Affinage

RHO

Rhodopsin · UniProt P08100

Round 2 corrected
Length
348 aa
Mass
38.9 kDa
Annotated
2026-04-28
130 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Rhodopsin (RHO) is a light-activated G protein–coupled receptor in rod photoreceptors that initiates the visual transduction cascade by coupling photon absorption to transducin activation. The 11-cis-retinal chromophore is held inactive by a Lys296–Glu113 salt bridge; photoisomerization breaks this constraint, driving stepwise TM5–TM6 rearrangement that opens a cytoplasmic crevice into which the Gαt C-terminal helix inserts to catalyze GDP/GTP exchange (PMID:1356370, PMID:19836958, PMID:29899450). Signal termination proceeds through rhodopsin kinase phosphorylation of C-terminal residues T336/S338, which form an intermolecular β-sheet with arrestin N-terminal β-strands, defining a conserved phosphorylation code for arrestin recruitment (PMID:28753425, PMID:26200343). Mutations in RHO cause autosomal dominant retinitis pigmentosa—with class II transmembrane/extracellular-domain mutations producing ER-retained misfolded protein, C-terminal mutations disrupting outer segment targeting, and constitutively activating mutations (e.g., A292E, G90D) causing congenital night blindness (PMID:2137202, PMID:8253795, PMID:8358437, PMID:7523628).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1984 High

    Cloning and sequencing of the human RHO gene established its exon-intron organization and 348-residue primary structure, providing the molecular foundation for all subsequent structure–function studies.

    Evidence Gene isolation and full nucleotide sequencing of human rhodopsin

    PMID:6589631

    Open questions at the time
    • No functional assays performed
    • Three-dimensional structure unknown at this stage
  2. 1988 High

    Identification of palmitoylation at Cys-322/Cys-323 revealed a post-translational lipid anchor that tethers the cytoplasmic tail to the membrane, defining a structural feature later recognized as helix 8.

    Evidence Biochemical peptide fractionation and chemical characterization of bovine rhodopsin C-terminal fragment

    PMID:3350146

    Open questions at the time
    • Functional consequence of palmitoylation for signaling or trafficking not tested
    • Human rhodopsin palmitoylation inferred from bovine data
  3. 1990 High

    Discovery of the Pro23His mutation and additional mutations at codons 58 and 347 as causes of autosomal dominant retinitis pigmentosa established RHO as the first identified ADRP gene and raised the question of how diverse mutations in a single receptor cause photoreceptor degeneration.

    Evidence PCR-based mutation screening in ADRP patient cohorts with cosegregation analysis

    PMID:2137202 PMID:2215617

    Open questions at the time
    • Molecular mechanism of degeneration for each mutation unknown
    • No biochemical classification of mutation effects yet
  4. 1990 High

    Mutagenesis of cytoplasmic loops demonstrated that distinct regions mediate transducin binding versus GDP/GTP exchange, dissecting the receptor–G protein coupling interface for the first time.

    Evidence Site-directed mutagenesis with flash photolysis and GTPase activity assays in vitro

    PMID:2218504

    Open questions at the time
    • Structural basis of loop–transducin contact not resolved
    • Role of helix 8 and C-terminus in G protein coupling not addressed
  5. 1992 High

    Demonstrating that disruption of the Lys296–Glu113 salt bridge causes constitutive transducin activation established the molecular constraint that holds dark-state rhodopsin inactive—a foundational insight for understanding both normal activation and gain-of-function disease mutations.

    Evidence Site-directed mutagenesis of K296 and E113 with in vitro transducin activation assays

    PMID:1356370

    Open questions at the time
    • Structural dynamics of salt bridge breakage during activation not visualized
    • Whether other interhelical contacts also restrain activation not addressed
  6. 1992 High

    Transgenic P23H mice reproduced human ADRP with dose-dependent photoreceptor degeneration, providing the first in vivo validation that a specific rhodopsin mutation is sufficient to cause the disease.

    Evidence Multiple transgenic mouse lines with graded expression; histology and ERG

    PMID:1418997

    Open questions at the time
    • Cellular mechanism of degeneration (misfolding, ER stress, proteasome impairment) not yet identified
    • Wild-type overexpression also caused degeneration, complicating interpretation
  7. 1993 High

    Systematic biochemical analysis of 21 ADRP mutants established two mechanistic classes: class II mutations (transmembrane/extracellular) cause misfolding and ER retention, while class I mutations (cytoplasmic/C-terminal) fold normally but affect function or trafficking, providing a framework that guided subsequent therapeutic strategies.

    Evidence HEK293S cell expression, retinal regeneration assay, immunofluorescence localization

    PMID:8253795

    Open questions at the time
    • Whether class II mutants trigger UPR or specific degradation pathways not tested
    • In vivo relevance of class assignments not yet confirmed
  8. 1993 High

    The A292E mutation was shown to constitutively activate transducin without chromophore, explaining congenital stationary night blindness as a gain-of-function mechanism distinct from the loss-of-function RP mutations.

    Evidence In vitro transducin activation assay with recombinant A292E opsin ± chromophore

    PMID:8358437

    Open questions at the time
    • Structural basis of A292E constitutive activity not resolved
    • Whether other night blindness mutations share this mechanism not fully explored
  9. 1994 High

    G90D was found to constitutively activate opsin by functionally substituting for the Glu-113 counterion, unifying the night-blindness mutations under a common salt-bridge disruption mechanism; separately, Q344ter truncation demonstrated that the C-terminus contains an outer segment targeting signal.

    Evidence Mutagenesis with suppressor analysis for G90D; transgenic mice with confocal immunofluorescence for Q344ter

    PMID:7523628 PMID:8107847

    Open questions at the time
    • Identity of the C-terminal targeting machinery unknown
    • Whether mislocalization alone is sufficient for degeneration not established
  10. 1996 High

    P347S transgenic mice showed rhodopsin-laden extracellular vesicles at the inner/outer segment junction, directly demonstrating that C-terminal mutations cause defective vectorial transport rather than protein misfolding.

    Evidence Transgenic mice with ultrastructural immunocytochemistry and confocal microscopy

    PMID:8943080

    Open questions at the time
    • Molecular machinery mediating C-terminal-dependent transport not identified
    • Contribution of vesicle shedding to photoreceptor death not quantified
  11. 2002 High

    P23H rhodopsin was shown to form high-molecular-weight aggregates in aggresomes and impair proteasome function, identifying proteostasis collapse as a specific toxic mechanism for class II misfolding mutants.

    Evidence FRET-based aggregation detection, immunofluorescence of aggresomes, proteasome activity assays in transfected cells

    PMID:12091393

    Open questions at the time
    • Whether proteasome impairment is the primary cause of photoreceptor death in vivo not established
    • Role of autophagy as alternative clearance pathway not tested
  12. 2003 High

    Mutagenesis of the NPxxY(x)5,6F motif revealed that the Y306–F313 interaction must break during Meta II formation but is separately required for G protein activation, defining helix 8 realignment as a distinct mechanistic step in receptor signaling.

    Evidence Alanine mutagenesis and disulfide trapping with UV-vis spectroscopy and transducin activation assays

    PMID:12601165

    Open questions at the time
    • Dynamics of helix 8 motion not captured at atomic resolution
    • Whether helix 8 rearrangement also controls arrestin recruitment not tested
  13. 2009 High

    Integration of crystal structures and biochemical data defined the complete activation cascade: retinal photoisomerization drives TM5–TM6 opening of a cytoplasmic crevice into which the Gα C-terminal helix inserts as a transmission rod to the nucleotide binding site, resolving the structural mechanism of GDP/GTP exchange.

    Evidence Synthesis of high-resolution crystal structures with biochemical activation studies

    PMID:19836958

    Open questions at the time
    • Full dynamics of the activation intermediate states not captured
    • Structural basis of kinetic selectivity for transducin over other G proteins not resolved
  14. 2015 High

    The first crystal structure of the rhodopsin–arrestin complex revealed that TM7 and helix 8 form the primary arrestin recruitment interface, and arrestin undergoes a ~20° inter-domain rotation to accommodate rhodopsin's second intracellular loop, establishing the structural basis of signal termination.

    Evidence Serial femtosecond XFEL crystallography with mutagenesis validation

    PMID:26200343

    Open questions at the time
    • Whether the pre-activated arrestin used captures the physiological binding mode debated
    • Membrane context and lipid contributions absent
  15. 2017 High

    Higher-resolution XFEL structure defined a phosphorylation code: phospho-T336, phospho-S338, and E341 of rhodopsin form an intermolecular β-sheet with three positively charged arrestin pockets, a mechanism generalizable across GPCRs.

    Evidence XFEL crystallography with phosphorylation-site identification and cross-GPCR mutagenesis validation

    PMID:28753425

    Open questions at the time
    • Full combinatorial phosphorylation code (barcode) not exhaustively mapped
    • Kinetic contribution of individual phosphorylation sites to arrestin affinity in vivo not determined
  16. 2018 High

    Cryo-EM structure of activated rhodopsin bound to Gi revealed unique structural signatures distinguishing Gi, Gs, and arrestin coupling, addressing the long-standing question of how a single GPCR architecture selects among effectors.

    Evidence Cryo-EM structure determination with comparative structural analysis

    PMID:29899450

    Open questions at the time
    • Transducin (Gt)-specific complex structure not yet determined at comparable resolution
    • How membrane composition modulates coupling selectivity remains unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of the native rhodopsin–transducin complex in a membrane environment, the precise contribution of each C-terminal phosphorylation site to arrestin affinity in vivo, and the mechanistic link between P23H aggregation/proteasome impairment and photoreceptor cell death.
  • No native rhodopsin–transducin complex structure at high resolution
  • In vivo phosphorylation barcode not fully mapped
  • Causal pathway from protein aggregation to rod cell death not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2 GO:0005929 cilium 2
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1643685 Disease 7 R-HSA-9709957 Sensory Perception 4
Partners
GNAI1GNAT1GNB1GRK1SAG

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 The human rhodopsin gene was isolated and fully sequenced, revealing a coding region interrupted by four introns at positions analogous to bovine rhodopsin, and a deduced amino acid sequence of 348 residues that is 93.4% homologous to bovine rhodopsin. Gene isolation and nucleotide sequencing Proceedings of the National Academy of Sciences of the United States of America High 6589631
1988 Two adjacent cysteine residues (Cys-322 and Cys-323) in the C-terminal cytoplasmic fragment of bovine rhodopsin are palmitoylated, identifying a post-translational lipid modification site on the protein. Covalent coupling to CPG-thiol glass, CNBr peptide separation and chemical characterization FEBS letters High 3350146
1990 A C→A transversion in codon 23 of the rhodopsin gene (Pro23His substitution) was identified as a mutation causing one form of autosomal dominant retinitis pigmentosa, establishing RHO as the disease gene. PCR-based mutation screening in patients vs. controls Nature High 2137202
1990 Three additional rhodopsin mutations (two in codon 347, one in codon 58) were found to cause autosomal dominant retinitis pigmentosa, and together with Pro23His account for ~18% of ADRP cases, with all patients showing abnormal rod function on ERG. Mutation screening of rhodopsin gene exons in 150 unrelated ADRP patients The New England journal of medicine High 2215617
1990 Mutations in the second and third cytoplasmic loops of rhodopsin (CD2 and EF1 mutants) allow normal transducin (Gt) binding but prevent Gt release in the presence of GTP, while a mutation at the cytoplasmic border of TM3 (CD1) prevents Gt binding entirely, demonstrating that distinct cytoplasmic loop regions are required for Gt activation vs. binding. Site-directed mutagenesis, flash photolysis to monitor Gt binding and dissociation, GTPase activity assay Science (New York, N.Y.) High 2218504
1991 Systematic screening identified 13 different point mutations at 12 amino acid positions in the rhodopsin gene among 161 ADRP patients, with mutation presence/absence correlating with disease status in 174/179 individuals tested in 17 families. PCR and denaturing gradient gel electrophoresis screening Proceedings of the National Academy of Sciences of the United States of America High 1862076
1991 A comprehensive survey of all rhodopsin gene exons in 150 ADRP patients identified 17 different mutations (all single amino acid substitutions), with class II mutations clustering in transmembrane and extracellular domains, establishing a mutational spectrum and preliminary structure-function map. Complete exon sequencing of rhodopsin gene in ADRP patients Proceedings of the National Academy of Sciences of the United States of America High 1833777
1992 Mutation of Lys-296 (retinal attachment site) or Glu-113 (Schiff base counterion) in rhodopsin causes constitutive activation of opsin (transducin activation in the absence of chromophore and light), establishing that a salt bridge between these two residues constrains rhodopsin to an inactive conformation. Site-directed mutagenesis, transducin activation assay in vitro Neuron High 1356370
1992 Transgenic mice expressing the human P23H rhodopsin mutation develop photoreceptor degeneration in all three lines, with severity correlated with transgene expression level, establishing the pathogenicity of this mutation in vivo; overexpression of wild-type human rod opsin also causes degeneration. Transgenic mouse generation, histology, ERG, immunostaining Neuron High 1418997
1993 Biochemical analysis of 21 ADRP rhodopsin mutants revealed two classes: class I mutants (G51V, V345M, P347S) resemble wild-type in yield, retinal regenerability, and plasma membrane localization; class II mutants are reduced in yield, fail to regenerate with 11-cis-retinal, and accumulate in the endoplasmic reticulum, with class II amino acids located in transmembrane and extracellular domains. Site-directed mutagenesis, transfection of HEK293S cells, immunofluorescence, retinal regeneration assay The Journal of biological chemistry High 8253795
1993 The GABA rho2 receptor was characterized, showing that it forms homooligomeric GABA-gated channels when expressed in Xenopus oocytes with pharmacological profiles similar to rho1 but with slower responses and higher potency for most agonists; this gene is distinct from the rhodopsin RHO gene. Xenopus oocyte expression, electrophysiology European journal of pharmacology Low 8386671
1993 The Ala292Glu rhodopsin mutation causes congenital stationary night blindness by anomalously activating transducin in the absence of chromophore (constitutive activation), while retaining normal light-dependent transducin activation, defining a mechanism for night blindness distinct from RP mutations. In vitro transducin activation assay with recombinant mutant opsin Nature genetics High 8358437
1994 The G90D rhodopsin mutation causes congenital night blindness by constitutively activating opsin; Asp-90 can substitute for the Schiff base counterion Glu-113, demonstrating proximity of these residues in 3D structure and a common mechanism for constitutively activating mutations that disrupt the Lys296–Glu113 salt bridge. Site-directed mutagenesis, transducin activation assay, suppressor mutation analysis Nature High 8107847
1994 A rhodopsin carboxy-terminus truncation mutation (Q344ter) does not impair transducin activation or rhodopsin kinase phosphorylation in vitro, but causes mislocalization of mutant protein to the plasma membrane of photoreceptor cell bodies in transgenic mice rather than outer segments, establishing that the C-terminus contains a signal required for outer segment targeting. Site-directed mutagenesis, transducin activation assay, transgenic mice, immunofluorescence confocal microscopy, electrophysiology The Journal of neuroscience : the official journal of the Society for Neuroscience High 7523628
1996 Transgenic mice expressing the P347S rhodopsin mutation show photoreceptor degeneration correlated with transgene expression, with accumulation of rhodopsin-laden extracellular vesicles near the inner/outer segment junction, indicating defective vectorial transport of rhodopsin to outer segment disc membranes as the pathogenic mechanism. Transgenic mice, ERG, immunocytochemistry, confocal microscopy, ultrastructural immunocytochemistry Proceedings of the National Academy of Sciences of the United States of America High 8943080
2002 The P23H rhodopsin mutation causes the protein to form high-molecular-weight oligomeric aggregates and accumulate in aggresomes (pericentriolar inclusion bodies requiring intact microtubules) in transfected cells; the aggregated protein is targeted for degradation by the ubiquitin-proteasome system, and its expression impairs overall proteasome function. Transfection, FRET, immunofluorescence, proteasome inhibitor treatment, dominant-negative ubiquitin co-expression The Journal of biological chemistry High 12091393
2003 The conserved NPxxY(x)5,6F motif in rhodopsin TM7 connects to cytoplasmic helix 8; the interaction between Y306 and F313 within this motif must be disrupted during Meta I/Meta II transition, as mutations eliminating this interaction rescue Meta II formation in 9-demethyl-retinal-reconstituted rhodopsin. However, these mutations dramatically reduce G protein activation, indicating helix 8 realignment is separately required for proper signal transduction. Site-directed mutagenesis (Ala replacements, disulfide bond engineering), UV-vis spectroscopy, transducin activation assay Proceedings of the National Academy of Sciences of the United States of America High 12601165
2005 Rhodopsin mutations causing ADRP can be classified into biochemical groups based on protein folding, retinal binding, membrane localization, and post-translational processing, with distinct gain-of-function (constitutive activation, dominant-negative) mechanisms underlying different mutations. Systematic review and classification of published biochemical and cellular studies Trends in molecular medicine Medium 15823756
2009 Activation of rhodopsin is mediated by photoisomerization of retinal triggering stepwise rearrangement of TM5-TM6 that opens a cytoplasmic crevice; the C-terminus of the Gα subunit of transducin binds into this crevice, and the Gα C-terminal helix acts as a transmission rod to the nucleotide binding site to catalyze GDP/GTP exchange. Integration of biochemical studies with high-resolution 3D crystal structures Trends in biochemical sciences High 19836958
2014 Molecular dynamics simulations of rhodopsin (and other GPCRs) reveal that a hydrophobic layer near the NPxxY motif acts as a gate that opens to form a continuous internal water channel only upon receptor activation; the conserved Y7.53 undergoes transitions between three conformations representing inactive, G-protein-activated, and metastates. Molecular dynamics simulation validated against available crystal structures Nature communications Medium 25203160
2015 Crystal structure of constitutively active human rhodopsin bound to pre-activated mouse visual arrestin (determined by serial femtosecond X-ray laser crystallography) reveals that rhodopsin uses TM7 and helix 8 to recruit arrestin, and arrestin adopts a ~20° inter-domain rotation that opens a cleft to accommodate a short helix from the second intracellular loop of rhodopsin. Serial femtosecond X-ray laser (XFEL) crystallography, biochemical mutagenesis validation Nature High 26200343
2017 XFEL crystal structure of the rhodopsin-arrestin complex shows that phosphorylated C-terminal tail residues T336 and S338 of rhodopsin, together with E341, form an intermolecular β-sheet with N-terminal β-strands of arrestin through electrostatic interactions with three positively charged pockets, defining a phosphorylation code for arrestin recruitment common to multiple GPCRs. X-ray free electron laser (XFEL) crystallography, phosphorylation site identification, mutagenesis and validation across multiple GPCRs Cell High 28753425
2018 Cryo-EM structure of activated human rhodopsin bound to inhibitory Gi protein reveals that major interactions are mediated by the C-terminal helix of the Giα subunit wedged into the cytoplasmic cavity of the TM helix bundle and contacting the N-terminus of helix 8 of rhodopsin; structural comparison with Gs-bound β2AR and arrestin-bound rhodopsin identifies unique structural signatures distinguishing Gs, Gi, and arrestin coupling. Cryo-electron microscopy structure determination, structural comparison Nature High 29899450

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Rho GTPases in cell biology. Nature 3906 12478284
2005 Rho GTPases: biochemistry and biology. Annual review of cell and developmental biology 2432 16212495
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2001 Rho GTPases and cell migration. Journal of cell science 965 11683406
1990 A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 885 2137202
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2016 Regulating Rho GTPases and their regulators. Nature reviews. Molecular cell biology 671 27301673
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2001 Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends in pharmacological sciences 652 11165670
2008 Rho GTPases in cancer cell biology. FEBS letters 629 18460342
2015 Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 611 26200343
1984 Isolation and nucleotide sequence of the gene encoding human rhodopsin. Proceedings of the National Academy of Sciences of the United States of America 491 6589631
1995 A role for Rho in Ras transformation. Proceedings of the National Academy of Sciences of the United States of America 485 8524848
2012 Rho family GTPases. Biochemical Society transactions 443 23176484
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1992 Constitutively active mutants of rhodopsin. Neuron 434 1356370
2003 Redox-dependent downregulation of Rho by Rac. Nature cell biology 433 12598902
1992 Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa. Neuron 416 1418997
1990 Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. The New England journal of medicine 398 2215617
1991 Rhodopsin mutations in autosomal dominant retinitis pigmentosa. Proceedings of the National Academy of Sciences of the United States of America 396 1862076
2005 Regulation of PTEN by Rho small GTPases. Nature cell biology 393 15793569
2005 Rho GTPases, statins, and nitric oxide. Circulation research 393 16339495
2003 The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nature neuroscience 382 12692556
2001 Cadherin engagement regulates Rho family GTPases. The Journal of biological chemistry 364 11457821
2017 Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors. Cell 359 28753425
1988 Two adjacent cysteine residues in the C-terminal cytoplasmic fragment of bovine rhodopsin are palmitylated. FEBS letters 339 3350146
2007 Rho kinase (ROCK) inhibitors. Journal of cardiovascular pharmacology 337 17666911
1999 Signaling to Rho GTPases. Experimental cell research 337 10579921
1990 Rhodopsin mutants that bind but fail to activate transducin. Science (New York, N.Y.) 330 2218504
2005 Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends in molecular medicine 316 15823756
1994 Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness. Nature 311 8107847
1992 Association between GTPase activators for Rho and Ras families. Nature 310 1522900
2003 Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation. Proceedings of the National Academy of Sciences of the United States of America 309 12601165
2006 FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling. Nature cell biology 308 16862148
1991 Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. Proceedings of the National Academy of Sciences of the United States of America 300 1833777
2009 A G protein-coupled receptor at work: the rhodopsin model. Trends in biochemical sciences 299 19836958
2005 Cytokinesis: welcome to the Rho zone. Trends in cell biology 299 16243528
2009 Wnt signaling pathways meet Rho GTPases. Genes & development 296 19204114
1994 A rhodopsin gene mutation responsible for autosomal dominant retinitis pigmentosa results in a protein that is defective in localization to the photoreceptor outer segment. The Journal of neuroscience : the official journal of the Society for Neuroscience 296 7523628
1999 Effectors for the Rho GTPases. Current opinion in cell biology 282 10047515
2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO reports 281 11256614
2002 Rho/Rho-kinase mediated signaling in physiology and pathophysiology. Journal of molecular medicine (Berlin, Germany) 280 12395147
2002 A rhodopsin mutant linked to autosomal dominant retinitis pigmentosa is prone to aggregate and interacts with the ubiquitin proteasome system. The Journal of biological chemistry 273 12091393
1993 Rhodopsin mutations responsible for autosomal dominant retinitis pigmentosa. Clustering of functional classes along the polypeptide chain. The Journal of biological chemistry 258 8253795
2003 Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nature cell biology 250 12510192
1993 Heterozygous missense mutation in the rhodopsin gene as a cause of congenital stationary night blindness. Nature genetics 248 8358437
1983 Human visual pigments: microspectrophotometric results from the eyes of seven persons. Proceedings of the Royal Society of London. Series B, Biological sciences 248 6140680
2007 Rho GTPases: functions and association with cancer. Clinical & experimental metastasis 224 18000759
1996 Transgenic mice carrying the dominant rhodopsin mutation P347S: evidence for defective vectorial transport of rhodopsin to the outer segments. Proceedings of the National Academy of Sciences of the United States of America 222 8943080
2012 Initiation of cell wall pattern by a Rho- and microtubule-driven symmetry breaking. Science (New York, N.Y.) 219 22984069
1994 GAPs for rho-related GTPases. Trends in genetics : TIG 217 7871593
2008 Regulation of cytokinesis by Rho GTPase flux. Nature cell biology 214 19060892
2018 Cryo-EM structure of human rhodopsin bound to an inhibitory G protein. Nature 212 29899450
1997 Characterization of RAC3, a novel member of the Rho family. The Journal of biological chemistry 210 9252344
2007 Development of Rho-kinase inhibitors for cardiovascular medicine. Trends in pharmacological sciences 209 17482681
2014 Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway. Nature communications 195 25203160
2013 Physiological roles of Rho and Rho effectors in mammals. European journal of cell biology 180 24183240
1989 Autosomal dominant retinitis pigmentosa (ADRP): localization of an ADRP gene to the long arm of chromosome 3. Genomics 176 2613244
2014 Rho GTPases: masters of cell migration. Small GTPases 172 24978113
2005 Targeting Rho and Rho-kinase in the treatment of cardiovascular disease. Trends in pharmacological sciences 169 16376997
2004 Rho proteins and cancer. Breast cancer research and treatment 156 14999150
2013 Rho GTPases in platelet function. Journal of thrombosis and haemostasis : JTH 145 23121917
2014 Epithelial junctions and Rho family GTPases: the zonular signalosome. Small GTPases 144 25483301
2014 Rho GTPases in collective cell migration. Small GTPases 143 25054920
2007 Taking Rho GTPases to the next level: the cellular functions of atypical Rho GTPases. Experimental cell research 140 17850788
2007 Involvement of Rho kinase in endothelial barrier maintenance. Arteriosclerosis, thrombosis, and vascular biology 139 17761936
2017 Paving the Rho in cancer metastasis: Rho GTPases and beyond. Pharmacology & therapeutics 137 28911825
2009 Rho GTPases in hematopoiesis and hemopathies. Blood 131 19965643
2019 Rho GTPases in cancer: friend or foe? Oncogene 123 31427738
1995 The Rho's progress: a potential role during neuritogenesis for the Rho family of GTPases. Trends in neurosciences 122 8592759
2001 Regulation of c-myc expression by PDGF through Rho GTPases. Nature cell biology 121 11389443
2004 Rho localization in cells and tissues. Experimental cell research 120 15093731
2015 Regulation of phagocytosis by Rho GTPases. Small GTPases 119 25941749
2017 Rho Protein: Roles and Mechanisms. Annual review of microbiology 113 28731845
1998 Different regions of Rho determine Rho-selective binding of different classes of Rho target molecules. The Journal of biological chemistry 106 9668072
2007 Rho/Rho-associated kinase-II signaling mediates disassembly of epithelial apical junctions. Molecular biology of the cell 104 17596509
2003 Regulation of endocytic traffic by Rho GTPases. The Biochemical journal 104 12564953
2005 Regulation of phagocytosis by Rho GTPases. Current topics in microbiology and immunology 103 15981459
2005 RhoGDIs revisited: novel roles in Rho regulation. Traffic (Copenhagen, Denmark) 103 16190977
2000 TraG from RP4 and TraG and VirD4 from Ti plasmids confer relaxosome specificity to the conjugal transfer system of pTiC58. Journal of bacteriology 102 10692358
2010 Rho kinase and hypertension. Biochimica et biophysica acta 101 20460153
2000 Tenascin-C suppresses Rho activation. The Journal of cell biology 99 10953015
2016 Rho Kinases and Cardiac Remodeling. Circulation journal : official journal of the Japanese Circulation Society 95 27251065
2006 Rho GTPases in animal cell mitosis. Current opinion in cell biology 92 16487696
2006 Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase. The Journal of biological chemistry 88 16574662
2002 Inhibition of Rho family GTPases by Rho GDP dissociation inhibitor disrupts cardiac morphogenesis and inhibits cardiomyocyte proliferation. Development (Cambridge, England) 86 11923206
2009 Rho GTPases in hepatocellular carcinoma. Biochimica et biophysica acta 84 19162129
2008 On the Rho'd: the regulation of membrane protrusions by Rho-GTPases. FEBS letters 84 18442478
1980 Physical and functional mapping of RP4-TOL plasmid recombinants: analysis of insertion and deletion mutants. Journal of bacteriology 84 6252192
2013 Hijacking of Rho GTPases during bacterial infection. Experimental cell research 83 23648569
1999 Cell adhesion and Rho small GTPases. Journal of cell science 82 10574699
1993 GABA rho 2 receptor pharmacological profile: GABA recognition site similarities to rho 1. European journal of pharmacology 82 8386671
1994 Rho and RNA: models for recognition and response. Molecular microbiology 80 8022288
1998 Regulation of inositol lipid kinases by Rho and Rac. Current opinion in genetics & development 79 9529607
2013 Mutationally activated Rho GTPases in cancer. Small GTPases 73 24088985
2004 Rho kinase regulates the intracellular micromechanical response of adherent cells to rho activation. Molecular biology of the cell 73 15146061
2002 B plexins activate Rho through PDZ-RhoGEF. FEBS letters 72 12372594
2013 Rho/Rho-associated kinase pathway in glaucoma (Review). International journal of oncology 68 24042317
1999 Distribution of Rho-kinase in the bovine brain. Biochemical and biophysical research communications 65 10491334
2006 The armadillo protein p0071 regulates Rho signalling during cytokinesis. Nature cell biology 64 17115030
2005 Clostridial Rho-inhibiting protein toxins. Current topics in microbiology and immunology 64 15981462
2020 Dysregulation of Rho GTPases in Human Cancers. Cancers 63 32392742
2008 Rho GTPases of the RhoBTB subfamily and tumorigenesis. Acta pharmacologica Sinica 62 18298893
2008 The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms. Molecular biology of the cell 62 18417612
1998 The Rho GTPases in macrophage motility and chemotaxis. Cell adhesion and communication 62 9823474
2018 Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer. World journal of gastroenterology 61 29531464
2014 Rho GTPases at the crossroad of signaling networks in mammals: impact of Rho-GTPases on microtubule organization and dynamics. Small GTPases 61 24691223
2007 Actin and Rho GTPases in herpesvirus biology. Trends in microbiology 61 17764949
2005 RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho. The Journal of biological chemistry 60 16014623
2006 Neuronal responses to myelin are mediated by rho kinase. Journal of neurochemistry 58 16441511
2005 Multifaceted role of Rho proteins in angiogenesis. Journal of mammary gland biology and neoplasia 58 16900393
2010 Plakoglobin regulates cell motility through Rho- and fibronectin-dependent Src signaling. Journal of cell science 57 20876660
2007 Transcription termination defective mutants of Rho: role of different functions of Rho in releasing RNA from the elongation complex. Journal of molecular biology 57 17599352
2009 Lysophosphatidylcholine induces glial cell activation: role of rho kinase. Glia 55 19115379
2013 Rho GTPases and cancer. BioFactors (Oxford, England) 54 24375503
2016 RHO binding to FAM65A regulates Golgi reorientation during cell migration. Journal of cell science 48 27807006
2014 Rho'ing in and out of cells: viral interactions with Rho GTPase signaling. Small GTPases 48 24691164
2012 Regulation of autophagosome formation by Rho kinase. Cellular signalling 47 22975682
1981 Introduction of bacteriophage Mu into bacteria of various genera and intergeneric gene transfer by RP4::Mu. Journal of bacteriology 47 6450749
2014 Rho GTPases in embryonic development. Small GTPases 46 25483305
2016 Rho Kinases in Autoimmune Diseases. Annual review of medicine 44 26768244
2005 Rho mediates cytokinesis and epiboly via ROCK in zebrafish. Molecular reproduction and development 44 15791595
2012 Historical overview of Rho GTPases. Methods in molecular biology (Clifton, N.J.) 43 22144264
2011 Functional role of Rho-kinase in ameloblast differentiation. Journal of cellular physiology 43 21792909
2004 Disruption of Rho signal transduction upon cell detachment. Journal of cell science 41 15226371
2000 Citron, a Rho target that affects contractility during cytokinesis. Microscopy research and technique 41 10816250
2006 Localization of the Rho GTPases and some Rho effector proteins in the sperm of several mammalian species. Zygote (Cambridge, England) 40 16822336
2010 RhoGDI: A rheostat for the Rho switch. Small GTPases 39 21686121
2010 RhoGTPases and Rho-effectors in hepatocellular carcinoma metastasis: ROCK N'Rho move it. Liver international : official journal of the International Association for the Study of the Liver 38 20726051