Affinage

SMAD9

SMAD family member 9 · UniProt O15198

Length
467 aa
Mass
52.5 kDa
Annotated
2026-06-10
44 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMAD9 (Smad8/MADH9) is a receptor-regulated SMAD that transduces bone morphogenetic protein (BMP) signaling and modulates BMP-dependent transcription, developmental patterning, and tissue homeostasis (PMID:9371779, PMID:10814522). It is phosphorylated at its C-terminal motif by constitutively active BMP type I receptors ALK-2, ALK-3, and ALK-6 but not by the TGF-β type I receptor ALK-5; phosphorylation drives association with SMAD4, nuclear translocation, and cooperative activation of BMP target promoters (PMID:10814522). Despite this canonical activity, constitutively active SMAD9 has intrinsically lower transcriptional output than SMAD1 or SMAD5—an effect localized to its linker region—and SMAD9 forms complexes with SMAD1 on target DNA that suppress transcription without inhibiting the receptor kinase, giving it a distinct repressive character among R-SMADs (PMID:25534700). SMAD9 expression is itself directly induced by BMP through BMP-responsive elements bound by phospho-SMADs, establishing a negative-feedback loop (PMID:26748560), and its protein level is set by ASB2-mediated ubiquitylation and proteasomal degradation, an axis essential for cardiogenesis in zebrafish (PMID:34845242). Beyond transcription, SMAD9 has a non-redundant role in BMP-induced microRNA processing (miR-21, miR-27a, miR-100) in pulmonary vascular cells and acts as a negative regulator of myomiRs (miR-1, miR-133a/b) in muscle (PMID:21920918, PMID:35886863). In mouse development SMAD9 is largely redundant with SMAD1/5—single nulls are viable and fertile—but loss contributes to pulmonary vascular pathology, and triple hepatocyte knockout reveals a redundant requirement in hepcidin-mediated iron homeostasis (PMID:16765933, PMID:19419974, PMID:31127639). Loss-of-function SMAD9 mutations are causally linked to pulmonary arterial hypertension (PMID:19211612).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    Established SMAD9 as a receptor-activated SMAD that couples a specific BMP-family receptor to mesodermal gene transcription, answering whether Smad8 is a functional signal transducer downstream of type I receptors.

    Evidence Receptor-specific phosphorylation, Co-IP with Smad4, reporter assays and genetic rescue in Xenopus embryos

    PMID:9371779

    Open questions at the time
    • Did not define the full receptor specificity beyond ALK-2
    • Did not resolve endogenous loss-of-function role
  2. 1998 High

    Introduced the concept that Smad8 acts in a BMP-induced negative-feedback loop, reframing it as a modulator rather than a purely activating transducer.

    Evidence Xenopus overexpression, explant assays and epistasis with dominant-negative and ligand-blocking reagents

    PMID:9449668

    Open questions at the time
    • Molecular basis of the negative feedback not defined
    • Relationship between feedback and phosphorylation status unresolved at the time
  3. 2000 High

    Defined the BMP type I receptor specificity of Smad8 (ALK-2/3/6 but not ALK-5) and linked it to osteogenic differentiation, cementing SMAD9 within the BMP rather than TGF-β arm.

    Evidence Phosphorylation with constitutively active receptors, Co-IP, nuclear translocation, promoter-reporter and ALP activity assays in mammalian cells

    PMID:10814522

    Open questions at the time
    • Quantitative comparison to other BMP R-SMADs not addressed
    • Endogenous in vivo requirement not tested
  4. 1999 Medium

    Showed that an SSXS-lacking splice variant acts as a dominant-negative, demonstrating that the phosphorylation motif governs nuclear translocation and signal output.

    Evidence Cloning, Co-IP, subcellular localization and dominant-negative functional assays in mammalian cells

    PMID:10583507

    Open questions at the time
    • Physiological abundance of the variant unknown
    • Single-lab finding without in vivo confirmation
  5. 2006 High

    Demonstrated that loss of Smad8 is tolerated in mouse development due to redundancy with Smad1/5, answering whether SMAD9 has a non-redundant developmental requirement.

    Evidence Gene targeting with compound mutant genetic epistasis and expression mapping in mice

    PMID:16765933

    Open questions at the time
    • Does not address tissue-specific non-redundant roles revealed later
    • No molecular mechanism of redundancy
  6. 2006 Medium

    Showed that an MH1-deleted constitutively active Smad8 can redirect MSC fate toward tendon while suppressing osteogenesis, indicating cell-fate control capacity.

    Evidence Engineered MSC transfection with in vitro profiling and in vivo tendon implantation

    PMID:16585960

    Open questions at the time
    • Mechanism of osteogenic inhibition not reconstituted biochemically
    • Used an engineered, non-physiological variant
  7. 2009 Medium

    Linked SMAD9 loss-of-function to pulmonary arterial hypertension through a truncating mutation that abolishes phosphorylation, SMAD4 binding and transcription, and through an in vivo PAH-like phenotype.

    Evidence Phosphorylation, Co-IP and reporter assays on a patient nonsense mutant; mouse loss-of-function histopathology

    PMID:19211612 PMID:19419974

    Open questions at the time
    • Single mutant analyzed biochemically
    • Mechanism connecting Smad8 loss to smooth muscle hyperplasia not fully defined
  8. 2011 Medium

    Identified a non-canonical, non-redundant role for SMAD9 in BMP-induced microRNA processing, distinguishing it from purely transcriptional R-SMAD function.

    Evidence Patient-derived pulmonary vascular cells with miRNA profiling and SMAD9 overexpression rescue of proliferation

    PMID:21920918

    Open questions at the time
    • Biochemical mechanism of SMAD9 in miRNA processing not resolved
    • Single-lab finding
  9. 2014 High

    Defined the mechanistic distinction of SMAD9 as a low-activity R-SMAD whose linker region dampens transcription and that can repress targets in complex with SMAD1, explaining why it behaves unlike SMAD1/5.

    Evidence Constitutively active DVD constructs, reporter, Co-IP, DNA-binding and linker domain-swap assays

    PMID:25534700

    Open questions at the time
    • Structural basis of linker-mediated repression unknown
    • Genome-wide repressive targets not mapped
  10. 2014 High

    Positioned smad9 within the BMP patterning hierarchy as a Smad5 transcriptional target acting redundantly with smad1, and in myelopoiesis.

    Evidence Morpholino knockdown, mRNA rescue, epistasis and transcriptional target validation in zebrafish

    PMID:24488494

    Open questions at the time
    • Mammalian conservation of mutual smad1/smad9 repression not shown
    • Myelopoiesis mechanism not detailed
  11. 2016 Medium

    Established that BMP directly induces SMAD9 transcription via promoter BREs bound by phospho-SMADs, providing the molecular basis for the negative-feedback loop.

    Evidence Promoter-reporter, ChIP for phospho-SMAD BRE binding, cycloheximide chase and BMP receptor inhibition across cell lines

    PMID:26748560

    Open questions at the time
    • Single-lab finding
    • Functional consequence of feedback on signal duration not quantified
  12. 2019 High

    Revealed a redundant but essential role for SMAD8 in hepatic hepcidin regulation and iron homeostasis, only unmasked in triple R-SMAD knockout.

    Evidence Hepatocyte-specific conditional knockouts with iron-loading, hepcidin and pathway-inhibitor analyses in mice

    PMID:31127639

    Open questions at the time
    • Relative contribution of SMAD9 versus SMAD1/5 not separable
    • No single-knockout iron phenotype
  13. 2021 High

    Identified ASB2 as the specific E3 ligase controlling SMAD9 protein stability and showed this axis is required for cardiogenesis, adding post-translational regulation to SMAD9 biology.

    Evidence Ubiquitylation and proteasome assays, Co-IP, and zebrafish knockdown with epistatic rescue

    PMID:34845242

    Open questions at the time
    • Conditions regulating ASB2-SMAD9 in mammalian heart not defined
    • Degron/recognition determinants on SMAD9 unmapped
  14. 2022 Medium

    Established SMAD9 as a negative regulator of myogenic microRNAs in dystrophic muscle, extending its non-canonical miRNA-regulatory role to a new tissue context.

    Evidence shRNA silencing in C2C12 myoblasts with BMP4 stimulation, miRNA/myogenic marker and cytokine readouts

    PMID:35886863

    Open questions at the time
    • Direct versus indirect effect on miRNA biogenesis unresolved
    • In vivo muscle relevance not tested
  15. 2022 Medium

    Defined a positive transcriptional feedback loop between SMAD9 and MYCN that sustains neuroblastoma proliferation, implicating SMAD9 in oncogenic transcriptional circuitry.

    Evidence ChIP-seq, CRISPRi, dual-luciferase reporter, knockdown and xenograft models

    PMID:36539767

    Open questions at the time
    • Single-lab finding
    • Generalizability beyond MYCN-amplified neuroblastoma unknown
  16. 2024 Low

    Proposed N-glycosylation of SMAD9 by MGAT1 as a regulatory modification influencing osteoblast differentiation, introducing a glycosylation control layer.

    Evidence Interaction and N-glycosylation assays, ALP and mineralization readouts in an exosome/circZNF638 study

    PMID:41744136

    Open questions at the time
    • How glycosylation alters SMAD9 function not resolved
    • Single-lab correlative pathway

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SMAD9's distinct biochemical properties—its low-activity linker, its non-canonical miRNA-processing function, and its post-translational control by ASB2 and glycosylation—are integrated mechanistically to produce its tissue-specific roles in vasculature, bone, muscle, iron homeostasis, and tumorigenesis.
  • No structural model linking the linker region to repressive complex formation
  • Molecular mechanism of SMAD9 in microRNA biogenesis undefined
  • Determinants of context-specific redundancy versus non-redundancy unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 2
Partners
ASB2CREBZFMGAT1MYCNSMAD1SMAD4

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SMAD9 (Smad8) is phosphorylated by constitutively active ALK-2 but not ALK-4, and upon ALK-2 signaling associates with Smad4, leading to synergistic transcriptional activation of mesoderm target genes; Smad8 can rescue expression of mesoderm genes blocked by truncated ALK-2 in Xenopus embryos. Xenopus embryo injection, receptor-specific phosphorylation assay, co-immunoprecipitation, transcriptional reporter assay, epistasis rescue experiment Proceedings of the National Academy of Sciences of the United States of America High 9371779
1998 Xenopus Smad8 lacks the C-terminal SSXS phosphorylation motif present in other receptor-Smads and functions in a negative feedback loop downstream of BMP-4: BMP signaling induces Smad8 expression, and Smad8 overexpression blocks BMP-4-mediated ventral mesoderm induction and partially blocks activin signaling, indicating Smad8 negatively modulates BMP and possibly other TGF-β family signals. Xenopus embryo overexpression, ectodermal explant assays, gene expression analysis, epistasis via dominant-negative and ligand-blocking experiments Development (Cambridge, England) High 9449668
1999 A splice variant of Smad8 (Smad8B) lacking 47 amino acids including the SSXS phosphorylation site forms specific complexes with Smad8 or Smad4 in mammalian cells, remains cytoplasmic upon ALK-2 activation (unlike full-length Smad8 which translocates to the nucleus), and acts as a dominant inhibitor of BMP signaling. Molecular cloning, co-immunoprecipitation in mammalian cells, subcellular localization assay, dominant-negative functional assay Genes to cells : devoted to molecular & cellular mechanisms Medium 10583507
2000 Mouse Smad8 is phosphorylated by constitutively active BMP type I receptors ALK-3 and ALK-6 (as well as ALK-2), inducing Smad8 interaction with Smad4 and nuclear translocation; ALK-5 (TGF-β type I receptor) does not act on Smad8. Smad8 and Smad4 cooperatively activate the Xvent2 promoter. Dominant-negative Smad8 inhibits BMP-2-induced alkaline phosphatase activity in mesenchymal and myoblastic cell lines. Phosphorylation assay with constitutively active receptors, co-immunoprecipitation, nuclear translocation assay, promoter-reporter assay, dominant-negative overexpression with ALP activity assay Biochemical and biophysical research communications High 10814522
2006 A constitutively active Smad8 variant (lacking the MH1 domain) transfected into MSCs coexpressing BMP2 drives differentiation toward tendon-like cells both in vitro and in vivo, while inhibiting the osteogenic pathway normally induced by BMP2. Transfection of engineered MSC line, in vitro morphological and gene expression profiling, in vivo implantation in Achilles tendon defect, double quantum filtered MRI The Journal of clinical investigation Medium 16585960
2006 Genetic epistasis in mouse embryos demonstrates that Smad8 homozygous null animals are viable and fertile, and loss of Smad8 does not exacerbate phenotypes of Smad1 or Smad5 single nulls, indicating functional redundancy among BMP R-Smads in early mouse development. Gene targeting (Smad8 null and conditional alleles), compound mutant genetic analysis, LacZ reporter for expression domain mapping Developmental biology High 16765933
2009 A nonsense mutation in SMAD9 (c.606C>A, p.C202X) produces a truncated protein that is not phosphorylated by constitutively active ALK3 or ALK1, cannot interact with SMAD4, and shows inefficient transcriptional activation compared to wild-type SMAD8, establishing loss-of-function of SMAD9 as causally linked to pulmonary arterial hypertension. Phosphorylation assay, co-immunoprecipitation, promoter-reporter transcriptional assay with SMAD4 and ca-ALK3 Journal of medical genetics Medium 19211612
2009 Smad8 loss-of-function in adult mice causes medial thickening and smooth muscle hyperplasia in distal pulmonary arteries characteristic of PAH, with upregulated Activin/TGF-β signaling and aberrant Prx1 and Tenascin-C expression; a subset of mutants also developed pulmonary adenomas, revealing a role for Smad8 in growth control. Gene targeting in mice (loss-of-function), histopathology, immunostaining for downstream signaling components Human molecular genetics Medium 19419974
2011 SMAD9 mutation completely abrogates BMP-induced processing of microRNAs (miR-21, miR-27a, miR-100) in pulmonary artery endothelial and smooth muscle cells, whereas canonical BMP-Smad signaling is only partially reduced, identifying a non-redundant non-canonical role for Smad8 in miRNA biogenesis; overexpression of SMAD9 corrects miRNA processing and reverses the hyperproliferative phenotype. Patient-derived cell lines (PAEC/PASMC), miRNA expression profiling, SMAD9 overexpression rescue experiment, antiproliferative assay American journal of respiratory and critical care medicine Medium 21920918
2012 CREBZF, a bZIP transcription factor, was identified as a novel Smad8-binding protein via yeast two-hybrid screening using the MH2 domain of Smad8 as bait; the interaction was confirmed by co-immunoprecipitation with Smads 1, 5, and 8 in a prostate cancer cell line. CREBZF overexpression inhibits BMP response element promoter activity and abolishes BMP-6-induced cell growth inhibition. Yeast two-hybrid screen, co-immunoprecipitation, promoter-reporter assay, cell growth assay Molecular and cellular biochemistry Medium 22707059
2014 Constitutively active Smad9(DVD) has lower transcriptional activity than Smad1(DVD) or Smad5(DVD) despite all three associating with Smad4 and binding target DNA; the linker region of Smad9 is sufficient to reduce transcriptional activity. Smad9 expression is induced by BMP signaling (similar to inhibitory Smads), and Smad9 forms complexes with Smad1 and binds DNA while suppressing target gene transcription, without inhibiting the type I receptor kinase (unlike I-Smads). Constitutively active Smad constructs (DVD mutants), transcriptional reporter assay, co-immunoprecipitation, DNA binding assay, gene expression analysis, domain-swap (linker region transfer) Scientific reports High 25534700
2014 In zebrafish, zygotic smad9 acts redundantly with smad1 downstream of smad5 to mediate dorso-ventral patterning; double knockdown of smad1 and smad9 strongly dorsalizes embryos and cannot be rescued by smad5 overexpression, whereas smad5 knockdown can be fully rescued by smad1 or smad9 overexpression. Smad1 and smad9 transcription initiations are repressed by each other, and both are direct transcriptional targets of Smad5. Smad9 is also required for myelopoiesis. Morpholino knockdown, mRNA overexpression rescue, genetic epistasis, transcriptional target validation The Journal of biological chemistry High 24488494
2016 BMP4 transcriptionally upregulates Smad8/9 expression in multiple cell lines through BMP-responsive elements (BREs) spanning nt -121 to nt -44 of the Smad8/9 promoter; phosphorylated Smad1/5/8/9 specifically binds these BREs, and BMP4-induced expression is cycloheximide-insensitive (direct) and blocked by LDN-193189 (BMP type I receptor inhibitor). Promoter-reporter assay, chromatin immunoprecipitation (phospho-Smad binding to BREs), cycloheximide chase, pharmacological inhibition Journal of cellular biochemistry Medium 26748560
2019 Hepatocyte-specific knockout of Smad1/5/8 (triple knockout) causes greater iron overload than Smad1/5 double knockout, demonstrating a redundant but critical role for SMAD8 in hepcidin production and iron homeostasis; Smad1/5/8 are required for hepcidin regulation by testosterone and EGF but not inflammation. Smad8 single knockout mice show no iron phenotype. Hepatocyte-specific conditional knockout mice (Cre/loxP), iron loading assays, hepcidin mRNA/protein measurement, pathway inhibitor treatments, dietary iron manipulation Hepatology (Baltimore, Md.) High 31127639
2019 A missense mutation in SMAD9 (c.65T>C, p.Leu22Pro) segregates with high bone mass in an autosomal dominant pedigree; in silico modeling predicts severe disruption of the MH1 DNA-binding domain, suggesting this is a loss-of-function mutation that reduces BMP inhibition and increases osteoblast activity. Whole exome sequencing, in silico protein structure modeling, genetic segregation analysis, pQCT bone measurement Journal of bone and mineral research Low 31525280
2021 ASB2 is the specific E3 ubiquitin ligase for SMAD9: ASB2 ubiquitylates SMAD9 (but not SMAD1 or SMAD5) and targets it for proteasomal degradation. In zebrafish, Asb2 knockdown causes thinned ventricular wall and dilated ventricle, phenotypes rescued by simultaneous Smad9 knockdown, establishing the ASB2-SMAD9 axis as essential for cardiogenesis. Ubiquitylation assay, proteasome inhibitor treatment, co-immunoprecipitation, zebrafish knockdown (morpholino), genetic epistasis rescue experiment, cardiac phenotype quantification Scientific reports High 34845242
2022 In DMD patient muscle and mdx mouse muscle, Smad8 mRNA is elevated 48-fold (whereas Smad1, 2, 3, 5 are minimally changed). Smad8 silencing in C2C12 myoblasts derepresses miR-1, miR-133a, and miR-133b, promotes myoblast differentiation, upregulates myogenic regulatory factors, and suppresses IL-6, identifying Smad8 as a negative regulator of muscle miRNAs downstream of BMP4 in dystrophic muscle. shRNA gene silencing in C2C12 myoblasts, BMP4 stimulation, western blot, RT-qPCR for miRNAs and myogenic markers, cytokine measurement International journal of molecular sciences Medium 35886863
2022 SMAD9 binds directly to the MYCN promoter and transcriptionally activates MYCN expression in neuroblastoma cells; reciprocally, MYCN binds the SMAD9 enhancer and transactivates SMAD9, forming a positive feedback loop. SMAD9 genetic suppression inhibits MYCN-amplified neuroblastoma cell proliferation and tumorigenicity in vitro and in vivo. ChIP-seq, CRISPRi, dual-luciferase reporter assay, gene knockdown, subcutaneous xenograft model, RNA-seq Journal of experimental & clinical cancer research : CR Medium 36539767
2024 SMAD9 undergoes N-glycosylation mediated by MGAT1; exosomal circZNF638 from osteoclasts recruits EWSR1 to upregulate MGAT1, which mediates N-glycosylation of SMAD9 and thereby inhibits osteoblast differentiation and mineralization. Co-immunoprecipitation/protein interaction assay, N-glycosylation measurement, ALP activity, alizarin red staining, western blot, exosome isolation Connective tissue research Low 41744136
2026 SMAD9 knockdown in hPSC-derived pancreatic differentiation impairs human β cell identity and insulin secretion function, establishing a role for SMAD9 in directing pancreatic β cell fate. RNA-seq transcriptomic profiling during hPSC differentiation, gene knockdown (loss-of-function), insulin secretion functional assay Cell death & disease Low 41807373
2015 A germline SMAD9 variant (V90M) predicted to be activating reduces PTEN (phosphatase and tensin homolog) expression when expressed in HEK cells, an effect also observed in patient polyp tissue, linking SMAD9 gain-of-function to hamartomatous polyposis. Transfection of SMAD9 V90M in HEK cells, western blot for PTEN expression, patient tissue analysis Gastroenterology Low 26122142
2021 Smad8 (phosphorylated) is expressed in the anterior necrotic zone of chick limb in a pattern correlating with programmed cell death areas; BMP and retinoic acid induce Smad8 expression before cell death onset, while sonic hedgehog inhibits Smad8 expression in the ANZ. However, phospho-SMAD1/5/8 and TUNEL staining do not co-localize in dying cells, indicating Smad8-mediated BMP signaling activates a molecular cascade leading to cell death rather than directly executing it. In situ hybridization, immunostaining (phospho-Smad1/5/8 and TUNEL), BMP/RA/SHH treatment of chick limb explants Development, growth & differentiation Low 21711459

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. The Journal of clinical investigation 187 16585960
2009 A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. Journal of medical genetics 171 19211612
1997 Smad8 mediates the signaling of the ALK-2 [corrected] receptor serine kinase. Proceedings of the National Academy of Sciences of the United States of America 131 9371779
2006 Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. Developmental biology 130 16765933
1998 Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning. Development (Cambridge, England) 106 9449668
2014 Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling. Scientific reports 95 25534700
2013 Correction of nonsense BMPR2 and SMAD9 mutations by ataluren in pulmonary arterial hypertension. American journal of respiratory cell and molecular biology 94 23590310
2011 Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8. American journal of respiratory and critical care medicine 92 21920918
2004 Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression. The Prostate 92 15042598
2009 Defective pulmonary vascular remodeling in Smad8 mutant mice. Human molecular genetics 61 19419974
2000 Mouse smad8 phosphorylation downstream of BMP receptors ALK-2, ALK-3, and ALK-6 induces its association with Smad4 and transcriptional activity. Biochemical and biophysical research communications 50 10814522
2019 Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice. Hepatology (Baltimore, Md.) 41 31127639
2019 A Rare Mutation in SMAD9 Associated With High Bone Mass Identifies the SMAD-Dependent BMP Signaling Pathway as a Potential Anabolic Target for Osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 35 31525280
2004 Elucidation of epigenetic inactivation of SMAD8 in cancer using targeted expressed gene display. Cancer research 32 14996722
2014 Transcriptional factors smad1 and smad9 act redundantly to mediate zebrafish ventral specification downstream of smad5. The Journal of biological chemistry 30 24488494
2014 Smad1 and 5 but not Smad8 establish stem cell quiescence which is critical to transform the premature hair follicle during morphogenesis toward the postnatal state. Stem cells (Dayton, Ohio) 28 24023003
1999 Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signalling. Genes to cells : devoted to molecular & cellular mechanisms 25 10583507
2015 Exome Sequencing Reveals Germline SMAD9 Mutation That Reduces Phosphatase and Tensin Homolog Expression and Is Associated With Hamartomatous Polyposis and Gastrointestinal Ganglioneuromas. Gastroenterology 24 26122142
2019 miR-203a-3p.1 is involved in the regulation of osteogenic differentiation by directly targeting Smad9 in MM-MSCs. Oncology letters 21 31788111
2005 Smad1 and Smad8 function similarly in mammalian central nervous system development. Molecular and cellular biology 20 15899870
2021 Thymopentin treatment of murine premature ovarian failure via attenuation of immune cell activity and promotion of the BMP4/Smad9 signalling pathway. International journal of medical sciences 16 34522181
2012 Inhibition of mTORC1 kinase activates Smads 1 and 5 but not Smad8 in human prostate cancer cells, mediating cytostatic response to rapamycin. Molecular cancer research : MCR 16 22452883
2021 Reduction of miR-744 delivered by NSCLC cell-derived extracellular vesicles upregulates SUV39H1 to promote NSCLC progression via activation of the Smad9/BMP9 axis. Journal of translational medicine 14 33472665
2016 Smad8/9 Is Regulated Through the BMP Pathway. Journal of cellular biochemistry 14 26748560
2022 Smad8 Is Increased in Duchenne Muscular Dystrophy and Suppresses miR-1, miR-133a, and miR-133b. International journal of molecular sciences 12 35886863
2022 SMAD9-MYCN positive feedback loop represents a unique dependency for MYCN-amplified neuroblastoma. Journal of experimental & clinical cancer research : CR 12 36539767
2012 CREBZF, a novel Smad8-binding protein. Molecular and cellular biochemistry 11 22707059
2021 ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis. Scientific reports 10 34845242
2022 BMP4/SMAD8 signaling pathway regulated granular cell proliferation to promote follicle development in Wanxi white goose. Poultry science 9 36435162
2018 A potential role for SMAD9 in goose follicular selection through regulation of mRNA levels of luteinizing hormone receptor. Theriogenology 6 30522699
2014 A novel SMAD family protein, SMAD9 is involved in follicular initiation and changes egg yield of geese via synonymous mutations in exon1 and intron2. Molecular biology reports 5 25280542
2024 Chondroitin polymerizing factor (CHPF) promotes the progression of colorectal cancer through ASB2-mediated ubiquitylation of SMAD9. Histology and histopathology 4 38591191
2023 Long noncoding RNA KCNMA1-AS1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by activating the SMAD9 signaling pathway. Biology direct 4 38017487
2011 Smad8 is expressed in the anterior necrotic zone: evidence for a role of bone morphogenetic proteins/SMAD signaling in the activation of a molecular cascade that culminates in cell death. Development, growth & differentiation 4 21711459
2021 Pharmacological Manipulation of Early Zebrafish Skeletal Development Shows an Important Role for Smad9 in Control of Skeletal Progenitor Populations. Biomolecules 3 33668680
2021 Refolding, purification, and characterization of constitutive-active human-Smad8 produced as inclusion bodies in ClearColi® BL21 (DE3). Protein expression and purification 3 33812004
2019 Association of the gene polymorphisms of BMPR2, ACVRL1, SMAD9 and their interactions with the risk of essential hypertension in the Chinese Han population. Bioscience reports 2 30617053
2026 Exosomal circZNF638 promotes postmenopausal osteoporosis progression through MGAT1-mediated SMAD9 glycosylation. Connective tissue research 0 41744136
2026 Dose-optimized HILT promotes peripheral nerve repair through BMP4-Smad9-mediated inhibition of neuroinflammation and oxidative stress. APL bioengineering 0 41799557
2026 RNA-seq at different stages of human pancreatic β cell differentiation reveals proliferation dynamics and SMAD9 in directing β cell fate. Cell death & disease 0 41807373
2026 Expression pattern of SMAD8 in geese at different reproductive stages and its effect on reproductive physiology and egg production performance. Journal of advanced veterinary and animal research 0 42180270
2024 The human SMAD9 (GCC) repeat links to natural selection and late-onset neurocognitive disorders. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 0 38877206
2024 A novel SMAD9 nonsense variant in an 11-year-old Japanese patient with diffuse pulmonary arteriovenous malformation: A case report. Journal of cardiology cases 0 40270704
2013 [Effect of bushen tiaojing recipe on the expressions of Smad1, Smad5, Smad8, and Smad4 in human mural granulosa cells]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine 0 23905376

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