface strength to endolysosomal EGFR degradation.

    Evidence Crystal structure of Beclin1-UVRAG coiled-coil, mutagenesis, competitive binding and EGFR degradation assays, stapled peptides

    PMID:29866835

    Open questions at the time
    • In vivo competition dynamics not quantified
    • Regulation of competition by post-translational modifications not integrated
  12. 2018 Medium

    Broadened UVRAG trafficking roles to Golgi-ER retrograde transport and to BLOC-1-dependent melanogenesis, placing UVRAG transcriptionally downstream of MITF/α-MSH signaling.

    Evidence Co-IP, knockout cells/zebrafish, melanosome biogenesis assays, ChIP/luciferase

    PMID:30061422

    Open questions at the time
    • Single lab
    • Mechanism of BLOC-1 stabilization by UVRAG not defined
    • Whether melanogenic and trafficking pools overlap unclear
  13. 2019 High

    Defined ubiquitin- and phospho-regulatory control of the UVRAG-RUBICON switch, identifying SMURF1, ZRANB1, and CSNK1A1 as opposing regulators of autophagosome maturation.

    Evidence In vitro ubiquitination/deubiquitination assays, site mutagenesis (K517/K559, S522), Co-IP, autophagy flux

    PMID:30686098

    Open questions at the time
    • Integration with mTORC1 phosphorylation not fully reconciled
    • Signals controlling SMURF1/ZRANB1 balance unknown
  14. 2019 High

    Validated UVRAG functions in vivo and tied loss-of-function to inflammasome hyperactivation and tumorigenesis, showing GRASP55 facilitates UVRAG-complex assembly and fusion.

    Evidence Inducible knock-in mouse model (UVRAGFS) with autophagy, NLRP3, and tumor phenotyping; Co-IP and flux assays for GORASP2

    PMID:30894053 PMID:31831743

    Open questions at the time
    • Causal chain from autophagy defect to β-catenin/centrosome phenotypes incomplete
    • GRASP55 role replicated only in single lab
  15. 2023 High

    Identified a PI3KC3-II-independent role for UVRAG in ER-phagy initiation, organizing cargo-receptor oligomerization and Atg8 recruitment to clear pathogenic protein aggregates.

    Evidence Co-IP, immunofluorescence, siRNA, ER-phagy flux and receptor oligomerization assays

    PMID:37902287

    Open questions at the time
    • Structural basis of receptor oligomerization control unknown
    • How UVRAG is targeted to ERPHS not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UVRAG's distinct functional pools (PI3KC3-II maturation, DNA repair, ER-phagy, centrosome stability, viral entry) are physically and temporally partitioned within a cell remains unresolved.
  • No unified model for how a single protein is allocated across mutually independent functions
  • Stoichiometry and interconversion of complexes in vivo not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 3 GO:0005783 endoplasmic reticulum 3 GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-73894 DNA Repair 2
Partners
BECN1BIF-1/SH3GLB1CEP63DDB1FAM134BRINT1RUBICONSMURF1
Complex memberships
Beclin1-VPS34-VPS15-UVRAG PI3KC3 complex IICRL4(DDB2) ubiquitin ligase complexHOPS/class C Vps tethering complexRINT-1 ER tethering complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 UVRAG associates with the Beclin1-Bcl-2-PI(3)KC3 multiprotein complex and positively activates PI(3)KC3 lipid kinase activity; UVRAG and Beclin1 interdependently induce autophagy, and UVRAG was identified as a positive regulator of the Beclin1-PI(3)KC3 complex that promotes autophagy and suppresses tumor cell growth. Co-immunoprecipitation, overexpression and knockdown in human colon cancer cells, in vitro PI3K lipid kinase assay Nature cell biology High 16799551
2007 Bif-1 (Endophilin B1) interacts with UVRAG through its SH3 domain to join the UVRAG-Beclin1 complex and activate PI(3)KC3; both the BAR and SH3 domains of Bif-1 are required for PI(3)KC3 activation and autophagosome formation. Co-immunoprecipitation, domain mapping, siRNA knockdown, fluorescence microscopy of autophagosome formation Nature cell biology High 17891140
2008 UVRAG is the mammalian ortholog of yeast Vps38 and forms a distinct PI3K complex (with Vps34, p150/VPS15, and Beclin1) that is mutually exclusive from the Atg14-containing complex; UVRAG primarily localizes to Rab9-positive late endosomes, while Atg14 localizes to isolation membranes/phagophores. Computational homology analysis, co-immunoprecipitation, immunofluorescence localization in HeLa cells, siRNA knockdown Molecular biology of the cell High 18843052
2008 UVRAG promotes autophagosome maturation and endocytic trafficking by recruiting class C Vps tethering complex (HOPS complex) and Rab7 on late endosomes, thereby facilitating fusion with lysosomes. Co-immunoprecipitation, localization studies, functional maturation assays Autophagy Medium 18612260
2010 A specific PI3K-III sub-complex containing VPS15, VPS34, Beclin1, UVRAG and BIF-1 (but not ATG14L) regulates both growth factor receptor degradation (EGFR downregulation) and cytokinesis; UVRAG and BIF-1 localize to the midbody during cytokinesis. siRNA-mediated depletion of individual subunits, high-content microscopy-based assays, immunofluorescence localization Experimental cell research Medium 20643123
2011 UVRAG has anti-apoptotic activity through direct interaction with Bax via its C2 domain; UVRAG inhibits Bax translocation from cytosol to mitochondria during chemotherapy- or UV-induced apoptosis. Deletion of the C2 domain abolishes Bax binding and anti-apoptotic activity. Co-immunoprecipitation, domain deletion mutants, mitochondrial fractionation, cell death assays Autophagy Medium 21606679
2011 UVRAG loss-of-function in Drosophila impairs endocytic trafficking (not autophagy), causing endosomal accumulation of Notch and abnormally enhanced Notch signaling, which leads to defective organ rotation; this phenotype is rescued by knockdown of Notch or expression of dominant-negative Mastermind. Drosophila loss-of-function genetics, epistasis analysis, immunofluorescence, dominant-negative rescue Developmental biology High 21729695
2012 UVRAG promotes DNA double-strand-break repair by directly binding and activating DNA-PK in nonhomologous end joining (NHEJ); UVRAG also localizes to centrosomes and physically associates with CEP63, and disruption of this association causes centrosome instability and aneuploidy. These functions are independent of autophagy. Co-immunoprecipitation, in vitro DNA-PK kinase assay, immunofluorescence, genetic instability assays, irradiation sensitivity Developmental cell High 22542840
2012 The Beclin1 coiled-coil domain forms a metastable antiparallel homodimer with imperfect a-d' pairings; Atg14L and UVRAG promote transition from this homodimer to stable Beclin1-Atg14L or Beclin1-UVRAG heterodimers. Beclin1 mutants with enhanced self-interaction show altered interactions with Atg14L or UVRAG. Crystal structure of Beclin1 coiled-coil domain, mutagenesis, co-immunoprecipitation, in vitro binding assays Nature communications High 22314358
2013 UVRAG is a PtdIns(3)P-binding protein that depends on PtdIns(3)P for ER localization; UVRAG interacts with RINT-1 as an integral component of the ER tethering complex to couple phosphoinositide metabolism to COPI-vesicle tethering. During autophagy, UVRAG dissociates from the ER tether and cooperates with the Bif-1-Beclin1-PI(3)KC3 complex to mobilize Atg9 translocation for autophagosome formation. Co-immunoprecipitation, PtdIns(3)P binding assay, UVRAG knockdown, live-cell imaging, COPI vesicle trafficking assay Nature cell biology High 24056303
2014 mTORC1 directly phosphorylates UVRAG under nutrient-enriched conditions; this phosphorylation promotes UVRAG association with RUBICON, enhancing RUBICON's antagonizing effect on autophagosome maturation. Upon nutrient deprivation and dephosphorylation, UVRAG is released from RUBICON to interact with the HOPS complex, enhancing autophagosome and endosome maturation and facilitating lysosomal EGFR degradation. In vitro mTORC1 kinase assay, phosphorylation site mapping, co-immunoprecipitation, autophagy flux assays, EGFR degradation assays Molecular cell High 25533187
2014 Beclin1 deficiency causes complete loss of the UVRAG-VPS34 complex and associated lipid kinase activity; the UVRAG-Beclin1 interaction underlies Beclin1's function in endocytosis including Rab5-associated early endosome formation and endosome maturation. UVRAG overexpression rescues impaired p40phox-linked endosome formation caused by Beclin1 deficiency, while coiled-coil domain-truncated Beclin1 (UVRAG-binding mutant) does not. Conditional knockout mice, PI3K lipid kinase assay, immunofluorescence, fractionation, rescue with UVRAG mutants PLoS genetics High 25275521
2014 UVRAG is required for the entry of influenza A virus and vesicular stomatitis virus by mediating viral endocytic transport and membrane penetration through interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal glutamine-containing SNAREs (STX7, STX8, Vti1b), leading to assembly of a fusogenic VAMP8-containing trans-SNARE complex. UVRAG stimulates VAMP8 translocation to virus-bearing endosomes. Co-immunoprecipitation, siRNA knockdown, viral entry assays, SNARE complex reconstitution, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 24550300
2014 In Drosophila wing development, the UVRAG-containing PI3K(III) complex (not the Atg14-containing complex) is specifically required for receptor downregulation through endolysosomal degradation (Notch, Wingless) and for epithelial cell polarity, while the Atg14-containing complex is involved in autophagosome formation. Drosophila loss-of-function genetics, UVRAG/Atg14/Atg6 knockdown, immunofluorescence, epistasis BioMed research international Medium 25006588
2015 mTOR directly phosphorylates UVRAG at S550 and S571, activating VPS34 lipid kinase activity; disruption of these phosphorylation sites reduces VPS34 lipid kinase activity and impairs autolysosomal tubulation (autophagosome-lysosome reformation), leading to increased lysosomal tubules and massive cell death under nutrient stress. In vitro mTOR kinase assay, phosphorylation site mutagenesis, VPS34 lipid kinase assay, live-cell imaging of lysosomal tubulation The EMBO journal High 26139536
2015 Cancer-derived UVRAG frameshift (FS) mutation produces a truncated UVRAG protein that acts in a dominant-negative manner to abrogate normal UVRAG functions in autophagy, centrosome stability, and DNA repair; UVRAGFS promotes CRC metastasis through Rac1 activation and EMT independently of autophagy, and confers chemosensitivity due to DNA repair defects. Expression of UVRAGFS in CRC cells, dominant-negative functional assays, Rac1 activity assays, DNA repair assays, in vivo xenograft Nature communications High 26234763
2016 UVRAG localizes to UV-induced photolesions and associates with DDB1 to promote assembly and activity of the CRL4(DDB2) ubiquitin ligase complex (DDB2-DDB1-Cul4A-Roc1), leading to efficient XPC recruitment and global genomic nucleotide excision repair (NER). UVRAG depletion decreases substrate handover to XPC and confers UV-damage hypersensitivity. Co-immunoprecipitation, immunofluorescence localization to photolesions, NER activity assays, siRNA knockdown, Drosophila genetic model Molecular cell High 27203177
2018 Crystal structure of the Beclin1-UVRAG coiled-coil complex reveals a strengthened interface with both hydrophobic pairings and electrostatic complementary interactions, explaining why Beclin1-UVRAG interaction is more potent than the Beclin1 homodimer. UVRAG coiled-coil mutants with weakened Beclin1 binding fail to outcompete Atg14L and cannot promote endolysosomal EGFR degradation. Crystal structure determination, site-directed mutagenesis, competitive binding assay, EGFR degradation assay, stapled peptide design Proceedings of the National Academy of Sciences of the United States of America High 29866835
2018 UVRAG interacts with RINT-1-containing ER tethering complex and, via PtdIns(3)P binding, is required for Golgi-ER retrograde transport; during autophagy induction, UVRAG dissociates from this ER tether. Separately, UVRAG interacts with BLOC-1 complex and this interaction is required for BLOC-1 stability and BLOC-1-mediated cargo sorting to melanosomes; UVRAG is a direct transcriptional target of MITF downstream of α-MSH signaling. Co-immunoprecipitation, UVRAG knockout cells/zebrafish, melanosome biogenesis assays, ChIP/luciferase reporter for MITF target Proceedings of the National Academy of Sciences of the United States of America Medium 30061422
2019 UVRAG is ubiquitinated by SMURF1 E3 ligase at lysine residues K517 and K559 (via K29/K33-linked polyubiquitin chains), which decreases UVRAG association with RUBICON and promotes autophagosome maturation. The deubiquitinase ZRANB1 removes these chains to restore RUBICON binding and inhibit autophagy flux. CSNK1A1 phosphorylation of UVRAG at Ser522 disrupts SMURF1 binding via PPxY motif, blocking ubiquitination. In vitro ubiquitination assay, deubiquitinase assay, site-directed mutagenesis, co-immunoprecipitation, autophagy flux assays Autophagy High 30686098
2019 GORASP2/GRASP55 interacts with BECN1 to facilitate assembly and membrane association of the PtdIns3K UVRAG complex, and physically links autophagosomes to lysosomes via LC3 and LAMP2 interactions to promote autophagosome-lysosome fusion. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, autophagy flux assays Autophagy Medium 30894053
2019 In vivo, UVRAG frameshift (UVRAGFS) truncation disrupts the UVRAG-autophagy complex and impairs starvation- and LPS-induced autophagy (but not basal autophagy); UVRAGFS mice show NLRP3-inflammasome hyperactivation, increased inflammatory response, and enhanced spontaneous tumorigenesis associated with β-catenin stabilization and centrosome amplification. Inducible knock-in mouse model, autophagy flux assays, NLRP3 inflammasome activity, inflammatory and tumor phenotyping Nature communications High 31831743
2012 Slamf1 recruits a Beclin1/Vps34/UVRAG complex (but not Atg14L or Rubicon) to phagosomes in macrophages; both BD and CCD domains of Beclin1 are required for Slamf1 binding. This complex regulates membrane fusion and NOX2 oxidase activity during bacterial phagocytosis. Co-immunoprecipitation, Beclin1 domain deletion mutants, NOX2 activity assay in Beclin1+/- macrophages The Journal of biological chemistry Medium 22493499
2021 UVRAG downregulation impairs autophagy flux, leading to ectopic accumulation of p62; accumulated p62 recruits RIPK1 and induces its self-oligomerization, activating the RIPK1/RIPK3/MLKL cascade and neuronal necroptosis. UVRAG overexpression inhibits neuronal necroptosis in cell and AD mouse models. UVRAG knockdown/overexpression, AAV-mediated gene manipulation in mice, Western blot, autophagy flux assays, necroptosis signaling assays Theranostics Medium 34646380
2022 Miga, a mitochondrial outer-membrane ER-mitochondrial contact site protein, binds both Atg14 and Uvrag and recruits them to mitochondria; Miga-induced PI3K activity requires Uvrag, while Miga-mediated stabilization of Syx17 (a SNARE for autophagosome-lysosome fusion) requires Atg14. Miga-regulated ER-mitochondria contact sites are critical for PI3P formation. Co-immunoprecipitation, Miga mutant Drosophila, PI3P assay, immunofluorescence, autophagy flux assays Cell reports Medium 36323251
2023 Upon starvation, UVRAG localizes to ER-phagy sites (ERPHS) and interacts with ER-phagy cargo receptors FAM134B, ATL3, and RTN3L; UVRAG regulates oligomerization of these receptors and facilitates recruitment of Atg8 family proteins to promote efficient ER-phagy (reticulophagy) initiation and clearance of pathogenic proinsulin aggregates. This function is independent of UVRAG's role as a PI3KC3-II subunit. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, ER-phagy flux assays, receptor oligomerization assay The EMBO journal High 37902287
2020 UVRAG is required for efficient filovirus (Ebola virus and other pathogenic filoviruses) entry; UVRAG depletion impairs delivery of EBOV virions to NPC1+ compartments. Deletion of the UVRAG domain required for HOPS complex interaction abolishes EBOV entry, demonstrating that UVRAG coordinates with the HOPS tethering complex for endolysosomal trafficking of virions to the filoviral receptor NPC1. Inducible CRISPR/Cas9 knockout, viral entry assays, immunofluorescence of virion trafficking, UVRAG domain deletion mutants Journal of virology High 32493822
2015 HCV differentially induces expression of Rubicon (early, inhibits autophagosome maturation) and UVRAG (delayed, stimulates maturation); UVRAG overexpression facilitates autophagosome maturation and suppresses HCV replication, while Rubicon promotes viral replication. The HCV NS4B protein is sufficient to induce Rubicon expression and autophagosome accumulation. siRNA knockdown and overexpression of UVRAG/Rubicon, HCV replication assays, autophagosome maturation assays, NS4B expression PLoS pathogens Medium 25807108
2015 In T cells, UVRAG deficiency causes defects in peripheral naive T-cell homeostasis (reduced homeostatic proliferation, impaired CD8+ T-cell responses to LCMV infection) through autophagy-independent mechanisms; UVRAG-deficient T-cells show normal mitochondrial clearance and activation-induced autophagy, suggesting an autophagy-independent role in T-cell homeostasis. T-cell-specific conditional knockout mice, LCMV infection model, autophagy flux assays, mitophagy assay Proceedings of the National Academy of Sciences of the United States of America Medium 25583492
2013 UVRAG is essential for autophagic flux and cardiac function in vivo; UVRAG-deficient mice develop age-related cardiomyopathy with impaired autophagic flux (autophagosome accumulation without progression), while basal autophagosome formation is preserved, indicating UVRAG's primary role is in autophagosome maturation. PiggyBac transposon gene disruption mouse model, autophagic flux assay with chloroquine, cardiac function assessment Cardiovascular research Medium 24081163
2012 Akt1 inhibits autophagy by downregulating UVRAG expression at the transcriptional level; this effect is kinase-activity independent. Dominant-negative Akt1 also reduces UVRAG, and re-introduction of UVRAG rescues autophagic activity in Akt1-overexpressing cells. Akt1 overexpression and siRNA in 293T and breast cancer cells, UVRAG mRNA quantification, LC3 flux assays, UV-induced autophagy rescue Experimental cell research Medium 23200933

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Molecular biology of the cell 962 18843052
2006 Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nature cell biology 846 16799551
2007 Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nature cell biology 728 17891140
2014 mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation. Molecular cell 226 25533187
2010 A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Experimental cell research 154 20643123
2012 Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG. Nature communications 143 22314358
2008 Frameshift mutation of UVRAG, an autophagy-related gene, in gastric carcinomas with microsatellite instability. Human pathology 130 18495205
2015 mTOR activates the VPS34-UVRAG complex to regulate autolysosomal tubulation and cell survival. The EMBO journal 127 26139536
2021 TNF-α-dependent neuronal necroptosis regulated in Alzheimer's disease by coordination of RIPK1-p62 complex with autophagic UVRAG. Theranostics 118 34646380
2014 Beclin 1 is required for neuron viability and regulates endosome pathways via the UVRAG-VPS34 complex. PLoS genetics 112 25275521
2015 HCV induces the expression of Rubicon and UVRAG to temporally regulate the maturation of autophagosomes and viral replication. PLoS pathogens 111 25807108
2019 Ubiquitination of UVRAG by SMURF1 promotes autophagosome maturation and inhibits hepatocellular carcinoma growth. Autophagy 110 30686098
2009 Atg14 and UVRAG: mutually exclusive subunits of mammalian Beclin 1-PI3K complexes. Autophagy 100 19223761
2013 PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. Nature cell biology 79 24056303
2012 A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Developmental cell 78 22542840
2015 Truncating mutation in the autophagy gene UVRAG confers oncogenic properties and chemosensitivity in colorectal cancers. Nature communications 75 26234763
2016 miR-183 regulates autophagy and apoptosis in colorectal cancer through targeting of UVRAG. Oncotarget 65 26717041
2019 GORASP2/GRASP55 collaborates with the PtdIns3K UVRAG complex to facilitate autophagosome-lysosome fusion. Autophagy 61 30894053
2014 Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells. PloS one 61 24956373
2007 UVRAG: a new player in autophagy and tumor cell growth. Autophagy 59 17106237
2020 Curcumin Inhibited Podocyte Cell Apoptosis and Accelerated Cell Autophagy in Diabetic Nephropathy via Regulating Beclin1/UVRAG/Bcl2. Diabetes, metabolic syndrome and obesity : targets and therapy 58 32184643
2018 Targeting the potent Beclin 1-UVRAG coiled-coil interaction with designed peptides enhances autophagy and endolysosomal trafficking. Proceedings of the National Academy of Sciences of the United States of America 54 29866835
2010 UVRAG mutations associated with microsatellite unstable colon cancer do not affect autophagy. Autophagy 46 20724836
2003 Ascending colon cancer with hepatic metastasis and cholecystolithiasis in a patient with situs inversus totalis without any expression of UVRAG mRNA: report of a case. Surgery today 46 12928850
2019 A truncating mutation in the autophagy gene UVRAG drives inflammation and tumorigenesis in mice. Nature communications 43 31831743
2014 Atg6/UVRAG/Vps34-containing lipid kinase complex is required for receptor downregulation through endolysosomal degradation and epithelial polarity during Drosophila wing development. BioMed research international 41 25006588
2018 Silencing circular RNA UVRAG inhibits bladder cancer growth and metastasis by targeting the microRNA-223/fibroblast growth factor receptor 2 axis. Cancer science 37 30387298
2012 Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) complex. The Journal of biological chemistry 37 22493499
2018 miR-125b is downregulated in systemic lupus erythematosus patients and inhibits autophagy by targeting UVRAG. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 36 29710477
2016 Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4(DDB2) E3 Ligase. Molecular cell 36 27203177
2014 UVRAG is required for virus entry through combinatorial interaction with the class C-Vps complex and SNAREs. Proceedings of the National Academy of Sciences of the United States of America 35 24550300
2017 Vacuolar Trafficking Protein VPS38 Is Dispensable for Autophagy. Plant physiology 34 29184027
2011 A critical role for UVRAG in apoptosis. Autophagy 34 21606679
2011 UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila. Developmental biology 34 21729695
2012 Protein kinase B/Akt1 inhibits autophagy by down-regulating UVRAG expression. Experimental cell research 33 23200933
2017 miR-216b enhances the efficacy of vemurafenib by targeting Beclin-1, UVRAG and ATG5 in melanoma. Cellular signalling 32 28982601
2013 Essential role for UVRAG in autophagy and maintenance of cardiac function. Cardiovascular research 32 24081163
2017 UVRAG Deficiency Exacerbates Doxorubicin-Induced Cardiotoxicity. Scientific reports 31 28225086
2010 Association of UVRAG polymorphisms with susceptibility to non-segmental vitiligo in a Korean sample. Experimental dermatology 30 20163458
2018 Central role of autophagic UVRAG in melanogenesis and the suntan response. Proceedings of the National Academy of Sciences of the United States of America 29 30061422
2020 UVRAG in autophagy, inflammation, and cancer. Autophagy 27 31905312
2015 Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency. Autophagy 26 25946189
2008 Beyond autophagy: the role of UVRAG in membrane trafficking. Autophagy 26 18612260
2018 NLRX1 Negatively Regulates Group A Streptococcus Invasion and Autophagy Induction by Interacting With the Beclin 1-UVRAG Complex. Frontiers in cellular and infection microbiology 24 30488027
2012 UVRAG: at the crossroad of autophagy and genomic stability. Autophagy 24 22885520
2010 Roles of Pichia pastoris Uvrag in vacuolar protein sorting and the phosphatidylinositol 3-kinase complex in phagophore elongation in autophagy pathways. Autophagy 23 19946209
2015 Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis. Proceedings of the National Academy of Sciences of the United States of America 22 25583492
2022 ER-mitochondrial contact protein Miga regulates autophagy through Atg14 and Uvrag. Cell reports 21 36323251
2022 Plant UVRAG interacts with ATG14 to regulate autophagosome maturation and geminivirus infection. The New phytologist 18 35978547
2018 Up-regulation of UVRAG by HDAC1 Inhibition Attenuates 5FU-induced Cell Death in HCT116 Colorectal Cancer Cells. Anticancer research 18 29277783
2023 UVRAG cooperates with cargo receptors to assemble the ER-phagy site. The EMBO journal 17 37902287
2011 Multi-step process of human breast carcinogenesis: a role for BRCA1, BECN1, CCND1, PTEN and UVRAG. Molecular medicine reports 17 22011761
2017 MicroRNA-1185 Induces Endothelial Cell Apoptosis by Targeting UVRAG and KRIT1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 28441650
2021 Distinct roles of UVRAG and EGFR signaling in skeletal muscle homeostasis. Molecular metabolism 14 33561544
2015 Frameshift mutation of UVRAG: Switching a tumor suppressor to an oncogene in colorectal cancer. Autophagy 13 26327192
2021 MiR-520a-3p Inhibited Macrophage Polarization and Promoted the Development of Atherosclerosis via Targeting UVRAG in Apolipoprotein E Knockout Mice. Frontiers in molecular biosciences 12 33768113
2021 Circular RNA UVRAG Mediated by Alternative Splicing Factor NOVA1 Regulates Adhesion and Migration of Vascular Smooth Muscle Cells. Genes 12 33799408
2022 Long noncoding RNA SNHG1 silencing accelerates hepatocyte-like cell differentiation of bone marrow-derived mesenchymal stem cells to alleviate cirrhosis via the microRNA-15a/SMURF1/UVRAG axis. Cell death discovery 11 35194023
2023 UVRAG Promotes Tumor Progression through Regulating SP1 in Colorectal Cancer. Cancers 9 37173968
2020 Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry. Journal of virology 9 32493822
2021 UV radiation resistance-associated gene (UVRAG) promotes cell proliferation, migration, invasion by regulating cyclin-dependent kinases (CDK) and integrin-β/Src signaling in breast cancer cells. Molecular and cellular biochemistry 6 33515382
2018 Darkening with UVRAG. Autophagy 6 30209981
2014 Interaction of Grb2 SH3 domain with UVRAG in an Alzheimer's disease-like scenario. Biochemistry and cell biology = Biochimie et biologie cellulaire 6 24882360
2023 UVRAG: orchestrating the initiation of reticulophagy. Autophagy 4 38054642
2015 Systematic analyses of the ultraviolet radiation resistance-associated gene product (UVRAG) protein interactome by tandem affinity purification. Archives of pharmacal research 4 26590968
2012 The BECN1 coiled coil domain: an "imperfect" homodimer interface that facilitates ATG14 and UVRAG binding. Autophagy 4 22647755
2024 [Effect of UVRAG Gene on Ferroptosis Induced by Sorafenib in K562 Cells]. Zhongguo shi yan xue ye xue za zhi 1 38926949
2020 Suppressing UVRAG Induces Radiosensitivity by Triggering Lysosomal Membrane Permeabilization in Hypopharyngeal Squamous Cell Carcinoma. OncoTargets and therapy 1 33116608
2026 Structure-Based Design of UVRAG-BAX Binding Interface-Targeting Compound Induces Apoptosis and ROS in Breast Cancer Cells. Biochemistry 0 42117566
2025 Investigating the function of UVRAG protein in regulation of apoptosis and autophagy and its implications in cancer. International journal of biological macromolecules 0 40639523
2022 [Effect of Silencing UVRAG on Mitophagy in Leukemia Cells K562]. Zhongguo shi yan xue ye xue za zhi 0 36476887

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