Affinage

MRC1

Macrophage mannose receptor 1 · UniProt P22897

Length
1456 aa
Mass
166.0 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The MRC1 symbol maps to two molecularly distinct, internally coherent proteins in this corpus, and the timeline supports both pictures independently. In yeast, Mrc1 (mediator of the replication checkpoint, the Claspin ortholog) is a replisome-associated factor that travels with the replication fork and couples fork progression to checkpoint signaling (PMID:12944972, PMID:12865299). It loads at early-firing origins before S phase and constrains their timing and efficiency independently of checkpoint function (PMID:21518960), and as part of a heterotrimeric Csm3-Tof1-Mrc1 mediator complex it associates with moving forks, with Tof1/Csm3 required for Mrc1 fork association (PMID:19819872). Mrc1 directly engages the replicative helicase and polymerase—binding Mcm6 through its central coiled-coil (PMID:19620285) and both halves of the Pol epsilon catalytic subunit Pol2 (PMID:18851837)—and stimulates the CMG helicase to set normal fork elongation rate (PMID:17652453, PMID:34387546). In its checkpoint role, Mec1/Rad3-Tel1-dependent phosphorylation at S/TQ clusters licenses Mrc1 to bridge Mec1 to Rad53/Cds1 as an enzyme-substrate platform, accelerating Rad53 activation ~70-fold via its conserved C-terminal domain (PMID:12865299, PMID:19457865, PMID:22298423); in fission yeast this requires Mrc1 binding the Cds1 FHA domain (PMID:15173168, PMID:14585996). Checkpoint and replicative functions are cleanly separable by mutation: the replicative arm supports sister chromatid cohesion, suppression of inappropriate recombination, telomere protection, and parental histone H3-H4 transfer to the lagging strand for heterochromatin inheritance, all independent of Rad53 signaling (PMID:16137625, PMID:15282308, PMID:17618841, PMID:39094566). Rad53-mediated phosphorylation of Mrc1 in turn slows fork elongation by blocking its CMG-stimulating activity, integrating checkpoint feedback into replication speed (PMID:34387546). The mammalian protein MRC1/CD206 is structurally and functionally unrelated: a transmembrane macrophage/dendritic-cell C-type lectin organized into a cysteine-rich domain, fibronectin type II repeat, and eight carbohydrate-recognition domains (PMID:1294118), whose CRD4 mediates Ca2+-dependent recognition of mannose, GlcNAc, fucose, and oligomannose glycans as defined by crystal structures (PMID:33545173, PMID:34089345). It functions as an endocytic receptor for mannosylated antigens and pathogen ligands (PMID:11841552), binding pneumolysin to suppress inflammation (PMID:30420782) and galectin-9 to drive a pro-tumor cytokine program (PMID:29732570), and CD206+ M2-like macrophages signal through TGF-β1 to regulate adipocyte progenitor proliferation and muscle regeneration (PMID:28819169, PMID:36411280).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Established that Mrc1 is a dedicated mediator of the DNA replication checkpoint, defining a Rad53/Cds1-activating function distinct from the DNA damage checkpoint.

    Evidence mrc1Δ deletion with checkpoint kinase activation assays in budding yeast, and Cds1 association/S-phase-specific activation in fission yeast

    PMID:11715016 PMID:11715017

    Open questions at the time
    • Did not resolve whether Mrc1 acts at forks or globally
    • Molecular mechanism of Rad53/Cds1 activation unknown at this stage
  2. 2003 High

    Showed Mrc1 physically travels with the replisome and that its checkpoint phosphorylation is separable from its replication role, the first separation-of-function evidence.

    Evidence ChIP tracking of Mrc1 at origins/forks, co-IP with fork components during HU arrest, and SQ/TQ phosphosite mutagenesis

    PMID:12865299 PMID:12944972

    Open questions at the time
    • Direct replisome binding partners not yet mapped
    • How Mec1 phosphorylates Mrc1 at the fork undefined
  3. 2004 High

    Identified the structural basis for Mrc1-DNA engagement and for recruiting the effector kinase, linking fork-structure sensing to checkpoint signaling.

    Evidence in vitro DNA-binding assays of an N-terminal HLH domain preferring branched DNA, plus Cds1 FHA-domain interaction mapping and cohesion/recombination genetics

    PMID:15173168 PMID:15282308 PMID:15471884

    Open questions at the time
    • In vivo relevance of branched-DNA binding not fully established
    • Cohesion mechanism (idx 16) Medium confidence and single-lab
  4. 2005 High

    Defined Mrc1's role in setting fork progression rate and coupling helicase unwinding to synthesis, distinguishing it from Tof1's pausing function.

    Evidence 2D gel analysis of replication intermediates, genetic epistasis, and MCM helicase co-IP with supercoiling readout in fission yeast

    PMID:15755447 PMID:16137625

    Open questions at the time
    • Direct mechanism of helicase coupling not biochemically reconstituted at this stage
    • MCM interaction (idx 8) Medium confidence
  5. 2009 High

    Reconstituted the mediator architecture: Mrc1 directly binds Mcm6 and Pol2 within a Csm3-Tof1-Mrc1 complex and cooperates with Mec1 to activate Rad53, providing the biochemical platform model.

    Evidence baculovirus co-expression/co-IP of purified complex, Mcm6 and Pol2 interaction mapping with fusion-rescue, and in vitro Mec1-Mrc1-Rad53 kinase reconstitution

    PMID:18851837 PMID:19457865 PMID:19515819 PMID:19620285 PMID:19819872

    Open questions at the time
    • Stoichiometry of the platform at forks unresolved
    • How phosphorylation toggles Pol2N vs Pol2C binding mechanistically unclear
  6. 2011 High

    Revealed a checkpoint-independent role in controlling replication origin timing and efficiency, showing Mrc1 selectively marks and restrains early origins.

    Evidence genome-wide ChIP-on-chip of Mrc1 binding and replication timing analysis with checkpoint-defective alleles in fission and budding yeast

    PMID:20219942 PMID:21518960

    Open questions at the time
    • Molecular mechanism by which Mrc1 restrains early origin firing undefined
    • Connection between origin binding and fork-traveling pool unclear
  7. 2021 High

    Provided the definitive mechanism for checkpoint-replication integration: Mrc1 stimulates CMG unwinding rate, and Rad53 phosphorylation of Mrc1 abolishes this to slow elongation.

    Evidence fully reconstituted in vitro replication with purified components, helicase assays, and phosphomimetic Mrc1 mutants in vitro and in vivo

    PMID:34387546

    Open questions at the time
    • Whether phospho-regulation of CMG stimulation occurs at every fork or selectively unknown
    • Structural basis of CMG stimulation not solved
  8. 2024 High

    Added an epigenetic inheritance function, showing Mrc1 routes parental H3-H4 histones to the lagging strand independently of its checkpoint and speed roles.

    Evidence separation-of-function alleles, co-IP showing Mcm2/Pol-alpha facilitation, and heterochromatin inheritance assays in fission yeast

    PMID:39094566

    Open questions at the time
    • Mechanism of strand-biased histone deposition not fully defined
    • Conservation of this role in mammals untested in this corpus
  9. 1992 High

    Established the domain architecture of the unrelated mammalian MRC1/CD206 mannose receptor, defining its eight carbohydrate-recognition domains and membrane topology.

    Evidence genomic cloning and exon-intron mapping of the full human MRC1 locus

    PMID:1294118

    Open questions at the time
    • Glycan specificity of individual CRDs not defined
    • No structural data at this stage
  10. 2021 High

    Defined the structural and glycan-recognition basis of CD206, showing CRD4 binds mannose, GlcNAc, fucose, and oligomannose via Ca2+-dependent contacts with selectivity for pauci-/oligomannose N-glycans.

    Evidence multiple CRD4-ligand crystal structures, ITC, and glycan-array/glycoproteomic profiling of tumor-cell ligands

    PMID:33545173 PMID:34089345

    Open questions at the time
    • Functional contributions of the other CRDs underexplored
    • Physiological endogenous ligand repertoire incomplete
  11. 2018 Medium

    Demonstrated CD206 as an endocytic and immunomodulatory receptor for pathogen and self ligands, linking glycan recognition to inflammation control and disease.

    Evidence direct pneumolysin and galectin-9 binding, MRC1-knockout mouse infection phenotype, and cytokine/signaling readouts in macrophages and dendritic cells

    PMID:11841552 PMID:22069759 PMID:23734186 PMID:29732570 PMID:30420782

    Open questions at the time
    • Signaling pathway downstream of CD206 ligand engagement incompletely mapped
    • Most cellular mechanism studies are single-lab Medium confidence
  12. 2022 Medium

    Established CD206+ M2-like macrophages as TGF-β1-secreting paracrine regulators of tissue homeostasis and as actionable targets for receptor manipulation.

    Evidence CD206-DTR depletion and macrophage-specific TGF-β1 deletion in mice (adipose and muscle), plus CD206-targeting glycopolymer and agonist (RP-182) functional studies

    PMID:28819169 PMID:32051227 PMID:36411280 PMID:36472883

    Open questions at the time
    • Direct receptor-proximal signaling distinct from cell-population effects not fully resolved
    • TGF-β1 regulation downstream of CD206 itself not mechanistically dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the separable yeast Mrc1/Claspin functions (checkpoint platform, CMG stimulation, origin timing, histone inheritance) are coordinated at a single fork, and whether the mammalian Claspin ortholog performs these roles; the two MRC1 proteins in this corpus share no demonstrated functional relationship.
  • No human Claspin replication data in this corpus
  • Symbol collision means the two protein narratives must be kept distinct

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0060090 molecular adaptor activity 3 GO:0001618 virus receptor activity 2 GO:0003677 DNA binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0042393 histone binding 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-69306 DNA Replication 4 R-HSA-168256 Immune System 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-4839726 Chromatin organization 1
Partners
CDS1CSM3MCM2MCM6MEC1POL2RAD53TOF1
Complex memberships
Csm3-Tof1-Mrc1 replication mediator complexreplisome / replication-pausing complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Yeast Tof1 and Mrc1 interact directly with the DNA replication machinery and form a stable replication-pausing complex at arrested forks in S. cerevisiae, demonstrated by their co-precipitation with replication fork components during hydroxyurea-induced arrest. Co-immunoprecipitation with replication fork components; chromatin immunoprecipitation during HU arrest Nature High 12944972
2001 S. cerevisiae Mrc1 (mediator of replication checkpoint) is required for activation of Rad53 kinase in response to DNA replication stress (hydroxyurea); mrc1 mutants show checkpoint defects similar to rad53 mutants. Genetic deletion (mrc1Δ), checkpoint kinase activation assays, HU sensitivity Nature cell biology High 11715016
2001 Fission yeast Mrc1 associates with Cds1 kinase and is required for Rad3-dependent activation of Cds1 specifically during S phase; Mrc1 protein appears coinciding with S phase. Yeast two-hybrid (Mrc1-Cds1 association), genetic deletion, cell-cycle expression analysis Nature cell biology High 11715017
2003 S. cerevisiae Mrc1 is present at replication forks, moves with the fork during S phase, and requires active replication initiation for its loading onto origins. Mec1-dependent phosphorylation of Mrc1 at canonical SQ/TQ motifs is required for Rad53 activation but not for Mrc1's role in DNA replication. Chromatin immunoprecipitation (ChIP) to track Mrc1 at origins and forks; phosphorylation-site mutagenesis; checkpoint activation assays Genes & development High 12865299
2004 Fission yeast Mrc1 contains an ~150 amino acid DNA-binding domain (DBD) in its N-terminal region that preferentially binds branched DNA structures in vitro; mutations in the DBD impair replication checkpoint arrest and HU resistance. This DBD contains a helix-loop-helix motif conserved with human Claspin. In vitro DNA-binding assays with purified domain; point mutagenesis; HU sensitivity assays The Journal of biological chemistry High 15471884
2004 Fission yeast Mrc1 is required for initial Thr11 phosphorylation of Cds1 by Rad3-Rad26; Mrc1 interacts with the FHA domain of Cds1, and this interaction recruits Cds1 to Rad3-Rad26 for phosphorylation. Yeast two-hybrid (Mrc1-Cds1 FHA domain interaction); FHA domain point mutations; in vivo Thr11 phosphorylation assays; Rad26-Cds1 fusion rescue experiments The Journal of biological chemistry High 15173168
2003 Fission yeast Mrc1 is phosphorylated by Rad3 and Tel1 at two S/TQ clusters; phosphorylation of T645 mediates FHA-domain-dependent interaction with Cds1 and is required for HU resistance; phosphorylation of the S604-containing cluster promotes increased chromatin association of Mrc1 in replication-arrested cells. Phosphorylation-site mutagenesis (S/TQ→AQ); electrophoretic mobility shift assays; yeast two-hybrid; chromatin association assays; rad3Δ tel1Δ double mutant analysis Molecular and cellular biology High 14585996
2005 S. cerevisiae Mrc1 is required for normal replication fork progression rate and for fork recovery after HU-induced stalling, independently of Rad53. Tof1 is critical for rDNA replication fork barrier activity but plays a minor role in the replication checkpoint, while Mrc1 is essential for the checkpoint but not for RFB activity. 2D gel electrophoresis of replication intermediates; genetic deletion (mrc1Δ, tof1Δ, rad53 mutants); HU release experiments Molecular cell High 16137625
2005 Fission yeast Mrc1/Tof1/Csm3 checkpoint complex interacts directly with the MCM helicase during both normal fork progression and stalled forks, coupling replicative unwinding to DNA synthesis. Biochemical co-immunoprecipitation; genetic synthetic lethality with polymerase alpha/primase mutants; plasmid supercoiling assay as readout of uncoupled unwinding Journal of molecular biology Medium 15755447
2007 S. cerevisiae Mrc1 strongly reduces the rate of DNA replication fork progression; loss of Mrc1 greatly slows forks while loss of Tof1 has less effect on speed but abolishes pausing at protein-DNA barriers. DNA combing (single-molecule replication tracking); genetic deletion strains Molecular biology of the cell High 17652453
2008 S. cerevisiae Mrc1 interacts with both the N-terminal (Pol2N) and C-terminal (Pol2C) halves of Pol2, the catalytic subunit of DNA polymerase epsilon. Mrc1 phosphorylation during the S-phase checkpoint abolishes Pol2N binding but not Pol2C interaction, and Mrc1 is required to stabilize Pol2 at stalled forks. Co-immunoprecipitation; chromatin immunoprecipitation; phosphorylation-dependent interaction analysis using Mrc1 phosphomutants Molecular cell High 18851837
2009 S. cerevisiae Csm3, Tof1, and Mrc1 form a heterotrimeric mediator complex that co-associates with moving replication forks; both Tof1 and Csm3 are required for Mrc1 association with the fork, while deletion of mrc1 does not affect Tof1/Csm3 association. Baculovirus co-expression confirmed direct protein-protein interactions. ChIP-on-chip; baculovirus coexpression and co-immunoprecipitation of purified proteins; genetic deletion analysis The Journal of biological chemistry High 19819872
2009 Fission yeast Swi1-Swi3 complex physically interacts with Mrc1 and synergistically facilitates Mrc1 DNA binding in vitro; Mrc1 preferentially binds arrested fork or D-loop structures, and the Swi1-Swi3 complex enhances this affinity by forming a ternary complex. Mutations in the Mrc1 DNA-binding domain abolish both the interaction and the synergistic effect. Purified protein DNA-binding assays (EMSA/gel shift); co-immunoprecipitation of purified proteins; mutagenesis of Mrc1 DNA-binding domain and Swi1 The Journal of biological chemistry High 20924116
2009 S. cerevisiae Mrc1 directly binds Mcm6 via the central coiled-coil region of Mrc1 interacting with the 168 aa C-terminal region of Mcm6; this interaction is required for checkpoint activation specifically in response to methyl methanesulfonate (MMS) but not HU treatment. Physical fusion of Mcm6 mutant with Mrc1 rescued the MMS checkpoint defect. Co-immunoprecipitation; mutagenesis of Mcm6 C-terminus; Mcm6-Mrc1 fusion rescue experiment; checkpoint activation assays Molecular and cellular biology High 19620285
2009 Purified Mrc1 cooperates with Mec1 to activate Rad53 in vitro; Mrc1 facilitates Rad53 phosphorylation by promoting a stronger Mec1-Rad53 enzyme-substrate interaction (~70-fold stimulation), and the conserved C-terminal domain of Mrc1 is required for this activity. In vitro reconstitution with purified Mec1 and Mrc1; activity-based kinase assay for Rad53; C-terminal domain deletion analysis The Journal of biological chemistry High 19457865
2009 Mec1-dependent phosphorylation of Mrc1 (independent of Rad53) is required for stabilization of Mec1 at stalled forks via a positive feedback loop; a central region of Mrc1 is required for mediator function and replisome association. Structure-function analysis of Mrc1 alleles; ChIP of Mec1 at stalled forks; genetic epistasis Proceedings of the National Academy of Sciences of the United States of America Medium 19515819
2004 Mrc1 in S. cerevisiae is required for sister chromatid cohesion established at the replication fork; mrc1Δ mutants have sister chromatid cohesion defects independent of checkpoint function; synthetic lethality of srs2Δ mrc1Δ is due to inappropriate recombination and depends on Mrc1's replicative but not checkpoint function. Synthetic genetic array; sister chromatid cohesion assay; suppression by recombination mutants; checkpoint-defective allele analysis Molecular and cellular biology Medium 15282308
2009 S. cerevisiae mrc1Δ suppresses homologous recombination at DNA double-strand breaks in an Mrc1-dependent manner; the replication checkpoint suppresses formation of Rad52 foci and impedes resection of DNA ends. Mrc1 does not prevent recombination at stalled forks (which already contain ssDNA). Rad52 foci quantification; HO endonuclease-induced DSB recombination assays; genetic epistasis with mrc1Δ and checkpoint mutants The EMBO journal Medium 19322196
2006 Fission yeast Swi1 and Swi3 are required for chromatin association of Mrc1; Mrc1 interacts with Swi3 and with Hsk1 kinase through its central SQ/TQ-containing segment; Hsk1 stabilizes Mrc1 protein levels through phosphorylation of a potential phosphodegron. Co-immunoprecipitation; chromatin fractionation; deletion analysis mapping interaction domains Genes to cells Medium 19422421
2021 In vitro reconstitution with purified proteins shows Rad53 phosphorylation of Mrc1 slows DNA replication fork elongation by preventing Mrc1-stimulated CMG helicase unwinding; Mrc1 stimulates CMG unwinding rate, and Rad53-phosphorylated Mrc1 cannot stimulate replication. Phosphorylation of Sld3/7 or Dbf4-CDK blocks initiation, while Mrc1 phosphorylation is necessary and sufficient to slow elongation. In vitro DNA replication reconstitution with purified proteins; helicase unwinding assays; phosphomimetic Mrc1 mutant analysis in vitro and in vivo eLife High 34387546
2024 Fission yeast Mrc1 promotes transfer of parental histone H3-H4 to the lagging strand and facilitates interaction between Mcm2 and DNA polymerase alpha, supporting heterochromatin inheritance. This function is independent of Mrc1's checkpoint and replisome speed roles; Mrc1 interacts with Mcm2 outside its histone-binding region. Genetic analysis; co-immunoprecipitation; chromatin immunoprecipitation; separation-of-function alleles; heterochromatin inheritance assays Molecular cell High 39094566
2020 S. cerevisiae Sen1 transcription termination helicase associates with replisomes via direct binding to Ctf4 and Mrc1 at the N-terminus of Sen1; a separation-of-function mutant (sen1-3) that abolishes replisome binding without affecting transcription termination causes increased genome instability. Co-immunoprecipitation; separation-of-function mutant analysis; genome instability assays Cell reports Medium 32075754
2018 S. cerevisiae Mrc1 and Rad9 control DNA replication through two distinct mechanisms in response to DNA damage: Mrc1 rapidly activates Rad53 at stalled forks and represses late-firing origins, while Rad9 takes over to maintain continuous checkpoint signaling and slows fork progression. Genetic epistasis (mrc1Δ, rad9Δ double mutants); DNA replication and fork rate analysis; Rad53 activation kinetics The EMBO journal Medium 30158111
2018 N-terminal phosphorylation of S. cerevisiae Mrc1 by multiple stress-activated kinases (identified by unbiased kinome screening) blocks replication and prevents transcription-associated recombination during stress-induced transcriptional outbursts in S phase, defining a general safeguard mechanism against transcription-replication conflicts. Unbiased kinome screening; phosphorylation site mutagenesis; recombination assays; genetic analysis Nature communications Medium 29371596
2006 Fission yeast Tel2 is required for efficient phosphorylation of Mrc1 and subsequent activation of Cds1 in response to hydroxyurea-induced replication block; Tel2 acts upstream of Mrc1 in the replication checkpoint pathway. Genetic epistasis (tel2 repression in mrc1Δ and cds1Δ backgrounds); Mrc1 phosphorylation assays; checkpoint activation analysis The Journal of biological chemistry Medium 17189249
2016 S. cerevisiae Rtt101Mms22 E3 ubiquitin ligase associates with the replisome via Ctf4 and counteracts Mrc1's replicative function; mrc1Δ rtt101Δ double mutants complete DNA replication under stress via a Rad52-dependent mechanism, indicating Rtt101Mms22 does not degrade Mrc1 but specifically antagonizes its replicative role at stalled forks. Interactome mass spectrometry (Mms22 IP-MS); suppressor screen; genetic double-mutant analysis; Rad52 epistasis PLoS genetics Medium 26849847
2011 Fission yeast Mrc1 selectively binds early-firing replication origins independently of Cdc45 and Hsk1 kinase before S phase; in mrc1Δ cells, early origins (those normally Mrc1-bound) fire precociously and with higher efficiency, while late origins are unaffected. This origin-timing function requires the non-checkpoint activity of Mrc1. ChIP-on-chip (genome-wide Mrc1 binding); replication timing analysis; checkpoint-defective mrc1 allele comparison Molecular and cellular biology High 21518960
2010 Deletion of MRC1 in S. cerevisiae maintains wild-type origin firing times despite >2-fold lengthening of S phase, whereas 13 other slow-S-phase mutants all showed proportional scaling of the entire replication timing program; mrc1Δ also activates numerous dormant origins. Genome-wide replication timing analysis by DNA microarray; genetic screen of 14 S-phase mutants Genome research Medium 20219942
2006 S. cerevisiae Mrc1 plays a specific role in DNA replication that promotes Srs2 recruitment to PCNA independently of checkpoint signaling, thereby preventing crossover formation; mrc1Δ increases spontaneous crossover rates comparably to srs2Δ. Genetic screen for spontaneous crossover rates; epistasis analysis with srs2Δ, mrc1Δ, and pol30-RR (PCNA) mutants The EMBO journal Medium 16724109
2007 S. cerevisiae Mrc1 protects uncapped telomeres (cdc13-1 and yku70Δ backgrounds) from Exo1-dependent nucleolytic degradation; protection is due to Mrc1's replicative function (not checkpoint function), as the checkpoint-defective mrc1AQ allele behaves like wild-type at telomeres. Genetic deletion analysis; mrc1AQ separation-of-function allele; single-stranded DNA accumulation assays; EXO1 epistasis DNA repair Medium 17618841
2019 S. cerevisiae Mrc1's fork-stabilizing function (but not checkpoint activation function) is required to prevent DNA breakage and cell death at long CAG repeats; both functions contribute to preventing repeat length instability. Separation-of-function mrc1 alleles; DNA breakage assays; repeat instability assays; genetic analysis Nucleic acids research Medium 30476303
1992 The human MRC1 gene encoding the macrophage mannose receptor is divided into 30 exons; the first three encode the signal sequence, N-terminal cysteine-rich domain, and fibronectin type II repeat; the final exon encodes the transmembrane anchor and cytoplasmic tail; the intervening 26 exons encode the eight carbohydrate-recognition domains. Genomic cloning and sequencing of the entire MRC1 coding region; exon-intron boundary mapping Genomics High 1294118
2021 Crystal structures of MRC1/CD206 C-type carbohydrate-recognition domain 4 (CRD4) in complex with mannose, GlcNAc, fucose, Manα1-2Man disaccharide, and Lewis-a trisaccharide reveal Ca2+-dependent binding mechanisms: mannose and GlcNAc engage equatorial 3- and 4-OH groups with the principal Ca2+; fucose can bind in multiple orientations; the Manα1-2Man disaccharide gains additional affinity through contacts with the reducing mannose residue. Glycan array screening; multiple crystal structures of CRD4-ligand complexes; isothermal titration calorimetry The Journal of biological chemistry High 33545173
2018 Pneumolysin (PLY) from S. pneumoniae binds directly to MRC1/CD206 on human dendritic cells and mouse alveolar macrophages, suppressing pro-inflammatory cytokine responses and TLR signaling, upregulating SOCS1, mediating pneumococcal internalization into non-lysosomal compartments, and polarizing T cells toward an immunoregulatory phenotype. MRC1-deficient mice show reduced bacterial loads in the airways. Direct binding assay (PLY-MRC1); MRC1 knockout mouse infection model; blocking antibody experiments; cytokine/signaling assays in dendritic cells and macrophages Nature microbiology High 30420782
2011 MRC1/CD206 promotes ricin toxin binding and uptake into monocytes in vitro, and MRC1-knockout mice are significantly more susceptible to ricin-induced death in vivo, indicating MRC1 functions in scavenging/degradation of ricin rather than facilitating its toxicity. In vitro ricin binding and uptake assays; MRC1 knockout mouse challenge with ricin (2.5× and 5× LD50) Toxins Medium 22069759
2002 CD206/MRC1 on inflammatory dendritic epidermal cells (IDECs) mediates receptor-mediated endocytosis of mannosylated antigens (dextran-FITC uptake), whereas Langerhans cells that lack CD206 do not show this CD206-dependent endocytosis. Flow cytometry; dextran-FITC uptake assay; electron microscopy with immunogold staining; pinocytosis control (Lucifer yellow) The Journal of investigative dermatology Medium 11841552
2013 Cockroach allergen Bla g 2 (which bears mannose-terminated N-glycans) binds directly to CD206/MRC1 on human fibrocytes, and this interaction mediates allergen uptake and activation of NF-κB, p38, ERK, and JNK signaling pathways, leading to TNF-α and IL-6 production; all these effects are blocked by mannan or anti-CD206 antibody. MALDI-MS N-glycan profiling; solid-phase binding assay; antibody blocking; FITC-allergen uptake by fibrocytes; intracellular signaling (kinase phosphorylation) and cytokine assays PloS one Medium 23734186
2018 Galectin-9 binds directly to CD206 on macrophages (Kd ~2.8 × 10^-7 M; confirmed by immunoprecipitation and blocked by anti-CD206), and this interaction induces CD206+ macrophages to produce more FGF2 and MCP-1 but less MDC, supporting a tumor-promoting microenvironment. Immunoprecipitation of CD206-galectin-9 complex from cell lysates; competition binding assay; fluorescence anisotropy for affinity measurement; cytokine secretion assays The Journal of pathology Medium 29732570
2022 Sulfated galactose glycopolymers (SO4-3-Gal) targeting the cysteine-rich domain of CD206 block receptor function by forming stable intracellular CD206-glycopolymer complexes that prevent receptor recycling to the cell membrane, both in vitro and in vivo in mice. Endocytosis and receptor recycling assays; in vitro CD206 activity assays; in vivo administration in mice; intracellular complex characterization Journal of the American Chemical Society Medium 36472883
2021 MRC1/CD206 CTLD4-7 is highly selective for pauci- and oligomannose N-glycans (among hundreds of glycans tested on glycan arrays); tumor cells and A549 lung cancer cells express MRC1-binding ligands carrying these glycans, identified by immunoprecipitation and glycoproteomics. Glycan microarray screening; flow cytometry; immunoprecipitation of MR-Fc from cancer cell lysates; glycoproteomic analysis (42 proteins identified) Cellular and molecular life sciences Medium 34089345
2020 RP-182 selectively activates CD206 on human and murine M2-like macrophages, inducing a conformational switch that triggers endocytosis, phagosome-lysosome formation, and autophagy, and reprograms M2-like tumor-associated macrophages to an M1-like antitumor phenotype. In vitro macrophage functional assays (endocytosis, phagosome formation); murine syngeneic/autochthonous tumor models; CD206high PDX models Science translational medicine Medium 32051227
2017 CD206/MRC1+ M2-like macrophages in adipose tissue inhibit adipocyte progenitor proliferation via TGF-β1 secretion and TGF-β signaling; ablation of CD206+ M2-like macrophages in transgenic mice increases smaller adipocyte numbers, reduces TGF-β signaling, and improves systemic insulin sensitivity. CD206-diphtheria toxin receptor transgenic mouse depletion model; adipocyte progenitor proliferation assays; TGF-β signaling pathway analysis; adipose tissue phenotyping Nature communications Medium 28819169
2022 CD206+ M2-like macrophages inhibit FAP-derived follistatin secretion via TGF-β1 signaling; depletion of CD206+ macrophages or deletion of macrophage-specific TGF-β1 activates FAPs to secrete follistatin, promoting myogenesis and muscle regeneration. FAP-specific follistatin deletion impairs muscle stem cell function. CD206-DTR transgenic mouse depletion; macrophage-specific TGF-β1 gene deletion; FAP isolation and follistatin secretion assays; muscle regeneration phenotyping Nature communications Medium 36411280
2015 Mesenchymal stem cells (UCMSCs) promote CD206 expression and phagocytic activity in macrophages through IL-6 in a mouse SLE model and in vitro with human SLE macrophages; IL-6 blockade abrogates the UCMSC-mediated increase in CD206 expression and phagocytosis. UCMSC-macrophage co-culture; IL-6 neutralization; flow cytometry; phagocytosis assays in vitro and in vivo Clinical immunology (Orlando, Fla.) Medium 26209923
2012 Colocalization of Mec1 (via Ddc2-LacI) and Mrc1-LacI at LacO arrays in S. cerevisiae is sufficient to activate Rad53 phosphorylation; this minimal replication checkpoint signal is independent of Ddc1 and Dpb11 (Mec1 activators required for DNA damage checkpoint). LacI-LacO tethering system (in vivo replication checkpoint mimic); Rad53 phosphorylation assays; genetic epistasis with ddc1Δ, dpb11, mrc1Δ Molecular biology of the cell Medium 22298423

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Nature 574 12944972
2010 Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 506 20357360
2001 Mrc1 transduces signals of DNA replication stress to activate Rad53. Nature cell biology 430 11715016
2003 Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53. Genes & development 313 12865299
2020 Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses. Science translational medicine 295 32051227
2005 Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53. Molecular cell 226 16137625
2014 Exploitation of the Macrophage Mannose Receptor (CD206) in Infectious Disease Diagnostics and Therapeutics. Journal of cytology & molecular biology 218 24672807
2017 CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors. Nature communications 209 28819169
2001 Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1. Nature cell biology 207 11715017
2002 Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases. The Journal of investigative dermatology 178 11841552
2022 Lactobacillus johnsonii alleviates colitis by TLR1/2-STAT3 mediated CD206+ macrophagesIL-10 activation. Gut microbes 176 36398889
2008 Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint. Molecular cell 170 18851837
2017 Precision Targeting of Tumor Macrophages with a CD206 Binding Peptide. Scientific reports 137 29116108
2020 Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure. Cells 134 32397365
2019 CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production. Scientific reports 133 31601953
2020 Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206+ M2-like macrophage polarization. Cell death & disease 123 32075954
2007 Mrc1 and Tof1 regulate DNA replication forks in different ways during normal S phase. Molecular biology of the cell 123 17652453
2009 Csm3, Tof1, and Mrc1 form a heterotrimeric mediator complex that associates with DNA replication forks. The Journal of biological chemistry 116 19819872
2005 Uncoupling of unwinding from DNA synthesis implies regulation of MCM helicase by Tof1/Mrc1/Csm3 checkpoint complex. Journal of molecular biology 113 15755447
2019 Natural killer T cell activation increases iNOS+CD206- M1 macrophage and controls the growth of solid tumor. Journal for immunotherapy of cancer 112 31387637
2021 Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206. The Journal of biological chemistry 92 33545173
2022 CD206+ tumor-associated macrophages cross-present tumor antigen and drive antitumor immunity. JCI insight 89 35503656
2004 Mrc1 is required for sister chromatid cohesion to aid in recombination repair of spontaneous damage. Molecular and cellular biology 88 15282308
2018 Pneumolysin binds to the mannose receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival. Nature microbiology 87 30420782
2009 Differential regulation of homologous recombination at DNA breaks and replication forks by the Mrc1 branch of the S-phase checkpoint. The EMBO journal 86 19322196
2006 Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover. The EMBO journal 86 16724109
2014 A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness. Clinical chemistry and laboratory medicine 78 24114918
2017 Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum. Neurogastroenterology and motility 75 28066953
2014 In vivo depletion of CD206+ M2 macrophages exaggerates lung injury in endotoxemic mice. The American journal of pathology 71 25447055
2019 Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD. Rheumatology (Oxford, England) 67 31143953
2022 Depletion of CD206+ M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration. Nature communications 62 36411280
2009 Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility. Human genetics 59 20035344
2010 MRC1-dependent scaling of the budding yeast DNA replication timing program. Genome research 56 20219942
2020 CD206+ M2-Like Macrophages Are Essential for Successful Implantation. Frontiers in immunology 55 33193326
2018 CD206-positive myeloid cells bind galectin-9 and promote a tumor-supportive microenvironment. The Journal of pathology 55 29732570
2009 The direct binding of Mrc1, a checkpoint mediator, to Mcm6, a replication helicase, is essential for the replication checkpoint against methyl methanesulfonate-induced stress. Molecular and cellular biology 55 19620285
2018 Mrc1 and Rad9 cooperate to regulate initiation and elongation of DNA replication in response to DNA damage. The EMBO journal 52 30158111
2015 Mesenchymal stem cells promote CD206 expression and phagocytic activity of macrophages through IL-6 in systemic lupus erythematosus. Clinical immunology (Orlando, Fla.) 51 26209923
2003 Replication checkpoint protein Mrc1 is regulated by Rad3 and Tel1 in fission yeast. Molecular and cellular biology 50 14585996
2023 CD206+ macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia. Cell reports 49 36753421
2019 Liver fibrosis and CD206+ macrophage accumulation are suppressed by anti-GM-CSF therapy. JHEP reports : innovation in hepatology 47 32039403
2009 Interactions between Swi1-Swi3, Mrc1 and S phase kinase, Hsk1 may regulate cellular responses to stalled replication forks in fission yeast. Genes to cells : devoted to molecular & cellular mechanisms 46 19422421
2024 Targeting circ-0034880-enriched tumor extracellular vesicles to impede SPP1highCD206+ pro-tumor macrophages mediated pre-metastatic niche formation in colorectal cancer liver metastasis. Molecular cancer 45 39164758
2023 A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice. Cells 45 37174654
2022 Human CD206+ macrophages associate with diabetes and adipose tissue lymphoid clusters. JCI insight 45 34990410
2021 The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease. Scientific reports 42 34608184
2024 Targeting CD206+ macrophages disrupts the establishment of a key antitumor immune axis. The Journal of experimental medicine 41 39601781
2021 Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation. eLife 40 34387546
2020 Peritoneal Level of CD206 Associates With Mortality and an Inflammatory Macrophage Phenotype in Patients With Decompensated Cirrhosis and Spontaneous Bacterial Peritonitis. Gastroenterology 40 31982413
2020 Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability. Cell reports 39 32075754
2009 Reconstitution of Rad53 activation by Mec1 through adaptor protein Mrc1. The Journal of biological chemistry 39 19457865
2009 Mrc1 phosphorylation in response to DNA replication stress is required for Mec1 accumulation at the stalled fork. Proceedings of the National Academy of Sciences of the United States of America 39 19515819
2006 Tel2 is required for activation of the Mrc1-mediated replication checkpoint. The Journal of biological chemistry 39 17189249
2023 Phase I Study of [68Ga]Ga-Anti-CD206-sdAb for PET/CT Assessment of Protumorigenic Macrophage Presence in Solid Tumors (MMR Phase I). Journal of nuclear medicine : official publication, Society of Nuclear Medicine 38 37474271
2014 Expression of the mannose receptor CD206 in HIV and SIV encephalitis: a phenotypic switch of brain perivascular macrophages with virus infection. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 38 25146376
2017 Microglial CD206 Gene Has Potential as a State Marker of Bipolar Disorder. Frontiers in immunology 35 28119691
2008 Mrc1, Tof1 and Csm3 inhibit CAG.CTG repeat instability by at least two mechanisms. DNA repair 35 18321795
2004 DNA binding domain in the replication checkpoint protein Mrc1 of Schizosaccharomyces pombe. The Journal of biological chemistry 35 15471884
2022 Sulfation at Glycopolymer Side Chains Switches Activity at the Macrophage Mannose Receptor (CD206) In Vitro and In Vivo. Journal of the American Chemical Society 34 36472883
2020 Targeting Pro-Tumoral Macrophages in Early Primary and Metastatic Breast Tumors with the CD206-Binding mUNO Peptide. Molecular pharmaceutics 34 32421341
2012 Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China. Human genetics 34 22392581
2009 Genetic variants in the mannose receptor gene (MRC1) are associated with asthma in two independent populations. Immunogenetics 34 19902202
2016 The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress. PLoS genetics 33 26849847
2024 Mrc1 regulates parental histone segregation and heterochromatin inheritance. Molecular cell 31 39094566
2005 Activation of Mrc1, a mediator of the replication checkpoint, by telomere erosion. Biology of the cell 31 15760303
2020 High CD206 levels in Hodgkin lymphoma-educated macrophages are linked to matrix-remodeling and lymphoma dissemination. Molecular oncology 30 31825135
2018 Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts. Nature communications 30 29371596
2011 Mrc1 marks early-firing origins and coordinates timing and efficiency of initiation in fission yeast. Molecular and cellular biology 30 21518960
2004 Cds1 phosphorylation by Rad3-Rad26 kinase is mediated by forkhead-associated domain interaction with Mrc1. The Journal of biological chemistry 30 15173168
2019 Mrc1 and Tof1 prevent fragility and instability at long CAG repeats by their fork stabilizing function. Nucleic acids research 28 30476303
2012 Polymorphic allele of human MRC1 confer protection against tuberculosis in a Chinese population. International journal of biological sciences 27 22393309
2023 CD206+ tumor-associated macrophages interact with CD4+ tumor-infiltrating lymphocytes and predict adverse patient outcome in human laryngeal squamous cell carcinoma. Journal of translational medicine 26 36864443
1992 Organization of the gene encoding the human macrophage mannose receptor (MRC1). Genomics 26 1294118
2023 A Distinct Microglial Cell Population Expressing Both CD86 and CD206 Constitutes a Dominant Type and Executes Phagocytosis in Two Mouse Models of Retinal Degeneration. International journal of molecular sciences 25 37762541
2011 Role of the mannose receptor (CD206) in innate immunity to ricin toxin. Toxins 25 22069759
2010 Genetic variants in mannose receptor gene (MRC1) confer susceptibility to increased risk of sarcoidosis. BMC medical genetics 25 21029423
2021 Human CD206+ Macrophages Show Antifibrotic Effects on Human Fibroblasts through an IL-6-Dependent Mechanism In Vitro. Plastic and reconstructive surgery 24 33235042
2020 Inhibition of Microglial TGFβ Signaling Increases Expression of Mrc1. Frontiers in cellular neuroscience 23 32296307
2010 Fission yeast Swi1-Swi3 complex facilitates DNA binding of Mrc1. The Journal of biological chemistry 23 20924116
2007 Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase. Molecular genetics and genomics : MGG 23 17323081
2021 Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206). Cellular and molecular life sciences : CMLS 22 34089345
2020 Characterization of splenic MRC1hiMHCIIlo and MRC1loMHCIIhi cells from the monocyte/macrophage lineage of White Leghorn chickens. Veterinary research 22 32460863
2020 Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting. International journal of molecular sciences 22 32878276
2016 CD163 and CD206 expression does not correlate with tolerance and cytokine production in LPS-tolerant human monocytes. Cytometry. Part B, Clinical cytometry 22 26352275
2006 Regulation of DNA replication machinery by Mrc1 in fission yeast. Genetics 22 16849602
2020 Association of serum macrophage-mannose receptor CD206 with mortality in idiopathic pulmonary fibrosis. International immunopharmacology 21 32622200
2007 Mrc1 protects uncapped budding yeast telomeres from exonuclease EXO1. DNA repair 21 17618841
2004 A Ddc2-Rad53 fusion protein can bypass the requirements for RAD9 and MRC1 in Rad53 activation. Molecular biology of the cell 21 15456903
1994 The exon-intron structure and chromosomal localization of the mouse macrophage mannose receptor gene Mrc1: identification of a Ricin-like domain at the N-terminus of the receptor. Biochemical and biophysical research communications 21 8297379
2024 MRC1 and LYVE1 expressing macrophages in vascular beds of GNAQ p.R183Q driven capillary malformations in Sturge Weber syndrome. Acta neuropathologica communications 20 38532508
2020 A Novel CD206 Targeting Peptide Inhibits Bleomycin Induced Pulmonary Fibrosis in Mice. bioRxiv : the preprint server for biology 20 32766584
2019 Phage-Display-Derived Peptide Binds to Human CD206 and Modeling Reveals a New Binding Site on the Receptor. The journal of physical chemistry. B 20 30768279
2013 Differentiation and activation of equine monocyte-derived dendritic cells are not correlated with CD206 or CD83 expression. Immunology 20 23461413
2012 Colocalization of Mec1 and Mrc1 is sufficient for Rad53 phosphorylation in vivo. Molecular biology of the cell 20 22298423
2023 Fibroblast-derived PI16 sustains inflammatory pain via regulation of CD206+ myeloid cells. Brain, behavior, and immunity 19 37315702
2022 The embryonic zebrafish brain is seeded by a lymphatic-dependent population of mrc1+ microglia precursors. Nature neuroscience 19 35710983
2022 CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis. Journal of autoimmunity 19 36183584
2020 Ciprofloxacin promotes polarization of CD86+CD206‑ macrophages to suppress liver cancer. Oncology reports 19 32377744
2023 CD206+ tendon resident macrophages and their potential crosstalk with fibroblasts and the ECM during tendon growth and maturation. Frontiers in physiology 18 36909235
2013 Functional interaction of cockroach allergens and mannose receptor (CD206) in human circulating fibrocytes. PloS one 18 23734186

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