Smad4 Gene Summary [Mouse]
Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; collagen binding activity; and identical protein binding activity. Involved in several processes, including cell surface receptor protein serine/threonine kinase signaling pathway; heart development; and regulation of DNA-templated transcription. Acts upstream of or within several processes, including positive regulation of gonadotropin secretion; regulation of DNA-templated transcription; and reproductive structure development. Located in cytoplasm and nucleus. Part of RNA polymerase II transcription regulator complex. Is expressed in several structures, including central nervous system; early conceptus; genitourinary system; jaw; and respiratory system. Used to study colorectal cancer; juvenile polyposis syndrome; and osteogenesis imperfecta. Human ortholog(s) of this gene implicated in several diseases, including female reproductive organ cancer (multiple); hereditary hemorrhagic telangiectasia; juvenile polyposis syndrome; juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome; and seminoma. Orthologous to human SMAD4 (SMAD family member 4). [provided by Alliance of Genome Resources, Jul 2025]
Details
| Type | Protein Coding |
| Official Symbol | Smad4 |
| Official Name | SMAD family member 4 [Source:MGI Symbol;Acc:MGI:894293] |
| Ensembl ID | ENSMUSG00000024515 |
| Bio databases IDs | |
| Aliases | SMAD family member 4 |
| Synonyms | AW743858, D18Wsu70e, DPC4, JIP, MADH4, MYHRS, SMAD family member 4, Smaug1 |
| Species | Mouse, Mus musculus |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in mouse Smad4 often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- SMAD binding
- transcription regulator
- transcription factor binding
- chromatin binding
- identical protein binding
- proline rich domain
- N-terminal Mad Homology 1 (MH1) domain
- RNA polymerase II transcription factor activity, sequence-specific DNA binding
- Smad4 activation domain
- cytoskeletal protein binding
- MH1 domain
- C-terminal Mad Homology 2 (MH2) domain
- RNA polymerase II transcription regulatory region sequence-specific binding transcriptional activator activity
- activation domain
- MH2 domain
- DNA binding domain
- MH domain
- nucleic acid binding
- linker domain
- protein binding
- sequence-specific DNA binding
- DNA binding
- binding protein
- double-stranded DNA binding
- collagen binding
- protein homodimerization
- transcription factor activity
Pathways
Biological processes and signaling networks where the Smad4 gene in mouse plays a role, providing insight into its function and relevance in health or disease.
- Antiproliferative Role of TOB in T Cell Signaling
- BMP signaling pathway
- Cardiomyocyte Differentiation via BMP Receptors
- Chronic Myeloid Leukemia Signaling
- Factors Promoting Cardiogenesis in Vertebrates
- GADD45 Signaling
- Glucocorticoid Receptor Signaling
- Hepatic Fibrosis / Hepatic Stellate Cell Activation
- HER-2 Signaling in Breast Cancer
- HIPPO signaling
- Human Embryonic Stem Cell Pluripotency
- Iron homeostasis signaling pathway
- Mouse Embryonic Stem Cell Pluripotency
- Osteoarthritis Pathway
- Pancreatic Adenocarcinoma Signaling
- PPARα/RXRα Activation
- Regulation of IL-2 Expression in Activated and Anergic T Lymphocytes
- Regulation of the Epithelial-Mesenchymal Transition Pathway
- Role of NANOG in Mammalian Embryonic Stem Cell Pluripotency
- Role of Osteoblasts, Osteoclasts and Chondrocytes in Rheumatoid Arthritis
- TGF-β Signaling
- Transcriptional Regulatory Network in Embryonic Stem Cells
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- neoplasia
- epithelial cancer
- epithelial neoplasia
- cancer
- pancreatic neoplasia
- breast adenocarcinoma
- urogenital cancer
- juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
- Myhre syndrome
- juvenile polyposis syndrome
role in cell
- mitochondrial respiration in
- production in
- expression in
- phosphorylation in
- apoptosis
- cellular infiltration by
- survival
- proliferation
- elongation
- elongation in
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Nucleus
- nuclear fraction
- Cytoplasm
- perinuclear region
- basal bodies
- centrosome
- Mitochondria
- cytosol
- nucleoplasm
- zona pellucida
- photoreceptor inner segments
- filopodia
- chromatin
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the mouse Smad4 gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- transforming growth factor beta receptor signaling pathway
- axon guidance
- transcription from RNA polymerase II promoter
- negative regulation of protein catabolic process
- positive regulation of cell proliferation involved in heart valve morphogenesis
- single fertilization
- embryonic digit morphogenesis
- activin receptor signaling pathway
- cellular iron ion homeostasis
- response to hypoxia
- negative regulation of transcription, DNA-dependent
- negative regulation of cardiac muscle hypertrophy
- positive regulation of transcription, DNA-dependent
- cellular response to glucose stimulus
- in utero embryonic development
- negative regulation of cell growth
- cellular response to BMP stimulus
- BMP signaling pathway
- gastrulation with mouth forming second
- somite rostral/caudal axis specification
- cardiac muscle hypertrophy in response to stress
- intracellular signal transduction
- neural crest cell differentiation
- SMAD protein signal transduction
- endocardial cell differentiation
- left ventricular cardiac muscle tissue morphogenesis
- cellular response to transforming growth factor beta stimulus
- nephrogenic mesenchyme morphogenesis
- positive regulation of gene expression
- metanephric mesenchyme morphogenesis
- positive regulation of cardiac muscle cell apoptotic process
- epithelial to mesenchymal transition
- positive regulation of luteinizing hormone secretion
- cell proliferation
- endothelial cell activation
- atrioventricular valve formation
- negative regulation of cell proliferation
- uterus development
- extrinsic apoptotic signaling pathway
- sebaceous gland development
- anatomical structure morphogenesis
- regulation of transforming growth factor beta2 production
- epithelial to mesenchymal transition involved in endocardial cushion formation
- positive regulation of transcription from RNA polymerase II promoter
- formation of anatomical boundary
- negative regulation of transcription from RNA polymerase II promoter
- outflow tract septum morphogenesis
- positive regulation of epithelial to mesenchymal transition
- neuron fate specification
- seminiferous tubule development
- positive regulation of follicle-stimulating hormone secretion
- osteoblast differentiation
- interleukin-6-mediated signaling pathway
- ovum-producing ovary morphogenesis
- positive regulation of SMAD protein import into nucleus
- mesendoderm development
- epithelial cell migration
- adrenal gland development
- response to transforming growth factor beta stimulus
- transcription, DNA-dependent
- spermatogenesis
- cardiac conduction system development
- brainstem development
- regulation of transcription, DNA-dependent
- developmental growth
- ventricular septum morphogenesis
- ovarian follicle development
- regulation of transcription from RNA polymerase II promoter
- negative regulation of canonical Wnt receptor signaling pathway
- ERK1 and ERK2 cascade
- regulation of hair follicle development
- negative regulation of ERK1 and ERK2 cascade
- branching involved in ureteric bud morphogenesis
- cell differentiation
- positive regulation of transforming growth factor beta receptor signaling pathway
Cellular Component
Where in the cell the gene product is active
- SMAD protein complex
- transcription factor complex
- nucleus
- centrosome
- cytoplasm
- SMAD2-SMAD3 protein complex
- activin responsive factor complex
- cytosol
- chromatin
- nucleoplasm
Molecular Function
What the gene product does at the molecular level
- identical protein binding
- protein homodimerization activity
- RNA polymerase II core promoter proximal region sequence-specific DNA binding
- transcription regulatory region sequence-specific DNA binding
- sulfate binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
- sequence-specific DNA binding
- chromatin binding
- transcription coactivator binding
- sequence-specific DNA binding RNA polymerase II transcription factor activity
- transcription corepressor binding
- DNA binding
- sequence-specific DNA binding transcription factor activity
- protein binding
- collagen binding
- metal ion binding
- R-SMAD binding
- I-SMAD binding
- filamin binding