Affinage

UNC5B

Netrin receptor UNC5B · UniProt Q8IZJ1

Length
945 aa
Mass
103.6 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UNC5B is a single-pass dependence receptor for netrin-1 that switches between pro-apoptotic/repulsive and pro-survival outputs depending on ligand occupancy, governing vascular morphogenesis, neuronal survival, and immune regulation (PMID:15510105, PMID:12598906). Its cytoplasmic ZU5-UPA-death-domain supramodule adopts a closed, autoinhibited conformation whose release activates apoptotic and vascular-patterning signaling (PMID:19328064). In the unliganded state, UNC5B drives apoptosis by engaging DAP-kinase (DAPK) through reciprocal death-domain contacts and by recruiting a PP2A/PR65β complex that dephosphorylates and activates DAPK (PMID:15729359, PMID:21172653); this apoptotic activity is a direct downstream effector of p53, which transcriptionally induces UNC5B (PMID:12598906), and is amplified by MST1-mediated phosphorylation of UNC5B at Thr428 during dopaminergic neuronal loss (PMID:32929029). Netrin-1 binding reverses this program: it recruits the PP2A inhibitor CIP2A to block DAPK activation (PMID:21172653) and engages PIKE-L/PIKE-A through Fyn- and Akt-dependent phosphorylation to drive PI3K/Akt survival signaling (PMID:18469807, PMID:21460185). As a repulsive guidance receptor in endothelial tip cells, UNC5B restrains filopodial extension and sprouting angiogenesis through its intracellular domain (PMID:15510105, PMID:17908930), is induced by Notch and required for shear-stress junctional stability (PMID:38866944), and partners with the netrin-1 co-receptor LRP6/LRP5 to sustain Wnt/β-catenin signaling that maintains blood-brain and blood-retina barrier integrity (PMID:35246514, PMID:36711611). UNC5B further interacts through its extracellular domain with Robo4 to preserve vascular integrity by suppressing VEGF signaling (PMID:21238923), with neogenin as an RGMa co-receptor that activates RhoA via LARG/FAK (PMID:19273616), and with FLRT2/FLRT3 to control cell adhesion, macrophage differentiation, and T-cell checkpoint function (PMID:19492039, PMID:28576770, PMID:38427724). An endothelial NOVA2-driven exon-8-skipping isoform (UNC5B-Δ8) is constitutively pro-apoptotic and netrin-1-insensitive (PMID:34381052), and full-length UNC5B apoptotic signaling is additionally tuned by Fut8-mediated fucosylation (PMID:36670464).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Established UNC5B as a p53-inducible dependence receptor whose cytoplasmic death domain executes apoptosis unless netrin-1 is bound, defining the survival/death switch at its core.

    Evidence Gene cloning, reporter assays, overexpression/knockdown and apoptosis assays in cell lines

    PMID:12598906

    Open questions at the time
    • Did not identify the death-domain effectors
    • Did not resolve how ligand binding mechanically blocks the apoptotic output
  2. 2004 High

    Identified UNC5B's physiological role as a repulsive netrin receptor in endothelial tip cells, linking the receptor to vascular morphogenesis beyond apoptosis.

    Evidence Genetic knockout in mice and morpholino knockdown in zebrafish with endothelial filopodial assays

    PMID:15510105

    Open questions at the time
    • Did not define the intracellular signaling required for repulsion
    • Did not connect repulsion to the apoptotic machinery
  3. 2005 High

    Resolved the proximal apoptotic effector by showing UNC5B binds and activates DAPK via death-domain interactions in a netrin-1-inhibitable manner.

    Evidence Reciprocal Co-IP in cells and mouse brain, dominant-negative mutants, DAPK-mutant MEFs, kinase activity assays

    PMID:15729359

    Open questions at the time
    • Mechanism by which UNC5B reduces DAPK autophosphorylation not yet defined
    • Did not identify the phosphatase involved
  4. 2007 High

    Mapped repulsive and anti-angiogenic signaling to the UNC5B intracellular domain, demonstrating it is required for endothelial repulsion and angiogenesis inhibition.

    Evidence Full-length vs. truncation constructs, genetic loss-of-function, in vitro repulsion and tumor angiogenesis models

    PMID:17908930

    Open questions at the time
    • Did not identify intracellular signaling partners mediating repulsion
    • Did not separate apoptotic from repulsive outputs of the intracellular domain
  5. 2009 High

    Defined the structural basis of receptor autoinhibition, showing the ZU5-UPA-DD supramodule locks UNC5B in a closed conformation that suppresses apoptotic and patterning activity.

    Evidence X-ray crystallography of the cytoplasmic domain with functional validation of open vs. closed states

    PMID:19328064

    Open questions at the time
    • How netrin-1 binding triggers conformational release not structurally resolved
    • Full-length receptor structure not determined
  6. 2009 Medium

    Broadened UNC5B's receptor repertoire beyond netrin by establishing it as a neogenin co-receptor for RGMa that activates RhoA through LARG and FAK.

    Evidence Co-IP, dominant-negative assays, kinase activity assays

    PMID:19273616

    Open questions at the time
    • Single-lab evidence
    • Stoichiometry of the UNC5B-neogenin co-receptor complex unresolved
  7. 2008 High

    Identified the netrin-1-induced survival arm, showing Fyn-dependent PIKE-L recruitment to UNC5B triggers PI3K signaling that suppresses apoptosis.

    Evidence Co-IP, PI3K activity assays, Fyn-null mice, overexpression/knockdown

    PMID:18469807

    Open questions at the time
    • Brain-specific PIKE-L limits generality to other tissues
    • Coupling between PIKE-L binding and conformational opening not defined
  8. 2010 High

    Reconstituted the apoptotic switch biochemically, showing UNC5B recruits PP2A/PR65β to activate DAPK and that netrin-1 recruits the PP2A inhibitor CIP2A to abort death.

    Evidence siRNA screen, Co-IP, PP2A activity assays, dominant-negative approaches

    PMID:21172653

    Open questions at the time
    • Spatial/temporal regulation of CIP2A recruitment not defined
    • Does not address vascular repulsion mechanism
  9. 2011 High

    Extended UNC5B into vascular barrier maintenance by identifying the extracellular Robo4-UNC5B interaction that preserves vessel integrity through VEGF suppression.

    Evidence Interaction screen, Co-IP, function-blocking antibodies, Robo4 KO mouse rescue

    PMID:21238923

    Open questions at the time
    • Intracellular signaling downstream of Robo4-UNC5B not defined
    • Relationship to netrin-1 signaling unclear
  10. 2020 High

    Identified MST1 as an apoptotic amplifier, mapping phosphorylation of UNC5B at Thr428 as a driver of dopaminergic neuron loss upon netrin-1 depletion.

    Evidence Co-IP, phospho-site mapping, UNC5B knockout, MST1 blockade in a Parkinson's model

    PMID:32929029

    Open questions at the time
    • How T428 phosphorylation alters the autoinhibited conformation unresolved
    • Whether MST1 acts upstream or parallel to PP2A/DAPK not defined
  11. 2022 High

    Established a non-apoptotic vascular barrier function in which netrin-1-bound UNC5B engages LRP6 to sustain Wnt/β-catenin signaling and blood-brain barrier integrity.

    Evidence Inducible endothelial KO, UNC5B-LRP6 Co-IP, LRP6 phosphorylation, β-catenin rescue, blocking antibodies

    PMID:35246514

    Open questions at the time
    • Mechanism coupling UNC5B to LRP6 phosphorylation not detailed
    • Whether barrier and repulsion functions share signaling unresolved
  12. 2021 High

    Revealed isoform-level control of apoptosis through a NOVA2-driven exon-8-skipping isoform (UNC5B-Δ8) that is constitutively pro-apoptotic and netrin-1-insensitive during vascular development.

    Evidence Isoform cloning, NOVA2 knockdown/overexpression, apoptosis assays, zebrafish and mouse vascular models

    PMID:34381052

    Open questions at the time
    • Structural basis of netrin-1 insensitivity not defined
    • Tissue distribution of the isoform beyond endothelium unclear
  13. 2024 High

    Connected UNC5B to upstream Notch transcriptional control and shear-stress junctional stabilization, integrating it into endothelial flow responses.

    Evidence Translated mRNA screen, endothelial loss/gain-of-function, shear stress, neonatal retinal vascular analysis

    PMID:38866944

    Open questions at the time
    • Notch-to-UNC5B transcriptional intermediates not defined
    • Junctional effectors downstream of UNC5B under shear unresolved
  14. 2024 Medium

    Defined UNC5B as an inducible T-cell checkpoint receptor engaged by tumor FLRT3, opening an immunotherapeutic axis.

    Evidence Gain-of-function genetic screen, T cell functional assays, humanized cancer models, antibody blockade

    PMID:38427724

    Open questions at the time
    • Single-lab evidence
    • Intracellular signaling driving T-cell suppression not defined
  15. 2023 Medium

    Identified post-translational fucosylation as a tuning mechanism for UNC5B, with Fut8-mediated α-1,6-fucosylation controlling macrophage migration via CDC42/PAK.

    Evidence Co-IP, fucosylation-site deletion, wound healing assay, ApoE-/- atherosclerosis model

    PMID:36670464

    Open questions at the time
    • Single-lab evidence
    • How fucosylation alters receptor signaling conformation unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor partitions its multiple, sometimes opposing outputs (apoptosis, endothelial repulsion, Wnt-dependent barrier maintenance, RhoA-mediated guidance, immune checkpoint signaling) into distinct ligand-, isoform-, PTM-, and tissue-dependent programs remains unresolved.
  • No unified model linking conformational state to choice of downstream effector
  • Combinatorial logic of co-receptors (neogenin, Robo4, LRP6/LRP5, FLRT2/3, integrin) not integrated
  • Structure of full-length ligand-engaged receptor unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2
Partners
CIP2ADAPK1FLRT2FLRT3LRP6NEO1PIKE-L/AGAP2ROBO4
Complex memberships
UNC5B-CDC14A-p53 complexUNC5B-PP2A(PR65β)-DAPK apoptotic complexUNC5B-neogenin RGMa co-receptor complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 UNC5B functions as a repulsive netrin receptor in endothelial tip cells; disruption of Unc5b in mice or zebrafish leads to aberrant filopodial extension and excessive vessel branching; netrin-1 causes endothelial filopodial retraction only when UNC5B is present, establishing UNC5B as a repulsive guidance receptor controlling vascular morphogenesis. Genetic knockout in mice, morpholino knockdown in zebrafish, endothelial cell assays Nature High 15510105
2003 UNC5B (p53RDL1) is a direct transcriptional target of p53 that mediates p53-dependent apoptosis through its cytoplasmic death domain; when the ligand netrin-1 binds to p53RDL1/UNC5B, p53-dependent apoptosis is blocked, identifying a netrin-p53RDL1 pathway that balances cell survival and death. Gene cloning, reporter assays, overexpression/knockdown in cell lines, apoptosis assays Nature cell biology High 12598906
2005 UNC5B (UNC5H2) physically interacts with the serine/threonine kinase DAP-kinase (DAPK) through their respective death domains both in cell culture and embryonic mouse brain. In the absence of netrin-1, UNC5B reduces DAP-kinase autophosphorylation on Ser308 and increases DAPK catalytic activity to promote apoptosis; netrin-1 blocks this UNC5B-dependent DAPK activation. Co-immunoprecipitation, dominant-negative mutants, DAPK-mutant MEFs, kinase activity assays The EMBO journal High 15729359
2007 UNC5B full-length receptor triggers endothelial cell repulsion and inhibits sprouting angiogenesis in response to netrin-1; a truncated UNC5B lacking the intracellular signaling domain fails to induce repulsion, establishing that the intracellular domain is required for repulsive signaling. Genetic loss of unc5b reduces netrin-1-mediated angiogenesis inhibition. Full-length vs. truncation constructs, loss-of-function genetic model, in vitro repulsion assay, Matrigel/tumor angiogenesis models Genes & development High 17908930
2008 Netrin-1 induces interaction of UNC5B with the brain-specific GTPase PIKE-L, triggering PI3K signaling that prevents UNC5B's pro-apoptotic activity and enhances neuronal survival. This interaction requires Fyn kinase-mediated tyrosine phosphorylation of PIKE-L and is absent in Fyn-null mice. Co-immunoprecipitation, PI3K activity assay, Fyn-null mice, overexpression/knockdown Nature cell biology High 18469807
2009 Crystal structure of the cytoplasmic portion of UNC5B reveals three domains (ZU5, UPA, death domain) forming a structural supramodule in which ZU5 binds both UPA and DD, locking the complex in a closed/autoinhibited conformation that suppresses apoptotic and vascular patterning activity; release of this closed conformation activates the receptor. X-ray crystallography of cytoplasmic domain, functional validation of open vs. closed conformations Molecular cell High 19328064
2009 UNC5B interacts with neogenin as a co-receptor for the repulsive guidance molecule RGMa; the guanine nucleotide exchange factor LARG associates with UNC5B to transduce RhoA activation; FAK is involved in RGMa-induced tyrosine phosphorylation of LARG and RhoA activation, mediating growth cone collapse. Co-immunoprecipitation, dominant-negative assays, kinase activity assays The Journal of cell biology Medium 19273616
2009 UNC5B and FLRT3 interact as high-affinity binding partners; UNC5B and FLRT3 synergize to induce cell deadhesion in Xenopus embryos; the small GTPase Rnd1, which mediates FLRT3 deadhesion activity, physically and functionally interacts with UNC5B to modulate cell adhesion. Expression screen, overexpression, morpholino knockdown, Co-immunoprecipitation in Xenopus PloS one Medium 19492039
2010 UNC5B (UNC5H2/B) recruits a complex containing the PP2A structural subunit PR65β and DAPK; PP2A dephosphorylates and thereby activates DAPK to promote apoptosis. Netrin-1 binding recruits the PP2A inhibitor CIP2A to UNC5B, blocking this mechanism and preventing cell death. siRNA screen, Co-immunoprecipitation, PP2A activity assays, dominant-negative approaches Molecular cell High 21172653
2011 Robo4 specifically binds to UNC5B via a protein-protein interaction between their extracellular domains; Robo4-UNC5B signaling maintains vascular integrity by inhibiting VEGF downstream signaling; function-blocking antibodies against either Robo4 or UNC5B increase angiogenesis and disrupt vessel integrity; soluble Robo4 rescues barrier defects in Robo4−/− mice via UNC5B. Protein-protein interaction screen, Co-immunoprecipitation, function-blocking antibodies, Robo4 KO mouse rescue experiments Developmental cell High 21238923
2008 Netrin-4 does not bind directly to UNC5B or UNC5C but binds neogenin; Netrin-4 increases association between UNC5B and neogenin (demonstrated by Co-IP); silencing either neogenin or UNC5B abolishes Netrin-4's inhibitory effect on endothelial cell migration, indicating both receptors are required for Netrin-4 anti-angiogenic function. Binding assays, Co-immunoprecipitation, siRNA knockdown, endothelial migration assays, in vivo angiogenesis models Proceedings of the National Academy of Sciences of the United States of America Medium 18719102
2002 The cytoplasmic domain of UNC5B (UNC5H2) binds activated GTP-bound Gαi2; this interaction sequesters Gαi2 from inhibiting adenylyl cyclase, thereby increasing intracellular cAMP levels, identifying UNC5B as a novel inhibitor of Gαi2 signaling. Binding assays with constitutively-activated Gαi2 (gip2), adenylyl cyclase activity assay Biochemical and biophysical research communications Low 12359238
2006 Crystal structure of the UNC5H2 (UNC5B) death domain at 2.1 Å resolution reveals a six-helix bundle fold; the death domain forms a homodimer in crystal and in solution through hydrophobic contacts, which may block caspase access to its cleavage site when netrin-1 is bound. X-ray crystallography, solution biophysics Acta crystallographica. Section D, Biological crystallography Medium 17139086
2011 UNC5B (Unc5H2) acts as a repulsive receptor in Schwann cells that functions as an intrinsic brake on peripheral nerve regeneration; local siRNA knockdown of Unc5H2 at the injury site facilitates axon regrowth, and forced DCC inhibition causes reciprocal upregulation of Unc5H2. In vivo siRNA knockdown at nerve injury site, axon regeneration functional assay Glia Medium 21656855
2009 Netrin-1 increases renal proximal tubular epithelial cell proliferation and migration through the UNC5B receptor; siRNA inhibition of UNC5B (but not UNC5C) completely blocks netrin-1-induced proliferation and migration; downstream signaling involves phosphorylation of Akt and ERK, with PI3K and MEK1/2 inhibition blocking proliferation but not migration. siRNA knockdown, proliferation assays, PI3K/MEK inhibitors, Western blot phosphorylation assays American journal of physiology. Renal physiology Medium 19211685
2022 Endothelial UNC5B controls blood-brain barrier integrity by maintaining Wnt/β-catenin signaling; inducible endothelial-specific UNC5B deletion reduces Claudin-5 and increases PLVAP, causing BBB leak. Mechanistically, netrin-1 enhances UNC5B interaction with the Wnt co-receptor LRP6, induces LRP6 phosphorylation, and activates Wnt/β-catenin signaling; β-catenin overexpression rescues UNC5B mutant BBB defects. Inducible endothelial-specific knockout, Co-immunoprecipitation (UNC5B-LRP6), Western blot for LRP6 phosphorylation, β-catenin rescue, function-blocking antibodies Nature communications High 35246514
2020 Netrin-1 reduction in Parkinson's disease activates MST1, which binds and phosphorylates UNC5B at T428, promoting its apoptotic activation and dopaminergic neuronal loss; knockout of UNC5B abolishes netrin depletion-induced dopaminergic loss; blockade of MST1 phosphorylation of UNC5B suppresses neuronal apoptosis. Co-immunoprecipitation, phosphorylation site mapping (T428), UNC5B knockout, MST1 blockade Proceedings of the National Academy of Sciences of the United States of America High 32929029
2011 Akt phosphorylates PIKE-A on Ser-472, enhancing PIKE-A interaction with UNC5B and inhibiting UNC5B-provoked apoptosis in a p53-dependent manner; overexpression of PIKE-A diminishes UNC5B expression through downregulation of p53; PIKE-A directly interacts with UNC5B regulated by netrin-1-activated Akt. Co-immunoprecipitation, phosphorylation-site mutagenesis, PIKE knockout MEFs, apoptosis assays Molecular biology of the cell Medium 21460185
2016 Netrin-4 acts through its receptor neogenin and recruits UNC5B; activation of UNC5B by Netrin-4/neogenin signaling leads to RhoA activation via SHP2 phosphatase in dorsal horn neurons; transient suppression of Netrin-4 or Unc5B after injury prevents allodynia, and intrathecal Netrin-4 protein enhances excitatory synaptic transmission and induces allodynia in naive rats. Netrin-4 mutant rats, in vivo siRNA, intrathecal protein administration, electrophysiology The Journal of experimental medicine Medium 27856613
2017 FLRT2 binds to UNC5B via its extracellular domain and activates Akt/mTOR signaling to drive monocyte-to-macrophage differentiation; endothelial repulsion in the placental labyrinth is mediated through FLRT2 binding to UNC5B; endothelial-specific FLRT2 deletion causes embryonic lethality with aberrant endothelial alignment in the placenta. Endothelial-specific knockout, binding assays, Co-immunoprecipitation, mTOR agonist rescue Development (Cambridge, England) Medium 28576770
2023 FLRT2 directly interacts with UNC5B via its extracellular domain and activates Akt/mTOR signaling to promote monocyte-to-macrophage differentiation; myeloid-specific Flrt2 deletion impairs macrophage generation; in vivo administration of mTOR agonist reverses impaired phenotypes in Flrt2 mutant mice. Myeloid-specific conditional knockout, Co-immunoprecipitation, mTOR agonist rescue in vivo Frontiers in immunology Medium 37090697
2021 An endothelial cell-specific UNC5B splicing isoform (UNC5B-Δ8), generated through exon-8 skipping by the alternative splicing factor NOVA2, is constitutively pro-apoptotic and insensitive to netrin-1; this isoform is required for specific blood vessel development in an apoptosis-dependent manner. Isoform cloning, NOVA2 knockdown/overexpression, apoptosis assays, zebrafish and mouse vascular development models Nature communications High 34381052
2016 Netrin-1 regulates UNC5B distribution at the plasma membrane: UNC5B expressed alone is recruited by netrin-1 to the plasma membrane; coexpressed DCC and UNC5B undergo netrin-1-induced colocalization and heterooligomerization via vesicular recruitment to the plasma membrane; this plasma membrane recruitment requires netrin-1-activated Src family kinase signaling. TIRF microscopy, temporal image cross-correlation spectroscopy (TICCS), fluorescently-tagged receptors in HEK293T cells, pharmacological Src inhibition Biophysical journal Medium 26840727
2024 Notch signaling in endothelial cells rapidly upregulates UNC5B expression; loss or gain of UNC5B recapitulates Notch-regulated phenotypes including inhibition of endothelial migration and proliferation; UNC5B is required for stabilization of endothelial junctions in response to shear stress; endothelial-specific loss of UNC5B leads to excessive vascularization and increased branchpoints in developing mouse retina. Translated mRNA screen, endothelial-specific UNC5B loss/gain-of-function, shear stress experiments, neonatal mouse retinal vascular analysis Scientific reports High 38866944
2020 UNC5B mediates G2/M phase cell cycle arrest in bladder cancer cells by forming a complex with CDC14A phosphatase and P53; this complex dephosphorylates P53 at Ser-315, reducing cyclin B1 expression and increasing p-CDK1, thereby inhibiting tumor proliferation; CDC14A knockdown suppresses UNC5B-induced G2/M arrest. Mass spectrometry, Co-immunoprecipitation, site-specific phosphorylation analysis, CDC14A knockdown, xenograft tumor model Cancer gene therapy Medium 32372016
2020 Netrin-1 promotes naive pluripotency in mESCs through a balance of Neo1 and Unc5B receptors that co-regulate Wnt and MAPK pathways; Netrin-1 induces FAK kinase to inactivate Gsk3α/β and stabilize β-catenin while increasing activity of a Ppp2r2c-containing PP2A complex to reduce Erk1/2 activity. Chemical inhibitor substitution assays, Western blot, phosphorylation analysis, PP2A activity assay, receptor knockdown in mESCs Nature cell biology High 32231305
2022 UNC5B overexpression in Schwann cells facilitates autophagic flux via phosphorylation of AMPK and ULK1 in a netrin-1-dependent manner; UNC5B helps recruit netrin-1 to the cell membrane; overexpression of UNC5B alleviates neuropathic pain and rescues myelin degeneration in a rat CCI model, and autophagy inhibitor reverses the analgesic effect. AAV-mediated UNC5B overexpression, autophagy flux assays, AMPK/ULK1 phosphorylation Western blot, autophagy inhibitor, CCI rat model Molecular neurobiology Medium 35668343
2023 Netrin-1 and UNC5B form heterocomplexes; biophysical analysis shows NET-1 exists in a monomer-dimer equilibrium (pH-sensitive antiparallel dimer) and UNC5B forms equimolar heterocomplexes with both monomeric and dimeric NET-1. Multi-wavelength analytical ultracentrifugation (AUC), sedimentation velocity experiments European biophysics journal : EBJ Medium 36939874
2023 Netrin-1 binding to endothelial Unc5B controls blood-retina barrier (BRB) integrity via the Norrin receptor LRP5; Unc5B deletion or Ntn1 deletion reduces LRP5 phosphorylation and β-catenin/LEF1 expression, converting retinal endothelium to a leaky phenotype; Unc5B in pericytes contributes to BRB permeability via regulation of endothelial Unc5B; mechanistically, Netrin-1-Unc5B signaling promotes LRP5 phosphorylation via the Dlg1 intracellular scaffolding protein. Inducible conditional knockout of Unc5B and Ntn1, tracer injection, phosphorylation/signaling analysis, β-catenin gain-of-function rescue, Ntn1 overexpression bioRxivpreprint Medium 36711611
2024 FLRT3 expressed on cancer cells inhibits T cell activity through UNC5B, which is upregulated on activated human T cells; FLRT3-UNC5B interaction suppresses CAR-T and BiTE+T cell killing; a monoclonal antibody blocking FLRT3-UNC5B interactions reverses T cell inhibition, identifying UNC5B as a T cell checkpoint receptor. Gain-of-function genetic screen, T cell functional assays, humanized cancer models, monoclonal antibody blockade Science advances Medium 38427724
2024 YAP induces UNC5B expression through TEAD transcription factors (blocked by TEAD1/4 loss, S94A YAP mutation, or netrin-1 VI-V peptide); UNC5B and netrin-1 cooperate with integrin-αV/β5 to mediate YAP-induced cytostasis in YAPoff cancers; CRISPR screens linked UNC5B to this anticancer pathway. CRISPR screens, TEAD mutant analysis, UNC5B knockout, integrin blocking assays, receptor decoy experiments Cancer research communications Medium 39172021
2023 Fucosyltransferase 8 (Fut8) regulates α-1,6-fucosylation of Unc5b predominantly in the ER; hypofucosylation of Unc5b (by Fut8 silencing or deletion of fucosylation sites) restores macrophage migration capacity; Unc5b-mediated inhibition of macrophage migration depends on activation of the p-CDC42/p-PAK pathway. Co-immunoprecipitation (Fut8-Unc5b), site-directed deletion of fucosylation sites, wound healing assay, in vivo ApoE-/- atherosclerosis model Cell & bioscience Medium 36670464
2025 Netrin-1 binding to UNC5B activates AMPK, which phosphorylates and inactivates the ferroptosis facilitator BACH1; co-immunoprecipitation confirms AMPK physically binds BACH1; UNC5B knockdown prevents netrin-1-mediated AMPK activation and BACH1 suppression; netrin-1/UNC5B/AMPK-BACH1 signaling protects neurons against ferroptosis after ischemic stroke. siRNA knockdown, AMPK inhibitor, BACH1 activator, Co-immunoprecipitation (AMPK-BACH1), photo-thrombosis stroke model European journal of pharmacology Medium 40086580

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 451 15510105
2007 Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis. Genes & development 198 17908930
2011 Robo4 maintains vessel integrity and inhibits angiogenesis by interacting with UNC5B. Developmental cell 174 21238923
2003 p53RDL1 regulates p53-dependent apoptosis. Nature cell biology 147 12598906
2005 The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase. The EMBO journal 143 15729359
2008 Netrin-4 inhibits angiogenesis via binding to neogenin and recruitment of Unc5B. Proceedings of the National Academy of Sciences of the United States of America 132 18719102
2010 Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. Journal of immunology (Baltimore, Md. : 1950) 115 20693423
2010 The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Molecular cell 110 21172653
2008 The netrin receptor UNC5B promotes angiogenesis in specific vascular beds. Development (Cambridge, England) 108 18223200
2022 Endothelial Unc5B controls blood-brain barrier integrity. Nature communications 97 35246514
2008 Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B. Nature cell biology 92 18469807
2013 Hypoxia induces netrin-1 and Unc5b in atherosclerotic plaques: mechanism for macrophage retention and survival. Arteriosclerosis, thrombosis, and vascular biology 90 23599441
2011 Schwann cells direct peripheral nerve regeneration through the Netrin-1 receptors, DCC and Unc5H2. Glia 79 21656855
2009 Autoinhibition of UNC5b revealed by the cytoplasmic domain structure of the receptor. Molecular cell 75 19328064
2009 Unc5B associates with LARG to mediate the action of repulsive guidance molecule. The Journal of cell biology 72 19273616
2017 Recombinant Netrin-1 binding UNC5B receptor attenuates neuroinflammation and brain injury via PPARγ/NFκB signaling pathway after subarachnoid hemorrhage in rats. Brain, behavior, and immunity 70 29162556
2011 Clinical significance of UNC5B expression in colorectal cancer. International journal of oncology 54 21922135
2001 Expression of netrin-1 and its receptors DCC and UNC-5H2 after axotomy and during regeneration of adult rat retinal ganglion cells. Experimental neurology 53 11170725
2009 Netrin-1 increases proliferation and migration of renal proximal tubular epithelial cells via the UNC5B receptor. American journal of physiology. Renal physiology 51 19211685
2015 Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor. Biochemical and biophysical research communications 48 26116534
2009 Unc5B interacts with FLRT3 and Rnd1 to modulate cell adhesion in Xenopus embryos. PloS one 47 19492039
2020 Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling. Nature cell biology 41 32231305
2020 Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 39 32929029
2011 Akt-phosphorylated PIKE-A inhibits UNC5B-induced apoptosis in cancer cell lines in a p53-dependent manner. Molecular biology of the cell 38 21460185
2003 Expression of Netrin-1 and its two receptors DCC and UNC5H2 in the developing mouse lung. Gene expression patterns : GEP 38 12799072
2007 Netrin-1 induces proliferation of Schwann cells through Unc5b receptor. Biochemical and biophysical research communications 37 17825258
2013 Association of neuroimmune guidance cue netrin-1 and its chemorepulsive receptor UNC5B with atherosclerotic plaque expression signatures and stability in human(s): Tampere Vascular Study (TVS). Circulation. Cardiovascular genetics 36 24122613
2022 PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics 33 35664063
2020 HIF-1α-dependent miR-424 induction confers cisplatin resistance on bladder cancer cells through down-regulation of pro-apoptotic UNC5B and SIRT4. Journal of experimental & clinical cancer research : CR 32 32522234
2022 Netrin-1 upregulates GPX4 and prevents ferroptosis after traumatic brain injury via the UNC5B/Nrf2 signaling pathway. CNS neuroscience & therapeutics 30 36468399
2021 A ligand-insensitive UNC5B splicing isoform regulates angiogenesis by promoting apoptosis. Nature communications 30 34381052
2019 The lncRNA UNC5B-AS1 promotes proliferation, migration, and invasion in papillary thyroid cancer cell lines. Human cell 30 30805847
2018 LncRNA TNRC6C-AS1 regulates UNC5B in thyroid cancer to influence cell proliferation, migration, and invasion as a competing endogenous RNA of miR-129-5p. Journal of cellular biochemistry 30 29893424
2016 Netrin-1 and its receptor Unc5b are novel targets for the treatment of inflammatory arthritis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 27502509
2017 Placental labyrinth formation in mice requires endothelial FLRT2/UNC5B signaling. Development (Cambridge, England) 29 28576770
2021 UNC5B Promotes Vascular Endothelial Cell Senescence via the ROS-Mediated P53 Pathway. Oxidative medicine and cellular longevity 27 34239689
2020 UNC5B-AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2. Cell biology international 24 31903696
2014 PKC α regulates netrin-1/UNC5B-mediated survival pathway in bladder cancer. BMC cancer 23 24528886
2013 UNC5B receptor deletion exacerbates tissue injury in response to AKI. Journal of the American Society of Nephrology : JASN 23 24115477
2009 Characterization and expression of netrin-1 and its receptors UNC5B and DCC in human placenta. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 23 19826074
2019 Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease. Frontiers of medicine 22 31884526
2021 UNC5B-AS1 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells via regulating miR-4306/KDM2A axis. Cell cycle (Georgetown, Tex.) 21 34612138
2016 Overexpression of UNC5B in bladder cancer cells inhibits proliferation and reduces the volume of transplantation tumors in nude mice. BMC cancer 20 27846823
2018 The role of UNC5b in ox-LDL inhibiting migration of RAW264.7 macrophages and the involvement of CCR7. Biochemical and biophysical research communications 18 30286954
2016 Netrin-1-Regulated Distribution of UNC5B and DCC in Live Cells Revealed by TICCS. Biophysical journal 18 26840727
2022 UNC5B Overexpression Alleviates Peripheral Neuropathic Pain by Stimulating Netrin-1-Dependent Autophagic Flux in Schwann Cells. Molecular neurobiology 17 35668343
2002 Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2. Biochemical and biophysical research communications 17 12359238
2022 Netrin-1 induces the anti-apoptotic and pro-survival effects of B-ALL cells through the Unc5b-MAPK axis. Cell communication and signaling : CCS 15 35974411
2021 Δ40p53 isoform up-regulates netrin-1/UNC5B expression and potentiates netrin-1 pro-oncogenic activity. Proceedings of the National Academy of Sciences of the United States of America 15 34470826
2012 Clinical significance of UNC5B expression in bladder cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 23055195
2024 Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching. Scientific reports 13 38866944
2022 Oleanolic Acid (OA) Targeting UNC5B Inhibits Proliferation and EMT of Ovarian Cancer Cell and Increases Chemotherapy Sensitivity of Niraparib. Journal of oncology 13 35035481
2020 LncRNA UNC5B-AS1 promotes malignant progression of prostate cancer by competitive binding to caspase-9. European review for medical and pharmacological sciences 13 32196578
2020 UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53. Cancer gene therapy 13 32372016
2019 Downregulation of the Netrin-1 Receptor UNC5b Underlies Increased Placental Angiogenesis in Human Gestational Diabetes Mellitus. International journal of molecular sciences 13 30897795
2013 CoCl2 induces PC12 cells apoptosis through p53 stability and regulating UNC5B. Brain research bulletin 13 23651544
2022 Isoflurane and Netrin-1 combination therapy enhances angiogenesis and neurological recovery by improving the expression of HIF-1α-Netrin-1-UNC5B/VEGF cascade to attenuate cerebral ischemia injury. Experimental neurology 12 35247371
2018 A network map of netrin receptor UNC5B-mediated signaling. Journal of cell communication and signaling 12 30084000
2013 PKCα is involved in the progression of kidney carcinoma through regulating netrin-1/UNC5B signaling pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 12 23526078
2013 The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury. PloS one 12 23936025
2012 Expression patterns and functional evaluation of the UNC5b receptor during the early phase of peripheral nerve regeneration using the mouse median nerve model. Microsurgery 12 23180484
2022 Netrin-1 attenuates hepatic steatosis via UNC5b/PPARγ-mediated suppression of inflammation and ER stress. Life sciences 11 36400204
2020 Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622. Artificial cells, nanomedicine, and biotechnology 11 31852293
2016 Dorsal horn interneuron-derived Netrin-4 contributes to spinal sensitization in chronic pain via Unc5B. The Journal of experimental medicine 11 27856613
2013 Interactional expression of netrin-1 and its dependence receptor UNC5B in prostate carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 23666553
2023 Fibronectin leucine-rich transmembrane protein 2 drives monocyte differentiation into macrophages via the UNC5B-Akt/mTOR axis. Frontiers in immunology 10 37090697
2021 Inhibition of the long non-coding RNA UNC5B-AS1/miR-4455/RSPO4 axis reduces cervical cancer growth in vitro and in vivo. The journal of gene medicine 10 34350661
2023 Hypofucosylation of Unc5b regulated by Fut8 enhances macrophage emigration and prevents atherosclerosis. Cell & bioscience 9 36670464
2020 Polyomavirus Small T Antigen Induces Apoptosis in Mammalian Cells through the UNC5B Pathway in a PP2A-Dependent Manner. Journal of virology 9 32404521
2019 Lack of Myosin X Enhances Osteoclastogenesis and Increases Cell Surface Unc5b in Osteoclast-Lineage Cells. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 9 30645777
2016 Unc-5 homolog B (UNC5B) is one of the key downstream targets of N-α-Acetyltransferase 10 (Naa10). Scientific reports 9 27910960
2015 Deletion of UNC5B in Kidney Epithelium Exacerbates Diabetic Nephropathy in Mice. American journal of nephrology 9 25896231
2025 Super-Enhancer-Driven LncRNA UNC5B-AS1 Inhibits Inflammatory Phenotypic Transition in Pulmonary Artery Smooth Muscle Cells via Lactylation. Arteriosclerosis, thrombosis, and vascular biology 8 40336475
2020 PKCα and Netrin-1/UNC5B positive feedback control in relation with chemical therapy in bladder cancer. European review for medical and pharmacological sciences 8 32141538
2008 Molecular cloning of a porcine (Sus scrofa) apoptosis inhibitory ligand, netrin-1, and its receptor, p53RDL1. The Journal of reproduction and development 8 18497489
2024 Targeting Unc5b in macrophages drives atherosclerosis regression and pro-resolving immune cell function. Proceedings of the National Academy of Sciences of the United States of America 7 39436659
2014 UNC5B receptor deletion exacerbates DSS-induced colitis in mice by increasing epithelial cell apoptosis. Journal of cellular and molecular medicine 7 24720832
2007 Expression pattern for unc5b, an axon guidance gene in embryonic zebrafish development. Gene expression 7 17708418
2020 The intracellular domain of UNC5B facilities proliferation and metastasis of bladder cancer cells. Journal of cellular and molecular medicine 6 33345442
2020 [Effects of LncRNA UNC5B-AS1 on adhesion, invasion and migration of lung cancer cells and its mechanism]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 6 33719270
2025 Netrin-1 binding to UNC5b improves post-stroke neuronal ferroptosis via AMPK-BACH1 pathway. European journal of pharmacology 5 40086580
2024 Unc5b prevents macrophage-derived foam cell migration and promotes atherosclerotic development via the P53-cuproptosis signaling pathway. Life sciences 5 39722317
2023 Netrin-1 binding to Unc5B regulates Blood-Retina Barrier integrity. bioRxiv : the preprint server for biology 5 36711611
2021 Long non-coding RNA PITPNA-AS1 regulates UNC5B expression in papillary thyroid cancer via sponging miR-129-5p. The International journal of biological markers 5 33706585
2006 Structure of the UNC5H2 death domain. Acta crystallographica. Section D, Biological crystallography 5 17139086
2024 Cinnamaldehyde attenuates streptozocin-induced diabetic osteoporosis in a rat model by modulating netrin-1/DCC-UNC5B signal transduction. Frontiers in pharmacology 4 38628640
2024 Identification of UNC5B as a novel aggressive biomarker for osteosarcoma based on basement membrane genes. Gene 4 39154972
2009 [Down-regulated expression of UNC5b related to hepatocellular carcinoma angiogenesis]. Zhonghua wai ke za zhi [Chinese journal of surgery] 4 20092749
2023 Investigation of dynamic solution interactions between NET-1 and UNC-5B by multi-wavelength analytical ultracentrifugation. European biophysics journal : EBJ 3 36939874
2025 Fut8 regulated Unc5b hyperfucosylation reduces macrophage emigration and accelerates atherosclerosis development via the ferroptosis pathway. Free radical biology & medicine 2 40262667
2025 Direction and modality of transcription changes caused by TAD boundary disruption in Slc29a3/Unc5b locus depends on tissue-specific epigenetic context. Epigenetics & chromatin 2 40796890
2025 Jiawei Qingxin Zishen Decoction mitigates granulosa cell apoptosis and enhances ovarian reserve through Netrin/UNC5B signaling pathway. Journal of ethnopharmacology 2 41072782
2024 The FLRT3-UNC5B checkpoint pathway inhibits T cell-based cancer immunotherapies. Science advances 2 38427724
2024 Long noncoding RNA UNC5B-AS1 suppresses cell proliferation by sponging miR-24-3p in glioblastoma multiforme. BMC medical genomics 2 38594690
2024 Netrin-1 and UNC5B Cooperate with Integrins to Mediate YAP-Driven Cytostasis. Cancer research communications 2 39172021
2024 Acute myeloid leukemia cells adhere to bone marrow and acquire chemoresistance by downregulating UNC5B expression. Frontiers in oncology 2 39381040
2019 Netrin-1 and its receptor Unc5b as markers of periodontal disease. Journal of periodontal research 2 31769036
2013 [Expressions of netrin-1 and UNC5B in prostate cancer and their clinical significance]. Zhonghua nan ke xue = National journal of andrology 2 24432616
2025 Characterization of Netrin-1 and Its Receptors UNC5B and Neogenin-1 in a Rat Rotator Cuff Tear Model: Associations with Inflammatory Mediators and Neurite Extension. Current issues in molecular biology 1 40728980
2022 Expression and Relationship of Netrin-1, DCC, UNC5B, and VEGF in Villous Tissues of Patients with Delayed Abortion. Contrast media & molecular imaging 1 36110982

Missed literature

Know a paper Affinage missed for UNC5B? Flag it for the maintainers and the community.

No submissions yet.