Affinage

SMAD5

SMAD family member 5 · UniProt Q99717

Length
465 aa
Mass
52.3 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMAD5 is a receptor-regulated R-Smad that transduces BMP signals from the cell surface to the nucleus to control developmental cell-fate decisions and tissue homeostasis (PMID:9442019, PMID:10079226, PMID:10079220). Upon BMP-2/BMP-7/BMP-9 ligand stimulation, SMAD5 is serine-phosphorylated at its C-terminus through direct association with BMP type I receptors (BMPR-IA/IB), an event dependent on BMPR-II kinase, after which it binds SMAD4 (DPC4) and the complex translocates to the nucleus; C-terminal serine-to-alanine or G419S point mutants act as dominant negatives that block BMP responses (PMID:9442019, PMID:9766532, PMID:16626664). In the nucleus, the SMAD5 MH1 domain recognizes GC-rich elements (consensus TGTGC) and, uniquely among BMP R-Smads, also the canonical SBE; crystal structures show a single β-hairpin engages both DNA modes, and SMAD5 directly occupies target promoters such as Dlx3 and Akt2 and recruits the p300/CBP coactivator (PMID:11527422, PMID:26304548, PMID:24647893, PMID:12857787). SMAD5 output is constrained by multiple negative regulators: Smurf1 binds the SMAD5 linker PPXY motif via its WW2 domain and targets SMAD5 for ubiquitin-mediated proteasomal degradation (PMID:12871975, PMID:17676934); miR-155 represses the SMAD5 3'UTR to disable TGF-β1/BMP growth arrest in DLBCL through the p15/p21/RB axis (PMID:20133617, PMID:24136167); and Jab1 and lncRNA TUG1 antagonize nuclear SMAD5 activity (PMID:17133595, PMID:31149038). Genetically, SMAD5 acts downstream of BMP2b/BMP4 in dorsoventral and left-right patterning, and is essential in vivo for yolk-sac angiogenesis, primordial germ cell specification, lefty-1-dependent L-R axis determination, stress erythropoiesis, endometrial receptivity, intestinal epithelial integrity, and cardiac homeostasis (PMID:10207140, PMID:10079226, PMID:10079220, PMID:10677256, PMID:11404080, PMID:15591122, PMID:34099644, PMID:21212325, PMID:17456754). Beyond canonical signaling, SMAD5 forms an unusual BMP4-induced SMAD2/SMAD5 complex that antagonizes Nodal signaling (PMID:22912414), and undergoes phosphorylation-, SMAD4-independent nucleocytoplasmic shuttling driven by intracellular pH, with cytoplasmic SMAD5 binding hexokinase 1 to accelerate glycolysis (PMID:28675158).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1997 Medium

    Established SMAD5 as a downstream intracellular mediator of BMP signaling, resolving whether overexpression alone could mimic ligand-driven osteoblast conversion and myogenic suppression.

    Evidence Wild-type and dominant-negative SMAD5 transfection with reporter and alkaline phosphatase assays in C2C12 cells, and mRNA injection epistasis in Xenopus

    PMID:9133445 PMID:9299554

    Open questions at the time
    • Did not show direct receptor phosphorylation of endogenous SMAD5
    • SMAD4 requirement inferred from epistasis rather than biochemistry
  2. 1998 High

    Defined the biochemical activation step: BMP type I receptors directly phosphorylate SMAD5 on C-terminal serines, triggering SMAD4 binding and nuclear translocation.

    Evidence Co-IP with BMPR-Ia/Ib, serine phosphorylation and in vitro kinase assays, and C-terminal serine/G419S dominant-negative mutants in C2C12 and ROB-C26 cells

    PMID:9442019 PMID:9766532

    Open questions at the time
    • Exact phosphoacceptor residues not enumerated at this stage
    • Stoichiometry and selectivity of receptor-Smad pairing not fully resolved
  3. 1998 Medium

    Demonstrated SMAD5 is functionally required in primary human hematopoiesis as a transducer of TGF-β inhibitory signaling.

    Evidence Antisense oligonucleotide knockdown of SMAD5 in CD34+ progenitors with colony formation assays

    PMID:9490674

    Open questions at the time
    • Antisense specificity vs other R-Smads not excluded
    • Direct transcriptional targets in hematopoietic cells not identified
  4. 1999 High

    Placed SMAD5 genetically downstream of BMP2b/BMP4 in dorsoventral patterning and established its essential in vivo developmental roles.

    Evidence Zebrafish somitabun antimorph genetics and double-mutant epistasis, plus two independent Smad5 knockout mouse studies with histology and in situ hybridization

    PMID:10079220 PMID:10079226 PMID:10207140

    Open questions at the time
    • Tissue-specific contributions not separable in global null
    • Molecular targets driving each phenotype not defined
  5. 1999 High

    Identified SMAD5 as required for endothelium-mesenchyme interactions in angiogenesis, explaining the vascular component of the null phenotype.

    Evidence Knockout mouse histology showing enlarged vessels, reduced VSMCs, and mesenchymal apoptosis, plus in vitro angiogenesis assay

    PMID:10079220

    Open questions at the time
    • Cell-autonomy of the vascular defect not resolved here
    • Downstream effectors of mesenchymal survival unknown
  6. 2000 High

    Positioned SMAD5 upstream of lefty-1 in the left-right axis determination cascade.

    Evidence Whole-mount in situ hybridization for lefty-1, lefty-2, nodal, and Pitx2 in Smad5 knockout embryos

    PMID:10677256

    Open questions at the time
    • Direct vs indirect regulation of lefty-1 not established
    • Mechanism linking SMAD5 to asymmetric gene expression unknown
  7. 2001 Medium

    Established SMAD5 as a BMP-pathway mediator of primordial germ cell generation and localization.

    Evidence Oct4 in situ and alkaline phosphatase staining in Smad5-null embryos, phenocopying Bmp4/Bmp8b mutants

    PMID:11404080

    Open questions at the time
    • Cell-intrinsic vs extrinsic requirement in PGC precursors unresolved
    • Target genes in PGC specification not defined
  8. 2001 Medium

    Defined the DNA-binding specificity of the SMAD5 MH1 domain, distinguishing it from other BMP R-Smads.

    Evidence SELEX with GST-SMAD5 MH1 fusion and mutational SBE binding analysis

    PMID:11527422

    Open questions at the time
    • In vitro binding not linked to specific endogenous promoters
    • Structural basis of dual recognition not yet known
  9. 2002 Medium

    Extended SMAD5 function into lineage-specific hematopoietic differentiation and progenitor self-renewal control.

    Evidence BMP4-induced phosphorylation/translocation with antisense knockdown in CD34+ cells, and Smad5-null yolk-sac/embryoid-body colony assays with gene-dosage analysis

    PMID:12064918 PMID:12393578

    Open questions at the time
    • Mechanism of erythroid vs myeloid selectivity unclear
    • Direct targets controlling progenitor self-renewal unidentified
  10. 2002 Medium

    Uncovered translational and apoptotic dimensions of SMAD5 regulation, including a cell-type-specific 5'UTR IRES and a requirement in H. pylori-induced apoptosis.

    Evidence Dicistronic IRES reporter assays in cell lines, and cDNA microarray with siRNA knockdown and apoptosis assays in gastric epithelial cells

    PMID:12087169 PMID:12473652

    Open questions at the time
    • IRES trans-acting factors not identified
    • Apoptotic effectors downstream of SMAD5 in H. pylori response unknown
  11. 2003 High

    Defined the degradation mechanism controlling SMAD5 protein levels via Smurf1-mediated ubiquitination.

    Evidence Smurf1 overexpression, siRNA, and SMAD5 rescue with Western blot of endogenous SMAD5 in C2C12 cells, plus p300/CBP co-IP showing coactivator recruitment in spermatogonia

    PMID:12857787 PMID:12871975

    Open questions at the time
    • Ubiquitin chain linkage and acceptor lysines not mapped
    • Regulation of Smurf1-SMAD5 engagement not defined
  12. 2004 High

    Identified the flexed-tail Smad5 locus as the genetic basis of stress erythropoiesis and revealed SMAD5-specific functions in neuronal differentiation and BMP-responsive transcription in vivo.

    Evidence Genetic mapping of the f mutation to Smad5 with in vivo anemia and progenitor assays, in vivo phosphorylation in cerebellar granule cells, and Id1-BRE transgenic reporters

    PMID:15197161 PMID:15331632 PMID:15591122

    Open questions at the time
    • Why stress but not steady-state erythropoiesis requires SMAD5 not mechanistically resolved
    • SMAD1/SMAD5 functional divergence basis unclear
  13. 2005 Medium

    Linked SMAD5 to protection of cardiomyocytes from mitochondria-dependent apoptosis, foreshadowing a cardiac homeostatic role.

    Evidence Smad5-null ES-derived cardiomyocytes analyzed by EM, JC-1 potential, cytochrome c fractionation, and p53/p21/caspase-3 Western blot

    PMID:15878335

    Open questions at the time
    • Transcriptional targets controlling mitochondrial integrity unidentified
    • In vitro model not yet validated in vivo at this step
  14. 2006 Medium

    Established cell-autonomous requirement of SMAD5 in cardiac contractility and identified Jab1 as a negative modulator of SMAD5-dependent BMP transcription.

    Evidence Sm22-Cre conditional knockout with echocardiography and cardiomyocyte fractional shortening, and yeast-2-hybrid/co-IP identifying Jab1 with reporter assays

    PMID:17133595 PMID:17456754

    Open questions at the time
    • Molecular basis of contractility defect undefined
    • Mechanism of Jab1 antagonism not resolved
  15. 2007 Medium

    Resolved the physical basis of Smurf1 recognition and demonstrated non-redundant SMAD5 functions distinct from SMAD1.

    Evidence Recombinant pull-downs mapping Smurf1 WW2 to the SMAD5 linker PPXY with in vitro ubiquitination, and reciprocal morpholino knockdown/cross-rescue plus microarray in zebrafish

    PMID:17676934 PMID:17761518

    Open questions at the time
    • Structural detail of WW2-PPXY interface absent
    • Sequence determinants of SMAD5-specific output unknown
  16. 2007 Medium

    Identified the flexed-tail intronic regulatory mutation causing tissue-specific Smad5 missplicing.

    Evidence Sequencing of Smad5 intron 4 poly(T) and RT-PCR of misspliced isoforms in f/f mice

    PMID:18060457

    Open questions at the time
    • Splicing factor reading the poly(T) element unidentified
    • Functional contribution of the truncated inhibitory isoform not quantified
  17. 2008 Medium

    Placed SMAD5 within a transcriptional network controlling erythroid lineage commitment through cooperative regulation of Eklf/KLF1.

    Evidence Transgenic reporters, embryoid-body loss-of-function, and ChIP-based binding in hematopoietic differentiation

    PMID:18448565

    Open questions at the time
    • Direct SMAD5 occupancy at Eklf vs cooperative effects not fully separated
    • Stage switch from Gata2 to Gata1 mechanism incomplete
  18. 2010 High

    Established a tumor-suppressive SMAD5 circuit silenced by miR-155 in DLBCL and a metabolic transcriptional role at the Akt2 gene.

    Evidence miR-155 overexpression/RNAi with 3'UTR luciferase, cell cycle and xenograft assays in DLBCL, and SMAD5 knockdown with ChIP at Akt2 and glucose uptake in L6 myotubes

    PMID:20079400 PMID:20133617

    Open questions at the time
    • Direct SMAD5 transcriptional targets mediating p21 induction not enumerated
    • Metabolic Akt2 regulation not validated in vivo
  19. 2012 High

    Revealed a non-canonical SMAD5 mechanism: a BMP4-induced SMAD2/SMAD5 complex that antagonizes Nodal signaling to restrain ectopic primitive streak formation.

    Evidence Smad5 knockout embryo analysis with co-IP of the Smad2/Smad5 complex and quantitative gene expression

    PMID:22912414

    Open questions at the time
    • Structural arrangement of the atypical complex unknown
    • Promoter-level interference with Foxh1 not mapped
  20. 2013 High

    Detailed the miR-155/SMAD5/p15/p21/RB circuit controlling B-cell cycle arrest in vivo.

    Evidence miR-155 knockout mice and DLBCL lines with genetic SMAD5/p15/p21 knockdown and cell cycle analysis

    PMID:24136167

    Open questions at the time
    • Direct vs indirect SMAD5 control of p15/p21 promoters not fully dissected
    • Contribution to lymphomagenesis in patients not addressed
  21. 2014 Medium

    Clarified the genetic architecture downstream of SMAD5 and the cooperating signals required for its transcriptional targets.

    Evidence Zebrafish reciprocal rescue placing smad1/smad9 as redundant SMAD5 targets, and EMSA/ChIP plus p38 inhibition defining SMAD5 binding at the Dlx3 promoter in MC3T3-E1 cells

    PMID:24488494 PMID:24647893

    Open questions at the time
    • Mechanism of p38-dependent SMAD5 phosphorylation not detailed
    • Generality of the SMAD5-driven feed-forward loop beyond fish unknown
  22. 2015 High

    Provided the atomic-resolution basis for SMAD5 MH1 recognition of both GC-rich and SBE DNA.

    Evidence X-ray crystallography of SMAD5 MH1–DNA complexes across GC-rich, SBE, and composite sequences

    PMID:26304548

    Open questions at the time
    • Full-length SMAD5 trimer assembly on chromatin not resolved
    • Coactivator engagement in the structural context not captured
  23. 2017 High

    Uncovered a phosphorylation- and SMAD4-independent SMAD5 function: pH-driven nucleocytoplasmic shuttling that couples cytoplasmic SMAD5 to hexokinase 1 and glycolysis.

    Evidence Live-cell imaging under pH/osmotic perturbation, hexokinase 1 co-IP, cytoplasmic-only rescue, and metabolic assays in human pluripotent stem cells

    PMID:28675158

    Open questions at the time
    • Physiological triggers of pHi shifts in vivo not defined
    • How cytoplasmic SMAD5 modulates HK1 catalysis mechanistically unknown
  24. 2019 Medium

    Extended SMAD1/5 function to iron homeostasis and additional layers of SMAD5 regulation via lncRNA TUG1.

    Evidence Hepatocyte-specific SMAD1/5 knockout with hepcidin/iron measurements and EGF/LPS challenge, and RIP plus domain mapping showing TUG1 blocks p-SMAD5 nuclear translocation

    PMID:31127639 PMID:31149038

    Open questions at the time
    • SMAD5-specific vs SMAD1 contribution to hepcidin not isolated
    • Structural basis of TUG1 binding to the MH1 region not resolved
  25. 2021 High

    Identified a conserved ACVR2A/SMAD1/5 axis required for endometrial receptivity and embryo implantation.

    Evidence PR-Cre conditional knockouts of SMAD1/5, ACVR2A, and ACVR2B with histology and fertility assays in mice

    PMID:34099644

    Open questions at the time
    • SMAD5-specific role separate from SMAD1 not isolated
    • Transcriptional targets driving apicobasal transformation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SMAD5's canonical transcriptional output, its degradation and RNA-mediated regulation, and its non-canonical pH-sensing/metabolic and Nodal-antagonizing functions are integrated within a single cell remains unresolved.
  • No unified model linking nuclear transcriptional and cytoplasmic metabolic SMAD5 pools
  • Direct genome-wide SMAD5 target set in mammalian tissues not defined
  • Determinants of SMAD5 vs SMAD1 functional specialization unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0140110 transcription regulator activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2
Partners
BMPR1ABMPR1BEP300HK1JAB1SMAD2SMAD4SMURF1
Complex memberships
BMP4-induced SMAD2–SMAD5 complexSMAD5–SMAD4 complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 BMP-2 causes serine phosphorylation of SMAD5 via direct physical association with BMP type Ia or Ib receptors; following phosphorylation, SMAD5 binds to DPC4 (SMAD4) and the complex translocates to the nucleus. A point mutant SMAD5 (G419S) or C-terminal deletion of DPC4 blocked BMP-2-induced osteoblastic differentiation of C2C12 cells. Co-immunoprecipitation, serine phosphorylation assays, dominant-negative mutagenesis, alkaline phosphatase/osteocalcin differentiation assays in C2C12 cells The Journal of biological chemistry High 9442019
1997 Overexpression of SMAD5 (or SMAD1) in C2C12 myoblasts induces alkaline phosphatase activity and decreases myogenin promoter activity without exogenous BMP-2, mimicking BMP signaling; C-terminal truncated SMAD5 blocks BMP signals from constitutively active BMPR-IB, establishing SMAD5 as a downstream mediator of BMP-induced osteoblast conversion and myogenic inhibition. Transient transfection of wild-type and dominant-negative SMAD5 constructs, CAT reporter assays, alkaline phosphatase activity assays in C2C12 cells Biochemical and biophysical research communications Medium 9299554
1997 SMAD5 misexpression in Xenopus embryos causes ventralization, induces ventral mesoderm and epidermis; these activities require SMAD4 (DPC4) activity, placing SMAD5 downstream of BMP4 signaling. mRNA injection into Xenopus embryos, epistasis with dominant-negative SMAD4 Developmental biology Medium 9133445
1998 OP-1 (BMP-7) stimulates phosphorylation of SMAD5 in ROB-C26 osteoprogenitor cells; SMAD1, SMAD5, and SMAD8 (but not SMAD2/3) stably interact with kinase-deficient BMPR-IB after phosphorylation by BMPR-II kinase; a SMAD5-2SA (C-terminal serine-to-alanine) mutant acts as a dominant negative inhibitor of OP-1 signaling. In vitro kinase/phosphorylation assays, co-immunoprecipitation with BMPR-IB, dominant-negative transfection assays Journal of cellular physiology High 9766532
1998 Antisense oligonucleotides to SMAD5 in human CD34+ hematopoietic progenitor cells reversed the inhibitory effects of TGF-β on myeloid, erythroid, megakaryocyte, and multilineage colony formation, demonstrating SMAD5 is required in the TGF-β inhibitory signaling pathway in primitive human hematopoiesis. Antisense oligonucleotide knockdown in primary CD34+ cells, semisolid colony formation assays Blood Medium 9490674
1999 The zebrafish smad5 mutant somitabun (sbntc24) carries a single amino-acid change in the L3 loop that converts SMAD5 into an antimorphic form inhibiting wild-type SMAD5 and related Smads; double mutant analyses place smad5 genetically downstream of bmp2b in dorsoventral patterning. ENU mutagenesis screen, double mutant analysis, RNA injection rescue experiments in zebrafish Development (Cambridge, England) High 10207140
1999 Smad5 knockout (homozygous null) mice die between E9.5–E11.5 with defects in amnion, gut, heart, turning, craniofacial structures, and yolk sac vasculature, demonstrating essential in vivo roles for SMAD5 in embryonic and extraembryonic development downstream of BMP signaling. Homologous recombination gene targeting in ES cells; whole-mount in situ hybridization, histology Development (Cambridge, England) High 10079220 10079226
1999 Loss of SMAD5 in mice causes enlarged blood vessels with decreased vascular smooth muscle cells and massive mesenchymal apoptosis, establishing SMAD5 as required for endothelium-mesenchyme interactions during angiogenesis. Homologous recombination knockout, histology, in vitro angiogenesis assay Development (Cambridge, England) High 10079220
2000 Smad5-deficient mouse embryos show defects in heart looping and embryonic turning (first signs of L-R asymmetry); lefty-1 expression is absent or very low, while nodal, lefty-2, and Pitx2 are expressed bilaterally, placing SMAD5 upstream of lefty-1 and the L-R axis determination cascade. Smad5 knockout mouse analysis, whole-mount in situ hybridization for lefty-1, lefty-2, nodal, Pitx2 Developmental biology High 10677256
2001 SMAD5 null embryos have greatly reduced or absent primordial germ cells (PGCs), with some ectopic PGC-like cells in the amnion, phenocopying Bmp4 and Bmp8b mutants and establishing SMAD5 as a downstream mediator of BMP signaling in PGC generation and localization. Oct4 whole-mount in situ hybridization, alkaline phosphatase staining in Smad5-/- mice Mechanisms of development Medium 11404080
2001 The MH1 domain of SMAD5 binds a consensus sequence TGTGC; unlike SMAD1 and SMAD8, SMAD5 also binds the canonical Smad-binding element (SBE: GTCTAGAC) at a level similar to SMAD3 and SMAD4, revealing unique DNA-binding properties among BMP-R-Smads. SELEX (random oligonucleotide selection) with GST-Smad5 MH1 fusion protein; mutational analysis of SBE binding Biochemical and biophysical research communications Medium 11527422
2002 BMP4 directs SMAD5 phosphorylation, nuclear translocation, and specific transcriptional responses in human hematopoietic CD34+ cells; antisense inhibition of SMAD5 significantly reduces BMP4-induced erythroid differentiation (BFU-E expansion and glycophorin-A+ cells) without affecting granulocyte-macrophage lineages. Protein phosphorylation assays, nuclear translocation assays, antisense oligonucleotide knockdown, colony formation assays in primary human CD34+ cells Blood cells, molecules & diseases Medium 12064918
2002 SMAD5-deficient yolk sacs contain elevated high-proliferative potential colony-forming cells (HPP-CFCs) with enhanced self-renewal and decreased sensitivity to TGF-β1 inhibition; Smad5-/- embryoid bodies show increased HPP-CFCs in a gene-dosage dependent manner, establishing SMAD5 as a negative regulator of primitive hematopoietic progenitors. Smad5 knockout mouse yolk sac colony assays, ES cell differentiation/embryoid body assays, gene dosage analysis Blood Medium 12393578
2002 H. pylori cagPAI-positive strains upregulate SMAD5 mRNA in gastric epithelial cells; RNAi knockdown of SMAD5 completely inhibits H. pylori-induced apoptosis, establishing SMAD5 as a required mediator of H. pylori-induced apoptosis. cDNA microarray, RT-PCR, Northern blot, siRNA knockdown with apoptosis assay The Journal of biological chemistry Medium 12473652
2002 Cbfa1 (RUNX2) induces osteoblastic differentiation in C2C12 cells without forming a complex with SMAD1 or SMAD5; however, interactions with SMAD1/SMAD5 enhance Cbfa1 osteogenic actions. Smad6 overexpression (preventing Cbfa1-Smad1/5 interaction) did not block Cbfa1-induced osteocalcin promoter transactivation. Co-immunoprecipitation, reporter gene assays, dominant-negative Cbfa1 and Smad6 overexpression in C2C12 cells Bone Medium 12151083
2002 The 5' UTR of human SMAD5 mRNA contains an internal ribosome entry site (IRES) located within 100 nt of the 3' end of the 5'UTR, which shows cell-type specificity (more active in C2C12 than 293T) and requires a nuclear event for efficient translation initiation. Dicistronic reporter assays in cell lines, transfection of in vitro transcripts vs. DNA constructs Nucleic acids research Medium 12087169
2003 Smurf1 promotes ubiquitin-mediated degradation of endogenous SMAD5 (selectively over SMAD2, SMAD3, SMAD7); elevated Smurf1 reduces SMAD5 protein levels and blocks BMP-induced osteogenic conversion of C2C12 cells; re-expression of SMAD5 from an exogenous source restores BMP osteogenic response. Smurf1 depletion by siRNA confirms its requirement for myogenic differentiation. Smurf1 overexpression, siRNA knockdown, SMAD5 rescue experiments, Western blot for protein levels in C2C12 cells The Journal of biological chemistry High 12871975
2003 BMP4 stimulation of cultured spermatogonia induces SMAD4/5 nuclear translocation and formation of a DNA-binding complex with transcriptional coactivator p300/CBP; BMP4 also induces Kit expression and mitogenic/differentiative effects, with SMAD5 expressed specifically in spermatogonia downstream of Sertoli cell-derived BMP4. Immunofluorescence for SMAD4/5 nuclear translocation, p300/CBP co-IP, in vitro BMP4 stimulation of spermatogonia Journal of cell science Medium 12857787
2004 BMP4/SMAD5-dependent signaling, regulated by hypoxia, initiates differentiation and expansion of stress erythroid progenitors in the adult spleen in response to acute anemia; flexed-tail (f) mutant mice carrying a Smad5 mutation cannot mount this stress erythropoiesis response. Genetic mapping identifying f mutation in Madh5/Smad5, in vivo anemia model, progenitor colony assays Blood High 15591122
2004 In developing cerebellum, Bmp2 signals through SMAD5 (not SMAD1) specifically in newly differentiated granule neurons; only SMAD5 is phosphorylated in vivo by Bmp2 in granule cells, and SMAD5 overexpression alone is sufficient to induce granule cell differentiation even in the presence of Shh, antagonizing Shh-mediated proliferation. In vivo phosphorylation assays, SMAD5 overexpression in cerebellar granule cell cultures, Shh proliferation assay Development (Cambridge, England) Medium 15197161
2004 An Id1 promoter-derived BRE (Smad1/5-specific response element) drives reporter activity in mouse ES cells and embryos where BMP/Smad1/5 signaling is active; used to map spatio-temporal transcriptional activity of SMAD1/5 in vivo, demonstrating autocrine BMP signaling in ES cells. Transgenic reporter mouse lines, luciferase/β-galactosidase assays in ES cells and chimeric embryos Journal of cell science Medium 15331632
2005 Loss of SMAD5 in cardiomyocytes (from ES cell differentiation) causes abnormal swollen mitochondria, reduced mitochondrial membrane potential (ΔΨm), cytochrome c leakage, and elevated p53, p21, and caspase-3, indicating SMAD5 protects cardiomyocytes from mitochondria-dependent apoptosis. ES cell differentiation from Smad5 null cells, electron microscopy, JC-1 mitochondrial potential assay, cytochrome c fractionation, Western blot Experimental cell research Medium 15878335
2006 Smad5 deletion in cardiomyocytes (via Sm22-Cre) results in decreased cardiac contractility (enlarged LV internal diameter, reduced fractional shortening) without cardiac hypertrophy, establishing a cell-autonomous requirement for SMAD5 in cardiac homeostasis; deletion in endothelial or vascular smooth muscle cells alone does not affect vasculature. Cre-loxP conditional knockout, echocardiography, isolated cardiomyocyte fractional shortening, treadmill test The American journal of pathology Medium 17456754
2007 In zebrafish, Smad1 and Smad5 have distinct and even opposite roles in embryonic hematopoiesis: Smad5 depletion causes defects in primitive erythropoiesis but normal macrophage numbers, while Smad1 depletion increases erythrocytes but impairs macrophages; Smad5 cannot rescue Smad1 loss-of-function, indicating inherently distinct activities. Microarray shows Smad5 uniquely regulates the BMP signaling pathway itself. Morpholino knockdown in zebrafish, rescue experiments, microarray analysis Blood Medium 17761518
2007 The WW2 domain of Smurf1 physically interacts with the PPXY motif in the linker region of SMAD5 (and SMAD1, SMAD6); deletion of the WW2 domain abolishes Smurf1 binding to Smads and its ubiquitination activity on Smad1 in an in vitro ubiquitination assay. Pull-down with purified recombinant proteins, WW2 domain deletion mutants, in vitro ubiquitination assay Journal of biomolecular structure & dynamics Medium 17676934
2008 Smad5 and Gata2 cooperate to induce Eklf (KLF1) expression in hematopoietic progenitors prior to erythroid commitment; upon erythroid commitment, Gata1 takes over regulation of Eklf, establishing a stage-dependent switch involving SMAD5 in lineage fate decisions. Transgenic reporter assays in ES cell differentiation and fetal liver, in vivo Smad5 loss-of-function in embryoid bodies, ChIP-based binding studies Development (Cambridge, England) Medium 18448565
2009 BMP4/Smad5-dependent stress erythropoiesis pathway expands stress erythroid progenitors in the fetal liver; defects in BMP4/Smad5 signaling preferentially impair expansion of stress (not steady-state) erythroid progenitors, causing fetal anemia in flexed-tail mutants. f/f mutant (Smad5 mutation) analysis, fetal liver progenitor assays, BFU-E colony assays Developmental biology Medium 18374325
2010 In DLBCL, a non-canonical TGF-β1/SMAD5 signaling module is active; miR-155 directly targets SMAD5 3'UTR; miR-155 overexpression renders cells resistant to TGF-β1 and BMP growth inhibition via defective p21 induction and impaired cell cycle arrest; RNAi-based SMAD5 knockdown recapitulates these effects in vitro and in vivo. miR-155 overexpression and RNAi knockdown of SMAD5, luciferase reporter assay, cell cycle assays, in vivo xenograft Proceedings of the National Academy of Sciences of the United States of America High 20133617
2011 Loss of SMAD5 in intestinal epithelial cells (Smad5ΔIEC) causes hypermigration, loss of E-cadherin from the apical junctional complex (displaced to cytoplasm), and deregulated claudin-1/claudin-2 expression, leading to increased susceptibility to DSS-induced colitis and impaired wound healing. Intestinal epithelium-specific Cre-loxP knockout, immunofluorescence, Western blot, DSS colitis model American journal of physiology. Gastrointestinal and liver physiology Medium 21212325
2012 BMP-activated SMAD5 antagonizes Nodal signaling by interfering with the Nodal-Smad2/4-Foxh1 autoregulatory pathway through formation of an unusual BMP4-induced Smad complex containing Smad2 and Smad5; loss of Smad5 in mouse embryos results in ectopic Nodal expression and ectopic primitive streak formation in the amnion. Smad5 knockout mouse analysis, cell culture BMP4 stimulation with co-immunoprecipitation of Smad2/Smad5 complex, quantitative gene expression analysis Development (Cambridge, England) High 22912414
2013 miR-155 expression in DLBCL blocks TGF-β1-mediated activation of retinoblastoma protein (RB) by suppressing SMAD5, which reduces TGF-β1-induced transcription of p15 and p21, sustaining RB phosphorylation and inactivity; miR-155 KO mice show elevated SMAD5 in mature B cells with heightened TGF-β1 sensitivity and G0/G1 arrest. miR-155 KO mouse analysis, DLBCL cell lines with ectopic miR-155 expression, genetic knockdown of SMAD5/p15/p21, cell cycle analysis Blood High 24136167
2014 In zebrafish, smad1 and smad9 act redundantly downstream of smad5 to mediate ventral specification: smad5 knockdown can be rescued by smad1 or smad9 overexpression, but smad5 overexpression cannot rescue smad1+smad9 double knockdown; smad1 and smad9 are direct transcriptional targets of Smad5. Morpholino knockdown in zebrafish, rescue experiments with mRNA injection, transcriptional target analysis The Journal of biological chemistry Medium 24488494
2015 Crystal structure of the SMAD5 MH1 domain in complex with the GC-rich sequence reveals that the same β-hairpin contacts both GC-rich and SBE DNA but with different interaction modes; a composite DNA sequence structure shows modular binding, with spacer length affecting MH1 assembly. X-ray crystallography of SMAD5 MH1 domain–DNA complexes (GC-rich, SBE, and composite sequences) Nucleic acids research High 26304548
2017 SMAD5 responds to intracellular pH (pHi) changes: increased pHi (cold, basic, hypertonic conditions) promotes proton dissociation from charged clusters in the MH1 domain, driving nuclear-to-cytoplasmic relocalization; decreased pHi blocks nuclear export causing nuclear accumulation. This nucleocytoplasmic shuttling is independent of BMP signaling, C-terminal phosphorylation, and Smad4. Cytoplasmic SMAD5 physically interacts with hexokinase 1 and accelerates glycolysis; ablation of SMAD5 causes dysregulation of bioenergetic homeostasis. Live-cell imaging of SMAD5 localization under pH/osmotic perturbations, co-IP with hexokinase 1, rescue experiments with cytoplasmic-only SMAD5, metabolic assays in human pluripotent stem cell differentiation model Cell research High 28675158
2019 Hepatocyte-specific deletion of SMAD1/5 (and SMAD1/5/8) causes severe hepcidin deficiency and iron overload; EGF fails to suppress hepcidin in SMAD1/5 knockout hepatocytes, establishing a requirement for SMAD1/5 in EGF-mediated hepcidin regulation; inflammatory hepcidin induction is preserved, demonstrating pathway specificity. Hepatocyte-specific Cre-loxP knockout, serum hepcidin and iron measurements, EGF/LPS challenge Hepatology (Baltimore, Md.) Medium 31127639
2019 LncRNA TUG1 directly binds the 50–90 aa region of SMAD5 (MH1 domain) and blocks nuclear translocation of phosphorylated SMAD5 after irradiation, suppressing osteogenic signaling in bone marrow MSCs despite increased SMAD5 phosphorylation. RNA immunoprecipitation (RIP), serial SMAD5 deletion constructs identifying binding region, immunofluorescence for p-SMAD5 nuclear translocation, osteogenic differentiation assays Theranostics Medium 31149038
2021 BMP signaling through a conserved ACVR2A/SMAD1/5 axis in the uterine endometrium is required for endometrial receptivity; SMAD1/5 conditional knockout (PR-cre) causes cystic endometrial glands, hyperproliferative epithelium during the implantation window, and impaired apicobasal transformation preventing embryo implantation. ACVR2B is dispensable. Conditional knockout (PR-Cre) for SMAD1/5, ACVR2A, and ACVR2B; histology, fertility assays in mice Nature communications High 34099644
2006 BMP9 causes phosphorylation of SMAD1 and SMAD5, formation of a SMAD4/SMAD1/SMAD5 complex, and nuclear translocation of this complex in cultured basal forebrain cells, establishing the canonical BMP signaling pathway for BMP9 in cholinergic neuron differentiation. Phosphorylation assays, co-immunoprecipitation, nuclear translocation assays in primary basal forebrain cultures Brain research Medium 16626664
2007 An intronic poly(T) element in intron 4 of Smad5 is mutated in flexed-tail (f/f) mice; loss of 1–2 T residues causes tissue-specific (spleen-predominant) splicing defects throughout Smad5, generating misspliced mRNAs including one encoding a truncated inhibitory Smad5 protein. Sequencing of f/f mouse Smad5 intron 4, RT-PCR analysis of misspliced isoforms, tissue-specific splicing analysis Mammalian genome Medium 18060457
2010 SMAD5 knockdown in L6 myotubes decreases Akt2 expression and serine phosphorylation and reduces insulin-induced glucose uptake while increasing Ship2 expression; ChIP demonstrates SMAD5 binding to the Akt2 gene, which is decreased by dexamethasone treatment. siRNA knockdown of SMAD5, glucose uptake assays, Western blot, chromatin immunoprecipitation (ChIP) for Akt2 gene Molecular and cellular endocrinology Medium 20079400
2014 BMP-2-induced Dlx3 expression in osteoblasts requires both SMAD5 and p38; SMAD5 binds to two TGTCT Smad-binding elements in the Dlx3 promoter region (−698 to −368) as shown by EMSA and ChIP; p38 activation is necessary for BMP-2-induced SMAD5 phosphorylation and nuclear translocation. EMSA, ChIP assay, promoter deletions/mutagenesis, Smad5 knockdown, p38 inhibitor, Western blot in MC3T3-E1 cells Journal of cellular physiology Medium 24647893
2006 Jun activation domain-binding protein 1 (Jab1) physically interacts with SMAD5 in chondrocytes (identified by yeast 2-hybrid, confirmed by co-IP); Jab1 overexpression attenuates BMP-dependent transcriptional responses, acting as a negative modulator of BMP signaling. Yeast 2-hybrid screen of cartilage cDNA library, co-immunoprecipitation, BMP-responsive transcriptional reporter assay Arthritis and rheumatism Medium 17133595

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development (Cambridge, England) 346 10079226
1999 Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development (Cambridge, England) 313 10079220
2009 BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development (Cambridge, England) 300 19224984
1998 Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. The Journal of biological chemistry 261 9442019
2007 Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Molecular and cellular biology 179 17967875
1997 Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts. Biochemical and biophysical research communications 179 9299554
2010 Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and lymphomagenesis. Proceedings of the National Academy of Sciences of the United States of America 175 20133617
1999 The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral patterning of the zebrafish embryo. Development (Cambridge, England) 170 10207140
2004 BMP4 and Madh5 regulate the erythroid response to acute anemia. Blood 169 15591122
2003 Developmental expression of BMP4/ALK3/SMAD5 signaling pathway in the mouse testis: a potential role of BMP4 in spermatogonia differentiation. Journal of cell science 168 12857787
2001 Smad5 is required for mouse primordial germ cell development. Mechanisms of development 155 11404080
1997 Smad5 induces ventral fates in Xenopus embryo. Developmental biology 143 9133445
2006 Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. Developmental biology 130 16765933
2019 Lnc SMAD5-AS1 as ceRNA inhibit proliferation of diffuse large B cell lymphoma via Wnt/β-catenin pathway by sponging miR-135b-5p to elevate expression of APC. Cell death & disease 124 30874550
2004 Bmp2 antagonizes sonic hedgehog-mediated proliferation of cerebellar granule neurones through Smad5 signalling. Development (Cambridge, England) 123 15197161
2000 Smad5 is essential for left-right asymmetry in mice. Developmental biology 113 10677256
2002 Core-binding factor alpha 1 (Cbfa1) induces osteoblastic differentiation of C2C12 cells without interactions with Smad1 and Smad5. Bone 108 12151083
2015 miR-23a and miR-27a promote human granulosa cell apoptosis by targeting SMAD5. Biology of reproduction 106 26400397
2020 Exosomal miRNA-128-3p from mesenchymal stem cells of aged rats regulates osteogenesis and bone fracture healing by targeting Smad5. Journal of nanobiotechnology 105 32178675
2017 MicroRNA-21 regulates Osteogenic Differentiation of Periodontal Ligament Stem Cells by targeting Smad5. Scientific reports 84 29192241
2011 Kaposi's sarcoma-associated herpesvirus-encoded microRNA miR-K12-11 attenuates transforming growth factor beta signaling through suppression of SMAD5. Journal of virology 81 22013049
2004 Spatio-temporal activation of Smad1 and Smad5 in vivo: monitoring transcriptional activity of Smad proteins. Journal of cell science 76 15331632
1998 The Smad5 gene is involved in the intracellular signaling pathways that mediate the inhibitory effects of transforming growth factor-beta on human hematopoiesis. Blood 75 9490674
1998 Intracellular signaling of osteogenic protein-1 through Smad5 activation. Journal of cellular physiology 72 9766532
2021 Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis. Nature communications 71 34099644
2003 Smurf1 facilitates myogenic differentiation and antagonizes the bone morphogenetic protein-2-induced osteoblast conversion by targeting Smad5 for degradation. The Journal of biological chemistry 71 12871975
2016 miR-106b-5p and miR-17-5p suppress osteogenic differentiation by targeting Smad5 and inhibit bone formation. Experimental cell research 67 27426726
2007 Smad1 and Smad5 differentially regulate embryonic hematopoiesis. Blood 66 17761518
2013 Genistein promotion of osteogenic differentiation through BMP2/SMAD5/RUNX2 signaling. International journal of biological sciences 62 24339730
2002 Maternally supplied Smad5 is required for ventral specification in zebrafish embryos prior to zygotic Bmp signaling. Developmental biology 62 12376102
1999 Smad1 and Smad5 have distinct roles during dorsoventral patterning of the zebrafish embryo. Developmental dynamics : an official publication of the American Association of Anatomists 62 10590480
2009 Smad1-Smad5 ovarian conditional knockout mice develop a disease profile similar to the juvenile form of human granulosa cell tumors. Endocrinology 57 19819941
2002 Disruption of Smad5 gene leads to enhanced proliferation of high-proliferative potential precursors during embryonic hematopoiesis. Blood 52 12393578
2008 Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment. Development (Cambridge, England) 51 18448565
2017 Smad5 acts as an intracellular pH messenger and maintains bioenergetic homeostasis. Cell research 49 28675158
2008 BMP4/Smad5 dependent stress erythropoiesis is required for the expansion of erythroid progenitors during fetal development. Developmental biology 49 18374325
1999 Screening SMAD1, SMAD2, SMAD3, and SMAD5 for germline mutations in juvenile polyposis syndrome. Gut 49 10446110
2003 Retinoic acid stimulates chondrocyte differentiation and enhances bone morphogenetic protein effects through induction of Smad1 and Smad5. Endocrinology 48 12746314
2009 Extramedullary erythropoiesis in the adult liver requires BMP-4/Smad5-dependent signaling. Experimental hematology 44 19375646
2016 Inhibition of miR-222-3p activity promoted osteogenic differentiation of hBMSCs by regulating Smad5-RUNX2 signal axis. Biochemical and biophysical research communications 43 26809090
2013 MicroRNA-155 controls RB phosphorylation in normal and malignant B lymphocytes via the noncanonical TGF-β1/SMAD5 signaling module. Blood 43 24136167
2004 Overexpression of Smurf1 negatively regulates mouse embryonic lung branching morphogenesis by specifically reducing Smad1 and Smad5 proteins. American journal of physiology. Lung cellular and molecular physiology 43 14711801
2017 miR-155 Inhibits Mouse Osteoblast Differentiation by Suppressing SMAD5 Expression. BioMed research international 42 28473977
2019 Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice. Hepatology (Baltimore, Md.) 41 31127639
1999 Characterization of zebrafish smad1, smad2 and smad5: the amino-terminus of smad1 and smad5 is required for specific function in the embryo. Mechanisms of development 41 10525190
2019 Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 39 31557058
2021 Silencing of long non-coding RNA HCP5 inhibits proliferation, invasion, migration, and promotes apoptosis via regulation of miR-299-3p/SMAD5 axis in gastric cancer cells. Bioengineered 38 33371778
2002 Inhibition of Smad5 in human hematopoietic progenitors blocks erythroid differentiation induced by BMP4. Blood cells, molecules & diseases 38 12064918
2021 Icariin regulates miR-23a-3p-mediated osteogenic differentiation of BMSCs via BMP-2/Smad5/Runx2 and WNT/β-catenin pathways in osteonecrosis of the femoral head. Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 37 35002378
2019 Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling. American journal of physiology. Cell physiology 37 31411918
2007 Inactivation of Smad5 in endothelial cells and smooth muscle cells demonstrates that Smad5 is required for cardiac homeostasis. The American journal of pathology 36 17456754
2015 Effect of Anti-Müllerian hormone (AMH) and bone morphogenetic protein 15 (BMP-15) on steroidogenesis in primary-cultured human luteinizing granulosa cells through Smad5 signalling. Journal of assisted reproduction and genetics 35 26003656
2014 A heterocyclic molecule kartogenin induces collagen synthesis of human dermal fibroblasts by activating the smad4/smad5 pathway. Biochemical and biophysical research communications 32 24928394
2006 Developmental pattern of expression of BMP receptors and Smads and activation of Smad1 and Smad5 by BMP9 in mouse basal forebrain. Brain research 32 16626664
2002 Up-regulated Smad5 mediates apoptosis of gastric epithelial cells induced by Helicobacter pylori infection. The Journal of biological chemistry 32 12473652
2019 Long noncoding RNA TUG1 inhibits osteogenesis of bone marrow mesenchymal stem cells via Smad5 after irradiation. Theranostics 31 31149038
2014 Transcriptional factors smad1 and smad9 act redundantly to mediate zebrafish ventral specification downstream of smad5. The Journal of biological chemistry 30 24488494
2006 Smad5 is dispensable for adult murine hematopoiesis. Blood 30 16896158
2013 c-Abl-dependent molecular circuitry involving Smad5 and phosphatidylinositol 3-kinase regulates bone morphogenetic protein-2-induced osteogenesis. The Journal of biological chemistry 28 23821550
2001 Characterization of the DNA-binding property of Smad5. Biochemical and biophysical research communications 27 11527422
2018 MicroRNA-145 promotes esophageal cancer cells proliferation and metastasis by targeting SMAD5. Scandinavian journal of gastroenterology 26 29852786
2017 Molecular targeting of the Aurora-A/SMAD5 oncogenic axis restores chemosensitivity in human breast cancer cells. Oncotarget 26 29207686
2014 BMP-2 induction of Dlx3 expression is mediated by p38/Smad5 signaling pathway in osteoblastic MC3T3-E1 cells. Journal of cellular physiology 26 24647893
2002 Internal ribosome entry site-mediated translation of Smad5 in vivo: requirement for a nuclear event. Nucleic acids research 26 12087169
2021 CircRNA FAT1 Regulates Osteoblastic Differentiation of Periodontal Ligament Stem Cells via miR-4781-3p/SMAD5 Pathway. Stem cells international 25 35003269
2020 LINC01410 promotes cell proliferation and migration of cholangiocarcinoma through modulating miR-124-3p/SMAD5 axis. The journal of gene medicine 25 31951299
2019 MALAT1 functions as a competing endogenous RNA to regulate SMAD5 expression by acting as a sponge for miR-142-3p in hepatocellular carcinoma. Cell & bioscience 25 31168355
2016 MicroRNA-135b inhibits odontoblast-like differentiation of human dental pulp cells by regulating Smad5 and Smad4. International endodontic journal 25 27422404
2011 Loss of Smad5 leads to the disassembly of the apical junctional complex and increased susceptibility to experimental colitis. American journal of physiology. Gastrointestinal and liver physiology 25 21212325
1997 Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60. Leukemia 25 9264367
1997 Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor. Cancer research 25 9288787
2020 miR-130a promotes immature porcine Sertoli cell growth by activating SMAD5 through the TGF-β-PI3K/AKT signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 32918760
2019 Long noncoding RNA UCA1 promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells via miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis. Biochemical and biophysical research communications 24 31036320
2012 Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion. Development (Cambridge, England) 24 22912414
2000 Differential expression of a novel C-terminally truncated splice form of SMAD5 in hematopoietic stem cells and leukemia. Blood 24 10845932
2020 Long non-coding RNA LINC01116 accelerates the progression of keloid formation by regulating miR-203/SMAD5 axis. Burns : journal of the International Society for Burn Injuries 22 32883538
2006 C-type natriuretic peptide enhances osteogenic protein-1-induced osteoblastic cell differentiation via Smad5 phosphorylation. Journal of cellular biochemistry 22 16187313
2020 KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis. European review for medical and pharmacological sciences 21 32271402
2020 Maternal high protein-diet programs impairment of offspring's bone mass through miR-24-1-5p mediated targeting of SMAD5 in osteoblasts. Cellular and molecular life sciences : CMLS 21 32734584
2007 Molecular Interaction Between Smurfl WW2 Domain and PPXY Motifs of Smadl, Smad5, and Smad6-Modeling and Analysis. Journal of biomolecular structure & dynamics 21 22670624
2001 Transforming growth factor beta signalling in vitro and in vivo: activin ligand-receptor interaction, Smad5 in vasculogenesis, and repression of target genes by the deltaEF1/ZEB-related SIP1 in the vertebrate embryo. Molecular and cellular endocrinology 21 11451567
2021 miR-20a-5p contributes to osteogenic differentiation of human dental pulp stem cells by regulating BAMBI and activating the phosphorylation of Smad5 and p38. Stem cell research & therapy 20 34294156
2018 Amniotic ectoderm expansion in mouse occurs via distinct modes and requires SMAD5-mediated signalling. Development (Cambridge, England) 20 29884675
2007 An intronic sequence mutated in flexed-tail mice regulates splicing of Smad5. Mammalian genome : official journal of the International Mammalian Genome Society 20 18060457
2004 Smad5: signaling roles in hematopoiesis and osteogenesis. The international journal of biochemistry & cell biology 20 15061132
2021 Repair abilities of mouse autologous adipose-derived stem cells and ShakeGel™3D complex local injection with intrauterine adhesion by BMP7-Smad5 signaling pathway activation. Stem cell research & therapy 19 33736694
2015 Structural basis for the Smad5 MH1 domain to recognize different DNA sequences. Nucleic acids research 19 26304548
2007 Molecular interaction between Smurf1 WW2 domain and PPXY motifs of Smad1, Smad5, and Smad6--modeling and analysis. Journal of biomolecular structure & dynamics 18 17676934
2006 Jun activation domain-binding protein 1 binds Smad5 and inhibits bone morphogenetic protein signaling. Arthritis and rheumatism 17 17133595
2016 MicroRNA-93-5p may participate in the formation of morphine tolerance in bone cancer pain mouse model by targeting Smad5. Oncotarget 16 27438143
2013 Genetic polymorphism of SMAD5 is associated with Kawasaki disease. Pediatric cardiology 16 24163009
2012 Smad1/Smad5 signaling in limb ectoderm functions redundantly and is required for interdigital programmed cell death. Developmental biology 16 22240098
2019 MicroRNA-132-3p represses Smad5 in MC3T3-E1 osteoblastic cells under cyclic tensile stress. Molecular and cellular biochemistry 15 31004309
2019 A New Insight of Kartogenin Induced the Mesenchymal Stem Cells (MSCs) Selectively Differentiate into Chondrocytes by Activating the Bone Morphogenetic Protein 7 (BMP-7)/Smad5 Pathway. Medical science monitor : international medical journal of experimental and clinical research 15 31271564
2017 Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP-2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling Activation. Nutrients 15 28513557
2015 TGFβ1a regulates zebrafish posterior lateral line formation via Smad5 mediated pathway. Journal of molecular cell biology 15 25603803
2014 Alk3/Alk3b and Smad5 mediate BMP signaling during lymphatic development in zebrafish. Molecules and cells 15 24608800
2014 Suppression of transforming growth factor β receptor 2 and Smad5 is associated with high levels of microRNA miR-155 in the oral mucosa during chronic simian immunodeficiency virus infection. Journal of virology 15 25540365
2010 Smad5 regulates Akt2 expression and insulin-induced glucose uptake in L6 myotubes. Molecular and cellular endocrinology 15 20079400
2005 Disruption of Smad5 gene induces mitochondria-dependent apoptosis in cardiomyocytes. Experimental cell research 15 15878335

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