Affinage

NID1

Nidogen-1 · UniProt P14543

Length
1247 aa
Mass
136.4 kDa
Annotated
2026-06-10
96 papers in source corpus 37 papers cited in narrative 36 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

NID1 (entactin/nidogen-1) is a sulfated, multidomain basement membrane glycoprotein that acts as a molecular bridge organizing the assembly of basement-membrane networks and as a ligand directing integrin-dependent cell adhesion and migration (PMID:6262321, PMID:2119632). Its C-terminal globular (G3) domain binds tightly to the inner short-arm segment of laminin and to type IV collagen, and ectopic expression of NID1 in cells lacking it drives incorporation of laminin and collagen IV into extracellular matrix, establishing its bridging role in matrix assembly (PMID:2119632, PMID:8433553). The protein presents two genetically separable cell-attachment activities: an RGD motif within an EGF-like repeat of the central stalk (E domain), recognized by alphaV-beta3 and the leukocyte response integrin, and an RGD-independent site in the G2 domain recognized by a beta1 integrin (alpha3-beta1); mutation of the RGD aspartate to glutamate abolishes RGD-dependent adhesion, chemotaxis, and trophoblast outgrowth (PMID:1469085, PMID:7797588, PMID:1527019, PMID:8491783). Through these domains NID1 also binds fibrinogen Aalpha/Bbeta chains and a G2-localized fibronectin site, integrating it into broader matrix and clotting networks (PMID:1680863, PMID:8147897). NID1 is a preferred substrate of matrix metalloproteinases, cleaved most efficiently by matrilysin at sites amino-terminal to Leu/Ile, and excessive stromelysin-1-mediated entactin cleavage in mammary basement membrane directly triggers epithelial apoptosis in vivo (PMID:8380588, PMID:8978831). Loss-of-function studies define its physiological roles: nidogen-1-null mice display neurological deficits and selective basement-membrane defects at brain capillaries and lens capsule, and in C. elegans laminin- and perlecan-dependent NID-1 deposition maintains basement-membrane integrity and patterns axon/dendrite guidance (PMID:12480912, PMID:30567930, PMID:29678816). Heterozygous NID1 mutations disrupting the NID1-laminin gamma1 interface cause autosomal dominant Dandy-Walker malformation, and a C-terminal-truncating NID1 deletion causes recessive cataract with neurological abnormalities in cattle (PMID:23674478, PMID:25347398). In cancer, NID1 is a direct transcriptional target of SNAIL and is repressed by the p53/miR-192/miR-215 axis; secreted NID1 acts in a paracrine fashion through ITGA3/ITGB1/ITGAV to drive EMT, invasion, and metastatic capacity (PMID:30831320, PMID:38001576).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1981 High

    Established that NID1/entactin is a distinct basement-membrane component, separating it biochemically and immunologically from the co-purifying laminin and fibronectin that had obscured it.

    Evidence Protein isolation, immunoelectron microscopy, peptide mapping and sulfate labeling from kidney matrix

    PMID:6262321

    Open questions at the time
    • Domain architecture and binding partners not yet defined
    • Function inferred only from localization at this stage
  2. 1988 High

    Defined the three-domain architecture (N-globular, EGF/thyroglobulin stalk, C-globular) and located an RGD cell-recognition motif, providing the structural framework for all subsequent functional dissection.

    Evidence Full-length mouse cDNA cloning and sequencing plus synthetic RGD peptide attachment assay; Golgi tyrosine sulfation mapped by metabolic labeling

    PMID:3042455 PMID:3264556

    Open questions at the time
    • Receptors for the RGD motif not identified
    • Functional contribution of non-RGD regions unknown
  3. 1990 Medium

    Showed NID1 functions as a matrix bridge by binding laminin short arms and type IV collagen through its C-terminal domain and driving their incorporation into matrix when expressed in deficient cells.

    Evidence Domain binding studies plus entactin cDNA transfection into entactin-lacking JAR cells with matrix incorporation readout; recombinant baculovirus protein with calcium-dependent self-aggregation

    PMID:2119632 PMID:2180961 PMID:2191952

    Open questions at the time
    • Stoichiometry and structural basis of the laminin/collagen bridge not resolved
    • RGD-independent attachment activity noted but not localized
  4. 1991 High

    Extended NID1's ligand repertoire beyond the canonical laminin/collagen network to fibrinogen and fibronectin, implying roles in provisional matrix and clotting contexts.

    Evidence Solid-phase binding with labeled entactin, transglutaminase cross-linking, and affinity chromatography/co-localization in laminin-deficient cells

    PMID:1680863 PMID:1872841

    Open questions at the time
    • Domain mediating fibrinogen binding not mapped here
    • Physiological relevance of fibrinogen/fibronectin binding in vivo untested
  5. 1992 High

    Identified specific integrin receptors and proved the RGD motif is functionally required, distinguishing RGD-dependent (alphaV-beta3/leukocyte response integrin) from cation-dependent, RGD-independent (alpha3-beta1) adhesion.

    Evidence Affinity isolation of alpha3-beta1 on entactin-Sepharose; RGD-to-RGE mutant entactin and anti-LRI blocking in neutrophil adhesion/chemotaxis; myotube maintenance antibody-blocking assay

    PMID:1469085 PMID:1527019 PMID:1734030

    Open questions at the time
    • Precise domain location of the alpha3-beta1 site not yet defined
    • Downstream signaling from integrin ligation uncharacterized
  6. 1993 High

    Defined NID1 as a metalloproteinase substrate, establishing matrilysin as a far more efficient protease than collagenase or gelatinase and mapping Leu/Ile-preceding cleavage sites.

    Evidence In vitro MMP kinetics (Km, Vmax) and Edman degradation of cleavage fragments; intracellular laminin complex assembly and vesicular transport shown by fractionation/transfection

    PMID:8380588 PMID:8433553 PMID:8491783

    Open questions at the time
    • In vivo consequences of cleavage not yet established at this stage
    • Whether cleavage products retain activity untested here
  7. 1995 High

    Resolved the two-site adhesion model at domain resolution, assigning the RGD/alphaV-beta3 activity to the E domain and a separate cysteine-rich EGF repeat in G2 to a beta1-integrin attachment site.

    Evidence GST-fusion domain constructs, RGD deletion/Glu-substitution mutagenesis in full-length protein, anti-integrin blocking; genomic exon-intron mapping correlating exons to domains

    PMID:7601446 PMID:7797588

    Open questions at the time
    • Exact beta1 integrin partner at G2 not definitively assigned
    • Crystal/structural basis of dual integrin engagement absent
  8. 1996 High

    Linked the two adhesion domains to distinct cellular outputs and showed matrilysin cleavage liberates functionally active fragments, connecting proteolysis to biological consequence.

    Evidence Domain GST fusions in neutrophil chemotaxis vs Fc-phagocytosis assays; transgenic stromelysin-1 x TIMP-1 epistasis tying entactin cleavage to mammary epithelial apoptosis in vivo

    PMID:8940031 PMID:8978831

    Open questions at the time
    • Molecular pathway from entactin loss to apoptosis not delineated
    • Generality of cleavage-driven apoptosis across tissues unknown
  9. 2003 High

    Defined physiological requirement in vivo: nidogen-1 loss causes neurological deficits and selective basement-membrane defects despite normal laminin/collagen distribution, indicating context-dependent rather than universal necessity.

    Evidence Targeted knockout mouse with behavioral, immunohistochemical, and quantitative immuno-EM analysis of brain capillary, lens, and glomerular basement membranes

    PMID:12480912 PMID:14566019

    Open questions at the time
    • Compensation by nidogen-2 not addressed
    • Mechanism linking NID1 loss to altered charge/permselectivity unresolved
  10. 2013 Medium

    Established a human Mendelian disease link, showing heterozygous NID1 mutations that disrupt the NID1-laminin gamma1 interface cause Dandy-Walker malformation, validating the laminin-binding bridge as developmentally critical.

    Evidence Whole-exome sequencing of families plus structural modeling of the NID1-LAMC1 complex; bovine recessive cataract from a C-terminal-truncating NID1 deletion confirmed by RT-PCR exon skipping

    PMID:23674478 PMID:25347398

    Open questions at the time
    • Functional binding disruption inferred from modeling, not biochemically measured for the mutant
    • Cellular pathology of posterior fossa development not directly tested
  11. 2019 Medium

    Recast NID1 as a paracrine cancer effector, showing it is a direct target of p53/miR-192/215 repression and of SNAIL activation, and that secreted NID1 drives EMT, invasion, and metastasis via integrins.

    Evidence miRNA target validation, conditioned-medium transfer, knockdown/rescue, ChIP for SNAIL at the NID1 E-box, and xenotransplant metastasis assays; COL4A1 co-IP and epistatic rescue in OSCC

    PMID:30831320 PMID:37006878 PMID:38001576

    Open questions at the time
    • Which integrin-engaged domain drives the metastatic signal not dissected
    • Single-lab cancer models; in-vivo human relevance limited to bioinformatic correlation
  12. 2021 Medium

    Identified non-tumor stromal sources of secreted NID1 (enteric neurons, muscle FAPs) that modulate cancer cell migration and tissue remodeling, broadening NID1's signaling role beyond classical matrix scaffolding.

    Evidence Ndrg4-knockout ENS secretome proteomics with organoid/migration assays; high-fat-diet muscle FAP secretome with myoblast and muscle stem cell functional assays

    PMID:33890711 PMID:35963565

    Open questions at the time
    • Receptor and signaling cascade for stromal NID1 not defined
    • Causal contribution in vivo vs correlative secretome change uncertain
  13. 2026 Medium

    Demonstrated a guidance function for NID-1 in axon regeneration, showing tissue-specific muscle/hypodermal NID-1 directs regenerating motor axons and synapse reformation in coordination with laminin and integrin.

    Evidence C. elegans nid-1 null with laser axotomy, tissue-specific rescue, synapse and functional recovery readouts, and genetic epistasis (preprint)

    PMID:41890084

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Molecular mechanism of axon-NID-1-integrin guidance not biochemically resolved
    • Conservation in mammals untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NID1's molecular bridging and integrin-signaling activities are differentially deployed across tissue-specific basement-membrane assembly, proteolytic remodeling, and paracrine cancer signaling remains unresolved.
  • No high-resolution structure of NID1 bound to laminin and collagen simultaneously
  • Mechanism connecting secreted NID1 to integrin signaling in cancer undefined
  • Redundancy with nidogen-2 not systematically resolved in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0005198 structural molecule activity 3 GO:0060089 molecular transducer activity 2 GO:0140313 molecular sequestering activity 1
Localization
GO:0005576 extracellular region 3 GO:0030312 external encapsulating structure 3 GO:0031012 extracellular matrix 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1474244 Extracellular matrix organization 3
Partners
COL4A1FGAFGBFN1ITGA3ITGAVITGB1LAMC1
Complex memberships
nidogen-laminin-type IV collagen basement membrane network

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1981 Entactin (NID1) is a sulfated glycoprotein of approximately 158 kDa isolated from extracellular basement membrane-like matrix; it is immunologically and biochemically distinct from laminin (GP-2) and fibronectin, and localizes predominantly at epithelial cell surfaces adjacent to basement membranes in mouse and rat kidney. Protein isolation, antibody preparation, immunoelectron microscopy, SDS-PAGE, cyanogen bromide peptide fragmentation, H235SO4 incorporation, chondroitinase ABC treatment The Journal of biological chemistry High 6262321
1988 The complete amino acid sequence of mouse entactin predicts a 1,245-residue polypeptide organized into three structural domains: an N-terminal globular domain (~70 kDa), a cysteine-rich stalk (~28 kDa) containing six EGF-type repeats and one thyroglobulin-type repeat, and a C-terminal globular domain (~36 kDa) with homology to EGF precursor and LDL receptor. Two potential Ca2+-binding sites are present. An RGD cell-recognition sequence is located in one EGF-type repeat and a synthetic RGD-containing peptide promotes mammary tumor cell attachment. cDNA cloning and sequencing, sequence analysis, synthetic peptide cell attachment assay The Journal of cell biology High 3264556
1990 Entactin promotes cell attachment of mouse mammary tumor, human melanoma, and other cells; the RGD sequence in entactin mediates approximately 60% of this attachment (inhibited by RGDS peptide), indicating additional non-RGD cell recognition sequences exist. Entactin directly binds calcium ions, with binding sites residing in the NH2-terminal region (demonstrated by recombinant N-terminal 330 aa fragment and synthetic calcium-binding peptides). Cell attachment assay, peptide inhibition assay, baculovirus-expressed recombinant entactin, 45Ca2+ binding assay, synthetic peptides The Journal of biological chemistry High 2191952
1990 Entactin's C-terminal globular domain binds tightly to the inner rod-like segment of laminin's short arms, and the same region mediates attachment to type IV collagen approximately 80 nm from its carboxyl non-collagenous end. Transfection of entactin cDNA into JAR choriocarcinoma cells (which lack entactin) stimulated incorporation of laminin and type IV collagen into extracellular matrix, demonstrating entactin's bridging role in basement membrane assembly. Transfection assay, immunofluorescence, binding studies, domain analysis American journal of respiratory cell and molecular biology Medium 2119632
1990 Recombinant entactin expressed in a baculovirus system is correctly processed (signal peptide cleaved), promotes cell attachment, and exhibits calcium- and temperature-dependent self-aggregation. Immunoelectron microscopy showed the majority of recombinant entactin localizes intracellularly forming insoluble aggregates in insect cells. Baculovirus expression system, amino terminus sequence analysis, cell attachment assay, calcium/temperature-dependent aggregation assay, immunoelectron microscopy The Journal of biological chemistry Medium 2180961
1991 Entactin specifically binds to the Aα and Bβ chains of fibrinogen in a divalent cation-independent, saturable, and concentration-dependent manner. Entactin can be cross-linked to itself and to fibrin(ogen) by transglutaminase. Solid phase binding assay with 35S-labeled entactin, competitive inhibition with antibodies and unlabeled ligands, transglutaminase cross-linking assay The Journal of biological chemistry High 1680863
1992 The cell surface receptor for entactin on PC-3 prostate carcinoma cells is integrin α3β1. The receptor was isolated by affinity chromatography on entactin-Sepharose, bound in a divalent cation-dependent manner (Ca2+, Mg2+, Mn2+), was eluted with EDTA but not RGD-containing peptides, and anti-α3 antibody (P1B5) inhibited cell attachment to entactin but not to laminin. Affinity chromatography on entactin-Sepharose, 125I surface labeling, anti-integrin antibody identification, purified α3β1 binding assay, liposome reconstitution, antibody inhibition of cell attachment The Journal of biological chemistry High 1527019
1992 Entactin mediates neutrophil (PMN) adhesion and chemotaxis through its RGD domain via the leukocyte response integrin (LRI). An RGD-containing synthetic peptide (S-RGD) reproduced the effect; a mutant entactin with RGE substitution at Asp674 had no adhesive or chemotactic activity. Anti-LRI monoclonal antibodies blocked both adhesion and chemotaxis, while anti-β1 and anti-β2 integrin antibodies had no effect. Cell adhesion assay, chemotaxis assay, synthetic peptide competition, site-directed mutant recombinant entactin (RGD→RGE), monoclonal antibody blocking, HL-60 differentiation model The Journal of clinical investigation High 1469085
1993 Entactin is a substrate for matrix metalloproteinases, with matrilysin being ~100-fold more effective than interstitial collagenase and ~600-fold more effective than 92-kDa gelatinase. The Km of matrilysin for entactin is 8.9×10−7 M and Vmax is 21 molecules/enzyme/min at 37°C. Cleavage sites consistently occur amino-terminal to leucine or isoleucine residues. In vitro MMP cleavage assay, kinetic analysis (Km, Vmax, Arrhenius plot), Edman degradation of cleavage fragments The Journal of biological chemistry High 8380588
1993 Entactin binds to laminin, collagen IV, fibrinogen, fibronectin, and is assembled into complex with laminin intracellularly in parietal endoderm M1536-B3 cells, then transported in membrane-enclosed vesicles to the extracellular compartment. Transfection of entactin into JAR cells (lacking entactin) results in entactin incorporation into extracellular matrix associated with laminin and collagen IV. Entactin also co-localizes with fibronectin in 4CQ cell extracellular matrix. Cell fractionation, immunofluorescence, cDNA transfection, indirect immunostaining Kidney international Medium 8433553
1993 Recombinant entactin promotes mouse primary trophoblast cell adhesion and migration (blastocyst outgrowth) in a dose-dependent manner via its RGD recognition site. A mutant recombinant entactin with Glu substituted for Asp at the RGD site provided no trophoblast adhesive activity, and RGD-containing peptide reversibly inhibited entactin-mediated outgrowth. Blastocyst outgrowth assay, site-directed mutagenesis (RGD→RGE), antibody inhibition, peptide competition assay The Journal of cell biology High 8491783
1994 The 29 kDa amino-terminal fragment of fibronectin binds specifically to the G2 domain of entactin (half-saturation ~5 nM), but not to G1, E, or G3 domains, identifying G2 as the fibronectin-binding domain of entactin. GST-fusion protein domain analysis, solid phase binding assay with 125I-labeled fibronectin fragment Biochemical and biophysical research communications Medium 8147897
1994 Entactin binds specifically to Candida albicans cell wall components in both yeast and hyphal forms; binding is partially inhibited by RGDS peptide and completely abolished by anti-entactin antiserum. Cell wall proteins of ~25, 44, and 65 kDa from both morphologies bind entactin in ligand affinity blotting. Indirect immunofluorescence, ELISA binding assay, ligand affinity blotting, RGDS peptide competition Infection and immunity Medium 7927722
1995 Entactin has two distinct cell attachment sites: (1) the RGD sequence in the EGF-like stalk (E domain), recognized by αvβ3 integrin; and (2) a 39-amino acid cysteine-rich EGF repeat in the G2 domain, which serves as a second attachment site recognized by a β1 family integrin (possibly α3β1), independent of RGD. GST-fusion protein domain constructs, RGD deletion and Glu-for-Asp substitution mutagenesis, full-length mutant entactin in baculovirus system, cell attachment assay, anti-integrin antibody inhibition The Journal of biological chemistry High 7797588
1996 Entactin E domain (containing RGD) ligates the leukocyte response integrin (beta3-like) and signals for neutrophil chemotaxis, while the G2 domain signals for enhancement of Fc receptor-mediated phagocytosis via ligation of α3β1. These are distinct receptor-domain interactions mediating different neutrophil functions. Matrilysin cleavage of entactin liberates peptides retaining both E domain-mediated chemotaxis and G2 domain-mediated phagocytosis enhancement. GST-domain fusion proteins (G1, G2, E, G3), neutrophil chemotaxis assay, phagocytosis assay, anti-integrin antibody blocking, matrilysin cleavage The Journal of biological chemistry High 8940031
1996 Stromelysin-1 (MMP-3) specifically cleaves entactin in the mammary gland extracellular matrix in vivo; enhanced entactin cleavage to above-normal levels was directly correlated with apoptosis of overlying mammary epithelial cells. TIMP-1 overexpression suppressed MMP activity, prevented entactin degradation, and extinguished the apoptosis. Transgenic mouse crosses (stromelysin-1 autoactivating transgene × TIMP-1 transgene), in vivo genetic epistasis, quantification of entactin cleavage products, apoptosis assay The Journal of cell biology High 8978831
1991 Entactin forms a complex with fibronectin and co-localizes in extracellular matrix of the 4CQ embryonal carcinoma cell line, which lacks laminin. The entactin-fibronectin interaction was confirmed by affinity column chromatography and solid phase assay, demonstrating direct binding. Immunofluorescence co-localization, affinity column chromatography, solid phase binding assay, Northern blot Biochemical and biophysical research communications Medium 1872841
1988 Tyrosine sulfation of entactin occurs in medial Golgi cisternae (not trans-Golgi), and is not the last modification before secretion. Four intracellular precursor forms of entactin (EN1–4) at different modification stages were identified; the mature secreted form is tyrosine-sulfated. Metabolic labeling with [35S]methionine and H235SO4, tunicamycin and monensin inhibitor experiments, pulse-chase analysis in 3T3-L1 adipocytes FEBS letters Medium 3042455
2002 Targeted disruption of the entactin-1 (nidogen-1) gene in mice causes neurological deficits (seizure-like symptoms, loss of hindleg muscle control) and selective structural alterations in basement membranes at brain capillaries and lens capsule, while basement membranes in most other tissues appeared morphologically normal. Gene targeting/knockout mouse, behavioral observation, immunohistochemistry, electron microscopy of basement membranes Laboratory investigation High 12480912
2003 In entactin-1-null mice, glomerular basement membranes show thickening, altered anionic charge distribution, and increased αv-integrin density at glomerular cell membranes compared to wild type. Filtration permselectivity is altered (endogenous albumin distribution across basement membrane is changed). Laminin and type IV collagen distributions remain unchanged. Immunocytochemistry, protein A-gold quantitative electron microscopy, albumin distribution assay in knockout vs. wild-type mice The journal of histochemistry and cytochemistry High 14566019
1992 Entactin is required for long-term adhesion and maintenance of contractile skeletal myotubes on diluted Matrigel. Anti-entactin antibodies did not inhibit myoblast attachment or fusion, but myotubes exposed to anti-entactin detached after spontaneous contractions began, identifying a specific role for entactin in post-fusion myotube stabilization. Antibody blocking with anti-entactin, anti-laminin, anti-collagen IV, anti-HSPG; myotube culture on Matrigel; contractility observation Journal of cellular physiology Medium 1734030
1994 A novel entactin epitope (recognized by monoclonal antibody 9H6) is selectively present at the synaptic cleft of the neuromuscular junction but not at extrasynaptic sites. This synaptic epitope is dependent on N-glycosylation (N-glycanase treatment reduces molecular mass and eliminates 9H6 binding), identifying a glycosylation-dependent, synapse-specific form of entactin. Monoclonal antibody generation, immunofluorescence, Western blot, N-glycanase treatment, N-terminal sequence analysis The Journal of neuroscience Medium 7514212
1995 The mouse entactin gene spans >65 kb, contains 20 exons, and its exon organization directly corresponds to the polypeptide's structural domains (each EGF-like repeat, the thyroglobulin repeat, and each globular domain encoded by separate exons), with regional homology to the LDL receptor gene including conservation of four intron positions, indicating evolution via exon shuffling. Genomic cloning, restriction mapping, DNA sequencing, exon-intron boundary determination Genomics Medium 7601446
1998 Human mesangial cells use both αvβ3 (via the RGD sequence in entactin's E/rod domain) and a β1-containing integrin to adhere to native entactin. Adhesion requires divalent cations. Recombinant entactin lacking the E domain RGD still supported some mesangial cell adhesion via β1 integrin, and tertiary structure of native entactin may contribute to binding properties. Cell adhesion assay, anti-integrin monoclonal antibody blocking, wild-type and RGD-mutant recombinant entactin fragments, metabolic labeling and immunoprecipitation Cell adhesion and communication Medium 9686320
2000 Entactin-1 (nidogen-1) is exclusively produced and secreted by mesenchymal peritubular cells (not Sertoli cells) in rat testis. Anti-entactin-1 monoclonal antibodies caused loss of adhesion specifically in peritubular cells but not Sertoli cells, demonstrating an autocrine adhesion function of entactin-1 for peritubular cells. DD-RT-PCR, Western blot of co-cultures and monocultures, antibody perturbation assay, immunofluorescence European journal of cell biology Medium 10727019
2001 Entactin significantly inhibits amyloid beta-protein (Aβ1-40) fibril formation in vitro at a 50:1 molar ratio (Aβ:entactin). The inhibitory mechanism involves entactin inducing a random coil structure in Aβ40, as shown by circular dichroism spectroscopy. Thioflavin T fluorometric assay, electron microscopy, circular dichroism spectroscopy Neuroscience letters Medium 11376898
2013 Heterozygous mutations in NID1 cause autosomal dominant Dandy-Walker malformation with occipital cephaloceles. Structural modeling of the NID1-LAMC1 complex showed that a NID1 mutation disrupts the NID1-LAMC1 (laminin γ1) protein interaction, identifying NID1 binding to laminin as functionally critical for posterior fossa development. Whole-exome sequencing, protein interaction network analysis, structural modeling of NID1-LAMC1 complex Human mutation Medium 23674478
2014 An 855 bp deletion in bovine NID1 spanning exon 19/intron 19 border causes skipping of exon 19, frameshifting, and premature stop (p.1164fs27X), truncating the C-terminal domain essential for binding with matrix assembly complexes. This causes autosomal recessive inherited cataract and neurological abnormalities in cattle. Genome-wide association study, homozygosity mapping, whole genome sequencing, RT-PCR (demonstrating exon skipping), pedigree analysis PloS one Medium 25347398
2018 In C. elegans, NID-1/Nidogen localizes to all basement membranes; its localization depends on Laminin (loss of Laminin strongly reduces NID-1 BM localization). Ndg/nid-1 null mutants have ultrastructural BM defects compromising barrier function and stability. Genetic epistasis places nid-1 in the same pathway as unc-52/Perlecan and the netrin axon guidance signaling cassette for establishing correct somatosensory dendrite number; UNC-52/Perlecan is required to correctly localize NID-1. Genetic knockout (Ndg-null and unc-52 mutants), ultrastructural analysis (EM), barrier function assay, genetic epistasis, fluorescence localization Development (Cambridge, England) High 29678816 30567930
2006 Entactin-1 overexpression in myoblasts (retroviral system) leads to higher proliferation rate and reduced expression of myogenic differentiation markers after induction, demonstrating that entactin-1 opposes myogenic differentiation. Conversely, entactin-2 is a primary response gene transiently induced during myogenesis. Retroviral overexpression, siRNA knockdown, RT-PCR for differentiation markers, cycloheximide and actinomycin D treatment, p38 MAPK inhibitors Differentiation; research in biological diversity Medium 17177854
2019 NID1 is a downstream target of p53/miR-192/miR-215 axis in colorectal cancer cells. p53 activates miR-192 and miR-215, which directly target NID1 mRNA to repress its expression. Secreted NID1 is required and sufficient for inducing EMT, invasion, and migration in epithelial-like CRC cells via paracrine signaling. miRNA target prediction and validation, conditioned medium transfer, NID1 knockdown and overexpression, CRC cell migration/invasion assays, cytokine array Cellular and molecular gastroenterology and hepatology Medium 30831320
2021 Nid1 is secreted by enteric neurons and elevated in the Ndrg4-/- enteric nervous system secretome. ENS-derived Nid1 (and Fibulin-2) enhances migration capacities of colorectal cancer cells and promotes organoid growth. Ndrg4 knockout mouse, in vitro co-culture of ENS cells and intestinal organoids, quantitative proteomics of secretome, CRC cell migration assay EMBO reports Medium 33890711
2022 NID-1 is highly secreted by skeletal muscle fibro-adipogenic/mesenchymal progenitors (FAPs) during obesity. Increased muscle NID-1 impairs muscle stem cell proliferation and primes FAPs for fibrogenic differentiation leading to excessive ECM deposition. High fat diet mouse model, cell secretome analysis, in vitro myoblast treatment with NID-1, immunofluorescence, muscle stem cell functional assay Matrix biology Medium 35963565
2023 NID1 is a direct transcriptional target of the EMT-inducing transcription factor SNAIL: ectopic SNAIL expression induces NID1, and SNAIL occupancy was detected at an E-box upstream of the NID1 transcription start site by ChIP. NID1 signals through its receptors ITGA3, ITGB1, and ITGAV; ectopic NID1 or NID1-conditioned medium conferred lung metastatic capacity to non-metastatic CRC cells in xenotransplantation. ChIP assay for SNAIL at NID1 E-box, ectopic expression of SNAIL and NID1, xenotransplantation lung metastasis model, bioinformatics of patient datasets, ITGAV knockdown viability assay Cancers Medium 38001576
2023 COL4A1 physically binds to NID1, as confirmed by co-immunoprecipitation in OSCC cells. NID1 overexpression rescues the inhibitory effects of COL4A1 knockdown on cell proliferation, migration, invasion, and EMT, placing NID1 downstream of COL4A1. Co-immunoprecipitation, COL4A1 knockdown, NID1 overexpression rescue experiment, proliferation/migration/invasion assays Experimental and therapeutic medicine Medium 37006878
2026 In C. elegans, NID-1 expressed by body wall muscles or hypodermis promotes local guidance of regenerating motor axons alongside neighboring neuronal processes (PVD dendrites). Loss of nid-1 disrupts axon-PVD colocalization, increases displacement from the pre-injury dorsal nerve cord contact point, and impairs synapse reformation and functional recovery. Muscle-derived NID-1 specifically is required for synapse reformation. Genetic data indicate NID-1 guides regenerating axons in coordination with laminin and integrin; ectopic integrin expression in GABAergic neurons reroutes their regenerating axons alongside PVD dendrites in a NID-1-dependent manner. nid-1 null mutant C. elegans, laser axotomy/axon regeneration assay, tissue-specific rescue (muscle, hypodermis, neuron), fluorescence imaging of axon guidance, synapse reformation assay, functional recovery assay, genetic epistasis with laminin and integrin bioRxivpreprint Medium 41890084

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1981 Entactin, a novel basal lamina-associated sulfated glycoprotein. The Journal of biological chemistry 417 6262321
1996 Rescue of mammary epithelial cell apoptosis and entactin degradation by a tissue inhibitor of metalloproteinases-1 transgene. The Journal of cell biology 195 8978831
1988 Amino acid sequence and domain structure of entactin. Homology with epidermal growth factor precursor and low density lipoprotein receptor. The Journal of cell biology 150 3264556
1992 The receptor for the basement membrane glycoprotein entactin is the integrin alpha 3/beta 1. The Journal of biological chemistry 131 1527019
1981 Immunolocalization of entactin, a sulfated basement membrane component, in rodent tissues, and comparison with GP-2 (laminin). The American journal of pathology 131 6165248
1983 Immunohistochemical localization of entactin and laminin in mouse embryos and fetuses. Developmental biology 126 6653883
1993 Degradation of entactin by matrix metalloproteinases. Susceptibility to matrilysin and identification of cleavage sites. The Journal of biological chemistry 124 8380588
1992 Entactin stimulates neutrophil adhesion and chemotaxis through interactions between its Arg-Gly-Asp (RGD) domain and the leukocyte response integrin. The Journal of clinical investigation 120 1469085
2002 Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1. Laboratory investigation; a journal of technical methods and pathology 109 12480912
1983 Synthesis of laminin and entactin by F9 cells induced with retinoic acid and dibutyryl cyclic AMP. The Journal of biological chemistry 104 6305950
1990 The basement membrane glycoprotein entactin promotes cell attachment and binds calcium ions. The Journal of biological chemistry 89 2191952
2020 BET protein inhibitor JQ1 downregulates chromatin accessibility and suppresses metastasis of gastric cancer via inactivating RUNX2/NID1 signaling. Oncogenesis 83 32157097
1989 Heterogenous distribution of type IV collagen, entactin, heparan sulfate proteoglycan, and laminin among renal basement membranes as demonstrated by quantitative immunocytochemistry. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 81 2723404
1990 Entactin: structure and function. American journal of respiratory cell and molecular biology 77 2119632
1983 Changes in the rate of laminin and entactin synthesis in F9 embryonal carcinoma cells treated with retinoic acid and cyclic amp. Developmental biology 73 6194034
1993 Recombinant entactin promotes mouse primary trophoblast cell adhesion and migration through the Arg-Gly-Asp (RGD) recognition sequence. The Journal of cell biology 72 8491783
1986 Distribution of fibronectin, laminin and entactin in the environment of migrating neural crest cells in early mouse embryos. Journal of embryology and experimental morphology 68 3519827
1991 The expression of the genes for entactin, laminin A, laminin B1 and laminin B2 in murine lens morphogenesis and eye development. Differentiation; research in biological diversity 67 1725162
1999 Transforming growth factor-beta1 stimulates the synthesis of basement membrane proteins laminin, collagen type IV and entactin in rat liver sinusoidal endothelial cells. Journal of hepatology 66 10551394
1998 Entactin-2: a new member of basement membrane protein with high homology to entactin/nidogen. Experimental cell research 60 9633511
1983 In vitro synthesis of laminin and entactin polypeptides. The Journal of biological chemistry 55 6189826
1995 Two distinct cell attachment sites in entactin are revealed by amino acid substitutions and deletion of the RGD sequence in the cysteine-rich epidermal growth factor repeat 2. The Journal of biological chemistry 54 7797588
2017 NID1, a new regulator of EMT required for metastasis and chemoresistance of ovarian cancer cells. Oncotarget 53 28416770
2011 Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk. Human molecular genetics 45 21478494
1993 Is neuronal intestinal dysplasia (NID) a primary disease or a secondary phenomenon? European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie 45 8218074
1994 Binding of the extracellular matrix component entactin to Candida albicans. Infection and immunity 44 7927722
2013 Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles. Human mutation 39 23674478
1993 Immunohistochemical localization of chondroitin sulfate, chondroitin sulfate proteoglycan, heparan sulfate proteoglycan, entactin, and laminin in basement membranes of postnatal developing and adult rat lungs. American journal of respiratory cell and molecular biology 37 8448015
1982 Localization of fibronectin, laminin-entactin, and entactin in Reichert's membrane by immunoelectron microscopy. The EMBO journal 37 7188248
1994 Interaction of enteropathogenic Yersinia enterocolitica with complex basement membranes and the extracellular matrix proteins collagen type IV, laminin-1 and -2, and nidogen/entactin. The Journal of biological chemistry 36 7961965
1993 Biological functions of entactin. Kidney international 36 8433553
1990 Characterization of the basement membrane glycoprotein entactin synthesized in a baculovirus expression system. The Journal of biological chemistry 35 2180961
1988 Analysis of the assembly of laminin and the laminin-entactin complex with laminin chain specific monoclonal and polyclonal antibodies. Biochemistry 35 3149508
2013 Transcriptome-wide analysis of TDP-43 binding small RNAs identifies miR-NID1 (miR-8485), a novel miRNA that represses NRXN1 expression. Genomics 34 23827811
1996 Domain-specific interactions between entactin and neutrophil integrins. G2 domain ligation of integrin alpha3beta1 and E domain ligation of the leukocyte response integrin signal for different responses. The Journal of biological chemistry 34 8940031
1991 Potential role of entactin in hemostasis. Specific interaction of entactin with fibrinogen A alpha and B beta chains. The Journal of biological chemistry 34 1680863
2021 Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2. EMBO reports 33 33890711
2019 Paracrine Induction of Epithelial-Mesenchymal Transition Between Colorectal Cancer Cells and its Suppression by a p53/miR-192/215/NID1 Axis. Cellular and molecular gastroenterology and hepatology 31 30831320
2019 Proteomic Profiling of Paired Interstitial Fluids Reveals Dysregulated Pathways and Salivary NID1 as a Biomarker of Oral Cavity Squamous Cell Carcinoma. Molecular & cellular proteomics : MCP 31 31315917
1996 Entactin expression by rat lung and rat alveolar epithelial cells. American journal of respiratory cell and molecular biology 31 8845174
1992 Entactin promotes adhesion and long-term maintenance of cultured regenerated skeletal myotubes. Journal of cellular physiology 30 1734030
1990 Entactin: a possible auto-antigen in the pathogenesis of non-Goodpasture anti-GBM nephritis. Kidney international 29 2119467
2004 Auditory brainstem evoked responses in insulin-dependent (ID) and non-insulin-dependent (NID) diabetic subjects with normal hearing. International journal of audiology 27 14974625
1987 Carboxyl-terminal sequence of entactin deduced from a cDNA clone. Proceedings of the National Academy of Sciences of the United States of America 27 3470744
1998 Adhesion of cultured human kidney mesangial cells to native entactin: role of integrin receptors. Cell adhesion and communication 26 9686320
1987 Effect of basement membrane entactin on epidermal cell attachment and growth. The Journal of investigative dermatology 26 3794389
2019 Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning. Development (Cambridge, England) 25 30567930
1992 Localization and synthesis of entactin in seminiferous tubules of the mouse. Biology of reproduction 25 1511084
2014 Looking the cow in the eye: deletion in the NID1 gene is associated with recessive inherited cataract in Romagnola cattle. PloS one 24 25347398
2016 Simultaneous Biodegradation of Polyaromatic Hydrocarbons by a Stenotrophomonas sp: Characterization of nid Genes and Effect of Surfactants on Degradation. Indian journal of microbiology 23 28148980
2014 Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. PloS one 20 24816743
2015 Impaired primary mouse myotube formation on crosslinked type I collagen films is enhanced by laminin and entactin. Acta biomaterialia 19 26555376
1996 Entactin immunoreactivity in immature and adult rat brain. Brain research. Developmental brain research 19 8874897
2001 Entactin-induced inhibition of human amyloid beta-protein fibril formation in vitro. Neuroscience letters 18 11376898
1991 Entactin forms a complex with fibronectin and co-localizes in the extracellular matrix of the embryonal carcinoma-derived 4CQ cell line. Biochemical and biophysical research communications 18 1872841
1995 Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene. Genomics 17 7601446
1994 The binding of fibronectin to entactin is mediated through the 29 kDa amino terminal fragment of fibronectin and the G2 domain of entactin. Biochemical and biophysical research communications 17 8147897
2006 Differential expression of entactin-1/nidogen-1 and entactin-2/nidogen-2 in myogenic differentiation. Differentiation; research in biological diversity 16 17177854
2005 Sumoylation of the net inhibitory domain (NID) is stimulated by PIAS1 and has a negative effect on the transcriptional activity of Net. Oncogene 16 15580297
1994 A novel epitope of entactin is present at the mammalian neuromuscular junction. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 7514212
2018 Four specific immunoglobulin domains in UNC-52/Perlecan function with NID-1/Nidogen during dendrite morphogenesis in Caenorhabditis elegans. Development (Cambridge, England) 15 29678816
2004 Upregulation of fibronectin but not of entactin, collagen IV and smooth muscle actin by anaphylatoxin C5a in rat hepatic stellate cells. Histology and histopathology 15 15375759
2023 COL4A1 promotes the proliferation and migration of oral squamous cell carcinoma cells by binding to NID1. Experimental and therapeutic medicine 13 37006878
2023 Nidogen-1/NID1 Function and Regulation during Progression and Metastasis of Colorectal Cancer. Cancers 13 38001576
2000 Mesenchymal entactin-1 (nidogen-1) is required for adhesion of peritubular cells of the rat testis in vitro. European journal of cell biology 13 10727019
2020 Matrigel-Free Laminin-Entactin Matrix to Induce Human Renal Proximal Tubule Structure Formation In Vitro. ACS biomaterials science & engineering 12 33320630
1996 Human trophoblast cell adhesion to extracellular matrix protein, entactin. American journal of reproductive immunology (New York, N.Y. : 1989) 12 8831898
2003 Morphofunctional studies of the glomerular wall in mice lacking entactin-1. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 11 14566019
1994 Entactin/nidogen: synthesis by bovine corneal endothelial cells and distribution in the human cornea. Investigative ophthalmology & visual science 11 8112999
2022 HIF-1α induced NID1 expression promotes pulmonary metastases via the PI3K-AKT pathway in salivary gland adenoid cystic carcinoma. Oral oncology 10 35689951
2009 Non-susceptibility genes to Bombyx densovirus type 1, Nid-1 and nsd-1, affect distinct steps of the viral infection pathway. Journal of invertebrate pathology 9 19836396
1993 Appearance and distribution of entactin in the early chick embryo. Differentiation; research in biological diversity 9 8243892
1988 Tyrosine sulfation is not the last modification of entactin before its secretion from 3T3-L1 adipocytes. FEBS letters 9 3042455
2022 Obesity impairs skeletal muscle repair through NID-1 mediated extracellular matrix remodeling by mesenchymal progenitors. Matrix biology : journal of the International Society for Matrix Biology 8 35963565
1995 Genomic sequences and structural organization of the human nidogen gene (NID). Genomics 8 7557988
2017 Laminin, laminin-entactin and extracellular matrix are equally appropriate adhesive substrates for isolated adult rat cardiomyocyte culture and experimentation. Cell adhesion & migration 7 29091577
1989 Entactin: ultrastructural localization of an ubiquitous basement membrane glycoprotein in mouse skin. Archives of dermatological research 7 2688563
2022 Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing. Endocrine connections 6 34941562
2020 Increased NID1 Expression among Breast Cancer Lung Metastatic Women; A Comparative Analysis between Naive and Treated Cases. Recent patents on anti-cancer drug discovery 6 32116201
2023 NID1-related autosomal dominant Dandy-Walker malformation with occipital cephalocele in three generations. European journal of medical genetics 5 36702440
1995 Trophoendodermal stem cell-derived extracellular matrices: absence of detectable entactin and presence of multiple laminin species. Placenta 5 8710801
1993 Characterization of the 5' end of the mouse Ent gene encoding the basement membrane protein, entactin. Gene 5 8224873
2024 LEDGF interacts with the NID domain of MeCP2 and modulates MeCP2 condensates. Structure (London, England : 1993) 4 39500316
2004 Quantification of the pathological changes in the temporal lobe of patients with a novel neurofilamentopathy: neurofilament inclusion disease (NID). Clinical neuropathology 4 15200288
1993 Embryonal carcinoma and the basement membrane glycoproteins laminin and entactin. The International journal of developmental biology 3 8507559
2024 NID1 promotes laryngeal cancer stemness via activating WNT pathway. Biology direct 2 39538332
1996 Interaction of mouse thymocytes and a thymocyte-like cell line with the ECM glycoprotein entactin. Cellular immunology 2 8548838
2025 Designing an Entactin-Inspired Short Bioactive Hydrogel as Biofunctional Scaffold. Chembiochem : a European journal of chemical biology 1 40404607
2025 ETV4 interacts with LOXL2 to induce epigenetic activation of NID1 during colorectal cancer progression. International journal of biological sciences 1 41281746
2025 Carpaine alleviates NASH-related fibrosis by targeting Nid1 to inhibit IL-6/JAK/STAT3 signaling and macrophage M1 polarization. International journal of biological macromolecules 1 41349744
2024 Identification of HSPG2 as a bladder pro-tumor protein through NID1/AKT signaling. Cancer cell international 1 39438949
2022 Resistance mechanism of Nid-1, a dominant non-susceptibility gene, against Bombyx mori densovirus 1 infection. Virus research 1 35691422
2001 Transcriptional state and chromatin structure of the murine entactin and laminin gamma1 genes. Journal of cellular biochemistry 1 11527148
2026 Nidogen/NID-1 guides regenerating motor axons in the mature nervous system. bioRxiv : the preprint server for biology 0 41890084
2026 MeCP2 NID interaction with RNA: implications for Rett syndrome-relevant protein regulation. Human molecular genetics 0 42051147
2026 Structural basis of NMI-IFP35 domains and swapping phenomenon in IFP35-NID. Journal of structural biology: X 0 42181032

Missed literature

Know a paper Affinage missed for NID1? Flag it for the maintainers and the community.

No submissions yet.