Affinage

CRX

Cone-rod homeobox protein · UniProt O43186

Length
299 aa
Mass
32.3 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRX is a photoreceptor- and pinealocyte-specific paired-like homeodomain transcription factor that serves as a master regulator of photoreceptor differentiation, outer segment morphogenesis, synaptogenesis, phototransduction gene expression, and pineal melatonin synthesis (PMID:10581037, PMID:15676071, PMID:30803008). CRX binds TAAT-containing cis-regulatory elements in photoreceptor and pineal gene promoters/enhancers and activates transcription by recruiting HAT-containing co-activators (CBP, p300, STAGA/GCN5) to promote histone H3 acetylation, while its transactivation depends on C-terminal domains including the OTX tail and WSP motif (PMID:17656371, PMID:10984472, PMID:18927113). CRX physically interacts with and acts synergistically with NRL, Nr2e3, Rax, Sp4, and OTX2 to specify rod and cone gene expression programs, and its activity is negatively modulated by phosducin isoforms, PANKY, and Samd7 (PMID:10887186, PMID:15689355, PMID:25986607, PMID:10866677, PMID:20026326). Dominant CRX mutations cause cone-rod dystrophy and Leber congenital amaurosis through mechanistically distinct pathways including loss of DNA binding, dominant-negative interference with wild-type CRX, enhanced transactivation, and altered DNA-binding specificity leading to ectopic genomic occupancy (PMID:9390563, PMID:9931337, PMID:24516401, PMID:37963072).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    Identification of CRX as a photoreceptor-specific homeodomain transcription factor and discovery that heterozygous mutations cause autosomal dominant cone-rod dystrophy established CRX as essential for photoreceptor function and linked it to inherited retinal disease.

    Evidence Human mutation identification and domain analysis in families with cone-rod dystrophy; parallel identification of CRX binding to the IRBP promoter element by EMSA and reporter assay

    PMID:9390563 PMID:9479006

    Open questions at the time
    • Mechanism of dominance (haploinsufficiency vs. dominant negative) was unresolved
    • Full spectrum of CRX target genes unknown
    • No animal model yet available
  2. 1999 High

    Crx knockout mice revealed that CRX is absolutely required for photoreceptor outer segment morphogenesis and phototransduction gene expression, moving beyond genetics to establish its developmental necessity, while the R90W mutation was shown to reduce DNA binding and cause Leber congenital amaurosis.

    Evidence Targeted Crx gene disruption in mice with ERG and gene expression analysis; EMSA and reporter assays for R90W mutation with clinical genetics

    PMID:10581037 PMID:9931337

    Open questions at the time
    • Downstream chromatin mechanism of transcriptional activation unknown
    • Full target gene repertoire not determined
    • Synaptic phenotype not yet examined
  3. 2000 High

    Systematic domain mapping and interaction studies defined the homeodomain as the DNA-binding unit, the OTX tail/WSP domain as transactivation modules, and the leucine zipper of NRL as a direct physical partner of the CRX homeodomain, while the NLS was mapped to residues 88–98 and phosducin isoforms were identified as CRX inhibitors.

    Evidence Deletion/point mutagenesis with EMSA and reporter assays; yeast two-hybrid and GST pull-down for NRL interaction; GFP-fusion live-cell imaging for NLS; yeast two-hybrid, GST pull-down, and reporter assays for phosducin

    PMID:10866677 PMID:10887186 PMID:10967037 PMID:10984472

    Open questions at the time
    • Chromatin-level mechanism of activation not yet addressed
    • CRX interactome beyond NRL and phosducin incomplete
    • Structural basis of homeodomain-NRL interaction unknown
  4. 2001 High

    Discovery that polyglutamine-expanded ataxin-7 physically interacts with CRX and suppresses its transactivation and DNA binding in SCA7 transgenic mice explained the cone-rod dystrophy phenotype in spinocerebellar ataxia type 7 as CRX transcription interference.

    Evidence Yeast two-hybrid, co-immunoprecipitation, EMSA, and RT-PCR in SCA7 transgenic mouse retinas

    PMID:11580893

    Open questions at the time
    • Whether ataxin-7 interaction is direct or through a complex was not fully resolved
    • Chromatin occupancy by ataxin-7 at CRX targets not yet tested
  5. 2003 High

    Domain mapping of the CRX–ataxin-7 interaction to glutamine-rich regions and demonstration by ChIP that both proteins co-occupy CRX-regulated promoters in vivo established that ataxin-7 acts directly at CRX target chromatin.

    Evidence Co-immunoprecipitation of truncation mutants, ChIP in retinal tissue, transactivation assays

    PMID:14613968

    Open questions at the time
    • Mechanism by which nuclear ataxin-7 represses CRX (e.g., HAT interference) not determined
    • Whether CRX displacement from DNA or coactivator blockade is the primary effect unclear
  6. 2005 High

    Multiple studies converged to show that CRX activates photoreceptor genes by recruiting HAT co-activators (STAGA, CBP, p300) to promote H3 acetylation, physically interacts with Nr2e3 and Sp4 to co-occupy rod and cone gene loci, and that Crx-null photoreceptors fail both outer segment elongation and synaptogenesis.

    Evidence ChIP for HATs and histone marks in Crx−/− retinas; co-IP and ChIP for Nr2e3 and Sp4; electron microscopy of Crx−/− retinas

    PMID:15001570 PMID:15676071 PMID:15689355 PMID:15781457 PMID:17656371

    Open questions at the time
    • Whether CRX recruits HATs directly or via NRL/Nr2e3 was unresolved
    • Genome-wide binding profile not yet available
    • Mechanism of synaptic gene regulation not characterized
  7. 2008 High

    Demonstration that CRX recruits CBP, p300, and GCN5 to the RS1 promoter through specific CRX-responsive elements, validated in transgenic Xenopus, generalized the HAT-recruitment mechanism to additional CRX target genes.

    Evidence ChIP, site-directed mutagenesis, transgenic Xenopus in vivo reporter assay

    PMID:18927113

    Open questions at the time
    • Whether RS1 regulation involves NRL or other cofactors not tested
    • Enhancer vs. promoter contribution to CRX-dependent activation at this locus unclear
  8. 2009 Medium

    Identification of PANKY as a CRX-regulated negative feedback factor and NR2E3 heterodimerization with CRX via BRET2 expanded the network of CRX modulators and showed that disease-causing NR2E3 mutations can act dominantly by titrating CRX.

    Evidence EMSA and reporter assays for PANKY; BRET2 in HEK293T cells for NR2E3–CRX interaction with disease mutants

    PMID:19823680 PMID:20026326

    Open questions at the time
    • PANKY mechanism (direct DNA-binding inhibition vs. coactivator sequestration) not fully distinguished
    • NR2E3–CRX interaction not validated by reciprocal endogenous co-IP in retinal tissue
    • In vivo relevance of PANKY inhibition not demonstrated in animal model
  9. 2014 High

    Knock-in mouse models of CRX R90W and E168d2 established that disease severity correlates with mutant protein level and distinguished antimorphic from loss-of-function mechanisms, while the CrxRip model revealed that dominant CRX frameshifts obliterate OTX2 binding at the Nrl promoter, arresting rod differentiation.

    Evidence Knock-in mice with ERG, transactivation assays, and protein quantification; ChIP and rescue experiments in CrxRip retinas; pineal knockdown/overexpression in primary pinealocytes

    PMID:24382353 PMID:24516401 PMID:24877634

    Open questions at the time
    • How mutant CRX protein interferes with OTX2 binding mechanistically was not resolved
    • Whether antimorphic mechanism involves direct WT–mutant dimerization or chromatin competition unclear
  10. 2018 High

    Integrated CRX ChIP-Seq and transcriptomic analysis identified CRX target genes encoding presynaptic cytomatrix active zone proteins, explaining the synaptic defects in Crx mutant retinas and extending CRX's role beyond phototransduction to synaptic architecture.

    Evidence ChIP-Seq, RNA-seq, and immunohistochemistry in Crx mutant mouse retinas

    PMID:30084954

    Open questions at the time
    • Whether CRX directly or indirectly regulates synaptic genes not fully resolved for all targets
    • Functional rescue of synaptic phenotype not attempted
  11. 2023 High

    Knock-in models of CRX E80A and K88N demonstrated two distinct gain-of-function mechanisms: E80A increases transactivation of canonical targets, while K88N alters DNA-binding specificity to cause ectopic genomic binding, establishing that dominant CRX mutations can act through neomorphic as well as antimorphic pathways.

    Evidence Knock-in mouse models with integrated in vitro and in vivo molecular/functional analysis

    PMID:37963072

    Open questions at the time
    • Structural basis of altered K88N binding specificity unknown
    • Whether ectopic binding activates or represses novel targets not fully catalogued
  12. 2024 High

    Massively parallel reporter assays in CRX mutant retinas revealed that the E168d2 effector-domain mutation has distinct effects on silencers compared to R90W, including derepression of cone gene silencers and conversion of silencers to enhancers, showing that CRX's effector domain is required for both activation and repression at cis-regulatory elements.

    Evidence MPRA in knock-in mouse retina explants with chromatin accessibility analysis

    PMID:38355306

    Open questions at the time
    • Identity of the repressive cofactors recruited by CRX's effector domain unknown
    • Whether silencer-to-enhancer conversion occurs genome-wide or is locus-specific not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CRX homeodomain interactions with its diverse partners, the full catalog of CRX-dependent enhancers and silencers across photoreceptor subtypes, the identity of repressive cofactors recruited by CRX, and the mechanism by which dominant-negative CRX mutants interfere with wild-type function at the chromatin level.
  • No high-resolution structure of CRX homeodomain bound to DNA or partner proteins
  • Genome-wide CRX occupancy not compared across rod vs. cone subtypes at single-cell resolution
  • Repressive cofactors mediating CRX-dependent silencing unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9709957 Sensory Perception 3 R-HSA-4839726 Chromatin organization 2
Partners
ATXN7CBPNR2E3NRLOTX2PDCRAXSP4

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CRX is a photoreceptor-specific homeodomain transcription factor; missense mutation E80A in the recognition helix and frameshift mutation E168Δ1bp in the WSP motif cause autosomal dominant cone-rod dystrophy, establishing that CRX is essential for photoreceptor maintenance through either haploinsufficiency or dominant negative mechanisms. Human genetics (mutation identification by sequencing), domain analysis of recognition helix and WSP motif Cell High 9390563
1999 Crx-knockout mice fail to elaborate photoreceptor outer segments, lack rod and cone activity by ERG, and show reduced expression of photoreceptor- and pineal-specific genes, demonstrating that Crx is required for photoreceptor outer segment morphogenesis and phototransduction gene expression. Targeted gene disruption (knockout mouse), ERG, gene expression analysis Nature genetics High 10581037
1998 CRX binds to a pineal regulatory element (PIRE) with consensus TAATC/T in vitro and transactivates PIRE-reporter constructs, indicating CRX regulates pineal-specific genes including serotonin N-acetyltransferase (NAT) and PINA through direct DNA binding. Electrophoretic mobility shift assay (EMSA), transient transfection reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 9465110
2000 The leucine zipper of NRL physically interacts with the CRX homeodomain (and flanking glutamine-rich and basic regions), as demonstrated by yeast two-hybrid and GST pull-down assays; disease-causing CRX homeodomain mutations R41W and R90W decrease this interaction and reduce transcriptional synergy with NRL on the rhodopsin promoter. Yeast two-hybrid, GST pull-down, transient transfection reporter assay, deletion/point mutagenesis The Journal of biological chemistry High 10887186
1999 The CRX R90W homeodomain mutation causes reduced DNA binding to cis-regulatory elements in the rhodopsin promoter and significantly reduced transactivation of rhodopsin promoter and synergistic activation with NRL, resulting in recessive Leber congenital amaurosis. EMSA (DNA binding assay), transient transfection reporter assay, clinical genetics Human molecular genetics High 9931337
2001 Polyglutamine-expanded ataxin-7 interacts with CRX (demonstrated by yeast two-hybrid and coimmunoprecipitation), colocalizes in photoreceptors, suppresses CRX transactivation, and reduces CRX DNA-binding activity in SCA7 transgenic mice, causing cone-rod dystrophy through CRX transcription interference. Yeast two-hybrid, co-immunoprecipitation, EMSA, RT-PCR, transgenic mouse model Neuron High 11580893
2002 CRX functional domain analysis by deletion and point mutagenesis identified that: (1) a complete homeodomain is required for DNA binding; (2) the C-terminal region between amino acids 200–284 is essential for transcriptional activation; (3) the OTX tail and WSP domain control positive regulatory activity; and (4) several homeodomain missense mutations reduce DNA binding and transactivation. EMSA, transient transfection reporter assay, deletion/point mutagenesis Human molecular genetics High 11971869
2000 The nuclear localization signal (NLS) of CRX resides between residues 88–98 in the C-terminus of the homeodomain; the R90W LCA mutation disrupts nuclear targeting, causing cytoplasmic mislocalization of the mutant protein. GFP fusion protein live-cell imaging, confocal microscopy, point and deletion mutagenesis in HEK293T cells Investigative ophthalmology & visual science High 10967037
2000 Phosducin (Phd) and phosducin-like orphan protein 1 (PhLOP1) physically interact with CRX (shown by yeast two-hybrid, in vitro binding, and GST pull-down) and inhibit CRX transactivation of the IRBP promoter by ~50–70%; inhibition does not affect CRX DNA binding; the CRX-interacting domain maps to the carboxyl terminus of Phd isoforms. Yeast two-hybrid, in vitro binding assay, GST pull-down, co-transfection reporter assay, EMSA, immunohistochemistry Molecular and cellular biology High 10866677
2003 Ataxin-7 interacts with CRX through their respective glutamine-rich regions (mapped by co-immunoprecipitation of truncation/point mutants); ataxin-7 must localize to the nucleus to repress CRX transactivation; chromatin immunoprecipitation showed CRX and ataxin-7 co-occupy promoter and enhancer regions of CRX-regulated retinal genes in vivo. Co-immunoprecipitation with truncation/point mutants, transactivation assays, chromatin immunoprecipitation (ChIP) Human molecular genetics High 14613968
2005 Nr2e3 interacts with CRX through the DNA-binding domain of each protein (yeast two-hybrid, co-immunoprecipitation); Nr2e3 and Crx co-occupy promoter/enhancer regions of rod and cone genes in rod photoreceptors (ChIP on mouse retina); Nr2e3 promoter/enhancer occupancy is CRX-dependent; Nr2e3 enhances rhodopsin transcription but represses cone opsin transcription when interacting with Crx. Yeast two-hybrid, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transient transfection reporter assay, quantitative RT-PCR Human molecular genetics High 15689355
2005 Crx activates transcription of photoreceptor genes (rod and cone opsins) by recruiting HAT-containing co-activators STAGA, CBP, and p300 to target gene promoters/enhancers, promoting histone H3 acetylation; in Crx-/- mice, HAT association and H3 acetylation at opsin chromatin are significantly reduced, correlating with loss of opsin expression. Protein-protein interaction assays, quantitative RT-PCR, chromatin immunoprecipitation (ChIP) in developing mouse retina, Crx knockout analysis Human molecular genetics High 17656371
2005 Sp4 physically interacts with CRX through its zinc finger domain and the CRX homeodomain (co-immunoprecipitation), and synergizes with CRX to activate the rod opsin promoter; both Sp4 and CRX co-occupy the rod opsin and β-PDE promoters in retinal chromatin (ChIP). Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transient transfection reporter assay, in situ hybridization, immunohistochemistry The Journal of biological chemistry High 15781457
2004 Crx and Nrl are both required for full transcriptional activity of the PDE6A (rod cGMP phosphodiesterase α-subunit) gene promoter: Crx binds three TAAT-containing sites in the proximal promoter (DNase I footprinting, EMSA), mutation of two sites reduces reporter activity by up to 69%, and Pde6a mRNA is reduced 87% in Crx-/- mouse retina. DNase I footprinting, EMSA, site-directed mutagenesis, transient transfection reporter assay, quantitative RT-PCR in Crx-/- mice The Journal of biological chemistry High 15001570
2005 Crx-null photoreceptors show blocked outer segment elongation (failure to form the phototransduction apparatus) and severely abnormal synaptic endings in the outer plexiform layer, revealing essential roles for Crx in both outer segment morphogenesis and synaptogenesis. Ultrastructural analysis (electron microscopy) of Crx-/- mouse retina BMC neuroscience High 15676071
2009 PANKY (Ankrd33), a novel ankyrin repeat protein expressed specifically in photoreceptors and pineal gland, is transcriptionally regulated by CRX and acts as a transcriptional cofactor that suppresses CRX-activated photoreceptor genes; PANKY inhibits CRX DNA-binding activity as shown by EMSA. Transactivation reporter assay, EMSA, subcellular localization analysis, immunohistochemistry FEBS letters Medium 20026326
2014 CRX directly regulates Aanat (arylalkylamine N-acetyltransferase) expression in the pineal gland; adenovirus-mediated shRNA knockdown of Crx reduces Aanat expression and overexpression of Crx induces Aanat transcription in primary rat pinealocytes; CRX protein levels exhibit circadian rhythm controlled by sympathetic innervation. Adenovirus-mediated shRNA knockdown in primary pinealocyte culture, overexpression assay, quantitative RT-PCR, circadian expression analysis Endocrinology Medium 24877634
2014 OTX2 maintains Nrl expression in developing rods by binding the Nrl promoter; in dominant CRX frameshift mutant (CrxRip) retinas, OTX2 binding at the Nrl promoter is obliterated, leading to loss of NRL and arrested rod differentiation; ectopic OTX2 expression rescues the rod differentiation defect. Transcriptome profiling (RNA-seq), chromatin immunoprecipitation (ChIP), ectopic expression rescue experiment in knock-in mouse model The Journal of clinical investigation High 24382353
2014 Two mechanistically distinct CRX knock-in mouse models show that CRX(E168d2) frameshift protein fails to activate transcription and acts as an antimorphic (dominant negative) factor more strongly than CRX(R90W); disease severity correlates with mutant CRX expression level; both mutant proteins fail to activate transcription in vitro. Knock-in mouse models, ERG, transactivation assay, gene expression analysis, protein quantification PLoS genetics High 24516401
2015 Rax physically interacts with Crx (co-immunoprecipitation in cultured cells) and cooperatively transactivates rhodopsin and cone opsin promoters; conditional knockout of Rax in postnatal photoreceptors decreases rod and cone photoreceptor gene expression and reduces cone cell numbers. Co-immunoprecipitation, luciferase reporter assay, conditional knockout mouse, immunohistochemistry Molecular and cellular biology High 25986607
2018 CRX controls the establishment of the cytomatrix active zone (CAZ) and anchoring of ribbon synapses in photoreceptor presynaptic terminals; integrated CRX-ChIP-Seq with retinal transcriptomes identified CRX target genes encoding presynaptic CAZ proteins (REEP6, PSD95, MPP4, UNC119, UNC13, RGS7, RGS11); Crx mutant retinas show aberrant ribbon shape, number, and length. ChIP-Seq, RNA-seq, immunohistochemistry in Crx mutant mice Human molecular genetics High 30084954
2008 CRX controls retinal expression of the RS1 (retinoschisin) gene through two CRX-responsive elements (CREs) in the proximal RS1 promoter; CRX, CBP, P300, GCN5, and acetylated histone H3 associate with the RS1 promoter in vivo (ChIP); mutation of either CRE strongly decreases RS1 expression in transgenic Xenopus. Chromatin immunoprecipitation, site-directed mutagenesis, reporter assay, transgenic Xenopus in vivo reporter Nucleic acids research High 18927113
2013 Samd7 is a novel CRX-regulated transcriptional repressor in the retina; Crx occupies Samd7 first-intron enhancer sequences containing conserved CRX binding motifs; Crx knockdown with shRNA reduces Samd7 reporter activity and endogenous Samd7 protein; Samd7 in turn suppresses CRX-mediated transactivation in a dose-dependent manner. ChIP (genome-wide dataset), in vitro electroporation of retinal reporters, shRNA knockdown, luciferase reporter assay PloS one Medium 23565263
2023 Two gain-of-function CRX homeodomain mutations cause dominant retinopathies through distinct mechanisms: p.E80A increases CRX-mediated transactivation of canonical CRX target genes in developing photoreceptors; p.K88N alters CRX DNA-binding specificity, causing binding at ectopic sites and severe perturbation of CRX target gene expression. Knock-in mouse models, molecular analysis in vitro and in vivo, integrated molecular/functional evidence eLife High 37963072
2024 Massively parallel reporter assays (MPRAs) in knock-in mouse retinas show that CRX p.R90W (DNA-binding domain) and p.E168d2 (effector domain) mutations affect overlapping sets of enhancers, but p.E168d2 has distinct effects on silencers; silencers near cone photoreceptor genes are derepressed in p.E168d2 retinas; some regulatory elements convert from silencers to enhancers when CRX lacks a functional effector domain. Massively parallel reporter assay (MPRA) in knock-in mouse retina explants, chromatin accessibility analysis Genome research High 38355306
2009 NR2E3 forms homodimers and heterodimerizes with CRX in vivo; disease-causing mutations in the NR2E3 DNA-binding domain impair both homodimerization and NR2E3/CRX complex formation as measured by Bioluminescence Resonance Energy Transfer (BRET2); the adRP-linked G56R mutant retains CRX interaction but acts as a dominant repressor by titrating CRX. BRET2 in HEK293T cells, transactivation assay with mutant proteins PloS one Medium 19823680
2000 CRX functional domains were mapped: an intact homeodomain is required for DNA binding; both the OTX tail and WSP domain control positive transcriptional regulatory activity; CRX-NRL synergy depends on the same mapped CRX transactivation domains including the OTX tail and WSP domain. Deletion analysis, EMSA, transient transfection reporter assay The Journal of biological chemistry High 10984472
2016 In the CrxRdy cat (frameshift mutation in Crx), mutant Crx allele is overexpressed producing high levels of mutant protein lacking transactivation activity, exerting a dominant negative effect on wild-type Crx; cone and rod Crx target gene expression is significantly downregulated; the mutant Crx protein fails transactivation in dual-luciferase assay. Quantitative RT-PCR, Western blot, immunohistochemistry, dual-luciferase transactivation assay, ERG in large animal model Investigative ophthalmology & visual science High 27427859
2019 In the rat pineal gland, OTX2 and CRX are exclusively present in melatonin-producing pinealocytes; siRNA knockdown of Crx reduces melatonin-synthesizing enzyme expression (transcript and protein) and melatonin release; simultaneous knockdown of both Otx2 and Crx produces an even larger reduction, demonstrating cooperative regulation of pineal melatonin synthesis. siRNA knockdown in primary rat pinealocytes, quantitative RT-PCR, Western blot, melatonin measurement, immunohistochemistry Journal of pineal research Medium 30803008
1997 A major cis-activator element of the IRBP gene (-70 to -45 region) contains a CRX consensus binding element (GATTAA); CRX binds this element in retinal nuclear extracts; mutation of this element suppresses promoter activity, establishing CRX as a direct transcriptional activator of IRBP gene expression. EMSA, deletion analysis, site-directed mutagenesis, transient transfection reporter assay in embryonic chick retina cells Molecular vision Medium 9479006

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell 483 9390563
1999 Retinopathy and attenuated circadian entrainment in Crx-deficient mice. Nature genetics 447 10581037
2009 Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell stem cell 444 19128794
1998 A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene. American journal of human genetics 229 9792858
2005 The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Human molecular genetics 227 15689355
2006 CRD-BP mediates stabilization of betaTrCP1 and c-myc mRNA in response to beta-catenin signalling. Nature 208 16778892
2001 Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron 194 11580893
2000 The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation. The Journal of biological chemistry 190 10887186
1999 Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function. Human molecular genetics 161 9931337
2009 A novel C-type lectin with two CRD domains from Chinese shrimp Fenneropenaeus chinensis functions as a pattern recognition protein. Molecular immunology 130 19328552
2004 Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney epithelial cells. Experimental cell research 119 15265686
1998 Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene. Investigative ophthalmology & visual science 112 9804150
2013 The TLR4 antagonist CRX-526 protects against advanced diabetic nephropathy. Kidney international 110 23423259
2004 Zebrafish cone-rod (crx) homeobox gene promotes retinogenesis. Developmental biology 108 15081370
1998 A pineal regulatory element (PIRE) mediates transactivation by the pineal/retina-specific transcription factor CRX. Proceedings of the National Academy of Sciences of the United States of America 100 9465110
1997 Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro. Oncogene 96 9178888
2021 Gene Therapy of Dominant CRX-Leber Congenital Amaurosis using Patient Stem Cell-Derived Retinal Organoids. Stem cell reports 76 33513359
2001 Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX. Human mutation 72 11748842
2002 Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy. Human molecular genetics 71 11971869
2007 Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation. Human molecular genetics 70 17656371
2005 The vacuolar DHHC-CRD protein Pfa3p is a protein acyltransferase for Vac8p. The Journal of cell biology 70 16186255
2003 Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization. Human molecular genetics 68 14613968
2018 Identification and Mapping of the Clubroot Resistance Gene CRd in Chinese Cabbage (Brassica rapa ssp. pekinensis). Frontiers in plant science 66 29868100
2018 A "Tug of War" Maintains a Dynamic Protein-Membrane Complex: Molecular Dynamics Simulations of C-Raf RBD-CRD Bound to K-Ras4B at an Anionic Membrane. ACS central science 64 29532030
2009 Differential CRX and OTX2 expression in human retina and retinoblastoma. Journal of neurochemistry 64 19686387
2014 OTX2 loss causes rod differentiation defect in CRX-associated congenital blindness. The Journal of clinical investigation 63 24382353
2000 Modulation of CRX transactivation activity by phosducin isoforms. Molecular and cellular biology 63 10866677
2005 Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice. BMC neuroscience 62 15676071
2014 The phenotypic variability of retinal dystrophies associated with mutations in CRX, with report of a novel macular dystrophy phenotype. Investigative ophthalmology & visual science 61 25270190
2000 Functional domains of the cone-rod homeobox (CRX) transcription factor. The Journal of biological chemistry 61 10984472
2007 CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a mammalian endoribonuclease. Nucleic acids research 60 17264115
2014 Mechanistically distinct mouse models for CRX-associated retinopathy. PLoS genetics 53 24516401
2010 Two novel CRX mutant proteins causing autosomal dominant Leber congenital amaurosis interact differently with NRL. Human mutation 51 20513135
2015 Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina. Molecular and cellular biology 50 25986607
2014 Mechanisms of blindness: animal models provide insight into distinct CRX-associated retinopathies. Developmental dynamics : an official publication of the American Association of Anatomists 49 24888636
2007 Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat. Experimental eye research 49 17467693
2004 Functional analysis of the rod photoreceptor cGMP phosphodiesterase alpha-subunit gene promoter: Nrl and Crx are required for full transcriptional activity. The Journal of biological chemistry 49 15001570
2000 A CRX null mutation is associated with both Leber congenital amaurosis and a normal ocular phenotype. Investigative ophthalmology & visual science 49 10892846
2014 MicroRNA-340-mediated degradation of microphthalmia-associated transcription factor (MITF) mRNA is inhibited by coding region determinant-binding protein (CRD-BP). The Journal of biological chemistry 48 25414259
2008 Overexpression of mRNA-binding protein CRD-BP in malignant melanomas. Oncogene 48 18454174
2016 A single-CRD C-type lectin is important for bacterial clearance in the silkworm. Developmental and comparative immunology 46 27519466
2021 Allele-specific gene editing to rescue dominant CRX-associated LCA7 phenotypes in a retinal organoid model. Stem cell reports 44 34653402
2012 CRX variants in cone-rod dystrophy and mutation overview. Biochemical and biophysical research communications 44 22960069
2019 CRX Expression in Pluripotent Stem Cell-Derived Photoreceptors Marks a Transplantable Subpopulation of Early Cones. Stem cells (Dayton, Ohio) 43 30681766
2003 The mammalian Crx genes are highly divergent representatives of the Otx5 gene family, a gnathostome orthology class of orthodenticle-related homeogenes involved in the differentiation of retinal photoreceptors and circadian entrainment. Molecular biology and evolution 43 12654938
2009 CRX is a diagnostic marker of retinal and pineal lineage tumors. PloS one 40 19936203
2005 Sp4 is expressed in retinal neurons, activates transcription of photoreceptor-specific genes, and synergizes with Crx. The Journal of biological chemistry 40 15781457
2010 Transcriptional Regulation of CRD-BP by c-myc: Implications for c-myc Functions. Genes & cancer 39 21779431
2014 Role of CRD-BP in the growth of human basal cell carcinoma cells. The Journal of investigative dermatology 37 24468749
2013 Involvement of a pattern recognition receptor C-type lectin 7 in enhancing cellular encapsulation and melanization due to its carboxyl-terminal CRD domain in the cotton bollworm, Helicoverpa armigera. Developmental and comparative immunology 37 24269901
2009 Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX. PloS one 37 19823680
2006 Docosahexaenoic acid promotes photoreceptor differentiation without altering Crx expression. Investigative ophthalmology & visual science 36 16799048
2012 Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD. PloS one 34 22558175
2005 Leukemia inhibitory factor blocks expression of Crx and Nrl transcription factors to inhibit photoreceptor differentiation. Investigative ophthalmology & visual science 33 15980254
2002 The rod cGMP-phosphodiesterase beta-subunit promoter is a specific target for Sp4 and is not activated by other Sp proteins or CRX. The Journal of biological chemistry 33 11943774
2005 spe-10 encodes a DHHC-CRD zinc-finger membrane protein required for endoplasmic reticulum/Golgi membrane morphogenesis during Caenorhabditis elegans spermatogenesis. Genetics 31 16143610
2001 Autosomal dominant retinal degeneration and bone loss in patients with a 12-bp deletion in the CRX gene. Investigative ophthalmology & visual science 31 11328746
2020 A C-type lectin with dual-CRD from Tribolium castaneum is induced in response to bacterial challenge. Pest management science 30 32519818
2014 Function of two novel single-CRD containing C-type lectins in innate immunity from Eriocheir sinensis. Fish & shellfish immunology 30 24561128
1997 A major cis activator of the IRBP gene contains CRX-binding and Ret-1/PCE-I elements. Molecular vision 30 9479006
2006 Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic rhinitis. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 29 17069098
2019 Pathogenicity discrimination and genetic test reference for CRX variants based on genotype-phenotype analysis. Experimental eye research 28 31626798
2014 Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N-acetyltransferase (AANAT). Endocrinology 28 24877634
2008 Induction of functional photoreceptor phenotype by exogenous Crx expression in mouse retinal stem cells. Investigative ophthalmology & visual science 28 18172122
2003 CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression. Anticancer research 28 12894594
2000 Nuclear trafficking of photoreceptor protein crx: the targeting sequence and pathologic implications. Investigative ophthalmology & visual science 28 10967037
2015 Using Zinc Finger Nuclease Technology to Generate CRX-Reporter Human Embryonic Stem Cells as a Tool to Identify and Study the Emergence of Photoreceptors Precursors During Pluripotent Stem Cell Differentiation. Stem cells (Dayton, Ohio) 27 26608863
2002 Electrophysiologic and phenotypic features of an autosomal cone-rod dystrophy caused by a novel CRX mutation. Ophthalmology 27 12359607
2019 A single-CRD C-type lectin (CgCLec-3) with novel DIN motif exhibits versatile immune functions in Crassostrea gigas. Fish & shellfish immunology 26 31279080
2018 A complete, homozygous CRX deletion causing nullizygosity is a new genetic mechanism for Leber congenital amaurosis. Scientific reports 26 29568065
2014 Derivation of human differential photoreceptor cells from adult human dermal fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD. Genes to cells : devoted to molecular & cellular mechanisms 26 24456169
2002 Identification, tissue expression, and functional characterization of Otx3, a novel member of the Otx family. The Journal of biological chemistry 26 12055180
2022 Exploring CRD mobility during RAS/RAF engagement at the membrane. Biophysical journal 24 35778842
2007 Genotype-phenotype correlation in a German family with a novel complex CRX mutation extending the open reading frame. Ophthalmology 24 17320181
2015 OTX2 is a therapeutic target for retinoblastoma and may function as a common factor between C-MYC, CRX, and phosphorylated RB pathways. International journal of oncology 23 26397460
2013 The evolutionary analysis reveals domain fusion of proteins with Frizzled-like CRD domain. Gene 23 24135643
2001 Screening for CRX gene mutations in Chinese patients with Leber congenital amaurosis and mutational phenotype. Ophthalmic genetics 23 11449318
2018 Cone-rod homeobox CRX controls presynaptic active zone formation in photoreceptors of mammalian retina. Human molecular genetics 22 30084954
2016 CrxRdy Cat: A Large Animal Model for CRX-Associated Leber Congenital Amaurosis. Investigative ophthalmology & visual science 22 27427859
2010 Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII. FEBS letters 22 20138881
2016 Autosomal recessive retinitis pigmentosa with homozygous rhodopsin mutation E150K and non-coding cis-regulatory variants in CRX-binding regions of SAMD7. Scientific reports 21 26887858
2008 Swf1p, a member of the DHHC-CRD family of palmitoyltransferases, regulates the actin cytoskeleton and polarized secretion independently of its DHHC motif. Molecular biology of the cell 21 18701706
2017 A novel dominant CRX mutation causes adult-onset macular dystrophy. Ophthalmic genetics 20 28945142
2013 Sterile alpha motif containing 7 (samd7) is a novel crx-regulated transcriptional repressor in the retina. PloS one 20 23565263
2019 Homeobox genes in melatonin-producing pinealocytes: Otx2 and Crx act to promote hormone synthesis in the mature rat pineal gland. Journal of pineal research 19 30803008
2023 Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms. eLife 18 37963072
2020 Association of CRX genotypes and retinal phenotypes confounded by variable expressivity and electronegative electroretinogram. Clinical & experimental ophthalmology 18 32112665
2016 Characterization of a dual-CRD galectin in the silkworm Bombyx mori. Developmental and comparative immunology 18 26944801
2009 Robust marking of photoreceptor cells and pinealocytes with several reporters under control of the Crx gene. Developmental dynamics : an official publication of the American Association of Anatomists 18 19882727
2002 Visual improvement in Leber congenital amaurosis and the CRX genotype. Ophthalmic genetics 18 11910559
2010 RegIV potentiates colorectal carcinoma cell migration and invasion via its CRD domain. Cancer genetics and cytogenetics 17 20417867
2004 Novel 615delC mutation in the CRX gene in a Japanese family with cone-rod dystrophy. American journal of ophthalmology 17 15531334
2002 Novel de novo mutation in CRX gene in a Japanese patient with leber congenital amaurosis. American journal of ophthalmology 17 12208271
2024 Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors. Genome research 16 38355306
2019 NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face. Glycobiology 16 31094416
2009 Generation of light-sensitive photoreceptor phenotypes by genetic modification of human adult ocular stem cells with Crx. Investigative ophthalmology & visual science 16 19850845
2009 Panky, a novel photoreceptor-specific ankyrin repeat protein, is a transcriptional cofactor that suppresses CRX-regulated photoreceptor genes. FEBS letters 16 20026326
2017 The functional characterization and comparison of two single CRD containing C-type lectins with novel and typical key motifs from Portunus trituberculatus. Fish & shellfish immunology 15 28916358
2012 Immunohistochemical expression of CRX in extracranial malignant small round cell tumors. The American journal of surgical pathology 15 22790857
2008 CRX controls retinal expression of the X-linked juvenile retinoschisis (RS1) gene. Nucleic acids research 15 18927113