| 1981 |
Entactin (NID1) is a sulfated glycoprotein component of basement membranes, distinct from laminin (GP-2), with a molecular weight of ~158 kDa, localized at the surface of epithelial cells adjacent to basement membranes in rodent kidney and other tissues. |
Biochemical isolation, immunoelectron microscopy, antibody-based characterization |
The Journal of biological chemistry |
High |
6262321
|
| 1988 |
Mouse entactin is organized into two globular domains (70 kDa N-terminal and 36 kDa C-terminal) separated by a cysteine-rich 28 kDa stalk; the C-terminal domain shows homology to EGF precursor and LDL receptor; the molecule contains six EGF-type cysteine-rich repeats, one thyroglobulin repeat, and an RGD cell-recognition sequence in one EGF-type repeat; synthetic RGD-containing peptide promotes mammary tumor cell attachment. |
cDNA sequencing, sequence analysis, synthetic peptide cell attachment assay |
The Journal of cell biology |
High |
3264556
|
| 1988 |
Entactin tyrosine sulfation occurs in the medial Golgi cisternae and is not the last modification before secretion; N-linked glycosylation and terminal glycosylation in the trans-Golgi occur after sulfation. |
Metabolic labeling with [35S]methionine and H2[35S]O4, tunicamycin and monensin inhibitor treatments, pulse-chase analysis |
FEBS letters |
Medium |
3042455
|
| 1990 |
Entactin promotes cell attachment through the integrin RGD recognition sequence; additionally, entactin directly binds calcium ions through sites in the N-terminal region, demonstrated with recombinant peptides containing the first 330 amino acids. |
Cell attachment assay with synthetic peptides and recombinant entactin, calcium binding assay with recombinant N-terminal fragment |
The Journal of biological chemistry |
High |
2191952
|
| 1990 |
Entactin forms a highly stable noncovalent complex with laminin intracellularly; transfection of entactin into JAR choriocarcinoma cells (which lack entactin but make laminin and collagen IV) stimulates incorporation of all three into extracellular matrix, indicating entactin bridges laminin and type IV collagen in basement membrane assembly. |
Cell transfection, immunofluorescence, extracellular matrix fractionation |
American journal of respiratory cell and molecular biology |
High |
2119632
|
| 1991 |
Entactin specifically binds fibrinogen through interactions with the Aα and Bβ chains of fibrinogen in a divalent cation-independent manner; entactin can be cross-linked to fibrinogen by transglutaminase. |
Solid phase binding assay with radiolabeled entactin, antibody inhibition, transglutaminase cross-linking |
The Journal of biological chemistry |
High |
1680863
|
| 1991 |
Entactin forms a complex with fibronectin (independent of laminin) and co-localizes in the extracellular matrix of 4CQ embryonal carcinoma cells; direct binding between entactin and fibronectin was demonstrated by affinity chromatography and solid phase assay. |
Affinity column chromatography, solid phase binding assay, immunofluorescence |
Biochemical and biophysical research communications |
Medium |
1872841
|
| 1992 |
The cell surface receptor for entactin on PC-3 prostate carcinoma cells is integrin α3β1; binding requires divalent cations (Ca2+, Mg2+, Mn2+) and is not inhibited by RGD-containing peptides; α3β1 purified from cells binds entactin-Sepharose, while α2β1 does not. |
Affinity chromatography on entactin-Sepharose, anti-integrin antibody identification, purified integrin 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 and the leukocyte response integrin (LRI); a recombinant RGE-substituted entactin mutant (Asp674→Glu) lost both adhesive and chemotactic activities; anti-β1 and anti-β2 antibodies did not block the response whereas anti-LRI did. |
Adhesion assay, chemotaxis assay, RGD/RGE synthetic peptides, recombinant site-directed mutant entactin, monoclonal antibody blocking, leukocyte adhesion deficiency patient PMNs |
The Journal of clinical investigation |
High |
1469085
|
| 1992 |
Entactin is required for long-term maintenance and adhesion of contractile skeletal myotubes; anti-entactin antibodies did not inhibit satellite cell attachment or fusion but caused myotube detachment after spontaneous contractions began, demonstrating a specific role for entactin in myotube maintenance. |
Anti-entactin antibody perturbation on Matrigel cultures of regenerated satellite cells, myotube adhesion assay |
Journal of cellular physiology |
Medium |
1734030
|
| 1993 |
Entactin is specifically degraded by matrix metalloproteinases; matrilysin (MMP-7) is ~100-fold more effective than interstitial collagenase and ~600-fold more effective than 92 kDa gelatinase; matrilysin cleaves entactin at sites amino-terminal to leucine or isoleucine residues producing fragments of 29–115 kDa. |
In vitro protease digestion assay, kinetic analysis (Km, Vmax), Edman degradation for cleavage site identification |
The Journal of biological chemistry |
High |
8380588
|
| 1993 |
Entactin binds laminin, collagen IV, fibrinogen, and fibronectin; the laminin-entactin complex is formed intracellularly in M1536-B3 cells and transported in membrane-enclosed vesicles to the extracellular compartment. |
Co-immunoprecipitation, cell fractionation, transfection experiments, indirect immunofluorescence |
Kidney international |
High |
8433553
|
| 1993 |
Recombinant entactin promotes primary trophoblast cell adhesion and migration through the RGD recognition sequence; a mutated entactin with Glu replacing Asp at the RGD site provided no trophoblast adhesive activity. |
Blastocyst outgrowth assay, RGD peptide inhibition, recombinant RGD→RGE mutant entactin, anti-entactin antibody |
The Journal of cell biology |
High |
8491783
|
| 1994 |
The binding of fibronectin to entactin is mediated through the 29 kDa amino-terminal fragment of fibronectin and the G2 domain of entactin (but not G1, E, or G3 domains); half-saturation for binding is ~5 nM. |
Solid phase binding assay with GST-domain fusion proteins of entactin and radiolabeled fibronectin fragment |
Biochemical and biophysical research communications |
Medium |
8147897
|
| 1994 |
A novel epitope of entactin at the neuromuscular junction is dependent on glycosylation; N-glycanase treatment reduces entactin molecular mass and eliminates the synaptic-specific 9H6 antibody epitope, indicating that synaptic entactin bears a distinct N-glycosylation pattern not found at extrasynaptic sites. |
Monoclonal antibody generation, Western blot, N-glycanase treatment, immunostaining of NMJ |
The Journal of neuroscience |
Medium |
7514212
|
| 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 second site in a 39-amino acid cysteine-rich EGF repeat of the G2 domain recognized by a β1 integrin family member; deletion/mutation of RGD reveals the second site. |
GST-domain fusion protein cell attachment assay, baculovirus-expressed full-length RGD deletion mutant, anti-integrin antibody inhibition |
The Journal of biological chemistry |
High |
7797588
|
| 1996 |
Entactin E domain (containing RGD) ligates the leukocyte response integrin (LRI/β3-like) and signals for neutrophil chemotaxis, while the G2 domain ligates α3β1 and signals for enhancement of Fc receptor-mediated phagocytosis; matrilysin cleavage of entactin liberates fragments retaining both activities. |
GST-domain fusion protein neutrophil activation assays (chemotaxis, phagocytosis), matrilysin cleavage, anti-integrin antibody blocking |
The Journal of biological chemistry |
High |
8940031
|
| 1996 |
Stromelysin-1 (MMP-3) cleaves entactin in mammary gland basement membrane in vivo; enhanced cleavage of entactin correlates directly with apoptosis of overlying mammary epithelial cells; TIMP-1 overexpression blocks both entactin cleavage and apoptosis. |
Transgenic mouse cross (stromelysin-1 × TIMP-1 overexpressing mice), apoptosis assay, in vivo entactin protein quantification |
The Journal of cell biology |
High |
8978831
|
| 1998 |
Human mesangial cells adhere to native entactin via both αvβ3 (binding to the RGD sequence on the E domain) and a β1 integrin receptor (binding to a non-RGD site); cation dependence was demonstrated and tertiary molecular structure of entactin contributes to binding. |
Anti-integrin antibody inhibition of adhesion, wild-type and mutant recombinant entactin fragments, immunoprecipitation of integrin receptors |
Cell adhesion and communication |
Medium |
9686320
|
| 2000 |
Nidogen-1/entactin-1 is exclusively produced and secreted by mesenchymal peritubular cells (not Sertoli cells) in the testis; monoclonal antibody perturbation against entactin-1 caused loss of peritubular cell adhesion (autocrine function) while Sertoli cells remained adherent. |
DD-RT-PCR, Western blotting of cell fractions and supernatants, monoclonal antibody perturbation of cell adhesion |
European journal of cell biology |
Medium |
10727019
|
| 2001 |
Entactin inhibits amyloid β-protein (Aβ1-40) fibril formation in vitro in a dose-dependent manner at a molar ratio of 50:1 (Aβ:entactin); entactin induces 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
|
| 2002 |
Targeted disruption of entactin-1/nidogen-1 in mice results in neurological deficits (seizure-like symptoms, loss of hind-leg muscle control) and selective structural alterations in basement membranes of brain capillaries and lens capsule, while other basement membranes appear morphologically normal. |
Gene targeting/knockout mouse, behavioral phenotyping, immunohistochemistry, electron microscopy |
Laboratory investigation |
High |
12480912
|
| 2003 |
In entactin-1-null mice, the glomerular basement membrane is thickened; distribution of anionic charges is significantly altered; αv-integrin density on glomerular cells is increased; glomerular filtration permselectivity (albumin distribution) is altered; type IV collagen and laminin distributions remain unchanged. |
Immunocytochemistry in knockout mice, morphometry, glomerular filtration analysis with endogenous albumin |
The journal of histochemistry and cytochemistry |
Medium |
14566019
|
| 2013 |
Mutations in NID1 and its binding partner LAMC1 cause autosomal dominant Dandy-Walker malformation; structural modeling of the NID1-LAMC1 complex shows each mutation disrupts the protein-protein interaction. |
Whole-exome sequencing, protein interaction network analysis, structural modeling of NID1-LAMC1 complex |
Human mutation |
Medium |
23674478
|
| 2017 |
NID1 activates ERK/MAPK signaling to promote epithelial-mesenchymal transition (EMT) in ovarian cancer cells; ectopic NID1 expression induces EMT with enhanced motility, invasiveness, and cisplatin resistance, while NID1 knockdown reverses these effects. |
Ectopic overexpression and siRNA knockdown, EMT marker analysis, migration/invasion assays, ERK/MAPK pathway analysis |
Oncotarget |
Medium |
28416770
|
| 2019 |
NID1 is secreted by mesenchymal-like colorectal cancer cells and induces EMT in neighboring epithelial-like CRC cells via paracrine signaling; p53 suppresses NID1 expression by inducing miR-192 and miR-215, which directly target the NID1 mRNA; NID1 is required and sufficient for inducing EMT in recipient cells. |
Conditioned medium transfer, cytokine array, miRNA target validation, p53 activation experiments, rescue assays |
Cellular and molecular gastroenterology and hepatology |
High |
30831320
|
| 2019 |
Drosophila Nidogen/entactin (NDG) is not essential for basement membrane assembly but mediates BM stability and ECM-dependent neural plasticity; loss of Laminin strongly affects BM localization of NDG; Ndg-null mutants have ultrastructural BM defects compromising barrier function, impaired larval crawling, and defects in chordotonal organs and neuromuscular junction. |
Drosophila Ndg-null mutants, TEM ultrastructure, in vivo barrier function assay, behavioral assays, confocal immunostaining |
Development (Cambridge, England) |
High |
30567930
|
| 2020 |
BRD4 inhibitor JQ1 reduces NID1 expression in gastric cancer cells via RUNX2; RUNX2 directly binds the NID1 promoter region (demonstrated by ChIP), and RUNX2/NID1 axis mediates JQ1-inhibited metastasis; NID1 knockdown inhibits migration and invasion by inducing MET. |
ATAC-seq, RNA-seq, ChIP, luciferase reporter assay, rescue experiments, in vivo tumor models |
Oncogenesis |
High |
32157097
|
| 2021 |
Enteric neuron-derived Nidogen-1 (NID1) is secreted by enteric neurons and promotes colorectal cancer cell migration; the NID1-enriched secretome of Ndrg4-/- ENS cells boosts intestinal organoid growth; NID1 is enriched in human CRC secretomes. |
Ndrg4 knockout mouse models, indirect co-culture, quantitative proteomics, in vitro migration assay, immunostaining |
EMBO reports |
Medium |
33890711
|
| 2022 |
NID1 overexpression promotes salivary gland adenoid cystic carcinoma (SACC) metastasis via PI3K/AKT pathway activation and subsequent EMT; HIF-1α directly binds the NID1 promoter and drives NID1 transcription under hypoxia, as confirmed by ChIP and dual-luciferase reporter assay. |
ChIP, dual-luciferase reporter assay, NID1 overexpression, PI3K/AKT pathway analysis, in vivo lung metastasis mouse model |
Oral oncology |
Medium |
35689951
|
| 2022 |
Skeletal muscle fibro-adipogenic progenitors (FAPs) are the primary source of elevated NID1 during obesity; increased NID1 impairs muscle stem cell proliferation and primes FAPs toward fibrogenic differentiation, causing excessive ECM deposition. |
High-fat diet mouse model, cell fractionation, in vitro myoblast/stem cell assays with recombinant NID1, immunostaining of endomysium |
Matrix biology |
Medium |
35963565
|
| 2023 |
NID1 is a direct transcriptional target of the EMT transcription factor SNAIL, which occupies an E-box upstream of the NID1 transcription start site; NID1-containing conditioned medium endows non-metastatic CRC cells with lung metastatic capacity after xenotransplantation; ITGAV (αv integrin) is the primary NID1 receptor mediating these effects in CRC. |
ChIP for SNAIL occupancy at NID1 E-box, conditioned medium transfer, xenograft lung metastasis assay, ITGAV knockdown |
Cancers |
High |
38001576
|
| 2023 |
COL4A1 binds to NID1 (confirmed by co-immunoprecipitation) and promotes OSCC cell proliferation, migration, invasion, and EMT; NID1 overexpression reverses the inhibitory effects of COL4A1 knockdown, placing NID1 downstream of COL4A1. |
Co-immunoprecipitation, siRNA knockdown, NID1 overexpression rescue, cell proliferation and invasion assays, EMT marker analysis |
Experimental and therapeutic medicine |
Medium |
37006878
|
| 2018 |
In C. elegans, NID-1/Nidogen is required for correct dendrite patterning of PVD somatosensory neurons; UNC-52/Perlecan localizes NID-1 via four conserved immunoglobulin domains; genetic epistasis places nid-1 in the same pathway as unc-52 and the netrin axon guidance signaling cassette for dendrite morphogenesis. |
C. elegans genetics, null mutant analysis, epistasis assay, confocal imaging of dendrite morphology |
Development (Cambridge, England) |
Medium |
29678816
|
| 2025 |
In C. elegans, NID-1 expressed by body wall muscles or hypodermis promotes guidance of regenerating cholinergic motor axons alongside PVD dendrites; muscle-derived NID-1 specifically is required for synapse reformation and functional recovery; NID-1 acts in coordination with laminin and integrin for axon guidance. |
C. elegans nid-1 null mutant, tissue-specific rescue, axon regeneration assay, synapse reformation assay, genetic epistasis with laminin and integrin mutants |
bioRxivpreprint |
Medium |
41890084
|
| 2025 |
Nid1 mediates NASH-related liver fibrosis by activating the JAK2/STAT3 pathway and IL-6 autocrine signaling in hepatic stellate cells; AAV8-mediated Nid1 knockdown attenuates fibrosis; recombinant Nid1 supplementation rescues the protective effect of CP treatment, confirming Nid1 as the mechanistic target. |
CDAHFD mouse model, AAV8-mediated knockdown, exogenous recombinant Nid1 rescue, co-culture systems, JAK2/STAT3 pathway analysis, proteomic/metabolomic analysis |
International journal of biological macromolecules |
Medium |
41349744
|
| 2024 |
HSPG2 upregulates NID1 expression, leading to activation of the AKT pro-survival signaling pathway and promotion of bladder cancer cell proliferation and chemotherapy resistance. |
HSPG2 overexpression in bladder cancer cell lines, Western blotting and immunostaining for NID1/AKT activation, patient-derived tumor organoid mouse models |
Cancer cell international |
Low |
39438949
|