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RNA category is based on mRNA expression levels in the analyzed samples (RNA assay description). The categories include: tissue/cell line enriched, group enriched, tissue/cell line enhanced, expressed in all, mixed and not detected. RNA category is calculated separately for The Cancer Genome Atlas (TCGA) data from cancer tissues and internally generated Human Protein Atlas (HPA) data from normal tissues and cell lines.
TCGA (cancer tissue):
Expressed in all
HPA (cell line):
Expressed in all
HPA (normal tissue):
Expressed in all
Protein evidencei
Protein evidence scores are generated from several independent sources and are classified as evidence at i) protein level, ii) transcript level, iii) no evidence, or iv) not available.
Evidence at protein level
Protein expression normal tissuei
A summary of the overall protein expression pattern across the analyzed normal tissues. The summary is based on knowledge-based annotation.
"Estimation of protein expression could not be performed. View primary data." is shown for genes analyzed with a knowledge-based approach where available RNA-seq and gene/protein characterization data has been evaluated as not sufficient in combination with immunohistochemistry data to yield a reliable estimation of the protein expression profile.
Cytoplasmic and nuclear expression in most tissues.
IMMUNOHISTOCHEMISTRY DATA RELIABILITY
Data reliability descriptioni
Standardized explanatory sentences with additional information required for full understanding of the knowledge-based expression profile.
Antibody staining mainly consistent with RNA expression data.
Reliability score - normal tissuesi
Reliability score (score description), divided into Enhanced, Supported, Approved, or Uncertain, is evaluated in normal tissues and based on consistency between antibody staining pattern, available RNA-Seq and gene/protein characterization data, as well as similarity between independent antibodies targeting the same protein.
Kaplan-Meier plots for all cancers where high expression of this gene has significant (p<0.001) association with patient survival are shown in this summary. Whether the prognosis is favourable or unfavourable is indicated in brackets. Each Kaplan-Meier plot is clickable and redirects to a detailed page that includes individual expression and survival data for patients with the selected cancer.
RNA expression overview shows RNA-seq data from The Cancer Genome Atlas (TCGA).
TCGA dataseti
RNA-seq data in 17 cancer types are reported as median FPKM (number Fragments Per Kilobase of exon per Million reads), generated by the The Cancer Genome Atlas (TCGA). RNA cancer tissue category is calculated based on mRNA expression levels across all 17 cancer tissues and include: cancer tissue enriched, cancer group enriched, cancer tissue enhanced, expressed in all, mixed and not detected. To access cancer specific RNA and prognostic data, click on the cancer name. The cancer types are color-coded according to which type of normal organ the cancer originates from.
Antibody staining in 20 different cancers is summarized by a selection of four standard cancer tissue samples representative of the overall staining pattern. From left: colorectal cancer, breast cancer, prostate cancer and lung cancer. An additional fifth image can be added as a complement. The assay and annotation is described here. Note that samples used for immunohistochemistry by the Human Protein Atlas do not correspond to samples in the TCGA dataset.
For each cancer, color-coded bars indicate the percentage of patients (maximum 12 patients) with high and medium protein expression level. The cancer types are color-coded according to which type of normal organ the cancer originates from. Low or not detected protein expression results in a white bar. Mouse-over function shows details about expression level and normal tissue of origin. The images and annotations can be accessed by clicking on the cancer name or protein expression bar. If more than one antibody is analyzed, the tabs at the top of the staining summary section can be used to toggle between the different antibodies.
A few cases of most tumor types showed moderate cytoplasmic positivity with additional nuclear staining in a few cases.
GENE INFORMATIONi
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Gene name
SMAD4 (HGNC Symbol)
Synonyms
DPC4, MADH4
Description
SMAD family member 4 (HGNC Symbol)
Entrez gene 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 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 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, Oct 2009]
The protein browser displays the antigen location on the target protein(s) and the features of the target protein. The tabs at the top of the protein view section can be used to switch between the different splice variants to which an antigen has been mapped.
At the top of the view, the position of the antigen (identified by the corresponding HPA identifier) is shown as a green bar. A yellow triangle on the bar indicates a <100% sequence identity to the protein target.
Under the antigens, the maximum percent sequence identity of the protein to all other proteins from other human genes is displayed, using a sliding window of 10 aa residues (HsID 10) or 50 aa residues (HsID 50). The region with the lowest possible identity is always selected for antigen design, with a maximum identity of 60% allowed for designing a single-target antigen (read more).
The curve in blue displays the predicted antigenicity i.e. the tendency for different regions of the protein to generate an immune response, with peak regions being predicted to be more antigenic.The curve shows average values based on a sliding window approach using an in-house propensity scale. (read more).
If a signal peptide is predicted by a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius (turquoise) and/or transmembrane regions (orange) are predicted by MDM, these are displayed.
Low complexity regions are shown in yellow and InterPro regions in green. Common (purple) and unique (grey) regions between different splice variants of the gene are also displayed (read more), and at the bottom of the protein view is the protein scale.
SMAD4-001
SMAD4-004
SMAD4-006
SMAD4-007
SMAD4-008
SMAD4-010
SMAD4-013
SMAD4-016
SMAD4-201
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
Q13485 [Direct mapping] Mothers against decapentaplegic homolog 4 A0A024R274 [Target identity:100%; Query identity:100%] Mothers against decapentaplegic homolog
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SCAMPI predicted membrane proteins Predicted intracellular proteins Transcription factors beta-Hairpin exposed by an alpha/beta-scaffold Cancer-related genes Candidate cancer biomarkers Mutated cancer genes Mutational cancer driver genes COSMIC somatic mutations in cancer genes COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Large Deletions COSMIC Germline Mutations COSMIC Frameshift Mutations Disease related genes Protein evidence (Ezkurdia et al 2014)
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GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] GO:0000790 [nuclear chromatin] GO:0000978 [RNA polymerase II core promoter proximal region sequence-specific DNA binding] GO:0000987 [core promoter proximal region sequence-specific DNA binding] GO:0000988 [transcription factor activity, protein binding] GO:0001077 [transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding] GO:0001666 [response to hypoxia] GO:0003148 [outflow tract septum morphogenesis] GO:0003220 [left ventricular cardiac muscle tissue morphogenesis] GO:0003677 [DNA binding] GO:0003700 [transcription factor activity, sequence-specific DNA binding] GO:0005515 [protein binding] GO:0005622 [intracellular] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005667 [transcription factor complex] GO:0005737 [cytoplasm] GO:0005813 [centrosome] GO:0005829 [cytosol] GO:0006351 [transcription, DNA-templated] GO:0006355 [regulation of transcription, DNA-templated] GO:0006366 [transcription from RNA polymerase II promoter] GO:0006879 [cellular iron ion homeostasis] GO:0007179 [transforming growth factor beta receptor signaling pathway] GO:0007183 [SMAD protein complex assembly] GO:0010614 [negative regulation of cardiac muscle hypertrophy] GO:0010718 [positive regulation of epithelial to mesenchymal transition] GO:0010862 [positive regulation of pathway-restricted SMAD protein phosphorylation] GO:0016579 [protein deubiquitination] GO:0017015 [regulation of transforming growth factor beta receptor signaling pathway] GO:0030308 [negative regulation of cell growth] GO:0030509 [BMP signaling pathway] GO:0030511 [positive regulation of transforming growth factor beta receptor signaling pathway] GO:0030513 [positive regulation of BMP signaling pathway] GO:0030616 [transforming growth factor beta receptor, common-partner cytoplasmic mediator activity] GO:0032444 [activin responsive factor complex] GO:0032909 [regulation of transforming growth factor beta2 production] GO:0035019 [somatic stem cell population maintenance] GO:0035556 [intracellular signal transduction] GO:0042802 [identical protein binding] GO:0042803 [protein homodimerization activity] GO:0043565 [sequence-specific DNA binding] GO:0044212 [transcription regulatory region DNA binding] GO:0045892 [negative regulation of transcription, DNA-templated] GO:0045893 [positive regulation of transcription, DNA-templated] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0046872 [metal ion binding] GO:0051571 [positive regulation of histone H3-K4 methylation] GO:0060021 [palate development] GO:0060391 [positive regulation of SMAD protein import into nucleus] GO:0060395 [SMAD protein signal transduction] GO:0060412 [ventricular septum morphogenesis] GO:0070102 [interleukin-6-mediated signaling pathway] GO:0070373 [negative regulation of ERK1 and ERK2 cascade] GO:0070411 [I-SMAD binding] GO:0070412 [R-SMAD binding] GO:0071141 [SMAD protein complex] GO:0071559 [response to transforming growth factor beta] GO:0071773 [cellular response to BMP stimulus] GO:1901522 [positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus] GO:1905305 [negative regulation of cardiac myofibril assembly] GO:2000617 [positive regulation of histone H3-K9 acetylation]
Q13485 [Direct mapping] Mothers against decapentaplegic homolog 4 A0A024R274 [Target identity:100%; Query identity:100%] Mothers against decapentaplegic homolog
Show all
SCAMPI predicted membrane proteins Predicted intracellular proteins Transcription factors beta-Hairpin exposed by an alpha/beta-scaffold Cancer-related genes Candidate cancer biomarkers Mutated cancer genes Mutational cancer driver genes COSMIC somatic mutations in cancer genes COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Large Deletions COSMIC Germline Mutations COSMIC Frameshift Mutations Disease related genes Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] GO:0000790 [nuclear chromatin] GO:0000977 [RNA polymerase II regulatory region sequence-specific DNA binding] GO:0000978 [RNA polymerase II core promoter proximal region sequence-specific DNA binding] GO:0000987 [core promoter proximal region sequence-specific DNA binding] GO:0000988 [transcription factor activity, protein binding] GO:0001076 [transcription factor activity, RNA polymerase II transcription factor binding] GO:0001077 [transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding] GO:0001085 [RNA polymerase II transcription factor binding] GO:0001228 [transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding] GO:0001541 [ovarian follicle development] GO:0001658 [branching involved in ureteric bud morphogenesis] GO:0001666 [response to hypoxia] GO:0001701 [in utero embryonic development] GO:0001702 [gastrulation with mouth forming second] GO:0001822 [kidney development] GO:0003148 [outflow tract septum morphogenesis] GO:0003190 [atrioventricular valve formation] GO:0003198 [epithelial to mesenchymal transition involved in endocardial cushion formation] GO:0003220 [left ventricular cardiac muscle tissue morphogenesis] GO:0003251 [positive regulation of cell proliferation involved in heart valve morphogenesis] GO:0003279 [cardiac septum development] GO:0003360 [brainstem development] GO:0003677 [DNA binding] GO:0003682 [chromatin binding] GO:0003700 [transcription factor activity, sequence-specific DNA binding] GO:0005515 [protein binding] GO:0005518 [collagen binding] GO:0005622 [intracellular] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005667 [transcription factor complex] GO:0005737 [cytoplasm] GO:0005813 [centrosome] GO:0005829 [cytosol] GO:0006351 [transcription, DNA-templated] GO:0006355 [regulation of transcription, DNA-templated] GO:0006357 [regulation of transcription from RNA polymerase II promoter] GO:0006366 [transcription from RNA polymerase II promoter] GO:0006879 [cellular iron ion homeostasis] GO:0007179 [transforming growth factor beta receptor signaling pathway] GO:0007183 [SMAD protein complex assembly] GO:0007283 [spermatogenesis] GO:0007338 [single fertilization] GO:0007369 [gastrulation] GO:0007411 [axon guidance] GO:0007492 [endoderm development] GO:0007498 [mesoderm development] GO:0008283 [cell proliferation] GO:0008285 [negative regulation of cell proliferation] GO:0008584 [male gonad development] GO:0008585 [female gonad development] GO:0009952 [anterior/posterior pattern specification] GO:0010614 [negative regulation of cardiac muscle hypertrophy] GO:0010718 [positive regulation of epithelial to mesenchymal transition] GO:0010862 [positive regulation of pathway-restricted SMAD protein phosphorylation] GO:0014033 [neural crest cell differentiation] GO:0016579 [protein deubiquitination] GO:0017015 [regulation of transforming growth factor beta receptor signaling pathway] GO:0030308 [negative regulation of cell growth] GO:0030509 [BMP signaling pathway] GO:0030511 [positive regulation of transforming growth factor beta receptor signaling pathway] GO:0030513 [positive regulation of BMP signaling pathway] GO:0030616 [transforming growth factor beta receptor, common-partner cytoplasmic mediator activity] GO:0032444 [activin responsive factor complex] GO:0032525 [somite rostral/caudal axis specification] GO:0032909 [regulation of transforming growth factor beta2 production] GO:0033686 [positive regulation of luteinizing hormone secretion] GO:0035019 [somatic stem cell population maintenance] GO:0035556 [intracellular signal transduction] GO:0036302 [atrioventricular canal development] GO:0042118 [endothelial cell activation] GO:0042127 [regulation of cell proliferation] GO:0042733 [embryonic digit morphogenesis] GO:0042802 [identical protein binding] GO:0042803 [protein homodimerization activity] GO:0043565 [sequence-specific DNA binding] GO:0044212 [transcription regulatory region DNA binding] GO:0045892 [negative regulation of transcription, DNA-templated] GO:0045893 [positive regulation of transcription, DNA-templated] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0046872 [metal ion binding] GO:0046881 [positive regulation of follicle-stimulating hormone secretion] GO:0046982 [protein heterodimerization activity] GO:0048589 [developmental growth] GO:0048663 [neuron fate commitment] GO:0048729 [tissue morphogenesis] GO:0048733 [sebaceous gland development] GO:0048859 [formation of anatomical boundary] GO:0051098 [regulation of binding] GO:0051571 [positive regulation of histone H3-K4 methylation] GO:0051797 [regulation of hair follicle development] GO:0060021 [palate development] GO:0060065 [uterus development] GO:0060391 [positive regulation of SMAD protein import into nucleus] GO:0060395 [SMAD protein signal transduction] GO:0060412 [ventricular septum morphogenesis] GO:0060548 [negative regulation of cell death] GO:0060956 [endocardial cell differentiation] GO:0061040 [female gonad morphogenesis] GO:0070102 [interleukin-6-mediated signaling pathway] GO:0070373 [negative regulation of ERK1 and ERK2 cascade] GO:0070411 [I-SMAD binding] GO:0070412 [R-SMAD binding] GO:0071141 [SMAD protein complex] GO:0071559 [response to transforming growth factor beta] GO:0071773 [cellular response to BMP stimulus] GO:0072133 [metanephric mesenchyme morphogenesis] GO:0072134 [nephrogenic mesenchyme morphogenesis] GO:0072520 [seminiferous tubule development] GO:0090575 [RNA polymerase II transcription factor complex] GO:1901522 [positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus] GO:1905305 [negative regulation of cardiac myofibril assembly] GO:2000617 [positive regulation of histone H3-K9 acetylation]
The Human Protein Atlas project is funded
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