Mothers against decapentaplegic homolog 4

SMAD4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DD1, 1G88, 1MR1, 1U7F, 1U7V, 1YGS, 5MEY, 5MEZ, 5MF0
Identifiers
Aliases	SMAD4, DPC4, JIP, MADH4, MYHRS, SMAD family member 4
External IDs	OMIM: 600993; MGI: 894293; HomoloGene: 31310; GeneCards: SMAD4; OMA:SMAD4 - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q21.2 Start 51,028,394 bp[1] End 51,085,045 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E2|18 49.51 cM Start 73,772,080 bp[2] End 73,836,851 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence Achilles tendon epithelium of colon stromal cell of endometrium left ovary gallbladder rectum popliteal artery tibial arteries Top expressed in Rostral migratory stream ciliary body Paneth cell vas deferens human fetus renal corpuscle medullary collecting duct conjunctival fornix medial ganglionic eminence retinal pigment epithelium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity protein heterodimerization activity RNA polymerase II transcription regulatory region sequence-specific DNA binding metal ion binding DNA binding DNA-binding transcription factor activity sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific I-SMAD binding collagen binding protein binding RNA polymerase II cis-regulatory region sequence-specific DNA binding R-SMAD binding identical protein binding sulfate binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription coregulator activity molecular function regulator chromatin binding Cellular component nucleus cytoplasm transcription regulator complex activin responsive factor complex intracellular anatomical structure RNA polymerase II transcription regulator complex nucleoplasm centrosome cytosol SMAD protein complex Biological process negative regulation of cell population proliferation spermatogenesis positive regulation of pathway-restricted SMAD protein phosphorylation positive regulation of luteinizing hormone secretion regulation of cell population proliferation cardiac septum development negative regulation of cell death regulation of hair follicle development cellular response to BMP stimulus epithelial to mesenchymal transition involved in endocardial cushion formation brainstem development cell population proliferation regulation of binding SMAD protein complex assembly metanephric mesenchyme morphogenesis positive regulation of epithelial to mesenchymal transition positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus regulation of transcription by RNA polymerase II branching involved in ureteric bud morphogenesis regulation of transcription, DNA-templated embryonic digit morphogenesis uterus development axon guidance somatic stem cell population maintenance gastrulation positive regulation of histone H3-K4 methylation negative regulation of transcription, DNA-templated response to transforming growth factor beta endothelial cell activation positive regulation of transforming growth factor beta receptor signaling pathway single fertilization transforming growth factor beta receptor signaling pathway anterior/posterior pattern specification in utero embryonic development positive regulation of cell proliferation involved in heart valve morphogenesis atrioventricular valve formation intracellular signal transduction developmental growth endoderm development cellular iron ion homeostasis kidney development formation of anatomical boundary positive regulation of histone H3-K9 acetylation regulation of transforming growth factor beta2 production interleukin-6-mediated signaling pathway negative regulation of transcription by RNA polymerase II male gonad development ovarian follicle development endocardial cell differentiation nephrogenic mesenchyme morphogenesis gastrulation with mouth forming second female gonad development SMAD protein signal transduction response to hypoxia atrioventricular canal development mesoderm development negative regulation of cell growth positive regulation of transcription, DNA-templated BMP signaling pathway tissue morphogenesis positive regulation of transcription by RNA polymerase II positive regulation of SMAD protein signal transduction somite rostral/caudal axis specification sebaceous gland development positive regulation of follicle-stimulating hormone secretion positive regulation of BMP signaling pathway neural crest cell differentiation seminiferous tubule development female gonad morphogenesis regulation of transforming growth factor beta receptor signaling pathway neuron fate commitment transcription, DNA-templated outflow tract septum morphogenesis left ventricular cardiac muscle tissue morphogenesis negative regulation of cardiac muscle hypertrophy protein deubiquitination ventricular septum morphogenesis negative regulation of ERK1 and ERK2 cascade negative regulation of cardiac myofibril assembly protein homotrimerization pri-miRNA transcription by RNA polymerase II secondary palate development anatomical structure morphogenesis cell differentiation mesendoderm development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4089 17128 Ensembl ENSG00000141646 ENSMUSG00000024515 UniProt Q13485 P97471 RefSeq (mRNA) NM_005359 NM_008540 NM_001364967 NM_001364968 RefSeq (protein) NP_005350 NP_032566 NP_001351896 NP_001351897 Location (UCSC) Chr 18: 51.03 – 51.09 Mb Chr 18: 73.77 – 73.84 Mb PubMed search [3] [4]
Wikidata
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SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction. The TGFβ family of cytokines regulates critical processes during the lifecycle of metazoans, with important roles during embryo development, tissue homeostasis, regeneration, and immune regulation.^[5]

SMAD 4 belongs to the co-SMAD group (common mediator SMAD), the second class of the SMAD family. SMAD4 is the only known co-SMAD in most metazoans. It also belongs to the Darwin family of proteins that modulate members of the TGFβ protein superfamily, a family of proteins that all play a role in the regulation of cellular responses. Mammalian SMAD4 is a homolog of the Drosophila protein "Mothers against decapentaplegic" named Medea.^[6]

SMAD4 interacts with R-Smads, such as SMAD2, SMAD3, SMAD1, SMAD5 and SMAD8 (also called SMAD9) to form heterotrimeric complexes. Transcriptional coregulators, such as WWTR1 (TAZ) interact with SMADs to promote their function. Once in the nucleus, the complex of SMAD4 and two R-SMADS binds to DNA and regulates the expression of different genes depending on the cellular context.^[6] Intracellular reactions involving SMAD4 are triggered by the binding, on the surface of the cells, of growth factors from the TGFβ family. The sequence of intracellular reactions involving SMADS is called the SMAD pathway or the transforming growth factor beta (TGF-β) pathway since the sequence starts with the recognition of TGF-β by cells.