Affinage

KREMEN1

Kremen protein 1 · UniProt Q96MU8

Length
473 aa
Mass
51.7 kDa
Annotated
2026-04-28
37 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KREMEN1 is a type-I transmembrane receptor that functions as a central modulator of Wnt/β-catenin signaling and as a dependence receptor coupling ligand availability to cell death, while also serving as an entry receptor for multiple enteroviruses and SARS-CoV-2. Its ectodomain, composed of Kringle, WSC, and CUB domains arranged in a rigid triangular architecture, forms a ternary complex with DKK1/DKK4 and LRP5/6, triggering clathrin-mediated endocytosis of LRP6 via a cytoplasmic dileucine motif to inhibit Wnt signaling; in the absence of DKK proteins, KREMEN1 instead promotes LRP6 surface retention and Wnt pathway activation, and restricts diffusion of secreted DKK to spatially pattern Wnt activity (PMID:12050670, PMID:17978005, PMID:25038040, PMID:23251700, PMID:27524201). Independent of its Wnt-modulatory role, KREMEN1 functions as a dependence receptor: in the absence of DKK1, homodimerization of KREMEN1 triggers autophagic cell death mediated by SEC24C and ATG9A through a placental-mammal-specific cytoplasmic motif, and this activity is antagonized by DKK1 binding or heterodimerization with KREMEN2 (PMID:26206087, PMID:31069116, PMID:41807954). Loss-of-function mutations in KREMEN1 (e.g., F209S in the WSC domain) cause autosomal recessive ectodermal dysplasia with oligodontia, associated with impaired glycosylation and defective ternary complex formation (PMID:27049303, PMID:40553753). KREMEN1 also serves as the essential cell-surface entry receptor for EV-A enteroviruses (CVA2–A6, A8, A10, A12), binding viral capsid VP1/VP2 in the canyon region to trigger pocket factor release and uncoating, and mediates SARS-CoV-2 spike-dependent cell entry (PMID:29681460, PMID:31911601, PMID:34837059).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 Medium

    Identification of KREMEN1 as a novel transmembrane protein with Kringle, WSC, and CUB ectodomains established the molecular architecture of this receptor family before any function was known.

    Evidence Molecular cloning, domain analysis, and expression profiling during embryonic development

    PMID:11267660

    Open questions at the time
    • No ligand or signaling pathway identified
    • No functional assays performed
    • Intracellular signaling mechanism unknown
  2. 2002 High

    The discovery that KREMEN1/2 are high-affinity DKK1 receptors that form a ternary complex with DKK1 and LRP6 to drive LRP6 endocytosis established the core mechanism of KREMEN-mediated Wnt inhibition and its role in anteroposterior CNS patterning.

    Evidence Co-IP, binding assays, endocytosis assays, Wnt reporters, and Xenopus morpholino knockdown with axis duplication assays

    PMID:12050670 PMID:12421700

    Open questions at the time
    • Endocytic machinery mediating LRP6 internalization not defined
    • Structural basis of ternary complex unknown
    • Whether KREMEN has DKK-independent functions unresolved
  3. 2006 High

    Kremen1 knockout mice revealed its requirement for thymic epithelial architecture and confirmed that endogenous KREMEN1 restrains canonical Wnt signaling in vivo.

    Evidence Krm1 knockout mouse with histology, FACS, and TOPFlash Wnt reporter assay in KO-derived TECs

    PMID:17162372

    Open questions at the time
    • Whether thymic phenotype is Wnt-dependent or reflects other KREMEN1 functions not resolved
    • Redundancy with KREMEN2 in other tissues not addressed
  4. 2007 High

    The finding that KREMEN2 promotes LRP6 surface retention and Wnt signaling in the absence of DKK proteins overturned the view that Kremens are purely Wnt-inhibitory and revealed a context-dependent positive role.

    Evidence Morpholino knockdown, overexpression, surface LRP6 localization assays, and Wnt reporter in Xenopus neural crest

    PMID:17978005

    Open questions at the time
    • Whether KREMEN1 has the same DKK-independent positive role as KREMEN2 not directly tested
    • Molecular basis of DKK-dependent vs. DKK-independent switching unknown
  5. 2008 High

    Mapping of DKK1 residues required for KREMEN binding (distinct from LRP6-binding surface) showed that the ternary complex involves bipartite DKK1 contacts, and revealed KREMEN is dispensable for Wnt antagonism at low LRP5/6 levels.

    Evidence Site-directed mutagenesis of DKK1 with binding and Wnt reporter assays

    PMID:18502762

    Open questions at the time
    • Atomic structure of ternary complex not yet available
    • Physiological LRP6 expression levels determining KREMEN requirement not defined
  6. 2012 High

    Identification of the cytoplasmic dileucine motif (DXXXLV) required for clathrin/AP-2-mediated KREMEN1 endocytosis provided the mechanistic basis for how KREMEN1 internalizes LRP6.

    Evidence Mutagenesis of dileucine motif, AP-2 siRNA, and clathrin inhibitor pitstop 2 with internalization assays

    PMID:23251700

    Open questions at the time
    • Whether the same motif mediates DKK1/LRP6-dependent co-endocytosis not directly shown
    • Adaptor protein interacting with the motif not identified
  7. 2014 High

    Discovery that KREMEN1 restricts the spatial diffusion range of secreted DKK proteins revealed a non-cell-autonomous mechanism distinct from ternary complex endocytosis, showing that KREMEN1 loss paradoxically decreases Wnt signaling by allowing DKK to spread further.

    Evidence Zebrafish krm1 mutant, cell transplantation, DKK1b-mTangerine fusion protein visualization, Wnt reporter

    PMID:25038040

    Open questions at the time
    • Whether this DKK-sequestration function operates in mammalian tissues not tested
    • Quantitative parameters of DKK diffusion restriction not modeled
  8. 2015 High

    KREMEN1 was established as a dependence receptor that triggers cell death in the absence of DKK1 ligand, via a placental-mammal-specific cytoplasmic motif separate from the Wnt-regulatory domain, linking KREMEN1 to cancer biology.

    Evidence Mutagenesis of cytoplasmic tail, apoptosis assays, phylogenetic analysis, analysis of cancer-associated mutations

    PMID:26206087

    Open questions at the time
    • Downstream death effectors not identified
    • Whether cell death is apoptotic, autophagic, or mixed not resolved
    • In vivo relevance of dependence receptor activity not demonstrated
  9. 2016 High

    Crystal structures of the KREMEN1 ectodomain and its ternary complex with DKK1-CRD2 and LRP6 provided atomic-level understanding of how the three proteins assemble, with DKK1 sandwiched between LRP6 and KRM1.

    Evidence X-ray crystallography at 1.9–3.2 Å resolution with SPR validation

    PMID:27524201

    Open questions at the time
    • Full-length ternary complex structure at high resolution not obtained
    • Conformational changes upon complex formation and endocytosis trigger not resolved
  10. 2016 Medium

    Human genetic evidence linked KREMEN1 loss-of-function (F209S in WSC domain) to autosomal recessive ectodermal dysplasia, establishing KREMEN1 as a Mendelian disease gene for ectodermal/dental development.

    Evidence Exome sequencing and segregation analysis in 4 consanguineous families

    PMID:27049303

    Open questions at the time
    • No direct functional assay of the F209S mutation in this study
    • Whether disease mechanism is purely Wnt-dependent or involves dependence receptor activity unknown
  11. 2018 High

    Genome-wide haploid genetic screening identified KREMEN1 as the essential entry receptor for CV-A10 and related EV-A enteroviruses, opening an entirely new functional dimension for this Wnt-pathway receptor.

    Evidence Haploid screen, KREMEN1 KO, overexpression, soluble ectodomain neutralization, mouse infection model

    PMID:29681460

    Open questions at the time
    • Structural basis of virus-receptor interaction not yet resolved
    • Which KREMEN1 domains mediate viral attachment unknown
  12. 2019 High

    Demonstration that KREMEN1 homodimerization is required for dependence receptor-mediated cell death — inhibited by DKK1 binding or KREMEN2 heterodimerization — resolved the molecular logic of how ligand availability switches KREMEN1 between survival and death signaling.

    Evidence Reciprocal co-immunoprecipitation, forced dimerization constructs, apoptosis assays

    PMID:31069116

    Open questions at the time
    • Downstream signaling cascade from the homodimer not identified
    • Structural basis of homo- vs. heterodimerization unknown
  13. 2020 High

    Cryo-EM and crystal structures of CV-A10 bound to KREMEN1 revealed the receptor spans the viral canyon of VP1 across adjacent protomers, triggering pocket factor release and conformational changes for uncoating — establishing KREMEN1 as a combined attachment and uncoating receptor.

    Evidence Cryo-EM structures at neutral and acidic pH, X-ray crystallography, in vitro uncoating assays

    PMID:31911601 PMID:32690697

    Open questions at the time
    • How receptor binding is coordinated with endosomal trafficking for genome release not defined
    • Whether the same structural mechanism applies to all KRM1-dependent enteroviruses not confirmed
  14. 2021 High

    Identification of KREMEN1 as a functional entry receptor for SARS-CoV-2, independent of ACE2, extended its viral receptor role to coronaviruses.

    Evidence Genome-wide receptome screen of 5054 membrane proteins, cell infection, in vivo mouse model

    PMID:34837059

    Open questions at the time
    • Structural basis of spike-KREMEN1 interaction not resolved
    • Relative physiological contribution vs. ACE2 in human tissues unclear
    • Whether KREMEN1 mediates uncoating for SARS-CoV-2 unknown
  15. 2023 High

    Identification of VP2 residue N142 as critical for KREMEN1 binding defined a specific virus-side contact point and validated the structural model across in vitro and in vivo systems.

    Evidence Neutralization-resistant mutant screening, soluble KREMEN1 binding, cell infection, and mouse pathogenicity assays

    PMID:37788227

    Open questions at the time
    • Atomic-level structure of VP2 N142 contact with KREMEN1 not directly resolved
  16. 2025 High

    Systematic mutagenesis across all KRM1-dependent enteroviruses identified VP2 K140 as a universally conserved contact engaged by KRM1 residue D90, unifying the receptor-binding mechanism and extending KRM1 usage to CVA8.

    Evidence Mutational analysis across CVA2–A6, A8, A10, A12 with binding, infection, and in vivo assays

    PMID:39817751

    Open questions at the time
    • Whether additional KREMEN1 residues contribute to serotype-specific binding not fully mapped
  17. 2025 High

    Functional characterization of ectodermal dysplasia-associated KREMEN1 variants showed that disease mutations impair N/O-glycosylation and ternary complex formation with DKK1-LRP6, causing WNT pathway dysregulation in patient fibroblasts.

    Evidence Glycosylation analysis, co-IP for complex formation, TOPFlash WNT reporter in patient fibroblasts

    PMID:40553753

    Open questions at the time
    • Whether glycosylation defects also impair viral receptor or dependence receptor functions not tested
    • Animal model rescue of ectodermal dysplasia not performed
  18. 2026 High

    Resolution of the downstream cell death pathway showed KREMEN1 triggers autophagic (not apoptotic) cell death via proximity interactions with SEC24C and ATG9A after vesicular trafficking, identifying the effector machinery of its dependence receptor activity.

    Evidence BioID proximity labeling, pharmacological autophagy inhibition, siRNA knockdown of SEC24C and ATG9A, cell death assays

    PMID:41807954

    Open questions at the time
    • How KREMEN1 homodimerization connects to SEC24C engagement not established
    • Whether SEC24C-dependent autophagy operates in vivo not shown
    • Structural basis of KREMEN1-SEC24C interaction not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how KREMEN1 switches between Wnt-inhibitory, Wnt-promoting, DKK-sequestering, and cell-death modes in different cellular contexts; the structural basis of KREMEN1 homodimerization and its coupling to SEC24C/ATG9A-mediated autophagy; and whether its Wnt-modulatory and viral receptor functions are physiologically interrelated.
  • No integrated structural model of full-length KREMEN1 in different signaling states
  • In vivo validation of SEC24C-dependent autophagic cell death pathway lacking
  • Functional crosstalk between viral entry and Wnt signaling through KREMEN1 not investigated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
ATG9ADKK1DKK3DKK4KREMEN2LRP5LRP6SEC24C
Complex memberships
DKK1-KREMEN1-LRP6 ternary complexKREMEN1 homodimer

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 KREMEN1 and KREMEN2 are high-affinity receptors for the Wnt antagonist DKK1. KREMEN2 forms a ternary complex with DKK1 and LRP6, inducing rapid endocytosis and removal of the Wnt co-receptor LRP6 from the plasma membrane, thereby blocking Wnt/beta-catenin signaling. Co-immunoprecipitation, cell surface binding assays, endocytosis assays, functional Wnt reporter assays, Xenopus embryo overexpression Nature High 12050670
2002 Kremen1 and Kremen2 functionally interact with DKK1 to regulate anteroposterior patterning of the CNS in Xenopus; morpholino knockdown of Krm1/2 leads to anterior neural defects, and Krm2 synergizes with dkk1 in inhibiting Wnt/LRP6 signaling in axis duplication assays. Antisense morpholino knockdown, axis duplication assays, rescue experiments with inhibitory anti-Dkk1 antibodies, Xenopus embryo overexpression Development (Cambridge, England) High 12421700
2001 KREMEN1 (Kremen) is a type-I transmembrane protein containing a kringle domain, a WSC domain, and CUB domains in the extracellular region, with no conserved intracellular signaling motif; its mRNA increases during embryonic development and cellular differentiation. Molecular cloning, domain analysis, in situ hybridization, northern blot Biochimica et biophysica acta Medium 11267660
2007 In the absence of DKK proteins, Kremen2 promotes LRP6 cell-surface localization and stimulates LRP6-mediated Wnt/beta-catenin signaling; Krm2 knockdown specifically reduces LRP6 protein levels in neural crest explants, indicating a positive role for Kremens in Wnt signaling when Dkks are absent. Morpholino knockdown, overexpression, cell surface LRP6 localization assays, Wnt reporter assays, Xenopus neural crest induction Development (Cambridge, England) High 17978005
2008 DKK1 residues Arg197, Ser198, and Lys232 are specifically required for binding to Kremen (but not LRP6); these Kremen-binding residues lie on the opposite face of DKK1 from the LRP6-binding surface. Kremen is dispensable for DKK1-mediated Wnt antagonism unless cells express high levels of LRP5/6. Site-directed mutagenesis of DKK1, binding assays, Wnt reporter assays, co-expression experiments The Journal of biological chemistry High 18502762
2006 Kremen1 knockout mice exhibit severe defects in thymic cortical architecture, with loss of defined cortical and medullary regions and failure of thymic epithelial cells to mature beyond the immature K5+K8+ stage; krm1-/- TEC lines show a 2-fold increase in canonical Wnt signaling by TOPFlash assay. Krm1 knockout mouse, histology, immunofluorescence, FACS, TOPFlash Wnt reporter assay Clinical & developmental immunology High 17162372
2012 KREMEN1 is internalized from the cell surface via clathrin-mediated endocytosis, dependent on an atypical dileucine motif (DXXXLV) in its cytoplasmic tail; mutation of LV to AA blocked internalization, and inhibition of AP-2 or clathrin also blocked Kremen1 internalization. Internalization assays, site-directed mutagenesis of dileucine motif, AP-2 siRNA knockdown, clathrin inhibitor (pitstop 2), cell surface assays PloS one High 23251700
2015 Kremen1 functions as a dependence receptor, triggering cell death (apoptosis) in the absence of its ligand DKK1; a specific motif in the cytoplasmic tail of Kremen1, conserved only in placental mammals, is required for apoptosis induction and is distinct from the Wnt-inhibitory function. Cancer-associated somatic mutations in Kremen1 can impair its pro-apoptotic activity. Whole embryo culture, Wnt activity assays, mutagenesis of cytoplasmic tail, phylogenetic analysis, apoptosis assays Cell death and differentiation High 26206087
2016 Crystal structures of the ectodomain of human KREMEN1 at 1.9–3.2 Å resolution reveal a rigid triangular arrangement of Kringle, WSC, and CUB domains; the WSC domain is homologous to hepatocyte growth factor. A low-resolution ternary complex structure shows DKK1-CRD2 sandwiched between LRP6PE3 and KRM1-Kringle-WSC; surface plasmon resonance and modeling suggest a direct interaction between Krm1-CUB and Lrp6-PE2. X-ray crystallography, surface plasmon resonance, complex crystal structure Structure (London, England : 1993) High 27524201
2016 KREMEN1 mutation p.F209S (in the WSC domain) causes autosomal recessive ectodermal dysplasia with oligodontia in humans, implicating Kremen1-mediated Wnt signaling regulation in ectodermal and dental development. Exome sequencing, genotyping of 56 relatives in 4 consanguineous families, mutation mapping to conserved WSC domain European journal of human genetics : EJHG Medium 27049303
2016 Kremen1 is expressed in cochlear prosensory cells during development and in supporting cells of the adult mouse cochlea; gain- and loss-of-function experiments show Kremen1 biases cells toward supporting cell fate and suppresses hair cell formation via Wnt pathway modulation. Immunofluorescence/localization, gain-of-function overexpression, loss-of-function, zebrafish lateral line hair cell counting Scientific reports Medium 27550540
2018 KREMEN1 is the entry receptor for Coxsackievirus A10 (CV-A10) and related group of EV-A enteroviruses; loss of KREMEN1 renders cells resistant to infection, and the extracellular domain of KREMEN1 binds CV-A10 directly and acts as a neutralizing agent; Kremen-deficient mice are resistant to CV-A10-induced lethal paralysis. Haploid genetic screen, KREMEN1 KO, overexpression, cell surface binding assay, soluble ectodomain neutralization, mouse infection model Cell host & microbe High 29681460
2018 miR-431 silences Kremen1 expression by targeting its 3'UTR, preventing amyloid-beta-mediated synapse loss in cortico-hippocampal neuronal cultures from 3xTg-AD mice; Kremen1 knockdown similarly prevents DKK1-induced synapse loss, placing Kremen1 downstream in DKK1-mediated synaptic degeneration. miRNA transfection, 3'UTR luciferase reporter, immunofluorescence of synaptic puncta, neuronal culture Frontiers in cellular neuroscience Medium 29643768
2019 Kremen1-induced apoptotic signaling requires homodimerization of the receptor; DKK1 binding inhibits Kremen1 multimerization and alleviates cell death; Kremen2, which has no intrinsic apoptotic activity, heterodimerizes with Kremen1 and inhibits Kremen1-induced cell death. Co-immunoprecipitation, forced dimerization constructs, apoptosis assays, Wnt reporter assays Cell death discovery High 31069116
2020 Crystal structures of CV-A10 mature virus alone and in complex with KRM1 show that KRM1 spans the viral canyon with a large footprint on VP1; receptor binding induces release of a pocket factor and initiates conformational changes (expanded A-particles) primed for viral uncoating. Cryo-EM and X-ray crystallography of virus-receptor complex Nature communications High 31911601
2020 Atomic structures of CV-A10 in complex with KRM1 under neutral and acidic conditions reveal KRM1 binds the mature viral particle above the canyon of VP1 across two adjacent asymmetric units; KRM1 binding induces pocket factor release (accelerated at acidic pH), and biochemical studies show receptor binding at acidic pH enables virion uncoating in vitro, identifying KRM1 as a two-in-one attachment and uncoating receptor. Cryo-EM structural determination, in vitro uncoating assay, biochemical binding studies under pH variation Proceedings of the National Academy of Sciences of the United States of America High 32690697
2020 DKK3 signals through Kremen-1 and DVL-1 to reduce JNK/AP-1-mediated neuroinflammation after intracerebral hemorrhage; Kremen-1 siRNA knockdown abrogates DKK3's neuroprotective effects, placing Kremen-1 as a necessary downstream mediator of DKK3 anti-inflammatory signaling. siRNA in vivo knockdown, Western blot, immunofluorescence, neurobehavioral assays in mouse ICH model Journal of neuroinflammation Medium 32331523
2014 In the zebrafish posterior lateral line primordium, Kremen1 restricts the spatial range of secreted DKK proteins; loss of Kremen1 results in increased spread of DKK1b protein and a decrease (not increase) in Wnt signaling, revealing a non-cell-autonomous mechanism whereby Kremen1 limits DKK diffusion to control Wnt activity. Zebrafish krm1 mutant, cell transplantation, DKK1b-mTangerine fusion protein visualization, Wnt reporter assays Development (Cambridge, England) High 25038040
2021 KREMEN1 is a functional entry receptor for SARS-CoV-2; KREMEN1 alone is sufficient to mediate SARS-CoV-2 spike-dependent cell entry in vitro and in vivo; KREMEN1 was identified by screening 5054 human membrane proteins for interaction with the SARS-CoV-2 spike protein. Genome-wide receptome screen, cell infection assay, in vivo mouse model, neutralizing antibody blockade Cell research High 34837059
2018 DKK4-CRD2 mediates high-affinity binding to both the E1E2 region of LRP6 and the Kremen1 extracellular domain; DKK4 and Krm family proteins function synergistically to inhibit Wnt signaling, and a diverse range of ternary complexes comprising Dkk, Krm, and LRP5/6 proteins can form. NMR structure determination, surface plasmon resonance, Wnt reporter assays The Journal of biological chemistry High 29925589
2026 Kremen1 induces cell death with autophagic (rather than apoptotic) features; protein proximity (BioID) assays identified SEC24C (a COP-II complex component) as a critical effector; Kremen1 is in proximity with SEC24C and ATG9A after vesicular trafficking, and this fosters SEC24C proximity with ATG8, ERGIC, and ATG9A, increasing autophagosome numbers and driving cell death. Pharmacological autophagy inhibition or genetic silencing of SEC24C or ATG9A suppresses this cell death. BioID proximity labeling, pharmacological autophagy inhibition, siRNA knockdown of autophagy effectors, cell death assays Cell communication and signaling : CCS High 41807954
2025 Disease-associated KREMEN1 variants (Cys111Ser, Gly166Asp, Phe209Ser, Phe258_Pro259del) show significantly reduced N- and O-glycosylation and impaired ternary complex formation with DKK1 and LRP6 compared to wild-type; patient fibroblasts exhibit higher basal WNT pathway activity followed by attenuated WNT3A response, demonstrating that these ectodermal dysplasia mutations broadly dysregulate WNT signaling. Ectopic expression in HEK293T cells, glycosylation analysis, co-immunoprecipitation for complex formation, TOPFlash WNT reporter in patient fibroblasts The Journal of investigative dermatology High 40553753
2023 VP2 residue N142 of CVA10 is critical for binding to KREMEN1; mutation of N142 drastically reduces KREMEN1 receptor-binding activity, viral attachment, cell infection, and in vivo pathogenicity in mice. Neutralization-resistant mutant screening, soluble KREMEN1 binding assay, cell infection assay, mouse pathogenicity model PLoS pathogens High 37788227
2025 VP2 residue K140 (K2140) is completely conserved among all KRM1-dependent enteroviruses (CVA2-CVA6, CVA10, CVA12) and is essential for receptor binding and infection; KRM1 residue D90 engages K2140 directly. CVA8 was experimentally demonstrated to use KRM1 as its receptor through this same interaction. Mutational analysis, binding assays, infection assays in vitro and in vivo, receptor identification for CVA8 mBio High 39817751

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 883 12050670
2021 Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2. Cell research 148 34837059
2002 Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning. Development (Cambridge, England) 105 12421700
2008 Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism. The Journal of biological chemistry 75 18502762
2007 Kremen is required for neural crest induction in Xenopus and promotes LRP6-mediated Wnt signaling. Development (Cambridge, England) 74 17978005
2018 KREMEN1 Is a Host Entry Receptor for a Major Group of Enteroviruses. Cell host & microbe 71 29681460
2019 Knockdown of lncRNA SNHG1 attenuated Aβ25-35-inudced neuronal injury via regulating KREMEN1 by acting as a ceRNA of miR-137 in neuronal cells. Biochemical and biophysical research communications 63 31447119
2006 The Wnt signaling antagonist Kremen1 is required for development of thymic architecture. Clinical & developmental immunology 61 17162372
2010 Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2. PloS one 52 20436912
2007 The functions and possible significance of Kremen as the gatekeeper of Wnt signalling in development and pathology. Journal of cellular and molecular medicine 51 18088386
2018 miRNA-431 Prevents Amyloid-β-Induced Synapse Loss in Neuronal Cell Culture Model of Alzheimer's Disease by Silencing Kremen1. Frontiers in cellular neuroscience 45 29643768
2001 Molecular cloning and characterization of Kremen, a novel kringle-containing transmembrane protein. Biochimica et biophysica acta 45 11267660
2008 Context-dependent activation or inhibition of Wnt-beta-catenin signaling by Kremen. Science signaling 43 18314504
2015 Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner. Cell death and differentiation 42 26206087
2020 Hand-foot-and-mouth disease virus receptor KREMEN1 binds the canyon of Coxsackie Virus A10. Nature communications 35 31911601
2016 Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf. Structure (London, England : 1993) 31 27524201
2018 DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis. Translational oncology 29 29772510
2020 DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage. Journal of neuroinflammation 26 32331523
2020 Molecular basis of Coxsackievirus A10 entry using the two-in-one attachment and uncoating receptor KRM1. Proceedings of the National Academy of Sciences of the United States of America 26 32690697
2018 Structural and functional analysis of Dickkopf 4 (Dkk4): New insights into Dkk evolution and regulation of Wnt signaling by Dkk and Kremen proteins. The Journal of biological chemistry 26 29925589
2016 Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families. European journal of human genetics : EJHG 26 27049303
2019 Kremen1-induced cell death is regulated by homo- and heterodimerization. Cell death discovery 21 31069116
2016 Kremen1 regulates mechanosensory hair cell development in the mammalian cochlea and the zebrafish lateral line. Scientific reports 21 27550540
2010 Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese population. Schizophrenia research 18 20153141
2012 High-affinity Dkk1 receptor Kremen1 is internalized by clathrin-mediated endocytosis. PloS one 17 23251700
2008 Roles of Dickkopf-1 and its receptor Kremen1 during embryonic implantation in mice. Fertility and sterility 15 18068158
2014 Kremen1 restricts Dkk activity during posterior lateral line development in zebrafish. Development (Cambridge, England) 11 25038040
2024 Noncoding RNA regulates the expression of Krm1 and Dkk2 to synergistically affect aortic valve lesions. Experimental & molecular medicine 10 38945954
2010 Embryonic expression and evolutionary analysis of the amphioxus Dickkopf and Kremen family genes. Journal of genetics and genomics = Yi chuan xue bao 8 20933216
2023 VP2 residue N142 of coxsackievirus A10 is critical for the interaction with KREMEN1 receptor and neutralizing antibodies and the pathogenicity in mice. PLoS pathogens 6 37788227
2025 Completely conserved VP2 residue K140 of KREMEN1-dependent enteroviruses is critical for virus-receptor interactions and viral infection. mBio 5 39817751
2023 Kremen1 regulates the regenerative capacity of support cells and mechanosensory hair cells in the zebrafish lateral line. iScience 3 38205258
2025 Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines. Virology journal 2 39825444
2023 Kremen1 regulates the regenerative capacity of support cells and mechanosensory hair cells in the zebrafish lateral line. bioRxiv : the preprint server for biology 1 37546780
2023 Presence of KREMEN receptors for DKK1 in the preimplantation bovine embryo. Reproduction & fertility 1 37582174
2026 Kremen1 dependence receptor induces SEC24C and ATG9A-dependent cell death. Cell communication and signaling : CCS 0 41807954
2025 KREMEN1 Variants Associated with Ectodermal Dysplasia Impair Complex Formation of KREMEN1 with DKK1 and LRP6 and Attenuate WNT3A Response. The Journal of investigative dermatology 0 40553753