Affinage

RCC1

Regulator of chromosome condensation · UniProt P18754

Length
421 aa
Mass
45.0 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RCC1 is the chromatin-bound guanine nucleotide exchange factor (GEF) for the Ran GTPase and the source of the nuclear/chromosomal RanGTP gradient that organizes nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope/pore reformation (PMID:1944575, PMID:10408446). It is a seven-bladed beta-propeller whose nucleotide-exchange active region sits opposite its chromosome-binding surface, with catalytically essential residues (conserved repeat histidines and D128/D182/H304) at the Ran interface contacting Ran's switch II and phosphate-binding region (PMID:9510255, PMID:8864848, PMID:10369786). Catalysis proceeds through ternary Ran·RCC1·nucleotide intermediates and a nucleotide-free Ran·RCC1 binary complex, accelerating GDP release ~10⁵-fold (PMID:7548002, PMID:11336674). RCC1 docks directly on nucleosomes and histones H2A/H2B via its N-terminal tail and a flexible switchback loop, an interaction that stimulates its GEF activity and couples RanGTP production to chromatin (PMID:11375490, PMID:20739938, PMID:20347844). Loss-of-function studies established that RCC1 acts solely as a Ran-GEF to license DNA replication, nuclear import, and importin-α recycling in interphase, and as a negative regulator of premature CDK1 activation that couples S-phase completion to mitosis (PMID:7988569, PMID:7929123, PMID:10885581, PMID:1851087, PMID:1855255). On mitotic chromosomes, RCC1 GEF activity alone is sufficient to drive bipolar spindle assembly (PMID:10408446, PMID:22215983). Chromatin association and activity are tuned by post-translational modification—CDK1/cyclin B phosphorylation of the N-terminal/NLS region that blocks importin binding and sustains chromosomal RanGTP production, NRMT-mediated α-N-methylation that stabilizes mitotic chromatin binding, and PRMT6 arginine methylation required for chromatin association—and by regulators including RanBP1 (inhibitory) and Nup50 (stimulatory during NPC reassembly) (PMID:15014043, PMID:15203004, PMID:17435751, PMID:20668449, PMID:33539787, PMID:7616957, PMID:34725842).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Establishing that RCC1 is the dedicated GEF for Ran defined its core biochemical activity and linked a chromatin protein to a specific GTPase switch.

    Evidence In vitro nucleotide exchange assays with substrate-specificity controls and biochemical co-purification of a stable RCC1·Ran complex from HeLa chromatin

    PMID:1944575 PMID:1961752

    Open questions at the time
    • Did not reveal the structural basis of exchange
    • Spatial coupling of GEF activity to chromatin not yet established
  2. 1991 High

    Genetic epistasis in fission yeast and loss-of-function in mammalian cells placed Ran downstream of the RCC1-family GEF and showed RCC1 prevents premature mitosis, connecting it to cell-cycle control.

    Evidence pim1/spi1 suppressor genetics in fission yeast and temperature-shift tsBN2 cells with CDK1 kinase and cyclin B readouts

    PMID:1851087 PMID:1855255

    Open questions at the time
    • Molecular intermediary between RCC1/Ran and CDK1 activation not fully defined
    • cdc25C requirement only partially characterized
  3. 1989 High

    Subcellular fractionation defined RCC1 as a chromatin-associated nuclear protein that disperses in mitosis, framing it as a chromatin-tethered enzyme.

    Evidence DNase I/NaCl extraction, DNA-cellulose binding, and immunofluorescence

    PMID:2677018

    Open questions at the time
    • Molecular determinants of chromatin binding unresolved
    • Direct histone contact not yet shown
  4. 1995 High

    Quantitative kinetics resolved the exchange mechanism as a multi-step ternary-complex pathway and assigned RanBP1 as a negative regulator, beginning the regulatory map.

    Evidence Transient/equilibrium fluorescence kinetics with fluorescent nucleotides and in vitro GEF-inhibition assays with mutant Ran and RanBP1

    PMID:7548002 PMID:7616957 PMID:7819259

    Open questions at the time
    • Structural basis of intermediates not yet visualized
    • RanBP1 regulation characterized largely in vitro/yeast
  5. 1994 High

    Reconstitution and microinjection established that RCC1 functions solely as a Ran-GEF in interphase to license DNA replication, nuclear import competence, and importin-α recycling.

    Evidence Immunodepletion/Ran(T24N) inactivation in Xenopus extracts and NLS-substrate microinjection in tsBN2 cells

    PMID:10885581 PMID:7929123 PMID:7988569

    Open questions at the time
    • Quantitative gradient parameters in interphase not defined
    • Importin recycling mechanism partly inferential
  6. 1998 High

    High-resolution crystallography and mutagenesis revealed the seven-bladed propeller architecture and identified catalytic residues, separating the exchange active site from the chromatin-binding surface.

    Evidence 1.7 Å crystal structure plus alanine-scanning kinetics identifying repeat histidines and D128/D182/H304

    PMID:10369786 PMID:8864848 PMID:9510255

    Open questions at the time
    • Conformational dynamics during catalysis not captured by a static structure
  7. 1999 High

    Epistasis and reconstitution placed RCC1 upstream of RanGTP in chromatin-driven spindle assembly, eventually showing GEF activity is sufficient to nucleate a bipolar spindle.

    Evidence Chromatin/RCC1-bead assays and immunodepletion in Xenopus M-phase extracts with Ran-GTP add-back

    PMID:10408446 PMID:22215983 PMID:40

    Open questions at the time
    • Downstream spindle assembly factors released by RanGTP only partly enumerated here
  8. 2001 High

    Direct demonstration that RCC1 binds nucleosomes/histones H2A-H2B and that this stimulates exchange activity established the mechanistic basis for chromatin-localized RanGTP production.

    Evidence Direct histone/mononucleosome binding assays coupled to in vitro GEF measurement, later the Ran·RCC1 nucleotide-free crystal structure

    PMID:11336674 PMID:11375490

    Open questions at the time
    • Atomic details of the nucleosome contact awaited the 2010 structure
  9. 2004 High

    Live-cell FRAP and an allosteric tail model showed RCC1 dynamically cycles on chromatin, with binary RCC1·Ran binding stably and successful exchange driving release, coupling catalysis to local RanGTP output.

    Evidence FRAP/FCS in living cells, kinetic modeling, FRET tail biosensor, and N-terminal tail/switchback-loop mutagenesis

    PMID:12604592 PMID:18762580 PMID:20347844 PMID:23601311

    Open questions at the time
    • In vivo RanGTP flux not directly quantified
    • Two mobility states' chromatin sites not molecularly defined
  10. 2004 High

    Identification of CDK1/cyclin B phosphorylation of the N-terminal/NLS region (including Ser11) explained how RCC1 is released from importin control to sustain chromosomal RanGTP during mitosis.

    Evidence In vitro kinase assays, phosphosite mutagenesis, importin-binding and FRAP readouts, phospho-specific antibodies

    PMID:15014043 PMID:15203004 PMID:17855385

    Open questions at the time
    • Isoform-specific contributions only partially resolved
    • Phosphatase that reverses the mark not defined here
  11. 2007 High

    Discovery of RCC1 α-N-methylation and its writer NRMT linked an N-terminal modification to stable mitotic chromatin binding and faithful spindle-pole formation.

    Evidence Mass spectrometry, site-directed mutagenesis, NRMT RNAi, live imaging and spindle-phenotype analysis

    PMID:17435751 PMID:20565941 PMID:20668449

    Open questions at the time
    • Interplay between methylation and phosphorylation on the same tail not fully resolved
  12. 2010 High

    The Drosophila RCC1–nucleosome core particle structure and switchback-loop mapping provided atomic detail for how RCC1 contacts histone and DNA, rationalizing nucleosome-enhanced exchange.

    Evidence 2.9 Å crystal structure of RCC1 on the nucleosome core particle plus loop/tail binding assays

    PMID:20347844 PMID:20739938

    Open questions at the time
    • Conformational coupling between loop docking and Ran-binding surface inferred, not directly visualized in action
  13. 2017 High

    Structural and affinity analyses explained the importin-α3 selectivity of RCC1 nuclear import as dependent on conformational accommodation of the beta-propeller flanking the NLS.

    Evidence Affinity measurements, SAXS/crystallography, and propeller-NLS junction mutagenesis, building on reconstituted import assays

    PMID:10744690 PMID:10811825 PMID:29042532

    Open questions at the time
    • Physiological role of the importin-independent import pathway underexplored
  14. 2021 High

    Identification of a PRMT6 arginine-methylation axis and Nup50 stimulation extended the regulatory network controlling RCC1 chromatin association and Ran activation during NPC reassembly.

    Evidence Co-IP, in vitro methylation, chromatin fractionation, PRMT6 inhibitor, and in vitro NPC assembly/GEF stimulation with Nup50 plus RanBP1 degron studies

    PMID:32594833 PMID:33539787 PMID:34725842

    Open questions at the time
    • Crosstalk among methylation, phosphorylation, and Nup50/RanBP1 inputs not integrated
    • Quantitative contribution of each input to the in vivo gradient unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple post-translational marks, chromatin mobility states, and Ran/Nup50/RanBP1 regulators are quantitatively integrated to shape the spatial RanGTP gradient in space and time remains unresolved.
  • No unified model linking modification state to gradient geometry
  • In vivo RanGTP flux during transitions not directly measured
  • Disease relevance not established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0003677 DNA binding 3 GO:0042393 histone binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-9609507 Protein localization 3 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
CDK1KPNA4NRMTNUP50PRMT6RANRANBP1
Complex memberships
Ran·RCC1 binary complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 RCC1 specifically catalyzes the exchange of guanine nucleotides on the Ran GTPase (but not on c-Ha-ras p21), establishing RCC1 as the guanine nucleotide exchange factor (GEF) for Ran. In vitro guanine nucleotide exchange assay with purified RCC1 and Ran/p21ras proteins Nature High 1944575
1991 RCC1 forms a stable complex with the 25 kDa Ran GTPase (ras-related nuclear protein) purified from HeLa cell chromatin; the complex is dissociated by excess Mg2+ and GDP or GTP. Biochemical purification from HeLa chromatin, co-purification, immunoprecipitation, guanine nucleotide binding assay Proceedings of the National Academy of Sciences of the United States of America High 1961752
1989 RCC1 protein (p45) localizes to the nucleus and binds chromatin; it is released by DNase I digestion or 0.3 M NaCl but not by 2 M NaCl alone after DNase I, indicating chromatin (not nuclear matrix) association. In mitotic cells, p45 disperses into the cytoplasm. Subcellular fractionation, DNase I digestion, NaCl extraction, DNA-cellulose binding, immunofluorescence The Journal of cell biology High 2677018
1998 Crystal structure of human RCC1 at 1.7 Å resolution reveals a seven-bladed beta-propeller formed from seven internal repeats of 51–68 residues; the nucleotide-exchange active region is located opposite the chromosome-binding region. X-ray crystallography at 1.7 Å resolution Nature High 9510255
2001 Crystal structure of the Ran·RCC1 nucleotide-free complex at 1.8 Å defines the GEF reaction intermediate; biochemical experiments show a sulfate ion in the P loop stabilizes the Ran·RCC1 complex and inhibits nucleotide dissociation. The P loop lysine interaction with an acidic residue is identified as a crucial element of the exchange mechanism. X-ray crystallography at 1.8 Å, biochemical GEF assays Cell High 11336674
1995 The kinetic mechanism of RCC1-catalyzed nucleotide exchange on Ran involves a four-step pathway forming ternary Ran·RCC1·nucleotide complexes and a nucleotide-free Ran·RCC1 binary complex; RCC1 increases GDP dissociation rate from ~1.5×10⁻⁵ s⁻¹ to 21 s⁻¹ (~10⁵-fold) and has similar affinity for Ran·GDP and Ran·GTP. Equilibrium and transient kinetic fluorescence measurements with fluorescent nucleotides Biochemistry High 7548002
1995 RCC1 stimulates guanine nucleotide exchange on Ran ~10⁵-fold under saturating conditions; RanGAP1 has no effect on the Ran(Q69L) GTPase-deficient mutant. Ran(T24N) interacts nearly normally with RCC1 but has decreased nucleotide affinity, leading to stabilization of the Ran(T24N)·RCC1 complex that depletes available RCC1 in vivo. Fluorescence-based GEF and GAP assay, kinetic analysis Biochemistry High 7819259
1999 Chromosome-associated RCC1 GEF activity is required for chromatin-induced mitotic spindle formation in Xenopus egg extracts; Ran-GTP alone induces microtubule nucleation and spindle-like structures in M-phase extract, placing RCC1 upstream of Ran-GTP in the spindle assembly pathway. Chromatin bead assay in Xenopus egg extracts, immunodepletion, addition of Ran-GTP Nature High 10408446
2001 RCC1 binds directly to mononucleosomes and to histones H2A and H2B; binding of RCC1 to nucleosomes or histones H2A/H2B stimulates its catalytic GEF activity toward Ran. Direct binding assays with purified histones/mononucleosomes, in vitro GEF activity assay Science High 11375490
2010 Crystal structure at 2.9 Å of Drosophila RCC1 bound to the nucleosome core particle reveals atomic details of how RCC1 contacts both histone and DNA components of the nucleosome. X-ray crystallography at 2.9 Å resolution Nature High 20739938
2007 RCC1 is alpha-N-methylated on its N-terminal serine or proline residue; methylation requires removal of the initiating methionine and the presence of Pro and Lys at positions 3 and 4. Methylation-defective RCC1 mutants bind chromatin less effectively during mitosis and cause spindle-pole defects, indicating alpha-N-methylation stabilizes chromatin association. Mass spectrometry identification of modification, site-directed mutagenesis, live-cell imaging, spindle phenotype analysis Nature cell biology High 17435751
2010 NRMT (N-terminal RCC1 methyltransferase) is identified as the alpha-N-methyltransferase responsible for methylating RCC1; knockdown of NRMT recapitulates the multi-spindle pole phenotype seen with methylation-defective RCC1 mutants. Enzyme identification by substrate docking and mutational analysis, RNAi knockdown with spindle phenotype readout Nature High 20668449
2004 Cdc2 (CDK1)/cyclin B kinase phosphorylates serines in or near the NLS of human RCC1; this phosphorylation is required for RCC1 to generate RanGTP on mitotic chromosomes, prevents importin alpha/beta binding to RCC1, and is necessary for proper spindle assembly and chromosome segregation. In vitro kinase assay, phosphomimetic/non-phosphorylatable mutants, importin binding assay, spindle assembly phenotype in mammalian cells Genes & development High 15014043
2021 PRMT6 arginine-methylates RCC1; this methylation is required for RCC1 association with chromatin and activation of Ran. CK2 phosphorylates and stabilizes PRMT6 (via deubiquitylation), defining a CK2α–PRMT6–RCC1 signaling axis. Disruption reduces Ran activation and causes mitotic defects. Co-immunoprecipitation, in vitro methylation assay, chromatin fractionation, PRMT6 inhibitor (EPZ020411), loss-of-function with mitotic phenotype readout Molecular cell High 33539787
2004 RCC1 rapidly and dynamically associates/dissociates with chromatin in living cells; this mobility is regulated during the cell cycle. The binary RCC1·Ran complex binds stably to chromatin, and successful nucleotide exchange dissociates the complex, releasing RCC1 and RanGTP, thereby coupling catalytic activity to RanGTP production on chromatin. FRAP in living cells, kinetic modeling, in vivo nucleotide exchange coupling experiment The Journal of cell biology High 12604592
2002 RCC1 localizes predominantly to chromosomes in mitotic human cells via an N-terminal lysine-rich region; mislocalization of RCC1 or perturbation of the Ran GTP/GDP cycle causes defects in spindle morphology including chromosome misalignment and abnormal spindle pole numbers. GFP fusion live imaging, deletion mutagenesis, dominant Ran mutant expression, spindle morphology analysis Current biology High 12194828
2004 CDK1/cyclin B phosphorylates serine 11 in the N-terminal region of RCC1 during mitosis; this phosphorylation inhibits importin alpha/beta binding to RCC1 and maintains high mobility of RCC1 on chromosomes during metaphase, supporting localized Ran-GTP production. FRAP, phosphosite mutagenesis, importin binding assay, phospho-specific antibody in mitotic cells Current biology High 15203004
2008 The N-terminal tail of RCC1 is essential for association with DNA but inhibits histone binding. Apo-Ran promotes RCC1 binding to both DNA and histones through a tail-mediated allosteric conformational switch; importin-alpha binding opposes this effect. FRET biosensor detects conformational changes in the tail during mitosis in living cells. Binding assays, FRET biosensor in living cells, mutagenesis The Journal of cell biology High 18762580
1991 Loss of RCC1 function in tsBN2 cells during S phase activates p34cdc2 histone H1 kinase (requires cyclin B complex), induces premature mitosis with spindle formation, and subsequent mitotic exit with cyclin B degradation — establishing RCC1 as a negative regulator of CDK1 activation that couples S phase completion to mitosis. Temperature-shift of tsBN2 cells, kinase activity assay, cell cycle phenotype analysis, DNA synthesis inhibitor controls The EMBO journal High 1851087
1992 Loss of RCC1 function in tsBN2 cells requires cdc25C (located in the cytoplasm) for chromosome condensation; cdc25C translocates to nuclei upon RCC1 loss and undergoes a molecular shift coincident with p34cdc2 kinase activation. Microinjection of anti-cdc25C antibody into tsBN2 cells, immunofluorescence localization, immunoblot Molecular biology of the cell Medium 1337289
1994 In Xenopus egg extracts, RCC1 is required for DNA replication (not chromatin decondensation or nuclear formation); the dominant-negative Ran(T24N) mutant inactivates RCC1 as a GEF by binding stably to it. Nuclear assembly and DNA replication are rescued by excess RCC1 or by high levels of GTP-bound Ran, indicating RCC1 functions solely as a GEF in interphase. Immunodepletion from Xenopus egg extracts, addition of recombinant Ran mutants, DNA replication and nuclear assembly assays, in vitro GEF binding assay The EMBO journal High 7988569
2000 Nuclear import of RCC1 occurs by at least two mechanisms: (1) a classical importin-alpha3-dependent pathway requiring the NLS in the N-terminal domain, a preexisting Ran gradient, and energy; (2) a second pathway independent of importin-alpha, importin-beta, soluble factors, existing Ran gradient, and energy. Permeabilized cell import assay, recombinant factor reconstitution, pA-RCC1 fusion construct, energy depletion, inhibitor analysis The Journal of cell biology High 10811825
2000 RCC1 nuclear import specifically requires karyopherin alpha3 (importin alpha3/Qip) and not alpha1 or alpha2 isoforms; binding depends on basic residues in the RCC1 NLS; karyopherin beta1 and Ran are also required. Permeabilized cell import assay with individual recombinant karyopherins, in vitro binding assay The Journal of biological chemistry High 10744690
2017 Importin alpha3 recognizes RCC1 with ~10-fold higher affinity than importin alpha1 despite identical NLS-binding grooves; selectivity depends on importin alpha3's greater conformational flexibility to accommodate the RCC1 beta-propeller flanking the NLS. Removing the beta-propeller or inserting a linker between NLS and propeller disrupts selectivity. Affinity measurements, structural analysis by SAXS/crystallography, mutagenesis of propeller-NLS junction Nature communications High 29042532
1992 RCC1 deletion of the DNA-binding N-terminal domain does not abolish complementation of tsBN2 cells; the deleted RCC1 still associates with the nucleosome fraction, indicating chromatin binding is mediated through other proteins and the N-terminal region serves primarily as a nuclear localization signal. Transfection of deletion mutants into tsBN2 cells, sucrose gradient fractionation, salt/DNase extraction Journal of cell science Medium 1506422
1996 Conserved histidine residues in the C-terminal part of each RCC1 repeat are essential for the catalytic rate (kcat) of nucleotide exchange on Ran, while N-terminal repeat residues affect substrate affinity (Km); alanine substitution of these histidines reduces catalytic activity, identifying them as the catalytic site. Alanine-scanning mutagenesis, steady-state kinetic analysis of GEF activity, microinjection into tsBN2 cells Journal of biochemistry High 8864848
1999 Alanine mutagenesis of conserved surface residues of RCC1 identifies D128, D182, and H304 as invariant residues critical for kcat of the GEF reaction; docking model places these at the center of the Ran-RCC1 interface, contacting switch II and the phosphate binding area of Ran. Alanine mutagenesis, steady-state kinetic analysis, surface plasmon resonance, computational docking Journal of molecular biology High 10369786
1995 RanBP1 inhibits RCC1-stimulated guanine nucleotide release from Ran in vitro; the inhibition depends on Ran, and overproduction of RanBP1 is detrimental to RCC1-deficient cells, establishing RanBP1 as a negative regulator of RCC1. In vitro GEF inhibition assay with purified GST-RanBP1, yeast genetic growth assay Molecular & general genetics Medium 7616957
2008 Histone H2B phosphorylation by caspase-activated Mst1 kinase immobilizes RCC1 on chromosomes and reduces nuclear RanGTP levels during early apoptosis, blocking nuclear transport (NLS-containing proteins including NF-kappaB remain bound to importins in the cytoplasm); RCC1 is proposed to 'read' the apoptotic histone code. Live-cell imaging of RCC1 mobility, phosphomimetic H2B expression, Mst1 knockdown, nuclear transport assay Nature cell biology Medium 19060893
2010 RCC1 uses a conformationally flexible 'switchback loop' and its N-terminal tail (not the face opposite to the Ran-binding face as previously proposed) to bind nucleosomes; this juxtaposes the loop to the Ran-binding surface, providing a mechanism for nucleosome-enhanced exchange activity. Biochemical binding assays, deletion/mutagenesis of RCC1 loop and tail Journal of molecular biology Medium 20347844
2010 The N-terminal tail of RCC1 stabilizes chromatin interaction in live cells; alpha-N-methylation of the tail (at K4) promotes chromatin binding, and this stabilization by Ran (RanT24N) requires the tail. Mutation D182A (exchange-deficient) increases RCC1 mobility on chromatin but retains ability to bind nucleotide-free Ran. FRAP in live cells, mutagenesis of RCC1 N-terminal tail, methylation-deficient mutants BMC cell biology Medium 20565941
2003 The dynamic association of RCC1 with chromatin is modulated by Ran-dependent nuclear export pathways; inhibition of Crm1/RanGTP-dependent export (leptomycin B) increases RCC1 mobility. Release of RCC1 from chromatin in permeabilized cells requires cytosol and GTP, not Ran alone. FRAP in live cells, leptomycin B treatment, permeabilized cell chromatin release assay Molecular biology of the cell Medium 14565978
1994 Loss of RCC1 in living tsBN2 cells suppresses nuclear protein import; the loss of import competence is intrinsic to the RCC1-deficient nucleus (not corrected by wild-type cytosol), demonstrating RCC1 is required for nuclear import competence. Microinjection of NLS substrate into tsBN2 heterokaryons and permeabilized cells at non-permissive temperature The Journal of biological chemistry Medium 7929123
2007 Human RCC1 is expressed as at least three isoforms (alpha, beta, gamma) differing in N-terminal regions; RCC1gamma has stronger chromatin affinity, weaker importin alpha3-beta interaction, and is more phosphorylated at serine 11 in mitosis than RCC1alpha. Serine 11 phosphorylation specifically controls RCC1gamma mitotic function. Isoform expression analysis, chromatin binding assays, importin binding assay, phospho-specific antibody, GFP localization, tsBN2 complementation Journal of cell science Medium 17855385
2014 Oxidative stress reduces RCC1 GEF exchange activity (restored by DTT); mass spectrometry identifies multiple solvent-exposed cysteines oxidized in cells treated with diamide, including Cys93 which is normally buried upon Ran contact. Cys93Ser substitution dramatically reduces exchange activity by impairing RCC1 binding to Ran·GDP. In vitro GEF assay, mass spectrometry of oxidized cysteines, site-directed mutagenesis (Cys93Ser), FRAP Molecular and cellular biology Medium 25452301
1996 Dis3 directly binds Ran and the Dis3·Ran complex enhances RCC1 GEF activity on Ran in vitro; in the presence of Dis3, the Km of RCC1 for Ran is reduced by half while kcat is unchanged. In vivo, a 200 kDa complex of Dis3, Spi1 (Ran homolog), and Pim1 (RCC1 homolog) is detected. Two-hybrid, direct binding assay, in vitro GEF kinetic analysis, size-exclusion chromatography co-fractionation The EMBO journal Medium 8896453
2021 Nup50 stimulates RCC1 GEF activity through an N-terminal fragment; Nup50 mutants defective in RCC1 binding and stimulation cannot support NPC assembly in vitro, while excess RCC1 can compensate for Nup50 loss, demonstrating Nup50 acts via the Ran/RCC1 system in nuclear pore complex reformation at mitotic exit. RNAi/immunodepletion in cells and Xenopus extracts, in vitro NPC assembly assay, GEF stimulation assay, rescue experiments The EMBO journal High 34725842
2020 RanBP1 controls mitotic RCC1 dynamics in human somatic cells; RanBP1 degradation (auxin-induced degron) alters RCC1 mobility and relocalization of the spindle assembly factor HURP, demonstrating RanBP1 modulates the spatial distribution and magnitude of Ran-GTP production on mitotic chromosomes. Auxin-induced degron depletion of RanBP1, FRAP/FLIP of GFP-RCC1, HURP localization imaging Cell cycle Medium 32594833
1991 The fission yeast RCC1 homolog pim1 is required to prevent premature mitosis; overexpression of spi1 (yeast Ran homolog TC4) rescues pim1 mutants, establishing genetic epistasis placing the Ran GTPase downstream of the RCC1-family GEF in cell cycle control. Yeast genetics, temperature-sensitive mutant, suppressor screen, gene disruption Cell High 1855255
1995 RCC1 loss in tsBN2 cells prevents efficient nuclear import; RanGTP (generated by nuclear RCC1) is required for recycling of importin alpha from the nucleus back to the cytoplasm, as importin alpha injected into tsBN2 nuclei at non-permissive temperature was retained rather than exported. Microinjection of importin alpha into tsBN2 cell nuclei, immunocytochemistry of endogenous importin alpha Cell structure and function Medium 10885581
2011 RCC1-coated beads in Xenopus egg extracts are sufficient to induce bipolar mitotic spindle formation, demonstrating that RCC1's GEF activity alone (generating a local RanGTP gradient) is sufficient to reconstitute chromatin-driven spindle assembly. Bead reconstitution assay in Xenopus M-phase egg extracts with purified RCC1 PLoS biology High 22215983
2003 Caffeine inhibits RCC1 GEF activity by preventing Ran·RCC1 binary complex formation in vitro; adenine and 2'-deoxyadenosine also inhibit RCC1 GEF activity by the same mechanism. In vitro GEF assay, nucleotide/base inhibitor screen Genes to cells Medium 12694532
2013 RCC1 on chromatin exists in two mobility states: a highly mobile state trapped within chromatin, and a transiently immobilized state that is stabilized during mitosis; only the immobilized state interacts with Ran, restricting GEF activity to specific chromatin sites. Fluorescence correlation spectroscopy in living cells Biophysical journal Medium 23601311

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature 595 1944575
1996 A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nature genetics 427 8673101
1999 Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature 413 10408446
1989 The RCC1 protein, a regulator for the onset of chromosome condensation locates in the nucleus and binds to DNA. The Journal of cell biology 329 2677018
2010 Structure of RCC1 chromatin factor bound to the nucleosome core particle. Nature 314 20739938
1995 Interaction of the nuclear GTP-binding protein Ran with its regulatory proteins RCC1 and RanGAP1. Biochemistry 289 7819259
1991 Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide. Proceedings of the National Academy of Sciences of the United States of America 251 1961752
1998 The 1.7 A crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller. Nature 250 9510255
1991 Premature initiation of mitosis in yeast lacking RCC1 or an interacting GTPase. Cell 217 1855255
2001 Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell 207 11336674
1995 The kinetic mechanism of Ran--nucleotide exchange catalyzed by RCC1. Biochemistry 200 7548002
1996 Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1. Human molecular genetics 196 8817343
1987 Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation. Genes & development 195 3678831
2001 Chromatin docking and exchange activity enhancement of RCC1 by histones H2A and H2B. Science (New York, N.Y.) 192 11375490
1991 Loss of RCC1, a nuclear DNA-binding protein, uncouples the completion of DNA replication from the activation of cdc2 protein kinase and mitosis. The EMBO journal 182 1851087
1993 RCC1 in the cell cycle: the regulator of chromosome condensation takes on new roles. Trends in biochemical sciences 181 8480369
1990 A yeast mutant, PRP20, altered in mRNA metabolism and maintenance of the nuclear structure, is defective in a gene homologous to the human gene RCC1 which is involved in the control of chromosome condensation. Molecular & general genetics : MGG 152 2277633
1994 A mutant form of the Ran/TC4 protein disrupts nuclear function in Xenopus laevis egg extracts by inhibiting the RCC1 protein, a regulator of chromosome condensation. The EMBO journal 131 7988569
2007 N-terminal alpha-methylation of RCC1 is necessary for stable chromatin association and normal mitosis. Nature cell biology 125 17435751
1994 A fission yeast RCC1-related protein is required for the mitosis to interphase transition. The EMBO journal 123 8313905
1998 Identification of a large Myc-binding protein that contains RCC1-like repeats. Proceedings of the National Academy of Sciences of the United States of America 118 9689053
1996 p619, a giant protein related to the chromosome condensation regulator RCC1, stimulates guanine nucleotide exchange on ARF1 and Rab proteins. The EMBO journal 117 8861955
2004 Phosphorylation of RCC1 in mitosis is essential for producing a high RanGTP concentration on chromosomes and for spindle assembly in mammalian cells. Genes & development 115 15014043
2008 The RCC1 superfamily: from genes, to function, to disease. Biochimica et biophysica acta 114 18442486
1995 Diverse effects of the guanine nucleotide exchange factor RCC1 on RNA transport. Science (New York, N.Y.) 113 7534442
1993 Small nucleolar RNAs encoded by introns of the human cell cycle regulatory gene RCC1. The EMBO journal 112 8335005
2010 NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Nature 111 20668449
1995 The C terminus of the nuclear RAN/TC4 GTPase stabilizes the GDP-bound state and mediates interactions with RCC1, RAN-GAP, and HTF9A/RANBP1. The Journal of biological chemistry 109 7782302
2021 PRMT6 methylation of RCC1 regulates mitosis, tumorigenicity, and radiation response of glioblastoma stem cells. Molecular cell 107 33539787
2002 Targeting of RCC1 to chromosomes is required for proper mitotic spindle assembly in human cells. Current biology : CB 105 12194828
2003 The mammalian passenger protein TD-60 is an RCC1 family member with an essential role in prometaphase to metaphase progression. Developmental cell 101 12919680
1994 Loss of RCC1 leads to suppression of nuclear protein import in living cells. The Journal of biological chemistry 100 7929123
1992 RCC1, a regulator of mitosis, is essential for DNA replication. Molecular and cellular biology 91 1630449
1990 A 47-kDa human nuclear protein recognized by antikinetochore autoimmune sera is homologous with the protein encoded by RCC1, a gene implicated in onset of chromosome condensation. Proceedings of the National Academy of Sciences of the United States of America 91 2236072
2002 An evolutionarily conserved fission yeast protein, Ned1, implicated in normal nuclear morphology and chromosome stability, interacts with Dis3, Pim1/RCC1 and an essential nucleoporin. Journal of cell science 88 12376568
1990 Premature chromosome condensation is induced by a point mutation in the hamster RCC1 gene. Molecular and cellular biology 85 2300055
2003 A mechanism of coupling RCC1 mobility to RanGTP production on the chromatin in vivo. The Journal of cell biology 83 12604592
1995 A mutation in the RCC1-related protein pim1 results in nuclear envelope fragmentation in fission yeast. Proceedings of the National Academy of Sciences of the United States of America 83 7877997
1996 Dis3, implicated in mitotic control, binds directly to Ran and enhances the GEF activity of RCC1. The EMBO journal 78 8896453
1991 The maternally expressed Drosophila gene encoding the chromatin-binding protein BJ1 is a homolog of the vertebrate gene Regulator of Chromatin Condensation, RCC1. The EMBO journal 76 2022188
1995 Ran-binding protein-1 is an essential component of the Ran/RCC1 molecular switch system in budding yeast. The Journal of biological chemistry 75 7836422
2000 Nuclear import of the ran exchange factor, RCC1, is mediated by at least two distinct mechanisms. The Journal of cell biology 73 10811825
1996 RCC1 in the Ran pathway. Journal of biochemistry 70 8889801
2004 Phosphorylation regulates the dynamic interaction of RCC1 with chromosomes during mitosis. Current biology : CB 69 15203004
1992 Chromosome condensation caused by loss of RCC1 function requires the cdc25C protein that is located in the cytoplasm. Molecular biology of the cell 66 1337289
1991 Analysis of yeast prp20 mutations and functional complementation by the human homologue RCC1, a protein involved in the control of chromosome condensation. Molecular & general genetics : MGG 62 1865879
1992 DNA-binding domain of RCC1 protein is not essential for coupling mitosis with DNA replication. Journal of cell science 58 1506422
2012 A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8. BMC genomics 57 22899815
2000 The nuclear import of RCC1 requires a specific nuclear localization sequence receptor, karyopherin alpha3/Qip. The Journal of biological chemistry 56 10744690
1991 Mutation of the hamster cell cycle gene RCC1 is complemented by the homologous genes of Drosophila and S.cerevisiae. The EMBO journal 56 2022190
2008 Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1. The Journal of cell biology 54 18762580
2008 Apoptotic histone modification inhibits nuclear transport by regulating RCC1. Nature cell biology 49 19060893
1999 A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppressor proteins. Biochemical and biophysical research communications 49 10581175
2017 Three-dimensional context rather than NLS amino acid sequence determines importin α subtype specificity for RCC1. Nature communications 46 29042532
2016 RCC1-dependent activation of Ran accelerates cell cycle and DNA repair, inhibiting DNA damage-induced cell senescence. Molecular biology of the cell 46 26864624
1994 Overexpression of yeast homologs of the mammalian checkpoint gene RCC1 suppresses the class of alpha-tubulin mutations that arrest with excess microtubules. Genetics 46 8070652
2010 RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex. Journal of molecular biology 45 20347844
2017 Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells. International journal of pharmaceutics 42 28163220
2011 Mitotic spindle assembly around RCC1-coated beads in Xenopus egg extracts. PLoS biology 42 22215983
1991 The yeast SRM1 protein and human RCC1 protein share analogous functions. Cell regulation 42 1666302
1999 Model of the ran-RCC1 interaction using biochemical and docking experiments. Journal of molecular biology 39 10369786
1997 Yrb2p is a nuclear protein that interacts with Prp20p, a yeast Rcc1 homologue. The Journal of biological chemistry 39 9395535
2023 Synergistic effect of HDAC inhibitor Chidamide with Cladribine on cell cycle arrest and apoptosis by targeting HDAC2/c-Myc/RCC1 axis in acute myeloid leukemia. Experimental hematology & oncology 37 36849955
1999 Conformational states of the nuclear GTP-binding protein Ran and its complexes with the exchange factor RCC1 and the effector protein RanBP1. Biochemistry 36 10471274
1997 The balance of RanBP1 and RCC1 is critical for nuclear assembly and nuclear transport. Molecular biology of the cell 36 9348536
1990 Cloning of Xenopus RCC1 cDNA, a homolog of the human RCC1 gene: complementation of tsBN2 mutation and identification of the product. Journal of biochemistry 36 2361953
1995 RanBP1, a Ras-like nuclear G protein binding to Ran/TC4, inhibits RCC1 via Ran/TC4. Molecular & general genetics : MGG 34 7616957
2019 Novel Ran-RCC1 Inhibitory Peptide-Loaded Nanoparticles Have Anti-Cancer Efficacy In Vitro and In Vivo. Cancers 33 30769871
1996 Conserved histidine residues of RCC1 are essential for nucleotide exchange on Ran. Journal of biochemistry 32 8864848
2020 The Multifaceted Roles of RCC1 in Tumorigenesis. Frontiers in molecular biosciences 31 33102517
1995 The RCC1 protein interacts with Ran, RanBP1, hsc70, and a 340-kDa protein in Xenopus extracts. The Journal of biological chemistry 31 7738003
1993 Prp20, the Saccharomyces cerevisiae homolog of the regulator of chromosome condensation, RCC1, interacts with double-stranded DNA through a multi-component complex containing GTP-binding proteins. Journal of cell science 30 8270631
2021 Enhancement of plant cold tolerance by soybean RCC1 family gene GmTCF1a. BMC plant biology 28 34384381
2007 RCC1 isoforms differ in their affinity for chromatin, molecular interactions and regulation by phosphorylation. Journal of cell science 28 17855385
2010 The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells. BMC cell biology 23 20565941
2002 CHC1-L, a candidate gene for prostate carcinogenesis at 13q14.2, is frequently affected by loss of heterozygosity and underexpressed in human prostate cancer. International journal of cancer 23 12115502
2021 The nucleoporin Nup50 activates the Ran guanine nucleotide exchange factor RCC1 to promote NPC assembly at the end of mitosis. The EMBO journal 22 34725842
2003 The dynamic association of RCC1 with chromatin is modulated by Ran-dependent nuclear transport. Molecular biology of the cell 22 14565978
2000 Recycling of importin alpha from the nucleus is suppressed by loss of RCC1 function in living mammalian cells. Cell structure and function 22 10885581
2018 Exome sequencing and case-control analyses identify RCC1 as a candidate breast cancer susceptibility gene. International journal of cancer 21 29363114
1997 Nucleocytoplasmic recycling of the nuclear localization signal receptor alpha subunit in vivo is dependent on a nuclear export signal, energy, and RCC1. The Journal of cell biology 20 9334337
2014 Disruption of the ran system by cysteine oxidation of the nucleotide exchange factor RCC1. Molecular and cellular biology 19 25452301
1998 cDNA cloning, gene characterization and 13q14.3 chromosomal assignment of CHC1-L, a chromosome condensation regulator-like guanine nucleotide exchange factor. Genomics 19 9806834
2021 Down-regulation of RCC1 sensitizes immunotherapy by up-regulating PD-L1 via p27kip1 /CDK4 axis in non-small cell lung cancer. Journal of cellular and molecular medicine 18 33630417
2021 Allelic variants of the NLR protein Rpi-chc1 differentially recognize members of the Phytophthora infestans PexRD12/31 effector superfamily through the leucine-rich repeat domain. The Plant journal : for cell and molecular biology 18 33882622
2003 Caffeine mimics adenine and 2'-deoxyadenosine, both of which inhibit the guanine-nucleotide exchange activity of RCC1 and the kinase activity of ATR. Genes to cells : devoted to molecular & cellular mechanisms 18 12694532
2008 RCC1-like repeat proteins: a pangenomic, structurally diverse new superfamily of beta-propeller domains. Proteins 17 17680689
1996 Genetic interaction of DED1 encoding a putative ATP-dependent RNA helicase with SRM1 encoding a mammalian RCC1 homolog in Saccharomyces cerevisiae. Molecular & general genetics : MGG 17 9003298
2020 RanBP1 controls the Ran pathway in mammalian cells through regulation of mitotic RCC1 dynamics. Cell cycle (Georgetown, Tex.) 16 32594833
2020 Evolution and function of bacterial RCC1 repeat effectors. Cellular microbiology 16 32720355
2015 Methylation-silencing RCC1 expression is associated with tumorigenesis and depth of invasion in gastric cancer. International journal of clinical and experimental pathology 16 26823742
2008 The RCC1 domain of protein associated with Myc (PAM) interacts with and regulates KCC2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 18769030
2005 Nd6p, a novel protein with RCC1-like domains involved in exocytosis in Paramecium tetraurelia. Eukaryotic cell 16 16339730
2004 The Drosophila RCC1 homolog, Bj1, regulates nucleocytoplasmic transport and neural differentiation during Drosophila development. Developmental biology 16 15136144
2013 Cell cycle-dependent binding modes of the ran exchange factor RCC1 to chromatin. Biophysical journal 15 23601311
2021 Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1). International journal of molecular sciences 14 34298996
2020 Divergent Evolution of Legionella RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets. mBio 14 32209684
2019 Identification and Expression Profiling of the Regulator of Chromosome Condensation 1 (RCC1) Gene Family in Gossypium Hirsutum L. under Abiotic Stress and Hormone Treatments. International journal of molecular sciences 14 30965557
2011 Involvement of a helix-loop-helix transcription factor CHC-1 in CO(2)-mediated conidiation suppression in Neurospora crassa. Fungal genetics and biology : FG & B 14 22001287
1996 Replication of herpes simplex virus type 1 DNA is inhibited in a temperature-sensitive mutant of BHK-21 cells lacking RCC1 (regulator of chromosome condensation) and virus DNA remains linear. The Journal of general virology 14 8811026

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