RORB (RAR-related orphan receptor beta, NR1F2) is a nuclear receptor transcription factor of the NR1 subfamily, expressed mainly in neural tissue: retina, pineal gland, thalamus, spinal cord and layer IV neurons of the neocortex. It binds DNA as a monomer through a C4 zinc-finger domain at ROR response elements (an AGGTCA half-site preceded by an A/T-rich sequence) and activates transcription constitutively. Its ligand-binding domain binds fatty acids, and all-trans retinoic acid and related retinoids bind it as inverse agonists that reduce its activity. Two isoforms arise from alternative promoters. In mouse, RORbeta drives rod photoreceptor development by inducing Nrl, activates the S-opsin gene in cones together with CRX, and its isoform RORbeta1 directs amacrine and horizontal interneuron differentiation by inducing Ptf1a with Foxn4. RORbeta also patterns layer IV barrel cytoarchitecture in the somatosensory cortex. Knockout mice have retinal degeneration, a duck-like gait and a lengthened circadian period. Overexpression suppresses osteoblast differentiation by antagonizing RUNX2. Heterozygous loss-of-function variants in human RORB cause generalized epilepsy, often with absence seizures.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: Chromatin localization inferred from TFClass membership as a sequence-specific DNA-binding TF. Reason: As a DNA-bound nuclear receptor, RORB acts on chromatin at RORE sites; this is a reasonable, non-controversial location for a DbTF. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. file:human/RORB/RORB-uniprot.txt Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: RNA pol II cis-regulatory region sequence-specific DNA binding, inferred phylogenetically across the ROR/HR3 clade. Reason: RORB binds RORE half-sites in promoters of target genes such as Opn1sw; the IBA is at an appropriate specificity for an NR1F receptor. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Same DNA-binding term transferred from mouse Rorb via Ensembl Compara. Reason: Consistent with the IBA and with experimental RORE binding by RORbeta. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: Pol II-specific DNA-binding TF activity from TFClass. Reason: RORB is a bona fide DNA-binding transcription factor acting at Pol II promoters (e.g. Opn1sw). Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: Pol II-specific DNA-binding TF activity transferred from mouse Rorb isoform 1. Reason: Consistent with mouse data showing RORbeta1 directs Ptf1a expression and RORbeta activates Opn1sw. Supporting Evidence: PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. PMID:23652001 RORΞ²1 and Foxn4 synergistically induce Ptf1a expression |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: DNA-binding transcription activator activity (Pol II), from mouse ortholog. Reason: RORB shows constitutive transactivation and activates Opn1sw, Nrl and Ptf1a; activator activity is well supported. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. PMID:16574740 activates the Opn1sw promoter modestly alone but strongly in synergy with the retinal cone-rod homeobox factor (CRX) |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: DNA binding from InterPro ROR receptor signature. Reason: Correct but general; RORB binds DNA through its C4 zinc-finger DBD. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: DNA-binding transcription factor activity (combined IEA). Reason: Correct, if general; more specific Pol II and nuclear receptor terms are also present. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity |
| GO:0003700 DNA-binding transcription factor activity | ISS GO_REF:0000024 | ACCEPT | Summary: DNA-binding TF activity transferred by similarity. Reason: Correct; RORB is a DNA-binding transcription factor. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. |
| GO:0003700 DNA-binding transcription factor activity | ISS GO_REF:0000024 | ACCEPT | Summary: DNA-binding TF activity transferred by similarity. Reason: Correct; RORB is a DNA-binding transcription factor. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. |
| GO:0004879 nuclear receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear receptor activity, inferred phylogenetically for the NR1F/HR3 clade. Reason: Core function. RORB has the C4 zinc-finger DBD and LBD defining nuclear receptors, binds RORE as a monomer, and its LBD binds fatty acids and retinoids that modulate its activity. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. PMID:11689423 In the crystal, the monomeric LBD adopts the canonical agonist-bound form. PMID:12958591 ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity |
| GO:0004879 nuclear receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Nuclear receptor activity from InterPro ROR receptor family. Reason: Core function; consistent with IBA and experimental data. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. PMID:11689423 In the crystal, the monomeric LBD adopts the canonical agonist-bound form. |
| GO:0004879 nuclear receptor activity | TAS PMID:7935491 RZRs, a new family of retinoid-related orphan receptors that... | ACCEPT | Summary: Nuclear receptor activity stated in the paper describing the cloning of RZR-beta (rat) and its monomeric RORE binding. Reason: The paper shows monomeric binding to (A/G)GGTCA half-sites and constitutive transactivation, which defines nuclear receptor activity. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity |
| GO:0005515 protein binding | IPI PMID:23555304 Dynamic circadian protein-protein interaction networks predi... | REMOVE | Summary: Protein binding from a circadian yeast two-hybrid screen reporting RORB interaction with mouse CLOCK. Reason: Generic protein binding carries no functional information. The Y2H hit (with a mouse partner, and RORB a strong auto-activator as bait) does not establish a specific molecular function; the interaction itself is not disputed. Supporting Evidence: PMID:23555304 we detected interactions between DEC1/2 and CRY1/2, between CLOCK and RORΞ²/Ξ³ |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleus as site of activity, inferred phylogenetically. Reason: RORB is a nuclear transcription factor; wild-type RORB localizes to the nucleus. Supporting Evidence: PMID:27352968 The wild-type protein was detected in the nucleus as expected |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nucleus from combined IEA. Reason: Consistent with experimental nuclear localization. Supporting Evidence: PMID:27352968 The wild-type protein was detected in the nucleus as expected |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Nucleus by similarity to mouse Rorb. Reason: Consistent with experimental nuclear localization of human RORB. Supporting Evidence: PMID:27352968 The wild-type protein was detected in the nucleus as expected |
| GO:0005654 nucleoplasm | IDA PMID:27352968 Loss of function of the retinoid-related nuclear receptor (R... | ACCEPT | Summary: Nucleoplasm, shown by transfection of tagged wild-type and mutant RORB in COS-7 cells. Reason: Wild-type RORB was nuclear, whereas the epilepsy-associated truncation was absent from the nucleoplasm. Supporting Evidence: PMID:27352968 The wild-type protein was detected in the nucleus as expected PMID:27352968 no mutant protein was detected in the nucleoplasm |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleoplasm from UniProt subcellular location mapping. Reason: Derived from the experimental localization in PMID:27352968. Supporting Evidence: PMID:27352968 The wild-type protein was detected in the nucleus as expected |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-376419 | ACCEPT | Summary: Nucleoplasm, from the Reactome NR-MED1 coactivator complex reaction. Reason: The location is correct for a nuclear receptor recruiting coactivators; RORB is nuclear. Supporting Evidence: PMID:27352968 The wild-type protein was detected in the nucleus as expected |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-382096 | ACCEPT | Summary: Nucleoplasm, from the Reactome NR-MED1 coactivator complex reaction. Reason: The location is correct for a nuclear receptor recruiting coactivators; RORB is nuclear. Supporting Evidence: PMID:27352968 The wild-type protein was detected in the nucleus as expected |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: Regulation of DNA-templated transcription from InterPro domains. Reason: Correct but general; RORB regulates transcription of target genes as a nuclear receptor. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity |
| GO:0006355 regulation of DNA-templated transcription | TAS PMID:7935491 RZRs, a new family of retinoid-related orphan receptors that... | ACCEPT | Summary: Regulation of transcription stated for RZRs in the original cloning paper. Reason: Correct, general; supported by constitutive transactivation from RORE sites. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of transcription by RNA polymerase II, inferred phylogenetically. Reason: Appropriate; RORB regulates Pol II target genes such as Opn1sw and Nrl. Supporting Evidence: PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. PMID:19805139 Rorb directs rod development and does so at least in part by inducing the Nrl-mediated pathway of rod differentiation. |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000108 | REMOVE | Summary: GPCR signaling pathway inferred by inter-ontology link from the melatonin receptor activity annotation. Reason: RORB is a nuclear receptor with no transmembrane domains and no G protein coupling. The inference depends entirely on the melatonin receptor activity IBA, which is itself unsupported; RORB knockout does not affect melatonin signaling. Supporting Evidence: PMID:17303680 We conclude that the RORbeta nuclear receptor is not involved in either the rhythmic production of pineal melatonin or in mediating phase shifts of circadian rhythms by melatonin |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Zinc ion binding from the nuclear receptor zinc-finger domain signature. Reason: The C4-type zinc fingers of the DBD coordinate zinc; structurally correct though not informative of function. Supporting Evidence: file:human/RORB/RORB-uniprot.txt Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site |
| GO:0008502 melatonin receptor activity | IBA GO_REF:0000033 | REMOVE | Summary: Melatonin receptor activity, propagated phylogenetically from a node seeded by a rat annotation. Reason: The early proposal that RZR/ROR receptors bind melatonin has not been upheld. RORB is a nuclear receptor whose LBD binds fatty acids and retinoids, and RORbeta knockout mice have normal melatonin production and melatonin-induced phase shifts. GO:0008502 is in practice the activity of the MTNR1A/B GPCRs; the PAINT node placement for this term in the ROR clade is not supported. Propagation Review Root cause: SOURCE BAD Failure modes: SOURCE EVIDENCE WEAK Sources checked: PANTHER:PTN008698560 SOURCE BAD Ancestral node carrying the melatonin receptor activity IBD within the ROR clade; the assertion appears to rest on the historic RZR/ROR-melatonin ligand proposal, which has not been upheld. RGD:1306778 SOURCE BAD Rat descendant annotation seeding the node; RORbeta knockout mice show normal melatonin production and melatonin-induced phase shifts, arguing against melatonin receptor activity for RORbeta. Supporting Evidence: PMID:17303680 We conclude that the RORbeta nuclear receptor is not involved in either the rhythmic production of pineal melatonin or in mediating phase shifts of circadian rhythms by melatonin PMID:12958591 all-trans retinoic acid (ATRA) and several retinoids bind to the ROR beta ligand-binding domain (LBD) PMID:11689423 In the crystal, the monomeric LBD adopts the canonical agonist-bound form. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | ACCEPT | Summary: Regulation of gene expression from ARBA. Reason: Very general but correct for a transcription factor. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity |
| GO:0030522 intracellular receptor signaling pathway | IEA GO_REF:0000108 | ACCEPT | Summary: Intracellular receptor signaling pathway inferred from nuclear receptor activity. Reason: Acceptable consequence of nuclear receptor activity; ligands (retinoids, fatty acids) act on RORB inside the cell. Supporting Evidence: PMID:12958591 ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity |
| GO:0035881 amacrine cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: Amacrine cell differentiation, transferred from mouse Rorb isoform 1 (RORbeta1). Reason: Mouse RORbeta1 is required for amacrine and horizontal cell differentiation and synergizes with Foxn4 to induce Ptf1a; it acts directly as a transcription factor in this pathway. The human isoform 1 (Q92753-1) corresponds to RORbeta1. Supporting Evidence: PMID:23652001 is critical for both amacrine and horizontal cell differentiation in mice PMID:23652001 RORΞ²1 and Foxn4 synergistically induce Ptf1a expression |
| GO:0042462 eye photoreceptor cell development | IEA GO_REF:0000107 | ACCEPT | Summary: Eye photoreceptor cell development, from mouse ortholog. Reason: Rorb is required for rod differentiation and cone S-opsin induction and outer segment formation. Supporting Evidence: PMID:19805139 Rorb(-/-) mice lacking retinoid-related orphan nuclear receptor beta lose rods but overproduce primitive S cones that lack outer segments. PMID:16574740 Photoreceptors in these mice also lack outer segments, indicating additional functions for RORbeta in photoreceptor morphological maturation. |
| GO:0042462 eye photoreceptor cell development | ISS GO_REF:0000024 | ACCEPT | Summary: Eye photoreceptor cell development by similarity to mouse Rorb. Reason: Same mouse evidence; RORB acts as a transcriptional regulator of photoreceptor genes. Supporting Evidence: PMID:19805139 Rorb(-/-) mice lacking retinoid-related orphan nuclear receptor beta lose rods but overproduce primitive S cones that lack outer segments. PMID:16574740 RORbeta-deficient mice fail to induce S opsin appropriately during postnatal cone development. |
| GO:0042752 regulation of circadian rhythm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of circadian rhythm, from mouse ortholog. Reason: Rorb knockout mice have a lengthened free-running period; the mechanism (core clock versus retina/SCN development) is not established, so this is a non-core phenotype-level process. Supporting Evidence: PMID:9670004 under conditions of constant darkness, RORbeta-/- mice display an extended period of free-running rhythmicity. PMID:17303680 RORbeta(C3H)(-/-) mice showing a significant increase in circadian period (tau) |
| GO:0042752 regulation of circadian rhythm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of circadian rhythm by similarity to mouse Rorb. Reason: Same phenotype-level evidence as the IEA; non-core. Supporting Evidence: PMID:9670004 under conditions of constant darkness, RORbeta-/- mice display an extended period of free-running rhythmicity. PMID:17303680 RORbeta(C3H)(-/-) mice showing a significant increase in circadian period (tau) |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: Sequence-specific DNA binding from combined IEA. Reason: RORB binds RORE half-sites with 5' A/T extension specificity. Supporting Evidence: PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. |
| GO:0045668 negative regulation of osteoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of osteoblast differentiation, from mouse ortholog. Reason: Supported by Rorb overexpression in MC3T3-E1 cells suppressing mineralization and Runx2 activity; a peripheral role relative to its neural/retinal functions. Supporting Evidence: PMID:22189870 RorΞ² inhibited Runx2-dependent activation of a Runx2-reporter construct. PMID:22189870 These cells displayed markedly suppressed bone nodule formation as well as reduced osteocalcin and osterix gene expression. |
| GO:0045668 negative regulation of osteoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of osteoblast differentiation by similarity to mouse Rorb. Reason: Same overexpression evidence; non-core. Supporting Evidence: PMID:22189870 RorΞ² inhibited Runx2-dependent activation of a Runx2-reporter construct. PMID:22189870 These cells displayed markedly suppressed bone nodule formation as well as reduced osteocalcin and osterix gene expression. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of DNA-templated transcription by similarity to rat RORbeta. Reason: RORB is mainly a constitutive activator; repression is seen when retinoid inverse agonists are bound or through antagonism of Runx2. Acceptable but not core. Supporting Evidence: PMID:12958591 ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity PMID:22189870 RorΞ² inhibited Runx2-dependent activation of a Runx2-reporter construct. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of DNA-templated transcription, from mouse ortholog. Reason: RORB is a constitutive transcriptional activator. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of DNA-templated transcription by similarity to rat RORbeta. Reason: Constitutive transactivation by RZRs. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of DNA-templated transcription by similarity to rat RORbeta. Reason: Constitutive transactivation by RZRs. Supporting Evidence: PMID:7935491 On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II, from mouse ortholog. Reason: Core; RORB activates Pol II target genes Opn1sw, Nrl and Ptf1a. Supporting Evidence: PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. PMID:16574740 activates the Opn1sw promoter modestly alone but strongly in synergy with the retinal cone-rod homeobox factor (CRX) PMID:19805139 Rorb directs rod development and does so at least in part by inducing the Nrl-mediated pathway of rod differentiation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of Pol II transcription by similarity to mouse RORbeta1. Reason: Core; supported by RORbeta1 induction of Ptf1a with Foxn4. Supporting Evidence: PMID:23652001 RORΞ²1 and Foxn4 synergistically induce Ptf1a expression |
| GO:0046548 retinal rod cell development | IEA GO_REF:0000107 | ACCEPT | Summary: Retinal rod cell development, from mouse ortholog. Reason: Rorb-/- mice lose rods; Rorb induces Nrl to drive rod differentiation. Supporting Evidence: PMID:19805139 Rorb(-/-) mice lacking retinoid-related orphan nuclear receptor beta lose rods but overproduce primitive S cones that lack outer segments. PMID:19805139 Rorb directs rod development and does so at least in part by inducing the Nrl-mediated pathway of rod differentiation. |
| GO:0046548 retinal rod cell development | ISS GO_REF:0000024 | ACCEPT | Summary: Retinal rod cell development by similarity to mouse Rorb. Reason: Same mouse evidence. Supporting Evidence: PMID:19805139 Rorb(-/-) mice lacking retinoid-related orphan nuclear receptor beta lose rods but overproduce primitive S cones that lack outer segments. PMID:19805139 Rorb directs rod development and does so at least in part by inducing the Nrl-mediated pathway of rod differentiation. |
| GO:0046549 retinal cone cell development | IEA GO_REF:0000107 | ACCEPT | Summary: Retinal cone cell development, from mouse ortholog. Reason: Rorb directly activates Opn1sw and is required for S-opsin induction and outer segment formation in cones. Supporting Evidence: PMID:16574740 RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. PMID:16574740 RORbeta-deficient mice fail to induce S opsin appropriately during postnatal cone development. PMID:16574740 Photoreceptors in these mice also lack outer segments, indicating additional functions for RORbeta in photoreceptor morphological maturation. |
| GO:0046549 retinal cone cell development | ISS GO_REF:0000024 | ACCEPT | Summary: Retinal cone cell development by similarity to mouse Rorb. Reason: Same mouse evidence. Supporting Evidence: PMID:16574740 RORbeta-deficient mice fail to induce S opsin appropriately during postnatal cone development. PMID:16574740 Photoreceptors in these mice also lack outer segments, indicating additional functions for RORbeta in photoreceptor morphological maturation. |
| GO:0060041 retina development in camera-type eye | ISS GO_REF:0000024 | ACCEPT | Summary: Retina development in camera-type eye by similarity to mouse RORbeta1. Reason: General but correct; Rorb is required for rods, cones, amacrine and horizontal cells and knockouts have a disorganized retina. Supporting Evidence: PMID:9670004 RORbeta-/- mice display a duck-like gait, transient male incapability to sexually reproduce, and a severely disorganized retina that suffers from postnatal degeneration. PMID:23652001 is critical for both amacrine and horizontal cell differentiation in mice |
| GO:0071300 cellular response to retinoic acid | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cellular response to retinoic acid by similarity to rat RORbeta. Reason: All-trans retinoic acid binds the RORbeta LBD and inhibits its transcriptional activity, so RORB does respond to retinoic acid; physiological relevance of this ligand in vivo is unclear. Supporting Evidence: PMID:12958591 all-trans retinoic acid (ATRA) and several retinoids bind to the ROR beta ligand-binding domain (LBD) PMID:12958591 ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: Sequence-specific double-stranded DNA binding from a genome-scale HT-SELEX study of human TF DNA-binding domains. Reason: RORB is not named in the main text (results are in supplementary tables), but sequence-specific dsDNA binding by RORB is independently well established; deferring to the curator. Supporting Evidence: PMID:28473536 we performed a HT-SELEX [high-throughput systematic evolution of ligands by exponential enrichment (21, 22)] analysis of ~1000 human TF extended DNA binding domains PMID:7935491 We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. |
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Download this section (compressed HTML)Q: Does RORB transcriptional activity, rather than its expression as a lineage marker, contribute to the selective vulnerability of RORB+ entorhinal excitatory neurons to tau pathology in Alzheimer disease?
Suggested experts: neurodegeneration and selective vulnerability researchers, nuclear receptor biologists
Q: Should the melatonin receptor activity assertion at PANTHER node PTN008698560 be retracted for the ROR clade, given that RORB/RZR melatonin binding has not been upheld?
Suggested experts: PAINT/PANTHER curators
Q: Is the lengthened circadian period of Rorb knockout mice a direct clock function of RORB or a secondary consequence of retinal/SCN developmental defects?
Suggested experts: circadian biologists
Experiment: In human iPSC-derived entorhinal-like excitatory neurons or a tauopathy mouse model, knock down or overexpress RORB (and express a DNA-binding-dead mutant), then measure tau accumulation, neuronal survival and the RORB-dependent transcriptome.
Hypothesis: RORB-driven gene expression programs, not merely RORB expression as a marker, modulate susceptibility of excitatory neurons to tau pathology.
Type: genetic perturbation in neuronal models
Experiment: Map genome-wide RORB occupancy (CUT&RUN/ChIP-seq) in human cortical layer IV-like neurons and retina organoids, with and without retinoid inverse agonists.
Hypothesis: Direct RORB target genes in neurons can be defined and are repressed by retinoid ligands.
Type: chromatin occupancy profiling
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