Affinage

BOC

Brother of CDO · UniProt Q9BWV1

Length
1114 aa
Mass
121.1 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 25 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

BOC is a cell-surface Ig/fibronectin-superfamily co-receptor that, together with the related co-receptors CDO and GAS1, is collectively and obligatorily required for Hedgehog (HH) pathway activation across multiple developmental tissues (PMID:21664577, PMID:21664576). BOC binds all three mammalian Hedgehog ligands (Shh, Ihh, Dhh) directly through a specific fibronectin type III repeat, an interaction resolved at atomic resolution and shown to be essential for activity (PMID:16647304, PMID:20519495); a missense mutation in this FN3 domain abolishes BOC's signaling function in vivo (PMID:34057474). BOC forms distinct receptor complexes with Patched: a Ptch1/BOC complex signals through Gli induction, distinguishing it from the Ptch2/GAS1 complex that engages a parallel Creb/Src branch, so that the spatiotemporal balance of BOC versus GAS1 expression tunes signaling output (PMID:32332736). BOC originally emerged as a partner of CDO in cis complexes that promote myogenic differentiation (PMID:11782431), and across contexts it acts as a context-dependent modulator that can either promote or restrain HH activity—driving cerebellar granule precursor proliferation and, when elevated, medulloblastoma progression via CyclinD1-dependent DNA damage (PMID:25263791), yet restraining HH output during craniofacial development (PMID:33060130). In neurons, BOC functions as a Shh receptor in axon guidance, mediating both attractive turning of commissural axons and repulsion of ipsilateral retinal ganglion cell axons (PMID:17086203, PMID:20053908); mechanistically it serves as a Shh-dependent endocytic platform, binding the adaptor Numb to drive its own internalization into early endosomes, which is in turn required for Ptch1 internalization and downstream signaling (PMID:31054872). BOC additionally promotes neuronal differentiation and neurite outgrowth through ABL kinase binding and JNK activation (PMID:27871935). In ligand-producing cells BOC participates in a Dispatched–BOC/CDON complex that supports cytoneme-mediated Shh transport (PMID:33570491). Human BOC missense variants act as gain- or loss-of-function modifiers of holoprosencephaly by altering SHH pathway activity, consistent with mouse genetics identifying Boc as a silent HPE modifier of Cdo (PMID:21183473, PMID:28677295).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 High

    Established BOC's first molecular partnership and cellular role by showing it acts with CDO to promote differentiation, defining BOC as a co-receptor rather than an autonomous signaling unit.

    Evidence Reciprocal Co-IP of ecto- and intracellular domains plus soluble-ectodomain and dominant-negative CDO assays in myoblasts

    PMID:11782431

    Open questions at the time
    • Ligand not yet identified at this stage
    • Did not connect CDO/BOC complex to Hedgehog signaling
  2. 2006 High

    Identified Shh as the BOC ligand and mapped binding to a specific fibronectin repeat, converting BOC from a differentiation factor of unknown ligand into a defined Hedgehog co-receptor.

    Evidence Domain-mapping binding assays with neural tube ectopic expression and loss-of-function

    PMID:16647304

    Open questions at the time
    • Did not resolve how BOC cooperates with Ptch1 at the receptor level
    • Cell-autonomous versus sequestration roles not fully separated
  3. 2006 High

    Demonstrated a signaling role distinct from canonical morphogen patterning by establishing BOC as a Shh receptor required for commissural axon guidance.

    Evidence RNAi knockdown, in vitro axon turning assay, and mouse Boc knockout with direct binding

    PMID:17086203

    Open questions at the time
    • Intracellular signaling mechanism in axons unresolved
    • Relationship to canonical Gli pathway in guidance unknown
  4. 2010 High

    Extended BOC's axon-guidance role to repulsion and showed cell-type-specific responses, establishing that BOC expression dictates whether an axon is attracted or repelled by Shh.

    Evidence In vitro retraction assay with Boc knockout mice and ectopic expression in contralateral RGCs

    PMID:20053908

    Open questions at the time
    • Molecular basis of attraction-versus-repulsion switch not defined
    • Downstream effectors in RGCs unidentified
  5. 2010 High

    Provided structural and biochemical proof that BOC binds all three mammalian Hedgehog ligands in a conserved manner, generalizing its co-receptor role beyond Shh.

    Evidence X-ray crystal structures of CDO/BOC-Hh complexes with biochemical binding assays

    PMID:20519495

    Open questions at the time
    • Functional consequences of pH-dependent CDO-Hh weakening not tested for BOC
    • Stoichiometry within full Ptch1 receptor complex unresolved
  6. 2010 High

    Defined BOC as a context-dependent HPE modifier and revealed evolutionary divergence from Drosophila, showing mammalian BOC/CDO are not strictly required for all Hh response.

    Evidence Cdo;Boc double knockout mouse genetics with Shh target gene analysis

    PMID:21183473

    Open questions at the time
    • Molecular basis of selective tissue requirement unclear
    • Human relevance not yet established at this stage
  7. 2010 Medium

    Drosophila orthologs Boi/Ihog illuminated upstream and ligand-handling roles—Smo accumulation, ligand sequestration, and cytoneme-associated distribution—providing mechanistic hypotheses for the vertebrate co-receptors.

    Evidence Clonal double-mutant analysis, FSC proliferation assays, and Hh localization/cytoneme imaging in fly tissues

    PMID:21044292 PMID:21098113 PMID:23276604

    Open questions at the time
    • Direct extrapolation to mammalian BOC not demonstrated
    • Cytoneme role in vertebrates not yet shown at this stage
  8. 2011 High

    Established the obligatory collective requirement of BOC, CDON, and GAS1 for HH activation and showed each forms a distinct Ptch1 complex, defining the co-receptor tier as a non-redundant gate on pathway activity.

    Evidence Co-IP of Boc/Gas1 with Ptch1, triple knockout epistasis in CGNPs and neural tube, and a Ptch1-binding mutant Hh ligand

    PMID:21664576 PMID:21664577

    Open questions at the time
    • How distinct complexes converge on Smo not resolved
    • Quantitative contribution of each co-receptor per tissue unclear
  9. 2014 Medium

    Linked BOC-driven Shh signaling to disease by showing it promotes granule precursor proliferation and accelerates medulloblastoma via CyclinD1-dependent DNA damage and Ptch1 LOH.

    Evidence Boc knockout and overexpression in GCPs with DNA damage, CyclinD1, and LOH analyses

    PMID:25263791

    Open questions at the time
    • Causal chain from BOC to DNA damage not fully mechanistically dissected
    • Single lab; human tumor validation limited
  10. 2015 Medium

    Showed CDON and BOC promote HH signaling by distinct molecular mechanisms despite redundancy, revealing non-equivalent membrane-attachment and ectodomain requirements.

    Evidence In vivo domain deletion/mutation structure-function in chick neural tube

    PMID:25848697

    Open questions at the time
    • Biochemical basis of mechanistic divergence unresolved
    • Single lab, gain-of-function context
  11. 2015 Medium

    Revealed a systemic metabolic role, with BOC promoting HH signaling to restrain adipogenesis and prevent age-related adiposity.

    Evidence Boc knockout mouse metabolic phenotyping and Boc-/- MEF adipogenesis assays with HH target readouts

    PMID:25576054

    Open questions at the time
    • Tissue source of relevant HH signal not identified
    • Cell-autonomous versus systemic contribution unclear
  12. 2016 Medium

    Identified a non-canonical intracellular effector arm, with BOC binding ABL kinase and activating JNK to drive neuronal differentiation, separating its signaling from the Gli axis.

    Evidence Co-IP, ABL-binding-defective mutants, JNK assays, and rescue in Boc-/- progenitors and P19 cells

    PMID:27871935

    Open questions at the time
    • Direct phosphorylation sites on BOC not mapped
    • Integration with canonical Gli signaling unresolved
  13. 2017 Medium

    Translated the modifier concept to humans by showing patient BOC variants act as gain- or loss-of-function alleles modulating SHH activity and HPE penetrance.

    Evidence Cell-based SHH signaling assays with patient-derived missense variants

    PMID:28677295

    Open questions at the time
    • No in vivo validation of variant effects
    • Genotype-phenotype correlation in larger cohorts lacking
  14. 2019 High

    Defined the mechanism of BOC in axon guidance as a Shh-dependent endocytic platform, showing Numb-driven BOC internalization is required upstream of Ptch1 internalization and turning.

    Evidence Numb-Boc Co-IP, endocytosis and growth-cone turning assays, and in vivo commissural axon guidance

    PMID:31054872

    Open questions at the time
    • Signaling events downstream of endosomal Ptch1 in guidance unclear
    • Whether this endocytic mechanism operates in canonical morphogen contexts unknown
  15. 2019 Medium

    Expanded BOC's developmental roles to oligodendrocyte/myelin biology, showing it is required for developmental myelination and myelin repair.

    Evidence Boc knockout mice with oligodendrocyte lineage markers, demyelination repair model, and microglial morphology analysis

    PMID:31048318

    Open questions at the time
    • Whether BOC acts cell-autonomously in oligodendroglia versus via niche signaling unresolved
    • Mechanistic link to HH pathway in repair not dissected
  16. 2020 Medium

    Resolved how co-receptor identity diversifies HH output, showing Ptch1/BOC signals through Gli whereas Ptch2/GAS1 adds a Creb/Src branch, and that BOC can also restrain HH activity in craniofacial tissues.

    Evidence Co-IP of Ptch1/Boc and Ptch2/Gas1 complexes, knockout genetics in PGC migration and craniofacial development, and phosphoprotein analysis

    PMID:32332736 PMID:33060130

    Open questions at the time
    • Molecular determinants selecting Ptch1 versus Ptch2 partnering unclear
    • Switch between promoting and restraining HH not mechanistically explained
  17. 2021 Medium

    Established BOC's role in the ligand-producing cell, as part of a Dispatched-BOC/CDON complex enabling Myo10-dependent cytoneme transport and rapid SHH deposition.

    Evidence DISP-BOC Co-IP, live-cell cytoneme imaging, Myo10 knockout mice, and rapid signaling assays

    PMID:33570491

    Open questions at the time
    • How the same BOC molecule functions in both sending and receiving cells unresolved
    • Stoichiometry and assembly of the DISP-BOC/CDON complex undefined
  18. 2021 Medium

    Confirmed in a vertebrate that Shh binding via the FN3 domain is necessary for BOC function, tying a discrete structural element to oligodendrocyte fate specification.

    Evidence Forward-genetic boc missense allele in the FN3 domain with Olig2 lineage analysis in zebrafish

    PMID:34057474

    Open questions at the time
    • Whether the same domain mediates non-canonical endocytic/ABL functions not tested
    • Downstream effectors in pMN maintenance unidentified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BOC's promoting versus restraining activity, its choice of Ptch1 versus Ptch2 partners, and its canonical (Gli) versus non-canonical (ABL/JNK, Numb-endocytic) outputs are selected within a single cell remains unresolved.
  • No unified model linking complex composition to signaling outcome
  • Structural basis for partner selection among Ptch1/Ptch2/CDON/DISP unknown
  • Mechanism switching BOC between attractive and repulsive guidance undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2
Partners
ABLCDODISPGAS1NUMBPTCH1PTCH2SHH
Complex memberships
BOC/CDO cis-complexDispatched-BOC/CDON co-receptor complexPtch1/BOC receptor complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 BOC associates with CDO to form cis complexes via both their ectodomains and intracellular domains, and positively regulates myogenic differentiation. A soluble BOC ectodomain fusion protein promotes differentiation independently of the intracellular region, while a dominant-negative CDO inhibits BOC's pro-myogenic effects, indicating BOC acts through CDO. Co-immunoprecipitation, soluble ectodomain fusion protein assays, dominant-negative CDO inhibition, myoblast differentiation assays The EMBO journal High 11782431
2006 BOC and CDO bind Sonic Hedgehog through a high-affinity interaction with a specific fibronectin repeat that is essential for activity. Ectopic expression of BOC promotes Shh-dependent, cell-autonomous ventral cell fates and non-cell-autonomous ventral expansion consistent with Shh sequestration. Binding assays (fibronectin repeat domain mapping), ectopic expression in neural tube, genetic loss-of-function Developmental cell High 16647304
2006 BOC binds specifically to Shh and functions as a receptor for Shh in commissural axon guidance. RNAi-mediated knockdown of Boc impairs the ability of commissural axons to turn toward an ectopic Shh source in vitro, and targeted disruption of Boc causes commissural axon misguidance in vivo. RNAi knockdown, in vitro axon turning assay, mouse genetic knockout, binding assays Nature High 17086203
2010 BOC is enriched in ipsilateral retinal ganglion cells (RGCs) and mediates Shh-dependent repulsion of ipsilateral RGC axons at the optic chiasm. Only Boc-positive RGC axons retract in response to Shh in vitro; Boc mutant RGCs lose this response. In vivo, Boc is required for normal segregation of ipsilateral axons, and ectopic Boc expression in contralateral RGCs prevents their crossing. In vitro axon retraction assay, Boc knockout mice, gain-of-function ectopic expression in contralateral RGCs The Journal of neuroscience High 20053908
2011 BOC and GAS1 each form distinct receptor complexes with Ptch1. In cerebellar granule neuron progenitors (CGNPs), Boc, Cdon, and Gas1 have an absolute collective requirement for Hh-dependent proliferation; CGNPs lacking all three molecules show complete loss of Hh-dependent proliferation. A mutated Hh ligand that binds Ptch1 but not Boc/Cdon/Gas1 cannot activate Hh signaling. Co-immunoprecipitation (Boc/Gas1 with Ptch1), triple genetic knockout in CGNPs, mutant Hh ligand assays, cell proliferation assays Developmental cell High 21664576 21664577
2011 GAS1, CDO, and BOC play overlapping and essential roles during Hedgehog-mediated ventral neural patterning, with an obligatory collective requirement for HH pathway activity in multiple tissues including early cell fate specification of neural progenitors and later motor neuron progenitor maintenance. Genetic loss-of-function (single, double, triple knockout mice), HH target gene expression analysis Developmental cell High 21664576
2010 Boc modifies the holoprosencephaly (HPE) spectrum caused by Cdo loss. Cdo;Boc double mutants display lobar HPE with defects in Shh target gene expression in the forebrain, identifying Boc as a silent HPE modifier gene. Cdo and Boc have selective roles: double mutants do not phenocopy Shh-null mice, indicating evolutionary divergence from Drosophila where Ihog/Boi loss abolishes all Hh response. Double knockout mouse genetics, Shh target gene expression analysis Disease models & mechanisms High 21183473
2010 All three mammalian Hedgehog proteins (Sonic, Indian, Desert Hh) bind CDO and BOC in the same manner, as demonstrated by biochemical binding assays and X-ray crystal structures of Hh proteins complexed with active domains of CDO and BOC. CDO-Hh interactions are weakened at low pH. X-ray crystallography, biochemical binding assays The Journal of biological chemistry High 20519495
2010 Drosophila Boi is expressed in apical cells of the ovary and suppresses follicle stem cell proliferation by binding to and sequestering Hedgehog on the apical cell surface, thereby inhibiting Hh diffusion to FSCs. Genetic loss-of-function, cell-specific expression analysis, FSC proliferation assays The Journal of cell biology Medium 21098113
2010 Drosophila Ihog and Boi are required for accumulation of Smoothened (Smo) in Hh-responsive cells, placing Ihog/Boi upstream of Smo in the Hh pathway. Cells mutant for both ihog and boi fail to activate Hh pathway responses and aberrantly sort out of the anterior wing compartment. Genetic loss-of-function (double mutant clonal analysis in eye and wing discs), Smo localization assay Neural development Medium 21044292
2012 Drosophila Boi (and Ihog) are required to prevent apical dispersion of Hedgehog and aid Hh recycling for basolateral release and long-range gradient formation. Boi and Ihog are components of cytoneme-associated protein complexes with Dally and Shifted/DmWif that regulate Hh distribution. Genetic loss-of-function in wing disc epithelium, Hh localization imaging, cytoneme analysis Developmental biology Medium 23276604
2013 Shh/Boc signaling is required for sustained generation of ipsilateral projecting retinal ganglion cells. In Boc-/- retinas, the number of Zic2-positive iRGCs is reduced and more Islet2/Shh-positive cRGCs are observed, indicating Boc expression is required to sustain Zic2 expression, likely by regulating levels of Shh signaling from neighboring cRGCs. Boc knockout mice, cell fate marker analysis, in vivo Shh/Boc gain-of-function injection experiments The Journal of neuroscience Medium 23678105
2014 BOC associates with Ptch1 and promotes Shh signaling in cerebellar granule cell precursors to drive proliferation. Mechanistically, Boc through elevated Shh signaling promotes high levels of DNA damage mediated by CyclinD1, which increases the incidence of Ptch1 loss of heterozygosity and medulloblastoma progression. Boc knockout mice, Boc overexpression in GCPs, DNA damage assays, CyclinD1 pathway analysis, LOH analysis Developmental cell Medium 25263791
2015 CDON and BOC use distinct molecular mechanisms to promote Hh signaling despite functional redundancy. Specifically, they have distinct membrane attachment requirements and distinct extracellular motifs required for HH-promoting activity. In vivo gain-of-function in developing chicken spinal cord, domain deletion/mutation analysis Developmental biology Medium 25848697
2016 BOC interacts with ABL non-receptor tyrosine kinase through its putative SH2-binding domain, is phosphorylated in an ABL activity-dependent manner, and activates JNK to promote neuronal differentiation and neurite outgrowth. ABL-binding-defective BOC mutants fail to activate JNK or rescue differentiation. Shh treatment enhances JNK activation in a BOC-dependent manner. Co-immunoprecipitation, ABL-binding domain mutants, JNK activation assays, Boc-/- neural progenitor cells, P19 cell differentiation assays Cellular signalling Medium 27871935
2019 Shh induces BOC internalization into early endosomes via the endocytic adaptor Numb, which binds to BOC. Numb is required for Boc internalization, Shh-mediated growth-cone turning in vitro, and commissural axon guidance in vivo. Shh binding to Boc is required for Ptch1 internalization and growth-cone turning; Shh binding to Ptch1 alone is insufficient. BOC thus acts as a Shh-dependent endocytic platform gating Ptch1 internalization and Shh signaling in axon guidance. Co-immunoprecipitation (Numb-Boc), endocytosis assays, growth-cone turning assay, Numb knockdown, Boc and Ptch1 internalization imaging Neuron High 31054872
2019 BOC is required for developmental myelination and myelin repair. Boc mutant mice display transient decreases in oligodendroglial cell density, delayed myelination, lower myelin basic protein production in adults, and impaired OPC differentiation during repair. Mutant microglia/macrophages also show altered morphology transition in vivo. Boc knockout mice, oligodendrocyte lineage marker analysis, myelin repair assay (demyelination model), microglial morphology analysis Development (Cambridge, England) Medium 31048318
2020 Ptch1/Boc and Ptch2/Gas1 form specific hetero-complexes that mediate Smo de-repression with different kinetics. Ptch1-mediated signaling through Boc proceeds through Gli induction, while Ptch2-mediated signaling induces phosphorylation of Creb and Src in parallel to Gli induction, identifying a Ptch2-specific signal pathway. Spatiotemporal expression of Boc versus Gas1 determines distinct HH signaling outcomes. Co-immunoprecipitation (Ptch1/Boc and Ptch2/Gas1 complexes), knockout mouse genetics, primordial germ cell migration assay, phosphoprotein analysis Nature communications Medium 32332736
2020 BOC acts as a multi-functional regulator of HH signaling during craniofacial development, alternately promoting or restraining HH pathway activity in a tissue-specific fashion. Boc deletion results in facial widening correlating with increased HH target gene expression, and partially ameliorates craniofacial defects in Gas1 null mice. Single and compound (Gas1;Boc) knockout mice, HH target gene expression analysis, craniofacial morphometric analysis Development (Cambridge, England) Medium 33060130
2021 BOC functions in ligand-producing cells as part of a Dispatched (DISP)-BOC/CDON co-receptor complex that promotes cytoneme occurrence and facilitates vesicular SHH transport via Myosin 10 for signal activation. Cytoneme-mediated SHH deposition onto receiving cells induces rapid (within seconds) receptor-dependent signaling. Co-immunoprecipitation (DISP-BOC complex), live-cell imaging of cytonemes, Myo10 knockout mice, SHH vesicular transport assay, rapid signaling assay eLife Medium 33570491
2021 Zebrafish boc is required to maintain pMN progenitors and thereby specify oligodendrocyte fate. A missense mutation in the Fibronectin type III (FN3) domain of Boc that binds Shh abolishes this function, demonstrating that Shh binding through the FN3 domain is necessary for BOC's role in oligodendrocyte specification. Forward genetic screen, boc mutant allele (bocco25) characterization, Olig2 lineage analysis, in situ hybridization Genetics Medium 34057474
2017 BOC is a modifier gene for holoprosencephaly in humans. Missense BOC variants identified in HPE patients have either loss- or gain-of-function properties in cell-based SHH signaling assays, demonstrating that BOC variant alleles modulate SHH pathway activity and HPE penetrance. Cell-based SHH signaling assays with patient-derived BOC missense variants, human genetic analysis Human mutation Medium 28677295
2015 Mice lacking BOC display age-related overweight and excess white adipose tissue. Boc-/- mouse embryo fibroblasts show enhanced adipogenesis in vitro with reduced HH pathway target gene expression, indicating BOC promotes HH signaling to inhibit adipogenesis. Boc knockout mice (body weight, adipose tissue analysis, high-fat diet challenge), Boc-/- MEF adipogenesis assay, HH target gene expression Diabetes Medium 25576054
2005 Zebrafish BOC functions as an axon-guidance molecule directing dorsoventrally projecting axon tracts in the embryonic brain. Morpholino-based loss-of-function of boc causes selective defects in ventrally projecting axons from the presumptive telencephalon. Antisense morpholino knockdown in zebrafish, axon tract analysis The Journal of comparative neurology Medium 15776441
2019 A novel BOC-PLAG1 fusion gene was identified in lipoblastoma, in which the constitutively active promoter of BOC drives overexpression of PLAG1, leading to PLAG1 expression 35.7-fold higher than in normal adipocytes. 5' RACE, sequence analysis, RT-PCR quantification of fusion transcript and PLAG1 expression Biochemical and biophysical research communications Low 30857637

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice. Developmental cell 298 16647304
2006 Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature 242 17086203
2011 Overlapping roles and collective requirement for the coreceptors GAS1, CDO, and BOC in SHH pathway function. Developmental cell 227 21664576
2011 Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation. Developmental cell 198 21664577
2002 BOC, an Ig superfamily member, associates with CDO to positively regulate myogenic differentiation. The EMBO journal 126 11782431
2013 Enantioconvergent cross-couplings of racemic alkylmetal reagents with unactivated secondary alkyl electrophiles: catalytic asymmetric Negishi α-alkylations of N-Boc-pyrrolidine. Journal of the American Chemical Society 120 23869442
2007 Cyclosporin H, Boc-MLF and Boc-FLFLF are antagonists that preferentially inhibit activity triggered through the formyl peptide receptor. Inflammation 117 17687636
2007 Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies. Journal of the American Chemical Society 111 18085777
1987 Autoradiography of CCK receptors in the rat brain using [(3)H]Boc[Nle(28)(31)]CCK(27)-(33) and [(125)I]bolton-hunter CCK(8). Functional significance of subregional distributions. Neurochemistry international 72 20501122
2010 Segregation of ipsilateral retinal ganglion cell axons at the optic chiasm requires the Shh receptor Boc. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 20053908
2016 Boc3Arg-Linked Ligands Induce Degradation by Localizing Target Proteins to the 20S Proteasome. ACS chemical biology 68 27704767
2012 Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif. Developmental biology 65 23276604
2010 Drosophila Boi limits Hedgehog levels to suppress follicle stem cell proliferation. The Journal of cell biology 63 21098113
2010 Formation of arginine modifications in a model system of Nα-tert-butoxycarbonyl (Boc)-arginine with methylglyoxal. Journal of agricultural and food chemistry 62 21126021
2006 Mechanistic studies of peroxynitrite-mediated tyrosine nitration in membranes using the hydrophobic probe N-t-BOC-L-tyrosine tert-butyl ester. Biochemistry 62 16734418
1994 Effects of BOC-CCK-4 and L 365.260 on cortical 5-HT release in guinea-pigs on exposure to the elevated plus maze. Neuropharmacology 61 7527129
1989 Alpha-helix and mixed 3(10)/alpha-helix in cocrystallized conformers of Boc-Aib-Val-Aib-Aib-Val-Val-Val-Aib-Val-Aib-OMe. Proceedings of the National Academy of Sciences of the United States of America 61 2915976
2004 Synthesis of all nineteen appropriately protected chiral alpha-hydroxy acid equivalents of the alpha-amino acids for Boc solid-phase depsi-peptide synthesis. Organic letters 60 14961607
2010 Boc modifies the holoprosencephaly spectrum of Cdo mutant mice. Disease models & mechanisms 57 21183473
2010 All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner. The Journal of biological chemistry 54 20519495
1986 Parallel packing of alpha-helices in crystals of the zervamicin IIA analog Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe.2H2O. Proceedings of the National Academy of Sciences of the United States of America 53 2432594
2004 Aza-amino acid scan for rapid identification of secondary structure based on the application of N-Boc-aza(1)-dipeptides in peptide synthesis. Journal of the American Chemical Society 51 15161304
2021 Cytoneme delivery of Sonic Hedgehog from ligand-producing cells requires Myosin 10 and a Dispatched-BOC/CDON co-receptor complex. eLife 49 33570491
2014 The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors. Developmental cell 48 25263791
1988 Aqueous channels within apolar peptide aggregates: solvated helix of the alpha-aminoisobutyric acid (Aib)-containing peptide Boc-(Aib-Ala-Leu)3-Aib-OMe.2H2O.CH3OH in crystals. Proceedings of the National Academy of Sciences of the United States of America 47 2448772
2001 Kinetics and mechanism of the (-)-sparteine-mediated deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine. Journal of the American Chemical Society 44 11457318
2010 Ihog and Boi are essential for Hedgehog signaling in Drosophila. Neural development 42 21044292
1999 BOC-CCK-4, CCK(B)receptor agonist, antagonizes anxiolytic-like action of morphine in elevated plus-maze. Neuropeptides 40 10657473
2002 Expression of the boc gene during murine embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 39 11891987
2013 Shh/Boc signaling is required for sustained generation of ipsilateral projecting ganglion cells in the mouse retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 23678105
2020 The hedgehog co-receptor BOC differentially regulates SHH signaling during craniofacial development. Development (Cambridge, England) 35 33060130
2012 Efficient synthesis of glycopeptide-α-thioesters with a high-mannose type oligosaccharide by means of tert-Boc-solid phase peptide synthesis. Carbohydrate research 34 23149340
1993 Design of peptides: crystal and molecular structure of a 3(10)-helical peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val-OCH3. Biopolymers 34 8467067
1991 Boc-CCK-4 derivatives containing side-chain ureas as potent and selective CCK-a receptor agonists. Journal of medicinal chemistry 34 1716682
1993 Peptide design 3(10)-helical conformation of a linear pentapeptide containing two dehydrophenylalanines, Boc-Gly-delta ZPhe-Leu-delta ZPhe-Ala-NHCH3. Biopolymers 31 8485295
1985 [3H] Boc [Nle28, 31]CCK27-33, a new highly labelled ligand for CCK receptors: binding on brain and on pancreas. Life sciences 31 3001463
2019 Boc Acts via Numb as a Shh-Dependent Endocytic Platform for Ptch1 Internalization and Shh-Mediated Axon Guidance. Neuron 30 31054872
2006 boc-Aspartyl(OMe)-fluoromethylketone attenuates mitochondrial release of cytochrome c and delays brain tissue loss after traumatic brain injury in rats. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 30 16736044
2007 Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine. Journal of medicinal chemistry 27 17990847
2019 Identification of a novel BOC-PLAG1 fusion gene in a case of lipoblastoma. Biochemical and biophysical research communications 26 30857637
2014 Boc modifies the spectrum of holoprosencephaly in the absence of Gas1 function. Biology open 26 25063195
2012 Cdon and Boc: Two transmembrane proteins implicated in cell-cell communication. The international journal of biochemistry & cell biology 26 22326621
1999 Fission yeast Pob1p, which is homologous to budding yeast Boi proteins and exhibits subcellular localization close to actin patches, is essential for cell elongation and separation. Molecular biology of the cell 26 10436025
1995 Synthesis, and crystal and molecular structure of the 3(10)-helical alpha,beta-dehydro pentapeptide Boc-Leu-Phe-Ala-delta Phe-Leu-OMe. Biopolymers 26 7696560
1992 Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP. Immunology 26 1282494
2011 Discovery of novel (4-piperidinyl)-piperazines as potent and orally active acetyl-CoA carboxylase 1/2 non-selective inhibitors: F-Boc and triF-Boc groups are acid-stable bioisosteres for the Boc group. Bioorganic & medicinal chemistry 25 21324704
2015 A highly efficient Mukaiyama-Mannich reaction of N-Boc isatin ketimines and other active cyclic ketimines using difluoroenol silyl ethers catalyzed by Ph3PAuOTf. Organic & biomolecular chemistry 24 26443467
2009 7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine: a novel compound capable of inducing cell death in epithelial ovarian cancer stem cells. Cancer biology & therapy 24 19738422
2005 BOC, brother of CDO, is a dorsoventral axon-guidance molecule in the embryonic vertebrate brain. The Journal of comparative neurology 24 15776441
1988 Monoclinic polymorph of Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe(anhydrous). Parallel packing of 3(10)-/alpha-helices and a transition of helix type. International journal of peptide and protein research 24 3079530
2019 A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On-Resin Ozonolysis to Install the Kynurenine Residue. Chemistry (Weinheim an der Bergstrasse, Germany) 23 31429133
2016 A Sonic hedgehog coreceptor, BOC regulates neuronal differentiation and neurite outgrowth via interaction with ABL and JNK activation. Cellular signalling 23 27871935
2020 Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration. Nature communications 22 32332736
1992 Crystal structure and conformation of a highly constrained linear tetrapeptide Boc-Leu-dehydro Phe-Ala-Leu-OCH3. International journal of peptide and protein research 22 1399261
1989 Automated synthesis of a C-terminal photoprobe using combined Fmoc and t-Boc synthesis strategies on a single automated peptide synthesizer. Peptide research 22 2520777
2017 BOC is a modifier gene in holoprosencephaly. Human mutation 21 28677295
2006 Boc-lysinated-betulonic acid: a potent, anti-prostate cancer agent. Bioorganic & medicinal chemistry 20 16777417
1992 Disulfide bond as peptide-resin linkage in Boc-Bzl SPPS, for potential biochemical applications. Peptide research 20 1330111
2016 HF-Free Boc Synthesis of Peptide Thioesters for Ligation and Cyclization. Angewandte Chemie (International ed. in English) 19 27654901
2015 Distinct structural requirements for CDON and BOC in the promotion of Hedgehog signaling. Developmental biology 19 25848697
2020 Design, characterization, and evaluation of antibacterial gels, Boc-D-Phe-γ4-L-Phe-PEA/chitosan and Boc-L-Phe-γ4-L-Phe-PEA/chitosan, for biomaterial-related infections. Materials science & engineering. C, Materials for biological applications 18 32204079
2019 The Shh receptor Boc is important for myelin formation and repair. Development (Cambridge, England) 18 31048318
2001 PNA synthesis using a novel Boc/acyl protecting group strategy. Journal of peptide science : an official publication of the European Peptide Society 18 11548056
1989 Regularly alternating L,D-peptides. I. The double-stranded left-handed antiparallel beta-helix in the structure of Boc-(L-Val-D-Val)4-OMe. Biopolymers 18 2720104
2011 Synthesis and oligomerization of Fmoc/Boc-protected PNA monomers of 2,6-diaminopurine, 2-aminopurine and thymine. Organic & biomolecular chemistry 17 22159214
2006 Pharmacokinetics and metabolism in mice of IDN 5390 (13-(N-Boc-3-i-butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III), a new oral c-seco-taxane derivative with antiangiogenic property effective on paclitaxel-resistant tumors. Drug metabolism and disposition: the biological fate of chemicals 17 16963486
2005 Semisynthesis of human ghrelin: condensation of a Boc-protected recombinant peptide with a synthetic O-acylated fragment. Biopolymers 17 16049959
1988 Aggregation studies in crystals of apolar helical peptides: Boc-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe. International journal of peptide and protein research 17 3246478
2021 Association of sonic hedgehog signaling pathway genes IHH, BOC, RAB23a and MIR195-5p, MIR509-3-5p, MIR6738-3p with gastric cancer stage. Scientific reports 16 33811245
2021 Synthesis of N-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation of N-Boc-α-aminosulfones. The Journal of organic chemistry 16 34550701
2020 Palladium-mediated Suzuki-Miyaura Cross-Coupling Reaction of Potassium Boc-protected aminomethyltrifluoroborate with DNA-Conjugated aryl bromides for DNA-Encoded chemical library synthesis. Biochemical and biophysical research communications 16 32376009
2022 5-O-(N-Boc-l-Alanine)-Renieramycin T Induces Cancer Stem Cell Apoptosis via Targeting Akt Signaling. Marine drugs 15 35447911
2021 Glypicans define unique roles for the Hedgehog co-receptors boi and ihog in cytoneme-mediated gradient formation. eLife 15 34355694
2020 Drug-interactive mPEG-b-PLA-Phe(Boc) micelles enhance the tolerance and anti-tumor efficacy of docetaxel. Drug delivery 15 32003299
2015 Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor boc. Diabetes 15 25576054
1990 Correlation between phospholipid breakdown, intracellular calcium mobilization and enzyme secretion in rat pancreatic acini treated with Boc-[Nle28, Nle31]-CCK-7 and JMV180, two cholecystokinin analogues. Cellular signalling 15 1701321
2020 Mild deprotection of the N-tert-butyloxycarbonyl (N-Boc) group using oxalyl chloride. RSC advances 14 33456769
2006 Mixed-sequence pyrrolidine-amide oligonucleotide mimics: Boc(Z) synthesis and DNA/RNA binding properties. Organic & biomolecular chemistry 14 17205168
1995 CCK-A receptor selective antagonists derived from the CCK-A receptor selective tetrapeptide agonist Boc-Trp-Lys(Tac)-Asp-MePhe-NH2 (A-71623). Journal of medicinal chemistry 14 7837233
2022 Chemical Synthesis of Proteins with Base-Labile Posttranslational Modifications Enabled by a Boc-SPPS Based General Strategy Towards Peptide C-Terminal Salicylaldehyde Esters. Angewandte Chemie (International ed. in English) 13 36344442
2015 Rapid Synthesis of Boc-2',6'-dimethyl-l-tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics. ACS medicinal chemistry letters 13 26713104
2012 The Drosophila WIF1 homolog Shifted maintains glypican-independent Hedgehog signaling and interacts with the Hedgehog co-receptors Ihog and Boi. Development (Cambridge, England) 13 23154411
2011 Anti-thyroid cancer properties of a novel isoflavone derivative, 7-(O)-carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine in vitro and in vivo. The Journal of steroid biochemistry and molecular biology 13 21600982
2005 Dynamic kinetic resolution of N-Boc-2-lithiopyrrolidine. Chemical communications (Cambridge, England) 13 15959592
1992 Helix packing of leucine-rich peptides: a parallel leucine ladder in the structure of Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe. Proteins 13 1579566
2021 Differential Expression of BOC, SPOCK2, and GJD3 Is Associated with Brain Metastasis of ER-Negative Breast Cancers. Cancers 12 34203581
2020 D-Peptide analogues of Boc-Phe-Leu-Phe-Leu-Phe-COOH induce neovascularization via endothelial N-formyl peptide receptor 3. Angiogenesis 12 32152757
2007 Incorporation of the hydrophobic probe N-t-BOC-L-tyrosine tert-butyl ester to red blood cell membranes to study peroxynitrite-dependent reactions. Chemical research in toxicology 12 17941688
2004 Highly enantioselective reaction of lithiated N-Boc-thiazolidine: a new chiral formyl anion equivalent. Organic & biomolecular chemistry 12 15280949
2003 Overexpression of the immunoglobulin superfamily members CDO and BOC enhances differentiation of the human rhabdomyosarcoma cell line RD. Molecular carcinogenesis 12 12720294
1992 Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N epsilon)-amide residues. Journal of medicinal chemistry 12 1375964
2021 BOC-PLAG1, a new fusion gene of pleomorphic adenoma: Identified in a fine-needle aspirate by RNA next-generation sequencing. Diagnostic cytopathology 11 33710800
2012 Sonic hedgehog, BOC, and synaptic development: new players for an old game. Neuron 11 22445332
2012 Growth inhibition of human thyroid carcinoma and goiter cells in vitro by the isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to N-t-boc-hexylenediamine. Thyroid : official journal of the American Thyroid Association 11 22799572
1996 Helix termination and chain reversal: crystal and molecular structure of the alpha, beta-dehydrooctapeptide Boc-Val-DeltaPhe-Phe-Ala-Leu-Ala-DeltaPhe-Leu-OH. Journal of biomolecular structure & dynamics 11 8906884
2018 Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine. Molecules (Basel, Switzerland) 10 30487432
2008 Tyrosine nitration, dimerization, and hydroxylation by peroxynitrite in membranes as studied by the hydrophobic probe N-t-BOC-l-tyrosine tert-butyl ester. Methods in enzymology 10 18554537
2003 Effects of intrathecal administration of a cell permeant caspase inhibitor, boc-D-fluoromethylketone (BDFMK), on behavioral deficits following spinal cord ischemia: a dose-response analysis. Brain research 10 12493605
2003 Clinical and immunomodulatory effects of fun-boi, an herbal medicine, on collagen-induced arthritis in vivo. Clinical and experimental rheumatology 10 12673890
2021 Zebrafish spinal cord oligodendrocyte formation requires boc function. Genetics 9 34057474

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