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Showing RBP3 — IRBP is a alias.

RBP3

Retinol-binding protein 3 · UniProt P10745

Length
1247 aa
Mass
135.4 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 30 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

RBP3 (IRBP) is a large secreted glycoprotein synthesized exclusively by rod and cone photoreceptors and pinealocytes that serves as the principal extracellular retinoid carrier of the interphotoreceptor matrix, supporting the visual cycle and photoreceptor maintenance (PMID:6686234, PMID:3770208, PMID:1987260). It is co-translationally directed through the secretory pathway and rapidly secreted by the neural retina but not the RPE-choroid (PMID:6538412, PMID:3900095). The mature protein is built from four homologous ~300-amino-acid modules, each of which independently binds retinoids (retinol, 11-cis-retinal, retinoic acid) and fatty acids and protects retinol from degradation, with crystal structures of individual modules revealing distinct hydrophobic ligand-binding cavities (PMID:9873071, PMID:9479008, PMID:17683573, PMID:19608538, PMID:26344741). IRBP binds retinol at functionally distinct sites whose occupancy is allosterically and competitively modulated by long-chain fatty acids such as docosahexaenoic and oleic acid, the latter directly displacing retinol from the binding pocket (PMID:9374503, PMID:19608538, PMID:26344741). Functionally, IRBP drives directional retinoid flux: it removes 11-cis-retinal and all-trans-retinol from RPE membranes and bleached retinas and transfers retinol unidirectionally to higher-affinity acceptors, supporting rhodopsin regeneration (PMID:7835405, PMID:10655150, PMID:15935345). Genetic ablation in mice causes photoreceptor degeneration, outer-segment disruption, and reduced ERG responses despite a grossly intact rhodopsin cycle, and additionally produces exaggerated axial eye growth and myopia driven by increased cell death, establishing a role beyond the visual cycle in ocular development and photoreceptor survival (PMID:10750831, PMID:21642628). Transcription is governed by photoreceptor-specific activators OTX2 and a Ret-1/CRX element acting on a compact proximal promoter, antagonized by the repressors MOK2 and KLF15 through overlapping or G-rich elements and dependent on site-specific promoter hypomethylation (PMID:9479006, PMID:10372988, PMID:11278819, PMID:15963234, PMID:11134609). The autosomal recessive retinitis pigmentosa mutation p.Asp1080Asn disrupts a conserved salt bridge in a retinol-binding domain, causing IRBP misfolding, disulfide-linked aggregation, ER retention with chaperone binding, and ER-stress-induced apoptotic signaling (PMID:19074801, PMID:23486466).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1983 High

    Established that the interphotoreceptor space contains a dedicated extracellular retinol carrier, defining where retinoid handling occurs between retina and RPE.

    Evidence Biochemical fractionation, sedimentation, HPLC, and retinol-binding assays on monkey IPS wash

    PMID:6686234

    Open questions at the time
    • Ligand-binding architecture and number of sites unresolved
    • Cellular source not yet localized
  2. 1984 High

    Determined that IRBP is made by the neural retina and routed through the secretory pathway, distinguishing the retina from the RPE as the synthetic source.

    Evidence Monkey retina organ culture metabolic labeling with monensin secretion block

    PMID:6538412

    Open questions at the time
    • Specific cell type within retina not resolved
  3. 1986 High

    Localized IRBP synthesis to rod and cone photoreceptors and pinealocytes, anchoring its expression to the cells that bleach visual pigment.

    Evidence In situ hybridization in bovine, monkey, human, and ground squirrel retina; cross-species immunoblotting

    PMID:1987260 PMID:3093630 PMID:3770208

    Open questions at the time
    • Mechanism restricting expression to these cell types not yet defined
  4. 1993 Medium

    Framed IRBP as a bidirectional shuttle in the visual cycle that also protects its ligand from chemical degradation, defining its physiological role.

    Evidence Review synthesizing detached-retina and in vitro retinoid transfer/protection experiments

    PMID:8318167

    Open questions at the time
    • Directionality of transfer not yet quantified
    • Review rather than primary data
  5. 1994 High

    Showed retinol transfer from IRBP to CRBP is fast and unidirectional, providing a thermodynamic basis for net retinol flow toward the RPE.

    Evidence Absorbance kinetics and size-exclusion HPLC of IRBP/CRBP retinol exchange

    PMID:7835405

    Open questions at the time
    • In-membrane and in-vivo flux not directly measured
  6. 1997 High

    Demonstrated that each of the four modules independently binds retinoids and fatty acids at multiple sites, with fatty acid acting as a site-selective allosteric regulator, resolving the protein's modular ligand logic.

    Evidence Reconstituted individual E. coli-expressed modules plus full-length protein; fluorescence, CD, absorption, and thermodynamic binding assays

    PMID:9374503 PMID:9479008 PMID:9873071

    Open questions at the time
    • Structural difference between sites not yet visualized
    • Physiological role of inter-module differences unclear
  7. 2000 High

    Established that IRBP uniquely extracts 11-cis-retinal from RPE membranes in a receptor-independent manner, and that gene knockout causes photoreceptor degeneration despite a near-normal rhodopsin cycle, separating its survival role from an essential isomerization role.

    Evidence Reconstituted RPE membrane retinoid extraction with purified proteins; IRBP knockout mice with histology, EM, ERG, and rhodopsin density

    PMID:10655150 PMID:10750831

    Open questions at the time
    • Mechanism linking IRBP loss to photoreceptor death not defined
    • Compensating carriers in knockout not identified
  8. 2005 High

    Confirmed in intact bleached retina that IRBP actively drives retinol release in a concentration-dependent, glycosylation-independent manner, validating its physiological transfer function.

    Evidence Isolated toad retina bleaching with HPLC retinoid analysis and BSA/lectin-variant controls

    PMID:15935345

    Open questions at the time
    • Quantitative contribution in vivo not established
  9. 2007 High

    Provided the first crystal structure of an IRBP module and quantified per-module binding affinities and ligand selectivity, grounding the modular model in structure.

    Evidence X-ray crystallography of Xenopus module 2, fluorescence binding, homology modeling

    PMID:17683573

    Open questions at the time
    • Structures of modules 1, 3, 4 only modeled
    • Full-length assembly architecture unknown
  10. 2009 High

    Mapped the retinol-binding pocket to a specific tryptophan-lined cavity and showed fatty acid competition, defining structure-function determinants of ligand binding.

    Evidence Crystallography plus W450F/W587F mutagenesis and oleic acid competition fluorescence assays

    PMID:19608538

    Open questions at the time
    • Mode of allosteric coupling between retinoid and fatty acid sites not fully defined
  11. 2015 High

    Captured oleic acid bound in the module 1 hydrophobic pocket and demonstrated it displaces retinol, giving direct structural evidence for fatty acid regulation of retinoid carriage.

    Evidence 1.90 Å crystal structure of zebrafish module 1 and fluorescence displacement titration

    PMID:26344741

    Open questions at the time
    • Physiological fatty acid occupancy in vivo not measured
  12. 2011 High

    Revealed that IRBP loss causes excessive axial eye growth and myopia through increased cell death rather than altered proliferation, extending its role to ocular development.

    Evidence IRBP knockout mice with laser micrometry, interferometry, photorefraction, BrdU and TUNEL assays

    PMID:21642628

    Open questions at the time
    • Molecular signal linking IRBP to eye-growth control unknown
  13. 2008 High

    Defined the transcriptional control of IRBP, identifying OTX2/CRX/Ret-1 activation and OTX2 transactivation-domain dependence as drivers of photoreceptor-specific expression.

    Evidence Promoter deletion/transgenic reporters, footprinting, EMSA, yeast one-hybrid, and OTX2 domain-mutant transactivation assays

    PMID:10372988 PMID:1426058 PMID:18628516 PMID:1958183 PMID:9479006

    Open questions at the time
    • In vivo requirement of each element in the native locus not all tested
  14. 2005 Medium

    Identified MOK2 and KLF15 as repressors competing with CRX/NRL at overlapping promoter elements, and DNA hypomethylation as a permissive layer, completing the activator-repressor-epigenetic logic of IRBP expression.

    Evidence EMSA, footprinting, reporter cotransfection, and methylation/Southern blot reporter assays

    PMID:11134609 PMID:11278819 PMID:15963234

    Open questions at the time
    • In vivo relevance of repression in photoreceptors not shown
    • Single-lab reporter-based evidence
  15. 2013 High

    Defined the molecular pathogenesis of the RP-causing D1080N mutation as misfolding-driven ER retention, disulfide aggregation, chaperone binding, and ER-stress apoptosis, connecting a salt-bridge disruption to disease.

    Evidence Mutant transfection, ER/Golgi colocalization, chaperone Co-IP, non-reducing SDS-PAGE, UPR markers, and Cys-mutant/PDIA2/chemical-chaperone rescue; preceded by homozygosity-mapping genetic identification

    PMID:19074801 PMID:23486466

    Open questions at the time
    • Salt-bridge disruption inferred from Xenopus structure, not crystallized for human D1080N
    • Link from photoreceptor ER stress to in vivo degeneration not directly traced
  16. 2013 Medium

    Broadened the IRBP ligand repertoire to carotenoids, showing high-affinity binding comparable to retinoids, hinting at a role in xanthophyll transport.

    Evidence Surface plasmon resonance with purified bovine IRBP and multiple ligands

    PMID:23876239

    Open questions at the time
    • Single method, single study
    • Physiological carotenoid carriage not demonstrated in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IRBP loss mechanistically triggers photoreceptor death and controls axial eye growth, and whether its carotenoid and fatty-acid carriage have distinct physiological roles, remain unresolved.
  • No molecular pathway from IRBP loss to apoptosis defined
  • Eye-growth signal unidentified
  • Full-length structural organization of the four-module protein unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0140104 molecular carrier activity 4 GO:0005215 transporter activity 3
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0031012 extracellular matrix 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1643685 Disease 2 R-HSA-9709957 Sensory Perception 2 R-HSA-1266738 Developmental Biology 1
Partners
BIPCRXKLF15MOK2NRLOTX2PDIA2

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1983 IRBP (RBP3) was identified as the major soluble constituent of the monkey interphotoreceptor space (IPS): a 146,000 Mr glycoprotein that binds [3H]retinol, sediments at 7S on sucrose gradients, and has an apparent native molecular weight of ~250,000 Da by size-exclusion HPLC. CRBP and CRALBP were not detected in the IPS wash, indicating IRBP is the primary retinol-binding protein in the extracellular compartment between retina and RPE. IPS wash fractionation, sucrose gradient sedimentation, size-exclusion HPLC, SDS-PAGE, radiolabeled retinol binding assay Journal of cellular physiology High 6686234
1984 IRBP is synthesized by the neural retina and rapidly secreted into the culture medium; no significant IRBP synthesis was observed in the pigment-epithelium-choroid complex. Secretion is blocked by monensin, indicating transit through the secretory pathway. Monkey retina organ culture, radiolabeled amino acid and glucosamine incorporation, SDS-PAGE fluorography, monensin inhibition Biochemical and biophysical research communications High 6538412
1985 Y-79 human retinoblastoma cells synthesize and secrete IRBP into culture medium; butyrate treatment dramatically increases IRBP synthesis and secretion. IRBP was shown to concentrate in the Golgi apparatus by double immunofluorescence with wheat-germ agglutinin, confirming transit through the secretory pathway. Indirect immunofluorescence, monensin Golgi trapping, radiolabeled amino acid/glucosamine incorporation, SDS-PAGE Journal of cellular physiology Medium 3900095
1986 IRBP mRNA is localized mainly in rod photoreceptor neurons within the outer nuclear layer of the bovine and monkey retina, and is also abundant in pinealocytes, establishing photoreceptors and pineal cells as the primary sites of IRBP synthesis. In situ hybridization with cDNA probes FEBS letters High 3770208
1986 IRBP is expressed in both rod and cone photoreceptors: in cone-dominant ground squirrel retina, cones are the principal source; in human retina, both rods and cones express IRBP mRNA, with ~4-fold higher density over rod inner segments. In situ hybridization with 35S- and 3H-labeled antisense riboprobes, semi-thin wax-embedded sections, quantitative grain density analysis The journal of histochemistry and cytochemistry High 1987260
1986 IRBP-like proteins with immunoreactivity to anti-bovine IRBP antibodies were detected in the interphotoreceptor matrix of all six major vertebrate classes (Osteichthyes, Chondrichthyes, Amphibia, Reptilia, Aves, Mammalia). Fish IRBP (~67,600 Mr) is approximately half the molecular weight of tetrapod IRBP (~134,200 Mr). Frog IRBP binds retinol and concanavalin A and is synthesized/secreted by isolated retina but not pigmented layers. Immunoblots with anti-bovine IRBP antibodies, SDS-PAGE, gel-filtration chromatography, radiolabeled retinol binding, concanavalin A binding, in vitro retina/RPE synthesis assay The Journal of experimental zoology High 3093630
1991 The human IRBP promoter directs photoreceptor-specific expression in transgenic mice: a 212 bp 5'-flanking fragment is sufficient to drive tissue-specific CAT reporter gene expression confined to the neuroretina and pineal gland. Transgenic mice with IRBP promoter-CAT reporter constructs of varying lengths (1.3 kb, 706 bp, 212 bp) Biochemical and biophysical research communications High 1958183
1992 The human IRBP promoter drives photoreceptor-specific expression in both rod and cone cells in transgenic mice, as confirmed by histological and electron microscopic examination of retinas expressing a lacZ reporter. Transgenic mice with IRBP promoter-lacZ construct, X-gal histochemistry, electron microscopy Experimental eye research High 1426058
1993 IRBP facilitates both delivery of all-trans retinol to the RPE and transfer of 11-cis retinal from the RPE to bleached rod photoreceptors, directly supporting rhodopsin regeneration in the visual cycle. Evidence from the acutely detached retina and in vitro experiments demonstrates IRBP protects its retinoid ligand from isomerization and oxidation. Review synthesizing in vitro retinoid transfer assays, detached retina experiments, rhodopsin bleaching/regeneration studies Molecular neurobiology Medium 8318167
1993 Xenopus IRBP is a 124 kDa glycoprotein synthesized by the neural retina and secreted into the interphotoreceptor matrix. The translated amino acid sequence shows ~70% identity with the fourth repeat of human IRBP. The protein contains conserved hydrophobic domains, and its expression correlates with photoreceptor differentiation. Immunoprecipitation, [3H]fucose in vitro incorporation, autoradiographic analysis, cDNA cloning and sequencing, in vitro/in vivo biosynthesis studies Journal of cell science High 8360278
1994 Retinol transfer from IRBP to CRBP is essentially complete (103 ± 11%) with a half-time of ~4 seconds and reaches equilibrium in 30–60 seconds. No transfer from CRBP to IRBP was detected, consistent with CRBP's ~100-fold higher affinity for retinol. This directionality supports a role for IRBP in driving retinol flow toward the RPE during bleaching. Absorbance spectroscopy at 350 nm, size-exclusion HPLC separation of IRBP and CRBP, diode-array detection of retinol content Experimental eye research High 7835405
1997 Each of the four ~300-amino-acid repeats of human IRBP independently binds retinoids (all-trans-retinol, 9-cis-retinal, all-trans-retinoic acid) and fatty acid analogs (docosahexaenoic acid, trans-parinaric acid). Each repeat can prevent retinol degradation in aqueous solution, indicating that a single repeat retains all functions of the whole protein and contradicting the hypothesis that two or more repeats are required for ligand binding. Individual repeats expressed in E. coli; whole protein in baculovirus; ligand fluorescence enhancement; protein fluorescence quenching; circular dichroism; absorption spectroscopy for retinol protection Molecular vision High 9479008 9873071
1997 IRBP binds retinol at two functionally distinct sites stabilized mainly by hydrophobic interactions; the hydroxyl head group of retinol is not involved in complex formation. Binding of 11-cis-retinal at one site (but not the other) is regulated by docosahexaenoic acid, demonstrating site-selective allosteric regulation by fatty acid. Thermodynamic analysis of retinol binding; fluorescence spectroscopy; referenced prior DHA-regulation study The Journal of biological chemistry High 9374503
1997 The murine IRBP promoter region from -70 to -45 bp contains a Ret-1/PCE-I element and a CRX-binding element (GATTAA). Mutation of either element suppresses promoter activity; both elements are required for binding of a sequence-specific protein complex found in retina and brain extracts. This interval is identified as a major cis-activator of IRBP transcription. Nested deletion analysis of 1783 bp promoter fragment, transient transfection in primary embryonic chick retina cells, electrophoretic mobility shift assay (EMSA), site-directed mutagenesis Molecular vision High 9479006
1999 OTX2 binds to the core promoter element IP1 of the human IRBP gene and transactivates the IRBP promoter in normally non-expressing HeLa cells. A region from -1620 to -1411 has enhancer properties. An IP4 element (-202 to -180) can silence OTX2-mediated transactivation. DNase I footprinting, gel mobility-shift assay, yeast one-hybrid system, transient transfection/cotransfection in HeLa and WERI-Rb1 cells Current eye research High 10372988
2000 IRBP is uniquely capable of removing 11-cis-retinal from RPE membranes (18–35% removal at 25 µM), unlike serum RBP or BSA which remove little retinal. IRBP is also superior to RBP and BSA in removing all-trans-retinol from RPE membranes, but all three proteins deliver comparable amounts of retinol to membranes. The effect does not depend on an RPE surface receptor for IRBP. Isolated bovine RPE membranes loaded with radioactive 11-cis-retinal; centrifugation separation; HPLC analysis; comparison with liver membranes Experimental eye research High 10655150
2000 IRBP knockout mice lacking the IRBP gene show significant loss of photoreceptor nuclei and profound structural changes in rod outer segments, and reduced ERG amplitudes for both rod- and cone-mediated potentials. However, the rhodopsin cycle (bleaching and regeneration) was not grossly abnormal, with recovery rates even more rapid than wild-type mice. Homologous recombination gene knockout, light and electron microscopy, electroretinography (ERG), fundus reflectometry, rhodopsin density measurements Visual neuroscience High 10750831
2001 MOK2 zinc finger protein binds to an 8-bp sequence in the IRBP promoter that overlaps with the CRX-binding element, and represses IRBP transcription when overexpressed in Weri-RB1 cells. MOK2 competes with CRX for DNA binding, thereby reducing CRX-mediated transactivation of IRBP. Sequence comparison, electrophoretic mobility shift assay (EMSA), transient transfection/luciferase reporter assay in Weri-RB1 cells The Journal of biological chemistry Medium 11278819
2005 IRBP promotes release of all-trans retinol from isolated bleached toad retinas in a concentration-dependent manner (≥10 µM), with the released retinol accompanied by a decrease in total retinoids in the retina. BSA at equivalent concentrations did not mimic this effect, while a lectin-binding variant of IRBP (IRBP II) was also active, indicating the effect is not dependent on glycosylation. Isolated toad retina bleaching assay, HPLC retinoid analysis, extracellular medium retinoid quantification, comparison with BSA controls Experimental eye research High 15935345
2005 KLF15 zinc-finger domains bind multiple sites (9 bp consensus CGCCCC core) in the IRBP promoter, including the CRS-1 and G-rich repressor elements. KLF15 represses IRBP promoter activity and reduces CRX/NRL-mediated transactivation in reporter assays. EMSA, DNase I footprinting, KLF15-GST fusion protein binding assays, luciferase reporter transfection assay, CRX/NRL cotransfection BMC molecular biology Medium 15963234
2007 Crystal structure of Xenopus IRBP module 2 (X2IRBP) combined with fluorescence binding studies revealed two ligand-binding sites per module. Module 2 showed selectivity for all-trans retinol over 11-cis retinaldehyde. Binding affinities for the full-length Xenopus IRBP were Kd 0.2–0.3 µM for both all-trans retinol and 11-cis retinaldehyde at 3–4 sites. Homology modeling of modules 1, 3, and 4 indicates structural differences among binding domains. X-ray crystallography (module 2), fluorescence spectroscopy (ligand fluorescence enhancement, protein fluorescence quenching, energy transfer), LC-MS/MS sequence verification, homology modeling BMC biochemistry High 17683573
2008 OTX2 protein (wild-type) localizes to the nucleus, binds target sequences within the IRBP promoter, and markedly transactivates the IRBP promoter (~27-fold). A frameshift mutant OTX2 retaining the homeodomain but lacking the transactivation domain barely retains this activity and has no dominant-negative effect, demonstrating that the OTX2 transactivation domain is required for IRBP promoter activation. Transactivation reporter assays in transfected cells, nuclear localization imaging, promoter binding studies with wild-type vs. mutant OTX2 The Journal of clinical endocrinology and metabolism Medium 18628516
2008 A homozygous missense mutation p.Asp1080Asn in RBP3/IRBP causes autosomal recessive retinitis pigmentosa. Based on the Xenopus IRBP crystal structure, Asp1080 participates in a conserved salt bridge scaffolding the retinol-binding domain; the D1080N substitution is predicted to abolish this salt bridge and alter protein conformation. Homozygosity mapping with SNP microarrays, RBP3 sequencing, structural prediction based on published Xenopus IRBP crystal structure Investigative ophthalmology & visual science Medium 19074801
2009 The retinol-binding site in IRBP module 2 is a novel hydrophobic cavity (containing W450) distinct from the shallow cleft (W587). Site-directed mutagenesis (W450F) markedly reduced fluorescence quenching for both 11-cis and all-trans retinol binding, while W587F had little effect. Oleic acid inhibited retinol binding in an apparent noncompetitive manner, suggesting distinct but interacting binding sites for retinoids and long-chain fatty acids. X-ray crystallography (Xenopus module 2), site-directed mutagenesis (W450F, W587F), fluorescence spectroscopy (retinol fluorescence enhancement, tryptophan quenching, energy transfer), oleic acid competition assay Investigative ophthalmology & visual science High 19608538
2013 The RP-associated D1080N mutation in IRBP abolishes secretion of IRBP: the mutant protein forms insoluble high-molecular-weight complexes via disulfide bonds, accumulates in the ER (not Golgi), and binds ER-resident chaperones (BiP, protein disulfide isomerase, HSPs). D1080N IRBP induces ER stress (XBP-1 splicing, ATF4 expression, ATF6 cleavage) and upregulates the proapoptotic transcription factor CHOP. Co-expression of PDIA2 or Cys304Ala/Cys1175Ala double substitution rescued secretion. Chemical chaperones and low temperature also rescued secretion, indicating misfolding as the molecular basis. Transfection of mutant IRBP constructs, immunofluorescence co-localization with ER/Golgi markers, co-immunoprecipitation with chaperones (BiP, PDI, HSPs), non-reducing SDS-PAGE for disulfide complexes, XBP-1 splicing assay, ATF4/ATF6 western blot, CHOP nuclear translocation assay, rescue experiments with PDIA2 co-expression and Cys-to-Ala mutagenesis The Journal of biological chemistry High 23486466
2013 IRBP binds carotenoids (lutein, zeaxanthin) with similar affinity to retinoids (~1–2 µM Kd), while fatty acids show ~10-fold lower affinity. This was established by surface plasmon resonance (SPR) biosensor assays with purified IRBP. Surface plasmon resonance (SPR) biosensor assays with purified bovine IRBP and various ligands (retinoids, fatty acids, carotenoids) Archives of biochemistry and biophysics Medium 23876239
2013 IRBP binds specifically to pericellular matrix domains of cone outer segments and Müller cell microvilli in Xenopus retina. Wash-resistant native IRBP and exogenously added IRBP-Alexa 647 both localized to these domains; unlabeled IRBP competed away binding while ovalbumin did not. Immunogold EM revealed IRBP associated with filamentous structures and flocculant material coating outer segments and filling the rod periciliary ridge. Immunofluorescence microscopy with wash-resistant native IRBP, fluorescent IRBP-Alexa 647 binding competition assay, immunogold electron microscopy, wheat germ agglutinin and peanut agglutinin co-labeling Experimental eye research Medium 23470504
2015 X-ray crystal structure of zebrafish IRBP module 1 (z1) at 1.90 Å resolution reveals a two-domain organization (domains A and B) with a deep hydrophobic pocket in domain A containing a single bound molecule of oleic acid. Fluorescence titration assays showed oleic acid displaces all-trans retinol from zebrafish IRBP, providing structural evidence for fatty acid regulation of retinoid binding. X-ray crystallography (1.90 Å resolution), fluorescence titration assays (ligand displacement) Experimental eye research High 26344741
2011 IRBP knockout mice develop exaggerated eye growth starting between P7–P10, with retinal arc lengths 18% greater than wild-type from P10–P30, outer nuclear layer thinning (20–38% thinner), and 30% fewer cones by P30. A spike in apoptosis was observed at P25 in the ONL. Eyes became profoundly myopic (−4.56 D vs +9.98 D in WT by P60), and BrdU labeling showed equal cell birth in KO and WT, indicating IRBP loss causes increased cell death rather than altered proliferation. These findings establish a role for IRBP in normal ocular development beyond the visual cycle. IRBP knockout mice, histology, laser micrometry, partial coherence interferometry, cycloplegic photorefractions, BrdU labeling, TUNEL apoptosis assay Investigative ophthalmology & visual science High 21642628
2000 Specific CpG dinucleotides in the IRBP gene promoter are hypomethylated in photoreceptor cells and pinealocytes but methylated in non-photoreceptor tissues. Exogenous methylation of these sites suppressed IRBP promoter activity in reporter assays and diminished DNA:protein binding in EMSA, indicating that site-specific DNA hypomethylation is required for IRBP expression. Southern blotting of HpaII/MspI digests of DNA from multiple tissues, EMSA with methylated vs. unmethylated probes, CAT reporter transfection with methylated constructs in embryonic chick retinal cells Brain research Medium 11134609

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1983 The presence of a soluble interphotoreceptor retinol-binding protein (IRBP) in the retinal interphotoreceptor space. Journal of cellular physiology 141 6686234
2004 Phylogeny of muroid rodents: relationships within and among major lineages as determined by IRBP gene sequences. Molecular phylogenetics and evolution 134 15019624
1993 Interphotoreceptor retinoid-binding protein (IRBP). Molecular biology and physiological role in the visual cycle of rhodopsin. Molecular neurobiology 127 8318167
2009 Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy. Diabetologia 126 19823802
1989 Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP). The Journal of experimental medicine 112 2471769
1986 Rhodopsin, 11-cis vitamin A, and interstitial retinol-binding protein (IRBP) during retinal development in normal and rd mutant mice. Developmental biology 109 3732615
2000 Identification of a new epitope of human IRBP that induces autoimmune uveoretinitis in mice of the H-2b haplotype. Investigative ophthalmology & visual science 107 10634611
1986 Retinal photoreceptor neurons and pinealocytes accumulate mRNA for interphotoreceptor retinoid-binding protein (IRBP). FEBS letters 107 3770208
1999 Macrophages and dendritic cells in IRBP-induced experimental autoimmune uveoretinitis in B10RIII mice. Investigative ophthalmology & visual science 105 10586940
2008 A homozygous missense mutation in the IRBP gene (RBP3) associated with autosomal recessive retinitis pigmentosa. Investigative ophthalmology & visual science 92 19074801
1996 Drosophila IRBP/Ku p70 corresponds to the mutagen-sensitive mus309 gene and is involved in P-element excision in vivo. Genes & development 91 8608940
2000 The rhodopsin cycle is preserved in IRBP "knockout" mice despite abnormalities in retinal structure and function. Visual neuroscience 84 10750831
1996 Molecular phylogeny of the New World monkeys (Platyrrhini, primates) based on two unlinked nuclear genes: IRBP intron 1 and epsilon-globin sequences. American journal of physical anthropology 82 8771309
1986 Induction of experimental autoimmune uveoretinitis and pinealitis by IRBP. Comparison to uveoretinitis induced by S-antigen and opsin. Current eye research 81 2938889
1999 The requirement for pertussis to induce EAU is strain-dependent: B10.RIII, but not B10.A mice, develop EAU and Th1 responses to IRBP without pertussis treatment. Investigative ophthalmology & visual science 79 10549650
1996 Mammalian evolution and the interphotoreceptor retinoid binding protein (IRBP) gene: convincing evidence for several superordinal clades. Journal of molecular evolution 78 8660440
1995 Identification of a major pathogenic epitope in the human IRBP molecule recognized by mice of the H-2r haplotype. Investigative ophthalmology & visual science 75 7706044
2002 Phylogeny of the genus Apodemus with a special emphasis on the subgenus Sylvaemus using the nuclear IRBP gene and two mitochondrial markers: cytochrome b and 12S rRNA. Molecular phylogenetics and evolution 70 12069545
2006 Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity. The Journal of experimental medicine 65 16585264
1987 Experimental autoimmune uveoretinitis (EAU) induced by retinal interphotoreceptor retinoid-binding protein (IRBP): differences between EAU induced by IRBP and by S-antigen. Clinical immunology and immunopathology 64 3494559
2004 Primate phylogeny, evolutionary rate variations, and divergence times: a contribution from the nuclear gene IRBP. American journal of physical anthropology 62 15085543
1987 Bgl II RFLP recognized by a human IRBP cDNA localized to chromosome 10. Nucleic acids research 59 2882488
2008 OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters. The Journal of clinical endocrinology and metabolism 58 18628516
1991 Detection of interphotoreceptor retinoid binding protein (IRBP) mRNA in human and cone-dominant squirrel retinas by in situ hybridization. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 57 1987260
1985 Butyrate enhances the synthesis of interphotoreceptor retinoid-binding protein (IRBP) by Y-79 human retinoblastoma cells. Journal of cellular physiology 55 3900095
2011 Exaggerated eye growth in IRBP-deficient mice in early development. Investigative ophthalmology & visual science 52 21642628
2003 Phylogeny of Neotropical oryzomyine rodents (Muridae: Sigmodontinae) based on the nuclear IRBP exon. Molecular phylogenetics and evolution 52 13678688
2015 Lack of Interphotoreceptor Retinoid Binding Protein Caused by Homozygous Mutation of RBP3 Is Associated With High Myopia and Retinal Dystrophy. Investigative ophthalmology & visual science 47 25766589
2001 Phylogeny of rodentia (Mammalia) inferred from the nuclear-encoded gene IRBP. Molecular phylogenetics and evolution 46 11341810
1988 A developmental study of interphotoreceptor retinoid-binding protein (IRBP) in single and double homozygous rd and rds mutant mouse retinae. Experimental eye research 46 3044810
2015 Characterization of a New Epitope of IRBP That Induces Moderate to Severe Uveoretinitis in Mice With H-2b Haplotype. Investigative ophthalmology & visual science 41 26284549
1988 Synthetic peptides derived from IRBP induce EAU and EAP in Lewis rats. Current eye research 41 3262040
1989 Rat T-cell lines specific to a nonimmunodominant determinant of a retinal protein (IRBP) produce uveoretinitis and pinealitis. Cellular immunology 38 2473846
1986 Distribution of interstitial retinol-binding protein (IRBP) in the vertebrates. The Journal of experimental zoology 37 3093630
2008 Repertoire analysis and new pathogenic epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) mice. Investigative ophthalmology & visual science 36 18436827
1999 Elements regulating the transcription of human interstitial retinoid-binding protein (IRBP) gene in cultured retinoblastoma cells. Current eye research 36 10372988
1987 Human interstitial retinol-binding protein (IRBP): cloning, partial sequence, and chromosomal localization. Somatic cell and molecular genetics 36 3455009
2016 Preventive effect of chrysin on experimental autoimmune uveitis triggered by injection of human IRBP peptide 1-20 in mice. Cellular & molecular immunology 35 26996065
2000 Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and immunological responses in interferon gamma deficient mice. Experimental eye research 35 10930316
1992 Early expression and localization of rhodopsin and interphotoreceptor retinoid-binding protein (IRBP) in the developing fetal bovine retina. Experimental eye research 35 1623951
2013 Secretory defect and cytotoxicity: the potential disease mechanisms for the retinitis pigmentosa (RP)-associated interphotoreceptor retinoid-binding protein (IRBP). The Journal of biological chemistry 34 23486466
2013 Carotenoids as possible interphotoreceptor retinoid-binding protein (IRBP) ligands: a surface plasmon resonance (SPR) based study. Archives of biochemistry and biophysics 34 23876239
2001 IL-18 not required for IRBP peptide-induced EAU: studies in gene-deficient mice. Investigative ophthalmology & visual science 34 11133864
1992 Photoreceptor-specific activity of the human interphotoreceptor retinoid-binding protein (IRBP) promoter in transgenic mice. Experimental eye research 34 1426058
2000 IRBP enhances removal of 11- cis -retinaldehyde from isolated RPE membranes. Experimental eye research 33 10655150
1998 Novel expression pattern of interphotoreceptor retinoid-binding protein (IRBP) in the adult and developing zebrafish retina and RPE. Molecular vision 33 9841935
1991 Retina-specific expression from the IRBP promoter in transgenic mice is conferred by 212 bp of the 5'-flanking region. Biochemical and biophysical research communications 33 1958183
1989 Cloning of cDNAs encoding human interphotoreceptor retinoid-binding protein (IRBP) and comparison with bovine IRBP sequences. Gene 33 2792773
1986 Bovine interstitial retinol-binding protein (IRBP)--isolation and sequence analysis of cDNA clones, characterization and in vitro translation of mRNA. Vision research 31 3617506
1984 Synthesis of interphotoreceptor retinoid-binding protein (IRBP) by monkey retina in organ culture: effect of monensin. Biochemical and biophysical research communications 31 6538412
2020 Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease. Frontiers in cellular neuroscience 30 33328889
2005 Interphotoreceptor retinoid-binding protein (IRBP) promotes the release of all-trans retinol from the isolated retina following rhodopsin bleaching illumination. Experimental eye research 30 15935345
1997 A major cis activator of the IRBP gene contains CRX-binding and Ret-1/PCE-I elements. Molecular vision 30 9479006
2013 Cone outer segment and Müller microvilli pericellular matrices provide binding domains for interphotoreceptor retinoid-binding protein (IRBP). Experimental eye research 29 23470504
2005 Chronic recurrent autoimmune uveitis with progressive photoreceptor damage induced in rats by transfer of IRBP-specific T cells. Journal of neuroimmunology 29 15885312
1988 Human IRBP: characterization of uveitopathogenic sites. Current eye research 28 2468449
1993 Interphotoreceptor retinoid-binding protein (IRBP), a major 124 kDa glycoprotein in the interphotoreceptor matrix of Xenopus laevis. Characterization, molecular cloning and biosynthesis. Journal of cell science 27 8360278
1989 Close linkage of MEN2A with RBP3 locus in Japanese kindreds. Human genetics 27 2567278
2016 Drosophila IRBP bZIP heterodimer binds P-element DNA and affects hybrid dysgenesis. Proceedings of the National Academy of Sciences of the United States of America 26 27799520
2007 Minimally activated CD8 autoreactive T cells specific for IRBP express a high level of Foxp3 and are functionally suppressive. Investigative ophthalmology & visual science 26 17460277
2008 New insights into the organization and evolution of vertebrate IRBP genes and utility of IRBP gene sequences for the phylogenetic study of the Acanthomorpha (Actinopterygii: Teleostei). Molecular phylogenetics and evolution 25 18499481
1989 Reduced level of interphotoreceptor retinoid-binding protein (IRBP), a possible cause for retinal degeneration in the Abyssinian cat. Cell and tissue research 25 2790940
2018 A Glycine-Rich RNA-Binding Protein, CsGR-RBP3, Is Involved in Defense Responses Against Cold Stress in Harvested Cucumber (Cucumis sativus L.) Fruit. Frontiers in plant science 23 29740470
2013 HMGB1 is an early and critical mediator in an animal model of uveitis induced by IRBP-specific T cells. Journal of leukocyte biology 23 24374967
1990 Repeated determinants within the retinal interphotoreceptor retinoid-binding protein (IRBP): immunological properties of the repeats of an immunodominant determinant. Cellular immunology 23 1690082
1990 Hypomethylation of the interphotoreceptor retinoid-binding protein (IRBP) promotor and first exon is linked to expression of the gene. Nucleic acids research 23 2402443
1989 Immune responses to peptides derived from the retinal protein IRBP: immunopathogenic determinants are not necessarily immunodominant. Clinical immunology and immunopathology 23 2477180
1987 Levels of alpha- and gamma-tocopherol in human eyes: evaluation of the possible role of IRBP in intraocular alpha-tocopherol transport. The American journal of clinical nutrition 23 3630966
2003 Interphotoreceptor retinoid-binding protein (IRBP)-deficient C57BL/6 mice have enhanced immunological and immunopathogenic responses to IRBP and an altered recognition of IRBP epitopes. Journal of autoimmunity 22 14599843
1998 Structure-function relationships in the four repeats of human interphotoreceptor retinoid-binding protein (IRBP). Molecular vision 22 9873071
1997 The 5' flanking regions of IRBP and arrestin have promoter activity in primary embryonic chicken retina cell cultures. Experimental eye research 22 9176061
1990 Humoral autoimmune response against S-antigen and IRBP in ocular onchocerciasis. Investigative ophthalmology & visual science 21 2365568
1987 Immunohistochemical analysis of experimental autoimmune uveoretinitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) in the rat. Immunological investigations 21 3497100
2016 IRBP deficiency permits precocious ocular development and myopia. Molecular vision 20 27829784
2007 Module structure of interphotoreceptor retinoid-binding protein (IRBP) may provide bases for its complex role in the visual cycle - structure/function study of Xenopus IRBP. BMC biochemistry 20 17683573
2005 Zinc-finger domains of the transcriptional repressor KLF15 bind multiple sites in rhodopsin and IRBP promoters including the CRS-1 and G-rich repressor elements. BMC molecular biology 20 15963234
1996 Interphotoreceptor retinoid-binding protein (IRBP): expression in the adult and developing Xenopus retina. The Journal of comparative neurology 20 8698895
1993 Interphotoreceptor retinoid binding protein (IRBP) enhances rhodopsin regeneration in the experimentally detached retina. Experimental eye research 20 8150029
1989 mRNA for interphotoreceptor retinoid-binding protein (IRBP): distribution and size diversity in vertebrate species. Experimental eye research 20 2767165
1990 Autoimmune responsiveness to retinal IRBP, S-antigen and opsin in proliferative vitreoretinopathy. Experimental eye research 19 2138091
1985 Interstitial retinol-binding protein (IRBP) in the RCS rat: effect of dark-rearing. Investigative ophthalmology & visual science 19 4044166
1991 Interphotoreceptor retinoid-binding protein (IRBP) in progressive rod-cone degeneration (prcd)--biochemical, immunocytochemical and immunologic studies. Experimental eye research 18 1936175
1987 Uveitis induced in primates by IRBP: humoral and cellular immune responses. Experimental eye research 18 3428394
2009 Retinol-binding site in interphotoreceptor retinoid-binding protein (IRBP): a novel hydrophobic cavity. Investigative ophthalmology & visual science 17 19608538
2000 Site-specific DNA hypomethylation permits expression of the IRBP gene. Brain research 17 11134609
1997 Structure-function relationships in interphotoreceptor retinoid-binding protein (IRBP). Molecular vision 17 9479008
2007 S-nitrosoglutathione prevents interphotoreceptor retinoid-binding protein (IRBP(161-180))-induced experimental autoimmune uveitis. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 16 17593005
2023 Towards a New Biomarker for Diabetic Retinopathy: Exploring RBP3 Structure and Retinoids Binding for Functional Imaging of Eyes In Vivo. International journal of molecular sciences 15 36901838
2015 Structure of zebrafish IRBP reveals fatty acid binding. Experimental eye research 15 26344741
2011 Early involvement of nitric oxide in mechanisms of pathogenesis of experimental autoimmune uveitis induced by interphotoreceptor retinoid-binding protein (IRBP). Journal francais d'ophtalmologie 15 22015071
1998 A CAT reporter construct containing 277bp GNAT2 promoter and 214bp IRBP enhancer is specifically expressed by cone photoreceptor cells in transgenic mice. Current eye research 15 9723991
1997 Binding of retinol in both retinoid-binding sites of interphotoreceptor retinoid-binding protein (IRBP) is stabilized mainly by hydrophobic interactions. The Journal of biological chemistry 15 9374503
1988 IRBP-like proteins in the eyes of six cephalopod species--immunochemical relationship to vertebrate interstitial retinol-binding protein (IRBP) and cephalopod retinal-binding protein. Vision research 15 3195063
1986 Interstitial retinol-binding protein (IRBP) in subretinal fluid. Investigative ophthalmology & visual science 15 3721782
2005 Different patterns of selection on the nuclear genes IRBP and DMP-1 affect the efficiency but not the outcome of phylogeny estimation for didelphid marsupials. Molecular phylogenetics and evolution 14 16054401
2002 The effect of retinoids and butyrate on the expression of CRX and IRBP in retinoblastoma cells. Vision research 14 11934446
2001 The zinc finger transcription factor, MOK2, negatively modulates expression of the interphotoreceptor retinoid-binding protein gene, IRBP. The Journal of biological chemistry 14 11278819
1996 Generalized autoimmunity of the nervous system (GANS) induced by a recombinant protein composed of major pathogenic determinants of MBP, IRBP, and P2 protein: suppression of inflammation by a monoclonal antibody against activated rat T line cells. Journal of neuroscience research 14 8841991
1994 Exchange of retinol between IRBP and CRBP. Experimental eye research 14 7835405
1994 Identification of heat shock proteins binding to an immunodominant uveitopathogenic peptide of IRBP. Current eye research 14 8033590

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