Affinage

M6PR

Cation-dependent mannose-6-phosphate receptor · UniProt P20645

Round 2 corrected
Length
277 aa
Mass
31.0 kDa
Annotated
2026-04-28
53 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

M6PR (cation-dependent mannose-6-phosphate receptor, CD-M6PR) is a transmembrane cargo receptor that cycles between the trans-Golgi network (TGN) and late endosomes/multivesicular bodies to deliver mannose-6-phosphate-tagged lysosomal hydrolases to the endolysosomal compartment (PMID:1964415, PMID:15078902). Anterograde exit from the TGN is driven by GGA proteins that recognize acidic-cluster-dileucine motifs in the CD-M6PR cytoplasmic tail, while retrograde retrieval from endosomes depends on TIP47, PACS-1, the retromer complex, and tethering factors such as GCC88 and RUFY1-dynein (PMID:11387475, PMID:9590177, PMID:9695949, PMID:15078902, PMID:30791178, PMID:36282215). Beyond lysosomal biogenesis, the lumenal domain of CD-M6PR directly binds the HA2 ectodomain of influenza A hemagglutinin to promote viral membrane fusion in late endosomes, facilitates endosomal escape of phosphorothioate antisense oligonucleotides, and sorts STING into endosomes for degradation to suppress innate immune signaling and senescence (PMID:38038885, PMID:31840180, PMID:40714423). The structurally distinct cation-independent M6PR (CI-M6PR/IGF2R) shares overlapping trafficking itineraries and acts as a tumour suppressor lost in hepatocellular carcinoma, and interacts with CLN3 (Batten disease protein) to coordinate Golgi-lysosome vesicular trafficking and autophagic lysosomal reformation (PMID:7493029, PMID:37400440).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1987 High

    Establishing that the cation-independent M6PR is identical to the IGF-II receptor resolved a long-standing question about how IGF-II clearance and lysosomal enzyme sorting are linked through one bifunctional receptor.

    Evidence cDNA cloning and complete sequence analysis of the human IGF-II receptor

    PMID:2957598

    Open questions at the time
    • Functional relationship between IGF-II binding and M6P-dependent trafficking not delineated
    • No equivalent identity question resolved for the smaller CD-M6PR
  2. 1990 Medium

    Demonstrating that CD-M6PR concentrates in Golgi cisternae and cycles to the same late endosome/prelysosome population as CI-M6PR established the shared itinerary of both receptors and linked receptor trafficking to lysosomal biogenesis.

    Evidence Immunofluorescence and immunoperoxidase double-labeling; chloroquine/NH4Cl perturbation causing receptor accumulation in swollen multivesicular endosomes

    PMID:1964415

    Open questions at the time
    • Molecular signals governing CD-M6PR cycling were unknown
    • Functional redundancy or division of labor between CD-M6PR and CI-M6PR not resolved
  3. 1995 High

    Identifying frequent LOH and inactivating mutations at the M6P/IGF2R locus in hepatocellular carcinoma established CI-M6PR as a tumour suppressor, linking lysosomal receptor biology to cancer genetics.

    Evidence LOH analysis and sequencing of tumour DNA from hepatocellular carcinoma samples

    PMID:7493029

    Open questions at the time
    • Whether tumour suppression operates through IGF-II clearance, TGF-β activation, or both was not resolved
    • No equivalent tumour suppressor role demonstrated for CD-M6PR
  4. 1998 High

    Identification of TIP47 and PACS-1 as cytosolic adaptors that bind MPR cytoplasmic tails revealed the molecular machinery for endosome-to-TGN retrieval, answering how receptors are recycled after cargo delivery.

    Evidence In vitro transport reconstitution, binding assays with cytoplasmic-domain peptides, antisense knockdown, and mutagenesis identifying the Phe/Trp sorting signal

    PMID:9590177 PMID:9695949

    Open questions at the time
    • Relationship between TIP47 and retromer-mediated retrieval unclear
    • In vivo redundancy among retrieval adaptors not tested
  5. 2001 High

    Demonstrating that GGA proteins bind acidic-cluster-dileucine motifs in MPR tails and mediate TGN exit resolved the anterograde sorting step, completing a minimal framework for the forward and return legs of MPR trafficking.

    Evidence VHS domain binding assays, dominant-negative GGA expression blocking TGN exit, co-localization and subcellular fractionation

    PMID:11387475

    Open questions at the time
    • How GGA and AP-1 adaptors cooperate or compete at the TGN was not fully resolved
    • Cargo selectivity differences between GGA family members not determined
  6. 2004 High

    Parallel studies established that the retromer complex (via VPS26) is essential for CI-M6PR endosome-to-TGN retrieval, and that CK2-site acidic residues in the CD-M6PR tail determine differential GGA1 versus AP-1 binding affinity, refining the adaptor hierarchy.

    Evidence VPS26 depletion with CD8-M6PR chimera trafficking and immunoEM localization; in vitro binding with systematic cytoplasmic-tail mutants and quantitative affinity measurements

    PMID:15044437 PMID:15078902

    Open questions at the time
    • Whether retromer directly contacts CD-M6PR or acts primarily on CI-M6PR was ambiguous
    • Structural basis of GGA–tail interaction not resolved at atomic level in this period
  7. 2012 Medium

    Tracking retromer-dependent CI-M6PR retrieval through recycling endosomes distinguished an intermediate compartment in the retrograde pathway and separated CI-M6PR retrieval from EHD1-dependent Shiga toxin transport.

    Evidence siRNA knockdown of retromer components and recycling-endosome ablation with CD8-CI-M6PR chimera trafficking

    PMID:22540229

    Open questions at the time
    • Whether CD-M6PR uses the same recycling-endosome intermediate is untested
    • Single-lab study; independent replication of route segregation awaited
  8. 2019 Medium

    Identification of GCC88 as a TGN tethering factor required for CI-M6PR retrieval, and characterization of luminal-domain contributions to CI-M6PR trafficking, expanded the machinery beyond cytoplasmic-tail adaptors to include golgin-mediated vesicle capture and lumenal determinants.

    Evidence GCC88 CRISPR knockout with CI-M6PR localization and cathepsin-D processing assays; chimeric luminal-domain deletion constructs with immunofluorescence

    PMID:29988026 PMID:30791178

    Open questions at the time
    • Direct physical interaction between GCC88 and M6PR-containing vesicles not shown
    • Relative contributions of luminal versus cytoplasmic sorting signals not quantified
  9. 2020 Medium

    Discovering that CD-M6PR facilitates phosphorothioate antisense oligonucleotide endosomal escape via GCC2-mediated recruitment to late endosomes revealed an unexpected non-canonical function for CD-M6PR in nucleic acid delivery.

    Evidence siRNA knockdown of M6PR and GCC2 in human cells and in vivo mouse liver; PS-ASO activity assays and immunofluorescence co-localization

    PMID:31840180

    Open questions at the time
    • Mechanism by which M6PR promotes membrane destabilization for ASO escape is unknown
    • Whether this function involves M6P-ligand binding or a distinct interaction surface is unresolved
  10. 2022 Medium

    Multiple studies expanded the CD-M6PR and CI-M6PR interactome and trafficking regulators: RUFY1-dynein was shown to drive endosome-to-TGN retrieval, RAB31 (regulated by RUNX1) was required for early endosomal M6PR trafficking in megakaryocytes, and CD-M6PR was found to participate in EV71 uncoating in late endosomes.

    Evidence Co-IP and RUFY1 siRNA with CI-M6PR retrograde assay (JCB); CRISPR/siRNA knockdown of RAB31 in iPSC-megakaryocytes (Blood Adv); CD-M6PR siRNA with EV71 uncoating assay (Biol Open)

    PMID:35839075 PMID:35929543 PMID:36282215

    Open questions at the time
    • RUFY1's direct versus indirect interaction with M6PR not resolved
    • RAB31 effect on M6PR may be indirect via general endosomal morphology
    • EV71 uncoating mechanism and whether CD-M6PR contacts viral capsid are unclear
  11. 2023 High

    CLN3 (Batten disease protein) was identified as a physical interactor of CI-M6PR that coordinates Golgi-lysosome trafficking and autophagic lysosomal reformation, and CD-M6PR was shown to directly bind influenza A HA2 to promote viral membrane fusion, revealing disease-relevant receptor functions beyond hydrolase sorting.

    Evidence Co-IP/mass spectrometry with CLN3 gain- and loss-of-function plus lysosomal enzyme assays (Nat Commun); domain-mapped co-IP of M6PR lumenal domain with HA2 ectodomain, siRNA knockdown with rescue and membrane fusion assay (Sci China Life Sci)

    PMID:37400440 PMID:38038885

    Open questions at the time
    • Structural basis of M6PR lumenal domain–HA2 interaction unknown
    • Whether CLN3 interaction is M6P-dependent or mediated by a distinct surface not determined
  12. 2025 Medium

    M6PR was found to bind STING and sort it into endosomes for degradation, directly linking M6PR to innate immune regulation and cellular senescence control.

    Evidence Co-immunoprecipitation, M6PR knockdown preventing berberine-mediated STING degradation, cell thermal shift assay, doxorubicin-induced senescence model

    PMID:40714423

    Open questions at the time
    • Whether M6PR-STING interaction is direct or adaptor-mediated needs reconstitution
    • Physiological relevance outside pharmacological (berberine) context not established
    • Single-lab finding awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of CD-M6PR lumenal domain interactions with non-canonical cargoes (HA2, STING, PS-ASOs), the degree of functional redundancy between CD-M6PR and CI-M6PR in vivo, and the mechanism by which M6PR promotes endosomal membrane destabilization for cargo escape.
  • No atomic-resolution structure of full-length CD-M6PR in complex with any cargo
  • In vivo genetic models (CD-M6PR knockout) not extensively characterized for non-canonical functions
  • Crosstalk between M6PR-mediated STING degradation and lysosomal hydrolase delivery pathways untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 6
Localization
GO:0005768 endosome 5 GO:0005794 Golgi apparatus 4 GO:0005764 lysosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 8 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 1
Partners
CLN3GCC88GGA1PACS1RUFY1STINGTIP47VPS26

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 The 46 kDa cation-dependent mannose-6-phosphate receptor (CD-M6PR) cycles between the Golgi complex (concentrated in middle and trans cisternae) and the same population of late endosomes (prelysosomes) as the 215 kDa CI-M6PR, as shown by immunofluorescence and immunoperoxidase labeling with antibodies to the C-terminal cytoplasmic domain; weak base treatment (chloroquine/NH4Cl) caused both receptors to accumulate in swollen multivesicular endosomes. Immunofluorescence and immunoperoxidase labeling with synthetic peptide antibodies; chloroquine/NH4Cl treatment; double-labeling of both receptors European journal of cell biology Medium 1964415
1987 The human IGF-II receptor is structurally identical to the cation-independent mannose-6-phosphate receptor (CI-M6PR/IGF2R), as determined from cDNA sequence, revealing a transmembrane receptor with a large extracellular domain of fifteen repeat sequences and a small fibronectin collagen-binding homology domain. cDNA cloning and sequence analysis Nature High 2957598
1995 The M6P/IGF2R gene functions as a tumour suppressor in human hepatocellular carcinogenesis; 70% of hepatocellular tumours show loss of heterozygosity at the M6P/IGF2R locus, and 25% of LOH tumours carry point mutations in the remaining allele producing truncated receptor protein or significant amino acid substitutions. Loss of heterozygosity analysis; mutation screening with sequencing of tumour DNA Nature genetics High 7493029
1998 TIP47, a 47 kDa cytosolic protein, binds selectively to the cytoplasmic domains of both CI-M6PR and CD-M6PR and is required for MPR transport from endosomes to the trans-Golgi network; TIP47 recognizes a phenylalanine/tryptophan signal in the cytoplasmic tail of CD-M6PR essential for proper endosomal sorting. Binding assays to cytoplasmic domain peptides; in vitro and in vivo transport assays; identification of critical sorting signal by mutagenesis Cell High 9590177
1998 PACS-1, a cytosolic sorting protein, is required for TGN localization of the mannose-6-phosphate receptor; PACS-1 connects MPR to clathrin-sorting machinery and mediates retrieval to the TGN via binding to phosphorylated cytosolic domains. Antisense knockdown; cell-free TGN localization assays; in vitro binding assays Cell High 9695949
2001 The GGA proteins (Golgi-localized, gamma-ear-containing, ARF-binding proteins) bind via their VHS domain to acidic-cluster-dileucine signals in the cytosolic tails of both CI-M6PR and CD-M6PR at the TGN, and mediate sorting of the receptors from the TGN onto tubulo-vesicular carriers; a dominant-negative GGA mutant blocked exit of MPRs from the TGN. VHS domain binding assays; co-localization by immunofluorescence; dominant-negative GGA expression; subcellular fractionation Science High 11387475
2004 The mammalian retromer complex (containing VPS26) is required for efficient endosome-to-Golgi retrieval of CI-M6PR; loss of mVPS26 causes CI-M6PR to be either rapidly degraded or mislocalized to the plasma membrane, and mVPS26 localizes to multivesicular body endosomes by electron microscopy. VPS26 knockout/depletion; CD8 reporter chimera trafficking assays; immunoelectron microscopy; immunofluorescence The Journal of cell biology High 15078902
2004 The acidic cluster (Glu58, Glu59) of the CK2 site in CD-M6PR cytoplasmic tail is essential for high-affinity GGA1 binding in vitro, while phosphorylation of Ser57 by CK2 is dispensable; AP-1 binding requires a broader set of glutamates (Glu55, Glu56, Glu58, Glu59) but is also independent of Ser57 phosphorylation. GGA1 binds CD-M6PR with 2.4-fold higher affinity than AP-1, suggesting competitive regulation. In vitro binding assays with mutant CD-M6PR cytoplasmic tail peptides; site-directed mutagenesis; in vivo co-immunoprecipitation with GGA1 The Journal of biological chemistry High 15044437
2012 Retromer is required for retrograde exit of CI-M6PR (chimeric CD8-CI-M6PR) from early endosomes; both CI-M6PR and Shiga toxin B pass through recycling endosomes en route to the TGN, and ablation of the recycling endosome diverts both cargos to an aberrant compartment. EHD1 is required for STxB but not CI-M6PR transport from recycling endosomes to the TGN. Retromer component knockdown; recycling endosome ablation; CD8-M6PR chimera trafficking assay; immunofluorescence co-localization Traffic Medium 22540229
2018 The luminal/extracellular domain of CI-M6PR influences its retrograde endosome-to-TGN trafficking; partial deletion or replacement of the luminal domain mistargeted the receptor to non-TGN compartments, while a short HA-hCI-M6PR-tail construct (transmembrane domain + C-terminus only) preferentially targeted to the TGN. The retromer complex, through interaction with SNX5, regulates trafficking of a luminal-truncated CI-M6PR chimera. Deletion/chimeric mutant expression; immunofluorescence localization; co-immunoprecipitation with SNX5 Journal of biomedical research Medium 29988026
2019 GCC88, a trans-Golgi golgin tethering factor, is required for endosome-to-TGN retrograde transport of CI-M6PR; GCC88 knockout perturbs CI-M6PR retrieval, decreases its steady-state cellular level, causes improper processing of newly synthesized cathepsin-D (a CI-M6PR-dependent lysosomal hydrolase), and reduces lysosomal proteolytic capacity without impairing autophagy. GCC88 knockout (CRISPR); CI-M6PR localization by immunofluorescence; cathepsin-D processing assay; lysosomal proteolysis assay Cell biology international Medium 30791178
2019 CI-M6PR mediates ligand internalization and trafficking to endolysosomal compartments; its cellular uptake involves simultaneous binding of two receptor units forming dimers, and topological arrangement of mannose-6-phosphate glycoclusters (valency and spatial organization) determines efficiency of CI-M6PR-mediated cell uptake. Synthesis of glycoclusters with defined valency; cell uptake assays in CI-M6PR-positive cells Bioconjugate chemistry Low 31538768
2020 M6PR (CD-M6PR) facilitates release of phosphorothioate antisense oligonucleotides (PS-ASOs) from late endosomes; GCC2 recruits M6PR to late endosomes upon PS-ASO treatment, M6PR co-localizes with PS-ASOs on late endosomal membranes, and M6PR reduction impairs PS-ASO endosomal escape and activity both in human cells and in mouse liver in vivo. siRNA knockdown of M6PR and GCC2; immunofluorescence co-localization; PS-ASO activity assays; in vivo mouse subcutaneous PS-ASO treatment Nucleic acids research Medium 31840180
2022 Arl8b GTPase binds RUFY1 and controls RUFY1 endosomal localization via Rab14 interaction; RUFY1 depletion delays CI-M6PR retrieval from endosomes to the TGN, impairing delivery of newly synthesized hydrolases to lysosomes. RUFY1 interacts with the dynein-dynactin complex via its coiled-coil region and mediates dynein-dependent organelle clustering. Co-immunoprecipitation; RUFY1 siRNA depletion; CI-M6PR retrograde trafficking assay; lysosomal hydrolase delivery assay; dynein interaction pulldown The Journal of cell biology High 36282215
2022 CD-M6PR is present in mature late endosomes containing hSCARB2, RAB9, BMP, and LAMP2, and CD-M6PR knockdown impairs EV71 (Enterovirus 71) uncoating; CI-M6PR interacts with hSCARB2 through M6P-binding sites, and CD-M6PR likely plays a role in EV71 uncoating in late endosomes. siRNA knockdown of CD-M6PR; immunofluorescence localization; viral growth/uncoating assay; EV71 infection time-course Biology open Medium 35929543
2022 RUNX1 transcriptionally regulates RAB31 expression by binding its promoter; RAB31 downregulation (via RUNX1 haplodeficiency or direct siRNA/CRISPR knockdown) causes striking enlargement of early endosomes and impairs early endosomal trafficking of M6PR (mannose-6-phosphate receptor), along with VWF and EGFR, in megakaryocytes. Promoter-reporter assays; siRNA/CRISPR knockdown; immunofluorescence with EEA1 and CD63 markers; iPS-derived megakaryocytes from patient Blood advances Medium 35839075
2023 CLN3 (Batten disease protein) physically interacts with CI-M6PR and functions as a vesicular trafficking hub connecting the Golgi and lysosome; CLN3 depletion causes mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. CLN3 overexpression promotes formation of lysosomal tubules in a CI-M6PR- and autophagy-dependent manner generating new proto-lysosomes. Proteomic analysis (co-immunoprecipitation + mass spectrometry); CLN3 depletion and overexpression; immunofluorescence; lysosomal enzyme sorting assays Nature communications High 37400440
2023 M6PR (CD-M6PR) is a critical host factor for influenza A virus (IAV) replication; the lumenal domain of M6PR interacts directly with the ectodomain of HA2 subunit of IAV hemagglutinin, and this interaction promotes fusion of the viral envelope with late endosomal membranes. M6PR knockdown inhibits nuclear accumulation of viral NP at early timepoints without affecting attachment, internalization, early endosome trafficking, or late endosome acidification. siRNA knockdown; exogenous M6PR complementation; nuclear NP accumulation assay; co-immunoprecipitation of M6PR with HA; domain mapping with lumenal-domain and HA2-ectodomain constructs; membrane fusion assay Science China. Life sciences High 38038885
2025 M6PR binds STING and sorts it into endosomes for degradation, thereby suppressing STING signaling and cellular senescence; berberine upregulates M6PR specifically in senescent cells, and M6PR knockdown prevents berberine-mediated STING degradation even when STING expression is reversed, demonstrating M6PR-dependent endosomal retention of STING. Immunoprecipitation; immunofluorescence; Western blotting; cell thermal shift assay; M6PR knockdown; STING dimerization assay; doxorubicin-induced senescence model Phytomedicine Medium 40714423

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
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
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2003 Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature biotechnology 1176 12754519
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1987 Insulin-like growth factor II receptor as a multifunctional binding protein. Nature 826 2957598
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2004 Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. The Journal of cell biology 535 15078902
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2018 The shieldin complex mediates 53BP1-dependent DNA repair. Nature 502 30022168
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2012 Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Molecular biology of the cell 445 22456507
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1996 Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours. Nature genetics 419 8896552
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2008 Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis. Human molecular genetics 366 19010793
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1991 Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell 337 1848481
1998 TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking. Cell 332 9590177
1998 PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell 331 9695949
2001 Sorting of mannose 6-phosphate receptors mediated by the GGAs. Science (New York, N.Y.) 330 11387475
1995 M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nature genetics 323 7493029
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2012 Retromer guides STxB and CD8-M6PR from early to recycling endosomes, EHD1 guides STxB from recycling endosome to Golgi. Traffic (Copenhagen, Denmark) 53 22540229
2020 Golgi-endosome transport mediated by M6PR facilitates release of antisense oligonucleotides from endosomes. Nucleic acids research 43 31840180
2023 Loss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation. Nature communications 39 37400440
1990 The recycling itinerary of the 46 kDa mannose 6-phosphate receptor--Golgi to late endosomes--coincides with that of the 215 kDa M6PR. European journal of cell biology 20 1964415
2023 M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression. International journal of biological sciences 18 36632458
2004 The acidic cluster of the CK2 site of the cation-dependent mannose 6-phosphate receptor (CD-MPR) but not its phosphorylation is required for GGA1 and AP-1 binding. The Journal of biological chemistry 16 15044437
2022 RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes. The Journal of cell biology 14 36282215
2021 Gimap5 Inhibits Lung Cancer Growth by Interacting With M6PR. Frontiers in oncology 10 34604035
2023 SEVs-mediated miR-6750 transfer inhibits pre-metastatic niche formation in nasopharyngeal carcinoma by targeting M6PR. Cell death discovery 9 36609569
2023 M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes. Science China. Life sciences 9 38038885
2022 Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR in RUNX1 deficiency. Blood advances 9 35839075
2022 The uncoating of EV71 in mature late endosomes requires CD-M6PR. Biology open 9 35929543
2019 Topological Requirements for CI-M6PR-Mediated Cell Uptake. Bioconjugate chemistry 9 31538768
2025 Fluvoxamine Inhibited NLRP3 and NF-κB Inflammatory Pathways and Maintained Genital Functions by Ameliorating CD-MPR, KISS-1, AQP4 and Claudin-1 Expressions. Basic & clinical pharmacology & toxicology 3 39891570
2023 Gimap5 promoted RSV degradation through interaction with M6PR. Journal of medical virology 2 36484389
2023 MNX1 Promotes Anti-HER2 Therapy Sensitivity via Transcriptional Regulation of CD-M6PR in HER2-Positive Breast Cancer. International journal of molecular sciences 2 38203393
2025 M6PR upregulation by berberine attenuates hepatic senescence via sorting STING into endosome for degradation. Phytomedicine : international journal of phytotherapy and phytopharmacology 1 40714423
2024 CD8α-CI-M6PR Particle Motility Assay to Study the Retrograde Motion of CI-M6PR Receptors in Cultured Living Cells. Bio-protocol 1 38737505
2019 A role of GCC88 in the retrograde transport of CI-M6PR and the maintenance of lysosomal activity. Cell biology international 1 30791178
2018 Luminal/extracellular domains of chimeric CI-M6PR-C proteins interfere with their retrograde endosome-to-TGN trafficking in the transient expression system. Journal of biomedical research 1 29988026
2017 Cloning of a functional mannose-6-phosphate reductase (M6PR) gene homolog from Egyptian celery plants (Apium graveolens): overexpression in non-mannitol producing plants resulted in mannitol accumulation in transgenic individuals. 3 Biotech 1 28955638
2025 Self-enhancing targeted nanoparticles mediating M6PR up-regulation on tumor cell membranes to promote Granzyme B internalization for sensitizing tumor immunotherapy. Journal of colloid and interface science 0 40929815
2025 Ligand Valency and Linker Design Dictate the Efficacy of CI-M6PR-Mediated Targeted Delivery of M6P-siRNA Conjugates. ACS omega 0 41487160