| 1996 |
MP25 (MAGP-2/MFAP5) was identified as a distinct component of elastin-associated microfibrils by immunofluorescence and immunoelectron microscopy. Its primary structure contains 173 amino acids with significant homology to MAGP-1 confined to a central 60-amino acid cysteine-rich region (7 conserved cysteines), and it contains an RGD motif but lacks proline-, glutamine-, and tyrosine-rich sequences and hydrophobic carboxyl terminus characteristic of MAGP-1, suggesting distinct functions. |
Peptide sequencing, cDNA cloning, immunofluorescence, immunoelectron microscopy, sequence homology analysis |
The Journal of biological chemistry |
High |
8557636
|
| 1998 |
MAGP-2 (MFAP5) is specifically associated with fibrillin-containing microfibrils in multiple tissues (nuchal ligament, dermis, adventitia, glomerular mesangium, perimysium) as confirmed by immunoelectron microscopy, but has a more restricted tissue distribution than MAGP-1, being absent from medial layer of fetal thoracic aorta and ocular zonule where MAGP-1 is present. |
Immunoelectron microscopy, immunolocalization, Northern blotting |
The journal of histochemistry and cytochemistry |
High |
9671438
|
| 2002 |
MAGP-2 (MFAP5) specifically interacts with fibrillin-1 and fibrillin-2 via a calcium-binding EGF-like repeat-containing region near the C-terminus of the fibrillins. Binding occurs through a core region of MAGP-2 containing 7 conserved cysteine residues. The fibrillin-1 binding site for MAGP-2 is distinct from the MAGP-1 binding site on fibrillin-1. Interaction was confirmed by co-immunoprecipitation from transfected COS-7 cells. |
Yeast two-hybrid library screen, deletion analysis, co-immunoprecipitation from transfected COS-7 cells |
The Journal of biological chemistry |
High |
12122015
|
| 2002 |
MAGP-2 (MFAP5) contains a matrix-binding domain similar to the 54-amino acid C-terminal cysteine-rich domain of MAGP-1, but a single amino acid change prevents MAGP-2 from associating with the ECM in the same mammalian cell model used to demonstrate MAGP-1 matrix binding. |
Deletion constructs expressed in mammalian cells, GFP fusion localization |
The Journal of biological chemistry |
Medium |
11796718
|
| 2005 |
MAGP-2 (MFAP5) interacts with the Notch ligand Jagged1 via the EGF-like repeats of Jagged1, and promotes shedding of the Jagged1 extracellular domain in a metalloproteinase-dependent manner (blocked by hydroxamate inhibitor BB3103). MAGP-2 also interacts with Jagged2 and Delta1 but does not facilitate their shedding. MAGP-1 interacts with DSL ligands but cannot facilitate Jagged1 shedding. |
Yeast two-hybrid, co-immunoprecipitation, conditioned media analysis, metalloproteinase inhibitor treatment |
The Journal of biological chemistry |
High |
15788413
|
| 2006 |
MAGP-2 (MFAP5) directly interacts with the EGF-like repeats of Notch1, and co-expression of MAGP-2 with Notch1 leads to cell surface release of the Notch1 extracellular domain and subsequent activation of Notch signaling. The C-terminal domain of MAGP-2 is required for Notch1 binding and activation. Notch1 extracellular domain release by MAGP-2 requires furin-like cleavage for Notch1 heterodimer formation but does not require subsequent ADAM metalloprotease cleavage. |
Co-expression studies, Notch signaling reporter assays, domain deletion analysis, cell surface release assays |
The Journal of biological chemistry |
High |
16492672
|
| 2006 |
Microfibril-associated MAGP-2 (MFAP5) stimulates elastic fiber assembly independently of extracellular tropoelastin levels. Electron microscopy showed MAGP-2 specifically associates with microfibrils and elastin globules co-localize with MAGP-2-associated microfibrils. The RGD motif of MAGP-2 is not required for this stimulation of elastic fiber assembly, ruling out integrin receptor binding as the mechanism. MAGP-2 overexpression did not change levels of fibrillin-1, MAGP-1, fibulin-2, fibulin-5, or emilin-1. |
Doxycycline-regulated conditional overexpression system, immunofluorescence, electron microscopy, mutation analysis of RGD motif |
The Journal of biological chemistry |
High |
17099216
|
| 2008 |
MAGP-2 (MFAP5) promotes angiogenic cell sprouting by antagonizing Notch signaling in endothelial cells specifically: MAGP-2 decreased basal and Jagged1-induced Hes-1 promoter activity and blocked Jagged1-stimulated Notch1 receptor processing in endothelial cells, but increased Hes-1 promoter activity in heterologous cell types. Constitutive activation of Notch blocked MAGP-2-promoted angiogenic sprouting. |
Hes-1 promoter luciferase reporter assay, Notch1 receptor processing assay in transfected 293T cells, angiogenic sprouting assay, constitutively active Notch rescue experiment |
Microvascular research |
High |
18417156
|
| 2013 |
MAGP2 (MFAP5) binds active TGFβ1, TGFβ2, and BMP2 in solid phase binding assays. Loss of MAGP2 in Mfap5-/- mice causes neutropenia (contrasting with monocytopenia in MAGP1-deficient mice), and MAGP1;MAGP2 double knockout mice show age-dependent aortic dilation, indicating shared primary functions of MAGPs in large vessel integrity. |
Solid phase binding assay, targeted gene inactivation (Mfap5-/- mice), blood cell counts, vascular compliance measurements |
The Journal of biological chemistry |
High |
23963447
|
| 2014 |
MFAP5 (MAGP-2) binding to microfibrils requires its conserved Matrix Binding Domain, and this matrix association is positively regulated by proprotein convertase (PC) cleavage of MAGP2. Mutation of the MAGP2 PC consensus site reduced matrix-associated MAGP2. The C-terminal 20-amino acid domain defined by the PC cleavage site also positively modulates matrix localization in a manner requiring the amino-terminal half of the protein. |
Immunofluorescence co-localization with fibrillin-2 microfibrils, PC consensus site mutagenesis, deletion analysis, overexpression in T3 ovarian cells |
Matrix biology |
Medium |
25153248
|
| 2014 |
MFAP5 (MAGP-2) activates FAK/CREB/TNNC1 signaling to promote ovarian cancer cell motility and invasion. Targeting stromal MFAP5 with siRNA in chitosan nanoparticles significantly decreased ovarian tumor growth and metastasis in vivo. |
siRNA knockdown, signaling pathway analysis, in vivo mouse tumor model with nanoparticle-delivered siRNA |
Nature communications |
Medium |
25277212
|
| 2016 |
MAGP2 (MFAP5) controls Notch signaling in a cell-type-dependent manner through its RGD motif interacting with RGD-binding integrins: in endothelial cells, wild-type MAGP2 suppresses Hes1 promoter activity while a RGD→RGE MAGP2 mutant increases Notch signaling. Inhibition of RGD-binding integrins with soluble RGD peptides or β1/β3 integrin blocking antibodies increased active N1ICD accumulation and Notch responsive promoter activity independently of changes in Notch1, Jag1, or Dll4 expression. |
Hes1 promoter luciferase reporter assay, RGD→RGE point mutagenesis, soluble RGD peptide inhibition, integrin blocking antibodies, N1ICD accumulation assay |
Experimental cell research |
High |
26808411
|
| 2018 |
MFAP5 promotes breast cancer cell proliferation and migration by increasing expression of MMP2 and MMP9 and activating the ERK signaling pathway (p-FAK, p-ERK1/2, p-cJun). Inhibition of MFAP5 suppressed these downstream signaling molecules. |
Overexpression and knockdown, Western blot for signaling proteins, cell proliferation and migration assays |
Biochemical and biophysical research communications |
Low |
29526753
|
| 2018 |
MFAP5 is enriched in cancer-associated fibroblast (CAF) secretomes relative to adjacent tissue fibroblasts, and recombinant MFAP5 activates OTSCC cell growth and migration via activation of MAPK and AKT pathways. |
Shotgun proteomics of CAF secretomes, in vitro recombinant protein treatment, MAPK/AKT pathway analysis |
Journal of proteome research |
Medium |
29681158
|
| 2019 |
MFAP5 knockdown in cervical cancer cells induces apoptosis through ROS production, activates JNK, reduces Bcl-xl and Bcl-2, and increases Bax and cleaved Caspase-3. MFAP5 knockdown also induces G2/M cell cycle arrest with reduced Cyclin B1, Cyclin D1, and CDK4, and increased p21 and p53. The growth inhibitory effect of MFAP5 knockdown is dependent on ROS production. |
siRNA knockdown, ROS measurement, cell cycle analysis, Western blot for apoptosis/cell cycle markers, in vivo xenograft, ROS rescue experiment |
Biochemical and biophysical research communications |
Medium |
30454902
|
| 2019 |
CAF-derived MFAP5 promotes bladder cancer proliferation and metastasis via direct interaction with the NOTCH2 receptor, stimulating N2ICD release and activating NOTCH2/HEY1 signaling. QKI directly downregulates MFAP5 in CAFs as shown by luciferase reporter and EMSA. MFAP5-mediated PI3K-AKT signaling activates the DLL4/NOTCH2 pathway axis. Downregulation of NOTCH2 by shRNA or NRR2Mab antibody reverses the adverse effects of MFAP5 stimulation. |
Co-IP (MFAP5 direct interaction with NOTCH2), luciferase reporter assay, EMSA, RNA-sequencing, shRNA knockdown, neutralizing antibody NRR2Mab, in vitro and in vivo rescue experiments |
FASEB journal |
High |
32293074
|
| 2019 |
CAF-secreted MFAP5 drives invasion and migration of MCF7 breast cancer cells via activation of Notch1 signaling, upregulating NICD1 and Slug. Notch1 knockdown in MCF7 cells decreased the ability of MFAP5 to promote invasion and migration. |
Proteomic analysis of CAF secretomes, Transwell and wound healing assays, Notch1 knockdown, Western blot for NICD1 and Slug |
Clinical & translational oncology |
Medium |
31190277
|
| 2019 |
MFAP5 promotes basal-like breast cancer metastasis via the TGF-β/Notch pathway: TGF-β or Notch inhibitors significantly reversed tumorigenicity and metastasis of MFAP5-induced BLBC cells in vitro and in vivo. |
Overexpression and knockdown, in vitro proliferation/migration/invasion assays, in vivo tail vein metastasis model, TGF-β and Notch pathway inhibitor rescue |
Cell & bioscience |
Medium |
30899449
|
| 2019 |
MFAP5 facilitates intrahepatic cholangiocarcinoma (ICC) cell growth and G1-to-S phase transition through regulation of the Notch1 signaling pathway, as revealed by RNA-seq and ATAC-seq of MFAP5-suppressed ICC cells. The Notch signaling inhibitor FLI-06 completely abolished MFAP5-dependent transcriptional programs. |
RNA-seq, ATAC-seq, shRNA knockdown, Notch inhibitor (FLI-06) treatment, CCK8 and colony formation assays, cell cycle analysis, xenograft model |
Journal of experimental & clinical cancer research |
Medium |
31775892
|
| 2021 |
Intracellular MAGP2 (MFAP5) directly interacts with urokinase-type plasminogen activator receptor (uPAR) and inhibits lysosomal-mediated degradation of uPAR, thereby increasing uPAR stability. Elevated MAGP2 promotes tumor cell proliferation through uPAR-mediated p38-NF-κB signaling axis activation, enhanced DNA damage repair, and reduction of S-phase cell stagnation. |
Co-immunoprecipitation (direct interaction with uPAR), proteomics analysis, lysosomal degradation assay, p38-NF-κB pathway analysis, xenograft model with uPAR knockdown rescue |
Cellular signalling |
Medium |
34915136
|
| 2023 |
MFAP5 deficiency in CAFs downregulates HAS2 and CXCL10 via MFAP5/RCN2/ERK/STAT1 axis in pancreatic cancer, leading to reduced angiogenesis, hyaluronic acid and collagen deposition, increased cytotoxic T cell infiltration, and tumor cell apoptosis. In vivo blockade of CXCL10 with AMG487 partially reverses the pro-tumor effect of MFAP5 overexpression in CAFs. |
MFAP5 knockdown in CAFs, Western blot for RCN2/ERK/STAT1 pathway, CXCL10/HAS2 measurement, in vivo tumor models, AMG487 CXCL10 inhibitor rescue |
Oncogene |
Medium |
37156839
|
| 2024 |
MAGP2 (MFAP5) promotes osteogenic differentiation and fracture healing through interaction with LRP5 and activation of β-catenin signaling. MAGP2 upregulates LRP5 expression, and LRP5 knockdown partially reverses MAGP2-promoted osteogenic differentiation and β-catenin activation. β-catenin/TCF4 increases MAGP2 expression by binding to the MAGP2 promoter, creating a feedback loop. |
Co-IP (MAGP2-LRP5 interaction), LRP5 knockdown rescue, ALP activity assay, mineralization assay, in vivo fracture mouse model, mRNA sequencing |
Journal of cellular physiology |
Medium |
38348695
|
| 2025 |
MFAP5 loss in Mfap5-/- mice impairs wound closure, reduces angiogenesis, enhances neutrophil and macrophage influx, and reduces collagen deposition in normal skin. Mfap5-/- fibroblasts exhibit reduced migration, contractility, proliferation, and ECM deposition in vitro, identifying a direct role for MFAP5 in fibroblast behavior relevant to wound healing. |
Mfap5-/- mouse wound healing model, single-cell RNA sequencing, in vitro fibroblast isolation and functional assays (migration, contractility, proliferation, ECM deposition), mRNA sequencing |
FASEB journal |
High |
41348119
|
| 2025 |
MFAP5 engages integrin alpha-5 (ITGA5) to activate ERK/MAPK signaling in odontoblast-lineage cells, promoting odontoblast differentiation and dentin deposition (matrix mineralization). |
Single-cell RNA sequencing, functional in vitro differentiation/mineralization assays, MFAP5-ITGA5 interaction and ERK/MAPK signaling pathway analysis |
International journal of molecular sciences |
Low |
41516268
|
| 2025 |
MFAP5 promotes stemness features of NSCLC cells by inducing degradation of FBW7 (a tumor suppressor), which stabilizes Sox9 (a cancer stem cell protein). MFAP5 knockdown increased FBW7 levels and accelerated Sox9 degradation (CHX chase assay). Sox9 overexpression rescued growth/stemness inhibition caused by MFAP5 knockdown. |
MFAP5 overexpression/knockdown, Western blot for FBW7 and Sox9, CHX degradation assay, Sox9 overexpression rescue, clone formation and sphere culture assays |
Current pharmaceutical biotechnology |
Low |
38415489
|
| 2019 |
Anti-MFAP5 antibody clone 130A downregulates MFAP5-induced collagen production in CAFs, suppresses intratumoral microvessel leakiness, and enhances paclitaxel bioavailability in ovarian and pancreatic cancer mouse models. Epitope mapping identified a common epitope shared between human and murine MFAP5. |
Hybridoma antibody development, Octet RED384 binding kinetics, epitope mapping, in vitro collagen production assay, in vivo tumor-bearing mouse models |
Clinical cancer research |
Medium |
31332047
|