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    SMAD4 SMAD family member 4 [ Homo sapiens (human) ]

    Gene ID: 4089, updated on 28-Oct-2018

    Summary

    Official Symbol
    SMAD4provided by HGNC
    Official Full Name
    SMAD family member 4provided by HGNC
    Primary source
    HGNC:HGNC:6770
    See related
    Ensembl:ENSG00000141646 MIM:600993; Vega:OTTHUMG00000132696
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    JIP; DPC4; MADH4; MYHRS
    Summary
    This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasng blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Aug 2017]
    Expression
    Ubiquitous expression in thyroid (RPKM 12.0), endometrium (RPKM 10.8) and 25 other tissues See more
    Orthologs

    Genomic context

    See SMAD4 in Genome Data Viewer
    Location:
    18q21.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 18 NC_000018.10 (51030213..51085042)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (48556583..48611412)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene malic enzyme 2 Neighboring gene uncharacterized LOC107985152 Neighboring gene elaC ribonuclease Z 1 Neighboring gene uncharacterized LOC105372117 Neighboring gene serine and arginine rich splicing factor 10 pseudogene 1 Neighboring gene uncharacterized LOC105372118 Neighboring gene mex-3 RNA binding family member C

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Phenotypes

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2012-04-19)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2012-04-19)

    ClinGen Genome Curation PagePubMed

    NHGRI GWAS Catalog

    Description
    A genome-wide association study of host genetic determinants of the antibody response to Anthrax Vaccine Adsorbed.
    NHGRI GWA Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat-treated pulmonary arterial smooth muscle cells downregulate levels of phosphorylated SMAD2/3 proteins and SMAD2/3-SMAD4 protein complex, which are repressed by cocaine exposure PubMed
    tat HIV-1 Tat-treated pulmonary arterial smooth muscle cells modulate levels of phosphorylated SMAD1/5/8 proteins and SMAD1/5/8-SMAD4 protein complex, which are repressed by cocaine exposure PubMed
    tat HIV-1 Tat proteins from different clades modulate differently Pur-alpha and SMAD4 to bind the JCV non-coding control region and affect differently on SMAD4 localization to the nucleus PubMed
    tat HIV-1 Tat enhances binding of SMAD2, -3 and -4 and their binding partner Fast1 to the JCV DNA control region (CR) to stimulate JCV gene transcription in living cells PubMed
    tat Smad-4 inhibits Smad-3 and HIV-1 Tat-induced transcription from the HIV-1 LTR promoter and the MCP promoter through a direct association with amino acids 1-40 of Tat PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    • AGE-RAGE signaling pathway in diabetic complications, organism-specific biosystem (from KEGG)
      AGE-RAGE signaling pathway in diabetic complications, organism-specific biosystemAdvanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and un...
    • AGE-RAGE signaling pathway in diabetic complications, conserved biosystem (from KEGG)
      AGE-RAGE signaling pathway in diabetic complications, conserved biosystemAdvanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and un...
    • ALK1 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      ALK1 signaling events, organism-specific biosystem
      ALK1 signaling events
    • ALK2 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      ALK2 signaling events, organism-specific biosystem
      ALK2 signaling events
    • Activin signaling, organism-specific biosystem (from KEGG)
      Activin signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
    • Activin signaling, conserved biosystem (from KEGG)
      Activin signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
    • Adherens junction, organism-specific biosystem (from KEGG)
      Adherens junction, organism-specific biosystemCell-cell adherens junctions (AJs), the most common type of intercellular adhesions, are important for maintaining tissue architecture and cell polarity and can limit cell movement and proliferation....
    • Adherens junction, conserved biosystem (from KEGG)
      Adherens junction, conserved biosystemCell-cell adherens junctions (AJs), the most common type of intercellular adhesions, are important for maintaining tissue architecture and cell polarity and can limit cell movement and proliferation....
    • Androgen receptor signaling pathway, organism-specific biosystem (from WikiPathways)
      Androgen receptor signaling pathway, organism-specific biosystemAndrogens, mainly testosterone and 5alpha-dihydrotestosterone (DHT) play significant role in the growth and development of the male reproductive organs. These steroid hormones bring about their biolo...
    • Apelin signaling pathway, organism-specific biosystem (from KEGG)
      Apelin signaling pathway, organism-specific biosystemApelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various ti...
    • BMP Signalling Pathway, organism-specific biosystem (from BIOCYC)
      BMP Signalling Pathway, organism-specific biosystemThe TGF-beta/BMP (bone morphogenetic protein) pathway incorporates several signalling pathways that share most, but not all, components of a central signal transduction engine. The general signalling...
    • BMP receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
      BMP receptor signaling, organism-specific biosystem
      BMP receptor signaling
    • BMP signaling, organism-specific biosystem (from KEGG)
      BMP signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
    • BMP signaling, conserved biosystem (from KEGG)
      BMP signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
    • Bone Morphogenic Protein (BMP) Signalling and Regulation, organism-specific biosystem (from WikiPathways)
      Bone Morphogenic Protein (BMP) Signalling and Regulation, organism-specific biosystem"BMP signals are mediated by type I and II BMP receptors and their downstream molecules Smad1, 5 and 8. Phosphorylated Smad1, 5 and 8 proteins form a complex with Smad4 and then are translocated into...
    • Canonical and Non-Canonical TGF-B signaling, organism-specific biosystem (from WikiPathways)
      Canonical and Non-Canonical TGF-B signaling, organism-specific biosystemThis pathway is modeled after Figure 9 in the article "Gremlin utilizes canonical and non-canonical TGFB signaling to induce lysyl oxidase (LOX) genes in human trabecular meshwork cells". Gremlin is ...
    • Cell Cycle, organism-specific biosystem (from WikiPathways)
      Cell Cycle, organism-specific biosystemThe cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle involves processes crucial to the survival of a c...
    • Cell cycle, organism-specific biosystem (from KEGG)
      Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cell cycle, conserved biosystem (from KEGG)
      Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Chronic myeloid leukemia, organism-specific biosystem (from KEGG)
      Chronic myeloid leukemia, organism-specific biosystemChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (C...
    • Chronic myeloid leukemia, conserved biosystem (from KEGG)
      Chronic myeloid leukemia, conserved biosystemChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (C...
    • Colorectal cancer, organism-specific biosystem (from KEGG)
      Colorectal cancer, organism-specific biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
    • Colorectal cancer, conserved biosystem (from KEGG)
      Colorectal cancer, conserved biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
    • DNA Damage Response (only ATM dependent), organism-specific biosystem (from WikiPathways)
      DNA Damage Response (only ATM dependent), organism-specific biosystemThis is the second pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and TP53) which are connected with the first DNA damage response pathway. In...
    • Deubiquitination, organism-specific biosystem (from REACTOME)
      Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
      Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
    • Downregulation of SMAD2/3:SMAD4 transcriptional activity, organism-specific biosystem (from REACTOME)
      Downregulation of SMAD2/3:SMAD4 transcriptional activity, organism-specific biosystemTranscriptional activity of SMAD2/3:SMAD4 heterotrimer can be inhibited by formation of a complex with SKI or SKIL (SNO), where SKI or SKIL recruit NCOR and possibly other transcriptional repressors ...
    • Ectoderm Differentiation, organism-specific biosystem (from WikiPathways)
      Ectoderm Differentiation, organism-specific biosystemModel depicting ectoderm specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell lin...
    • Endoderm Differentiation, organism-specific biosystem (from WikiPathways)
      Endoderm Differentiation, organism-specific biosystemModel depicting endoderm specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell lin...
    • Extracellular vesicle-mediated signaling in recipient cells, organism-specific biosystem (from WikiPathways)
      Extracellular vesicle-mediated signaling in recipient cells, organism-specific biosystemProtein sorting during formation of multivesicular bodies results in packaging of key molecules in exosomes. Exosomes bound-signaling ligands once released from host cells interacts with the receptor...
    • FoxO signaling pathway, organism-specific biosystem (from KEGG)
      FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
    • Gene Expression, organism-specific biosystem (from REACTOME)
      Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
    • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
      Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
    • HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      HIF-1-alpha transcription factor network, organism-specific biosystem
      HIF-1-alpha transcription factor network
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • Heart Development, organism-specific biosystem (from WikiPathways)
      Heart Development, organism-specific biosystemThis pathway has been largely adapted from an article by Deepak Srivastava, Cell. 2006 Sep 22;126(6):1037-48. In this pathway are known transcription factors, miRNAs and regulatory proteins that impa...
    • Hematopoietic Stem Cell Gene Regulation by GABP alpha/beta Complex, organism-specific biosystem (from WikiPathways)
      Hematopoietic Stem Cell Gene Regulation by GABP alpha/beta Complex, organism-specific biosystemGABP alpha/beta complex mediates the maintenance of hematopoietic stem cells (HSCs) through control of proteins necessary for epigenetic modification and transcription regulation. The activation of k...
    • Hepatitis B, organism-specific biosystem (from KEGG)
      Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
    • Hepatitis C and Hepatocellular Carcinoma, organism-specific biosystem (from WikiPathways)
      Hepatitis C and Hepatocellular Carcinoma, organism-specific biosystemPathway model based on hub miRNAs and their putative targets from network analysis. - From a set of differentially expressed genes in both chronic HCV (hepatitis C virus) and HCC (hepatocellular carc...
    • Hippo signaling pathway, organism-specific biosystem (from KEGG)
      Hippo signaling pathway, organism-specific biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
    • Hippo signaling pathway, conserved biosystem (from KEGG)
      Hippo signaling pathway, conserved biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
    • Hypothesized Pathways in Pathogenesis of Cardiovascular Disease, organism-specific biosystem (from WikiPathways)
      Hypothesized Pathways in Pathogenesis of Cardiovascular Disease, organism-specific biosystemThe pathways hypothesized to be involved in cardiovascular diseases begin with LTBPs and Fibrillins activating a TGFBR complex. The complex can begin the canonical TGFB pathway involving SMAD protei...
    • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
      Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
    • Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
      Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
    • LKB1 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      LKB1 signaling events, organism-specific biosystem
      LKB1 signaling events
    • Loss of Function of SMAD2/3 in Cancer, organism-specific biosystem (from REACTOME)
      Loss of Function of SMAD2/3 in Cancer, organism-specific biosystemLoss-of-function of SMAD2 and SMAD3 in cancer occurs less frequently than the loss of SMAD4 function and was studied in most detail in colorectal cancer (Fleming et al. 2013). Similarly to SMAD4, cod...
    • Loss of Function of SMAD4 in Cancer, organism-specific biosystem (from REACTOME)
      Loss of Function of SMAD4 in Cancer, organism-specific biosystemSMAD4 was identified as a gene homozygously deleted in ~30% of pancreatic cancers and was named DPC4 (DPC stands for deleted in pancreatic cancer). SMAD4 maps to the chromosomal band 18q21.1, and abo...
    • Mesodermal Commitment Pathway, organism-specific biosystem (from WikiPathways)
      Mesodermal Commitment Pathway, organism-specific biosystemModel depicting mesodermal specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell l...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • Pancreatic cancer, organism-specific biosystem (from KEGG)
      Pancreatic cancer, organism-specific biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Pancreatic cancer, conserved biosystem (from KEGG)
      Pancreatic cancer, conserved biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
    • Post-translational protein modification, organism-specific biosystem (from REACTOME)
      Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
    • Regulation of cytoplasmic and nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of cytoplasmic and nuclear SMAD2/3 signaling, organism-specific biosystem
      Regulation of cytoplasmic and nuclear SMAD2/3 signaling
    • Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
      Regulation of nuclear SMAD2/3 signaling
    • SMAD2/3 MH2 Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
      SMAD2/3 MH2 Domain Mutants in Cancer, organism-specific biosystemMutations in the MH2 domain of SMAD2 and SMAD3 affect their ability to form heterotrimers with SMAD4, thereby impairing TGF-beta signaling (Fleming et al. 2013).The SMAD2 and SMAD3 MH2 domain residue...
    • SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystem (from REACTOME)
      SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystemAfter phosphorylated SMAD2 and/or SMAD3 form a heterotrimer with SMAD4, SMAD2/3:SMAD4 complex translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003). In the nucleus, lin...
    • SMAD4 MH2 Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
      SMAD4 MH2 Domain Mutants in Cancer, organism-specific biosystemThe MH2 domain of SMAD4 is the most frequently mutated SMAD4 region in cancer. MH2 domain mutations result in the loss of function of SMAD4 by abrogating the formation of transcriptionally active het...
    • Senescence and Autophagy in Cancer, organism-specific biosystem (from WikiPathways)
      Senescence and Autophagy in Cancer, organism-specific biosystemSenescense and Autophagy Pathways in Cancer
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by Activin, organism-specific biosystem (from REACTOME)
      Signaling by Activin, organism-specific biosystemActivin was initially discovered as an activator of follicle stimulating hormone in the pituitary gland. It has since been shown to be an important participant in the differentiation of embryonic cel...
    • Signaling by BMP, organism-specific biosystem (from REACTOME)
      Signaling by BMP, organism-specific biosystemBone morphogenetic proteins (BMPs) have many biological activities in various tissues, including bone, cartilage, blood vessels, heart, kidney, neurons, liver and lung. They are members of the Transf...
    • Signaling by NODAL, organism-specific biosystem (from REACTOME)
      Signaling by NODAL, organism-specific biosystemSignaling by NODAL is essential for patterning of the axes of the embryo and formation of mesoderm and endoderm (reviewed in Schier 2009, Shen 2007). The NODAL proprotein is secreted and cleaved extr...
    • Signaling by TGF-beta Receptor Complex, organism-specific biosystem (from REACTOME)
      Signaling by TGF-beta Receptor Complex, organism-specific biosystemThe TGF-beta/BMP pathway incorporates several signaling pathways that share most, but not all, components of a central signal transduction engine. The general signaling scheme is rather simple: upon ...
    • Signaling by TGF-beta Receptor Complex in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by TGF-beta Receptor Complex in Cancer, organism-specific biosystemSignaling by the TGF-beta receptor complex is tumor suppressive, as it inhibits cell growth and promotes cell differentiation and apoptosis (Shipley et al. 1986, Hannon et al. 1994, Datto et al. 1995...
    • Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
      Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
    • Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
      Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
    • TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition, organism-specific biosystem (from WikiPathways)
      TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition, organism-specific biosystemThis pathway is based on the Figure 7 of "Cadherin 6 Is a New RUNX2 Target in TGF-? Signalling Pathway" (see bibliography). TGF-B is a target gene in thyroid cells in the causation of cancer. When TG...
    • TGF-beta Receptor Signaling, organism-specific biosystem (from WikiPathways)
      TGF-beta Receptor Signaling, organism-specific biosystemThe Transforming growth factor beta (TGFβ) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiat...
    • TGF-beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TGF-beta Signaling Pathway, organism-specific biosystemThe signal transduction mechanisms underlying the pathophysiological activities of transforming growth factor-? (TGF-?) have been extensively studied since its discovery nearly 30 years ago. TGF-? li...
    • TGF-beta receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
      TGF-beta receptor signaling, organism-specific biosystem
      TGF-beta receptor signaling
    • TGF-beta receptor signaling activates SMADs, organism-specific biosystem (from REACTOME)
      TGF-beta receptor signaling activates SMADs, organism-specific biosystemBinding of transforming growth factor beta 1 (TGF beta 1, i.e. TGFB1) to TGF beta receptor type 2 (TGFBR2) activates TGF beta receptor signaling cascade. TGFB1 is posttranslationally processed by fur...
    • TGF-beta signaling, organism-specific biosystem (from KEGG)
      TGF-beta signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
    • TGF-beta signaling, conserved biosystem (from KEGG)
      TGF-beta signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
    • TGF-beta signaling pathway, organism-specific biosystem (from KEGG)
      TGF-beta signaling pathway, organism-specific biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
    • TGF-beta signaling pathway, conserved biosystem (from KEGG)
      TGF-beta signaling pathway, conserved biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
    • Th17 cell differentiation, organism-specific biosystem (from KEGG)
      Th17 cell differentiation, organism-specific biosystemInterleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the p...
    • Th17 cell differentiation, conserved biosystem (from KEGG)
      Th17 cell differentiation, conserved biosystemInterleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the p...
    • Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystem (from REACTOME)
      Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystemIn the nucleus, SMAD2/3:SMAD4 heterotrimer complex acts as a transcriptional regulator. The activity of SMAD2/3 complex is regulated both positively and negatively by association with other transcrip...
    • Transcriptional regulation of pluripotent stem cells, organism-specific biosystem (from REACTOME)
      Transcriptional regulation of pluripotent stem cells, organism-specific biosystemPluripotent stem cells are undifferentiated cells posessing an abbreviated cell cycle (reviewed in Stein et al. 2012), a characteristic profile of gene expression (Rao et al. 2004, Kim et al. 2006, P...
    • Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
      Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...
    • Validated targets of C-MYC transcriptional activation, organism-specific biosystem (from Pathway Interaction Database)
      Validated targets of C-MYC transcriptional activation, organism-specific biosystem
      Validated targets of C-MYC transcriptional activation
    • Validated targets of C-MYC transcriptional repression, organism-specific biosystem (from Pathway Interaction Database)
      Validated targets of C-MYC transcriptional repression, organism-specific biosystem
      Validated targets of C-MYC transcriptional repression
    • Wnt signaling pathway, organism-specific biosystem (from KEGG)
      Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    • Wnt signaling pathway, conserved biosystem (from KEGG)
      Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Potential readthrough

    Included gene: ELAC1

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
     
    DNA-binding transcription factor activity, RNA polymerase II-specific ISM
    Inferred from Sequence Model
    more info
    PubMed 
    DNA-binding transcription factor activity, RNA polymerase II-specific NAS
    Non-traceable Author Statement
    more info
    PubMed 
    I-SMAD binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    R-SMAD binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    RNA polymerase II proximal promoter sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    RNA polymerase II transcription factor binding IEA
    Inferred from Electronic Annotation
    more info
     
    chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    collagen binding IEA
    Inferred from Electronic Annotation
    more info
     
    identical protein binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein heterodimerization activity IEA
    Inferred from Electronic Annotation
    more info
     
    protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    PubMed 
    proximal promoter sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    sulfate binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transcription coregulator activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription regulatory region DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transforming growth factor beta receptor, common-partner cytoplasmic mediator activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    BMP signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    BMP signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    BMP signaling pathway TAS
    Traceable Author Statement
    more info
     
    SMAD protein complex assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    SMAD protein signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    atrioventricular canal development IEA
    Inferred from Electronic Annotation
    more info
     
    atrioventricular valve formation IEA
    Inferred from Electronic Annotation
    more info
     
    axon guidance IEA
    Inferred from Electronic Annotation
    more info
     
    brainstem development IEA
    Inferred from Electronic Annotation
    more info
     
    branching involved in ureteric bud morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    cellular iron ion homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    cellular response to BMP stimulus NAS
    Non-traceable Author Statement
    more info
    PubMed 
    developmental growth IEA
    Inferred from Electronic Annotation
    more info
     
    embryonic digit morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    endocardial cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    endoderm development IEA
    Inferred from Electronic Annotation
    more info
     
    endothelial cell activation IEA
    Inferred from Electronic Annotation
    more info
     
    epithelial to mesenchymal transition involved in endocardial cushion formation IEA
    Inferred from Electronic Annotation
    more info
     
    female gonad morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    formation of anatomical boundary IEA
    Inferred from Electronic Annotation
    more info
     
    gastrulation with mouth forming second IEA
    Inferred from Electronic Annotation
    more info
     
    in utero embryonic development IEA
    Inferred from Electronic Annotation
    more info
     
    interleukin-6-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    intracellular signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    left ventricular cardiac muscle tissue morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    mesoderm development IEA
    Inferred from Electronic Annotation
    more info
     
    metanephric mesenchyme morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of ERK1 and ERK2 cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of cardiac muscle hypertrophy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of cardiac myofibril assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of cell death IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of cell growth IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
     
    negative regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nephrogenic mesenchyme morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    neural crest cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    neuron fate commitment IEA
    Inferred from Electronic Annotation
    more info
     
    outflow tract septum morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    ovarian follicle development IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of BMP signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of SMAD protein signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of cell proliferation involved in heart valve morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of epithelial to mesenchymal transition ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of follicle-stimulating hormone secretion IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of histone H3-K4 methylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of histone H3-K9 acetylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of luteinizing hormone secretion IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of pathway-restricted SMAD protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
     
    positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transforming growth factor beta receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    pri-miRNA transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    protein deubiquitination TAS
    Traceable Author Statement
    more info
     
    protein homotrimerization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of binding IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of hair follicle development IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of transforming growth factor beta receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of transforming growth factor beta2 production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to hypoxia IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to transforming growth factor beta IDA
    Inferred from Direct Assay
    more info
    PubMed 
    sebaceous gland development IEA
    Inferred from Electronic Annotation
    more info
     
    secondary palate development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    seminiferous tubule development IEA
    Inferred from Electronic Annotation
    more info
     
    single fertilization IEA
    Inferred from Electronic Annotation
    more info
     
    somatic stem cell population maintenance TAS
    Traceable Author Statement
    more info
     
    somite rostral/caudal axis specification IEA
    Inferred from Electronic Annotation
    more info
     
    spermatogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    transforming growth factor beta receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transforming growth factor beta receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transforming growth factor beta receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    transforming growth factor beta receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    uterus development IEA
    Inferred from Electronic Annotation
    more info
     
    ventricular septum morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    SMAD protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    SMAD protein complex IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    activin responsive factor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    centrosome IDA
    Inferred from Direct Assay
    more info
     
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    nuclear chromatin IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription factor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription factor complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 

    General protein information

    Preferred Names
    mothers against decapentaplegic homolog 4
    Names
    MAD homolog 4
    SMAD, mothers against DPP homolog 4
    deleted in pancreatic carcinoma locus 4
    deletion target in pancreatic carcinoma 4
    mothers against decapentaplegic, Drosophila, homolog of, 4

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_013013.2 RefSeqGene

      Range
      67174..122003
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_318

    mRNA and Protein(s)

    1. NM_005359.5NP_005350.1  mothers against decapentaplegic homolog 4

      See identical proteins and their annotated locations for NP_005350.1

      Status: REVIEWED

      Source sequence(s)
      AC091551, AU120224, BC002379, BM701399
      Consensus CDS
      CCDS11950.1
      UniProtKB/Swiss-Prot
      Q13485
      UniProtKB/TrEMBL
      A0A024R274
      Related
      ENSP00000341551.3, ENST00000342988.7
      Conserved Domains (3) summary
      pfam05539
      Location:176281
      Pneumo_att_G; Pneumovirinae attachment membrane glycoprotein G
      cd10492
      Location:14138
      MH1_SMAD_4; N-terminal Mad Homology 1 (MH1) domain in SMAD4
      cd10498
      Location:320541
      MH2_SMAD_4; C-terminal Mad Homology 2 (MH2) domain in SMAD4

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000018.10 Reference GRCh38.p12 Primary Assembly

      Range
      51030213..51085042
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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