Aliases for SMAD4 Gene
Aliases for SMAD4 Gene
- SMAD Family Member 4 2 3 4 5
- Deletion Target In Pancreatic Carcinoma 4 3 4
- MAD Homolog 4 3 4
- MADH4 3 4
- DPC4 3 4
- MAD, Mothers Against Decapentaplegic Homolog 4 (Drosophila) 2
- Mothers Against Decapentaplegic, Drosophila, Homolog Of, 4 3
- SMAD, Mothers Against DPP Homolog 4 (Drosophila) 2
- Mothers Against Decapentaplegic Homolog 4 3
External Ids for SMAD4 Gene
- HGNC: 6770
- Entrez Gene: 4089
- Ensembl: ENSG00000141646
- OMIM: 600993
- UniProtKB: Q13485
Previous HGNC Symbols for SMAD4 Gene
- MADH4
Previous GeneCards Identifiers for SMAD4 Gene
- GC18P046809
- GC18P046810
- GC18P048556
- GC18P045411
- GC18P048494
Summaries for SMAD4 Gene
-
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]
GeneCards Summary for SMAD4 Gene
SMAD4 (SMAD Family Member 4) is a Protein Coding gene. Diseases associated with SMAD4 include Juvenile Polyposis Syndrome and Myhre Syndrome. Among its related pathways are Ectoderm Differentiation and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is SMAD5.
UniProtKB/Swiss-Prot for SMAD4 Gene
-
In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5-GTCT/AGAC-3) within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
Additional gene information for SMAD4 Gene
- Monarch Initiative
- Search for SMAD4 at DataMed
- Search for SMAD4 at HumanCyc
No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SMAD4 Gene
Genomics for SMAD4 Gene
GeneHancer (GH) Regulatory Elements for SMAD4 Gene
Promoters and enhancers for SMAD4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association
Download GeneHancer data dump
GeneHancers around SMAD4 on UCSC Golden Path with GeneCards custom track
- Top Transcription factor binding sites by QIAGEN in the SMAD4 gene promoter:
Regulatory Element Products
Genomic Locations for SMAD4 Gene
Genomic Locations for SMAD4 Gene
- chr18:51,028,394-51,085,045
- (GRCh38/hg38)
- Size:
- 56,652 bases
- Orientation:
- Plus strand
- chr18:48,494,410-48,611,415
- (GRCh37/hg19)
Genomic View for SMAD4 Gene
Genes around SMAD4 on UCSC Golden Path with GeneCards custom track
- Cytogenetic band:
-
- 18q21.2 by Ensembl
- 18q21.2 by Entrez Gene
- 18q21.2 by HGNC
SMAD4 Gene in genomic location: bands according to
Ensembl, locations according to GeneLoc
(and/or Entrez Gene and/or Ensembl if different)
Genomic Neighborhood
• Exon Structure
• Gene Density
RefSeq DNA sequence for SMAD4 Gene
Proteins for SMAD4 Gene
-
Protein details for SMAD4 Gene (UniProtKB/Swiss-Prot)
- Protein Symbol:
- Q13485-SMAD4_HUMAN
- Recommended name:
- Mothers against decapentaplegic homolog 4
- Protein Accession:
- Q13485
- A8K405
Protein attributes for SMAD4 Gene
- Size:
- 552 amino acids
- Molecular mass:
- 60439 Da
- Quaternary structure:
-
- Found in a complex with SMAD1 and YY1 (By similarity). Interacts with CITED2 (By similarity). Monomer; in the absence of TGF-beta activation. Heterodimer; on TGF-beta activation. Composed of two molecules of a C-terminally phosphorylated R-SMAD molecule, SMAD2 or SMAD3, and one molecule of SMAD4 to form the transcriptional active SMAD2/SMAD3-SMAD4 complex. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Interacts with ZNF423; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with ZNF521; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with USP9X. Interacts (via the MH1 and MH2 domains) with RBPMS. Interacts with WWTR1 (via coiled-coil domain). Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. Interacts with CITED1. Interacts with PDPK1 (via PH domain) (By similarity). Interacts with VPS39; this interaction affects heterodimer formation with SMAD3, but not with SMAD2, and leads to inhibition of SMAD3-dependent transcription activation. Interactions with VPS39 and SMAD2 may be mutually exclusive. Interacts with ZC3H3 (By similarity). Interacts (via MH2 domain) with ZNF451 (via N-terminal zinc-finger domains) (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts weakly with ZNF8 (PubMed:12370310). Interacts with NUP93 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (PubMed:26878725). Interacts with CREB3L1, the interaction takes place upon TGFB1 induction and SMAD4 acts as CREB3L1 coactivator to induce the expression of genes involved in the assembly of collagen extracellular matrix (PubMed:25310401). Interacts with DLX1 (PubMed:14671321).
Protein Expression for SMAD4 Gene
Post-translational modifications for SMAD4 Gene
- Monoubiquitinated on Lys-519 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiquitination by USP9X restores its competence to mediate TGF-beta signaling.
- Phosphorylated by PDPK1.
- Ubiquitination at isoforms=113 and isoforms=519
Other Protein References for SMAD4 Gene
- ENSEMBL proteins:
- REFSEQ proteins:
Antibody Products
- R&D Systems Antibodies for SMAD4 (Smad4)
- Cell Signaling Technology (CST) Antibodies for SMAD4 (SMAD4)
-
Custom Antibody ServicesOriGene Antibodies for SMAD4
- Novus Biologicals Antibodies for SMAD4
-
Abcam antibodies for SMAD4
-
Cloud-Clone Corp. Antibodies for SMAD4
- Invitrogen Antibodies for SMAD4
- GeneTex SMAD4 antibody for SMAD4
-
Santa Cruz Biotechnology (SCBT) Antibodies for SMAD4
Protein Products
-
OriGene Purified Proteins for SMAD4
- Search Origene for MassSpec and Protein Over-expression Lysates for SMAD4
- Origene Custom Protein Services for SMAD4
- ProSpec Recombinant Proteins for SMAD4
-
Cloud-Clone Corp. Proteins for SMAD4
- Search GeneTex for Proteins for SMAD4
-
ProSci Proteins for SMAD4
-
Abcam proteins for SMAD4
Assay Products
-
Cloud-Clone Corp. Assay Kits for SMAD4
-
Abcam assays for SMAD4
No data available for DME Specific Peptides for SMAD4 Gene
Domains & Families for SMAD4 Gene
Gene Families for SMAD4 Gene
- HGNC:
- Human Protein Atlas (HPA):
-
- Cancer-related genes
- Disease related genes
- Predicted intracellular proteins
- Transcription factors
Protein Domains for SMAD4 Gene
- InterPro:
- Blocks:
- ProtoNet:
Suggested Antigen Peptide Sequences for SMAD4 Gene
- GenScript: Design optimal peptide antigens:
Graphical View of Domain Structure for InterPro Entry
Q13485UniProtKB/Swiss-Prot:
SMAD4_HUMAN :- The MH1 domain is required for DNA binding.
- Belongs to the dwarfin/SMAD family.
- Domain:
-
- The MH1 domain is required for DNA binding.
- The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.
- Family:
-
- Belongs to the dwarfin/SMAD family.
Function for SMAD4 Gene
Molecular function for SMAD4 Gene
- UniProtKB/Swiss-Prot Function:
- In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5-GTCT/AGAC-3) within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
Phenotypes From GWAS Catalog for SMAD4 Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000977 | RNA polymerase II regulatory region sequence-specific DNA binding | IEA | -- |
| GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IDA | 9389648 |
| GO:0000987 | proximal promoter sequence-specific DNA binding | IDA | 18832382 |
| GO:0000988 | contributes_to transcription factor activity, protein binding | IDA | 18832382 |
| GO:0001076 | transcription factor activity, RNA polymerase II transcription factor binding | IEA | -- |
Phenotypes for SMAD4 Gene
- MGI mutant phenotypes for SMAD4:
-
inferred from 18 alleles
- nervous system phenotype
- normal phenotype
- homeostasis/metabolism phenotype
- muscle phenotype
- cardiovascular system phenotype
- mortality/aging
- immune system phenotype
- cellular phenotype
- behavior/neurological phenotype
- growth/size/body region phenotype
- neoplasm
- digestive/alimentary phenotype
- endocrine/exocrine gland phenotype
- reproductive system phenotype
- integument phenotype
- embryo phenotype
- hematopoietic system phenotype
- skeleton phenotype
- renal/urinary system phenotype
- liver/biliary system phenotype
- craniofacial phenotype
- limbs/digits/tail phenotype
- GenomeRNAi human phenotypes for SMAD4:
-
- Increased vaccinia virus (VACV) infection
- Decreased viability in esophageal squamous lineage
- Increased shRNA abundance (Z-score > 2)
- Increased G1 DNA content
- G0/1 arrest
- Increased transcriptional activity
- Decreased shRNA abundance (Z-score < -2)
- Increased mitotic index
- Upregulation of Wnt/beta-catenin pathway after WNT3A stimulation
- Increased Nanog expression
- Downregulation of NFkappaB pathway
- Synthetic lethal with gemcitabine
- Decreased sensitivity to paclitaxel
Animal Models for SMAD4 Gene
Animal Model Products
- Taconic Biosciences: Generate A Custom CRISPR Mouse Model For Your Study
- Cyagen custom Knockout/knockin (KOKI) mouse models for SMAD4
-
-
ViGene Biosciences lentiviral particle packaged cDNA for SMAD4 gene
-
ViGene Biosciences ready-to-package AAV shRNAs for SMAD4 gene
- Search ViGene Biosciences for SMAD4
CRISPR Products
-
OriGene CRISPR knockouts for SMAD4
- genomics-online: gRNA clones - Search results for 98 available SMAD4 gene related products
- Overview of 98 available SMAD4 gene related products
- Applied Biological Materials CRISPR for SMAD4
-
Vectors and viruses for KO, Activation, Repression, and more
-
Santa Cruz Biotechnology (SCBT) CRISPR for SMAD4
- GenScript: Design CRISPR guide RNA sequences for SMAD4
miRNA for SMAD4 Gene
- miRTarBase miRNAs that target SMAD4
-
- hsa-mir-26a-5p (MIRT003803)
- hsa-mir-483-3p (MIRT004118)
- hsa-mir-18a-5p (MIRT004736)
- hsa-mir-17-5p (MIRT005629)
- hsa-mir-19a-3p (MIRT005630)
- hsa-mir-20a-5p (MIRT005631)
- hsa-mir-92a-3p (MIRT005632)
- hsa-mir-203a-3p (MIRT006038)
- hsa-mir-421 (MIRT006190)
- hsa-mir-146a-5p (MIRT006209)
- hsa-mir-224-5p (MIRT006527)
- hsa-mir-125a-5p (MIRT006809)
- hsa-mir-125b-5p (MIRT006810)
- hsa-mir-199a-5p (MIRT007013)
- hsa-mir-130a-3p (MIRT007144)
- hsa-mir-301a-3p (MIRT007250)
- hsa-mir-454-3p (MIRT007251)
- hsa-mir-182-5p (MIRT007306)
- hsa-mir-130b-3p (MIRT020189)
- hsa-mir-155-5p (MIRT020774)
- hsa-mir-186-5p (MIRT021160)
- hsa-mir-93-5p (MIRT028004)
- hsa-mir-19b-3p (MIRT031156)
- hsa-mir-204-5p (MIRT053029)
- hsa-mir-1260b (MIRT053328)
- hsa-mir-205-5p (MIRT053378)
- hsa-mir-452-5p (MIRT053460)
- hsa-mir-145-5p (MIRT053653)
- hsa-mir-183-5p (MIRT054867)
- hsa-mir-106a-5p (MIRT080224)
- hsa-mir-106b-5p (MIRT080225)
- hsa-mir-20b-5p (MIRT080226)
- hsa-mir-519c-3p (MIRT080227)
- hsa-mir-526b-3p (MIRT080228)
- hsa-mir-519b-3p (MIRT080229)
- hsa-mir-519d-3p (MIRT080230)
- hsa-mir-519a-3p (MIRT080231)
- hsa-mir-551b-5p (MIRT080232)
- hsa-mir-548c-3p (MIRT080233)
- hsa-mir-301b-3p (MIRT080234)
- hsa-mir-548f-5p (MIRT080235)
- hsa-mir-548g-5p (MIRT080236)
- hsa-mir-548t-5p (MIRT080237)
- hsa-mir-548x-5p (MIRT080238)
- hsa-mir-4295 (MIRT080239)
- hsa-mir-3666 (MIRT080240)
- hsa-mir-548aj-5p (MIRT080241)
- hsa-mir-548aw (MIRT080243)
- hsa-mir-548az-5p (MIRT080244)
- hsa-mir-6715b-3p (MIRT080245)
- hsa-mir-4528 (MIRT198909)
- hsa-mir-34a-5p (MIRT198918)
- hsa-mir-154-5p (MIRT198919)
- hsa-mir-34c-5p (MIRT198920)
- hsa-mir-449a (MIRT198921)
- hsa-mir-449b-5p (MIRT198922)
- hsa-mir-8062 (MIRT198927)
- hsa-mir-4668-5p (MIRT346455)
- hsa-mir-1468-3p (MIRT508703)
- hsa-mir-302a-5p (MIRT508704)
- hsa-mir-616-5p (MIRT508705)
- hsa-mir-373-5p (MIRT508706)
- hsa-mir-371b-5p (MIRT508707)
- hsa-mir-888-5p (MIRT508708)
- hsa-mir-6715a-3p (MIRT554140)
- hsa-mir-5701 (MIRT565564)
- hsa-mir-616-3p (MIRT565565)
- hsa-mir-548au-3p (MIRT565566)
- hsa-mir-8076 (MIRT565567)
- hsa-mir-670-3p (MIRT653369)
- hsa-mir-4799-5p (MIRT653370)
- hsa-mir-27b-3p (MIRT653371)
- hsa-mir-27a-3p (MIRT653372)
- hsa-mir-513a-5p (MIRT653373)
- hsa-mir-6731-3p (MIRT653374)
- hsa-mir-6891-3p (MIRT653375)
- hsa-mir-6072 (MIRT653376)
- hsa-mir-5582-3p (MIRT653377)
- hsa-mir-144-3p (MIRT731606)
- hsa-mir-574-3p (MIRT731875)
- hsa-mir-34a-3p (MIRT732323)
- hsa-mir-31-5p (MIRT733127)
- hsa-mir-144-5p (MIRT735483)
- hsa-mir-3661 (MIRT785060)
- hsa-mir-4783-5p (MIRT786756)
- hsa-mir-574-5p (MIRT787882)
- hsa-mir-631 (MIRT788162)
- hsa-mir-6867-5p (MIRT789220)
- hsa-mir-933 (MIRT789963)
Targeted motifs for SMAD4 Gene
HOMER Transcription Factor Regulatory Elements motif SMAD4
- Consensus sequence: VBSYGTCTGG Submotif: canonical Cell Type: ESC GEO ID: GSE29422
miRNA Products
- Search ViGene Biosciences for SMAD4
Inhibitory RNA Products
- Origene RNAi, shrna, and sirna products in human, mouse, rat for SMAD4
- Browse OriGene Inhibitory RNA Products For SMAD4
- genomics-online: shRNA clones - Search results for 98 available SMAD4 gene related products
- Overview of 98 available SMAD4 gene related products
-
ViGene Biosciences ready-to-package AAV shRNAs for SMAD4 gene
Clone Products
- Sino Biological Human cDNA Clone for SMAD4
- Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat
- VectorBuilder custom plasmid, inducible vectors for SMAD4
- VectorBuilder custom lentivirus, adenovirus, AAV vector/virus packaging for SMAD4
-
VectorBuilder Other custom vectors
- Mammalian expression: PiggyBac
- Mammalian Tet-on expression: plasmid
- Mammalian conditional (Cre-Lox): plasmid and PiggyBac
- Mammalian shRNA knockdown: lentiviral, adenoviral, AAV, and PiggyBac
- CRISPR: plasmid gRNA, lentiviral gRNA, and donor plasmid
- Bacterial expression: pET, pBAD, and pCS
- Yeast expression
- Addgene plasmids for SMAD4
- Applied Biological Materials Clones for SMAD4
-
Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more
Cell Line Products
-
Horizon Cell Lines for SMAD4
-
ViGene Biosciences adenoviral particle packaged cDNA for SMAD4 gene
-
ViGene Biosciences lentiviral particle packaged cDNA for SMAD4 gene
-
ViGene Biosciences ready-to-package AAV shRNAs for SMAD4 gene
No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targets for SMAD4 Gene
Localization for SMAD4 Gene
Subcellular locations from UniProtKB/Swiss-Prot for SMAD4 Gene
- Cytoplasm. Nucleus. Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD (PubMed:15799969). PDPK1 prevents its nuclear translocation in response to TGF-beta (PubMed:17327236). {ECO:0000269 PubMed:15799969, ECO:0000269 PubMed:17327236}.
| Compartment | Confidence |
|---|---|
| cytoskeleton | 5 |
| nucleus | 5 |
| cytosol | 5 |
| extracellular | 3 |
| plasma membrane | 2 |
- Cytosol (3)
- Nucleoplasm (3)
- Centrosome (2)
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000790 | nuclear chromatin | IDA | 21828274 |
| GO:0005622 | intracellular | IEA | -- |
| GO:0005634 | nucleus | IEA,IDA | 9311995 |
| GO:0005654 | nucleoplasm | TAS | -- |
| GO:0005667 | transcription factor complex | IPI | 12374795 |
Pathways & Interactions for SMAD4 Gene
| SuperPathway | Contained pathways | ||
|---|---|---|---|
| 1 | SMAD2/3 MH2 Domain Mutants in Cancer | ||
| 2 | Transcriptional activity of SMAD2/SMAD3-SMAD4 heterotrimer | ||
| 3 | TGF-Beta Pathway |
.60
.57
|
.51
|
| 4 | Signaling by BMP |
.33
|
|
| 5 | Cell cycle |
.58
|
.58
|
Pathways by source for SMAD4 Gene
2 GeneTex pathways for SMAD4 Gene
1 Cell Signaling Technology pathway for SMAD4 Gene
29 BioSystems pathways for SMAD4 Gene
24 Reactome pathways for SMAD4 Gene
18 KEGG pathways for SMAD4 Gene
7 GeneGo (Thomson Reuters) pathways for SMAD4 Gene
2 R&D Systems pathways for SMAD4 Gene
Interacting Proteins for SMAD4 Gene
Selected Interacting proteins:
Q13485-SMAD4_HUMAN
ENSP00000341551
for SMAD4 Gene via
MINT
STRING
IID
UniProtKB
SIGNOR curated interactions for SMAD4 Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000122 | negative regulation of transcription by RNA polymerase II | TAS | -- |
| GO:0001541 | ovarian follicle development | IEA | -- |
| GO:0001658 | branching involved in ureteric bud morphogenesis | IEA | -- |
| GO:0001666 | response to hypoxia | IMP | 12411310 |
| GO:0001701 | in utero embryonic development | IEA | -- |
Drugs & Compounds for SMAD4 Gene
| Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
|---|---|---|---|---|---|---|
| Capecitabine | Approved, Investigational | Pharma | RNA processing inhibitor and thymidylate synthase inhibitor, F-pyrimidines | 1402 | ||
| Gemcitabine | Approved | Pharma | Ribonucleotide reductase and DNA synthesis inhibitor, Nucleoside Analogs | 2100 | ||
| Paclitaxel | Approved, Vet_approved | Pharma | Tubulin and Bcl2 inhibitor, Taxanes | 3027 | ||
| Pirfenidone | Approved, Investigational | Pharma | TGF-β production inhibitor, Antifibrotic agent; regulates cytokine levels in vivo | 65 | ||
| Albumin-Bound Paclitaxel | Pharma | 3027 |
| Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
|---|
(4) ApexBio Compounds for SMAD4 Gene
| Compound | Action | Cas Number |
|---|---|---|
| LDN193189 Hydrochloride | ALK inhibitor,potent and selective | 1062368-62-0 |
| LY364947 | 396129-53-6 | |
| Pirfenidone | TGF-β production inhibitor | 53179-13-8 |
| RepSox | ALK5 inhibitor,potent and selective | 446859-33-2 |
Transcripts for SMAD4 Gene
mRNA/cDNA for SMAD4 Gene
- (1) REFSEQ mRNAs :
- (5) Additional mRNA sequences :
- (272) Selected AceView cDNA sequences:
- (17) Ensembl transcripts including schematic representations, and UCSC links where relevant :
CRISPR Products
-
OriGene CRISPR knockouts for SMAD4
- genomics-online: gRNA clones - Search results for 98 available SMAD4 gene related products
- Overview of 98 available SMAD4 gene related products
- Applied Biological Materials CRISPR for SMAD4
-
Vectors and viruses for KO, Activation, Repression, and more
-
Santa Cruz Biotechnology (SCBT) CRISPR for SMAD4
- GenScript: Design CRISPR guide RNA sequences for SMAD4
miRNA Products
- Search ViGene Biosciences for SMAD4
Inhibitory RNA Products
- Origene RNAi, shrna, and sirna products in human, mouse, rat for SMAD4
- Browse OriGene Inhibitory RNA Products For SMAD4
- genomics-online: shRNA clones - Search results for 98 available SMAD4 gene related products
- Overview of 98 available SMAD4 gene related products
-
ViGene Biosciences ready-to-package AAV shRNAs for SMAD4 gene
Clone Products
- Sino Biological Human cDNA Clone for SMAD4
- Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat
- VectorBuilder custom plasmid, inducible vectors for SMAD4
- VectorBuilder custom lentivirus, adenovirus, AAV vector/virus packaging for SMAD4
-
VectorBuilder Other custom vectors
- Mammalian expression: PiggyBac
- Mammalian Tet-on expression: plasmid
- Mammalian conditional (Cre-Lox): plasmid and PiggyBac
- Mammalian shRNA knockdown: lentiviral, adenoviral, AAV, and PiggyBac
- CRISPR: plasmid gRNA, lentiviral gRNA, and donor plasmid
- Bacterial expression: pET, pBAD, and pCS
- Yeast expression
- Addgene plasmids for SMAD4
- Applied Biological Materials Clones for SMAD4
-
Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more
| ExUns: | 1 | ^ | 2 | ^ | 3a | · | 3b | ^ | 4 | ^ | 5 | ^ | 6a | · | 6b | · | 6c | ^ | 7a | · | 7b | · | 7c | ^ | 8a | · | 8b | ^ | 9a | · | 9b | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14a | · | 14b | ^ | 15 | ^ | 16 | ^ | 17 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SP1: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
| SP2: | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
| SP3: | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||
| SP4: | |||||||||||||||||||||||||||||||||||||||||||||||||
| SP5: | |||||||||||||||||||||||||||||||||||||||||||||||||
| SP6: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
| SP7: | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
| SP8: | - | ||||||||||||||||||||||||||||||||||||||||||||||||
| SP9: | |||||||||||||||||||||||||||||||||||||||||||||||||
| SP10: | - | - |
Expression for SMAD4 Gene
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery
-
Neural Crest (Gastrulation Derivatives)
- Cardiac Neural Crest Cells Branchial Arch 3,4,6
- Neural Crest Outflow Tract Cells Outflow Tract
-
Primitive Streak (Early Embryo)
- Extraembryonic Mural Cells Extraembryonic Mesoderm
- Primitive Streak Cells Anterior Primitive Streak
-
Epiblast (Early Embryo)
- Extraembryonic Mural Cells Extraembryonic Mesoderm
- Primitive Streak Cells Anterior Primitive Streak
-
Head Mesenchyme (Muscoskeletal System)
- Cardiac Neural Crest Cells Branchial Arch 3,4,6
- Brain (Nervous System)
-
Extraembryonic Mesoderm (Extraembryonic Tissues)
- Extraembryonic Mural Cells Extraembryonic Mesoderm
-
Heart (Cardiovascular System)
- Neural Crest Outflow Tract Cells Outflow Tract
-
Ovary (Reproductive System)
-
Thyroid (Endocrine System)
-
Prostate (Endocrine System)
-
Uterus (Reproductive System)
This gene is overexpressed in Ovary (12.2), Liver (7.3), and Peripheral blood mononuclear cells (6.5).
Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SMAD4 Gene
- Elite partner
NURSA nuclear receptor signaling pathways regulating expression of SMAD4 Gene:
SMAD4SOURCE GeneReport for Unigene cluster for SMAD4 Gene:
Hs.75862Evidence on tissue expression from TISSUES for SMAD4 Gene
- Nervous system(4.8)
- Liver(4.6)
- Muscle(4.5)
- Intestine(3.2)
- Lung(2.9)
- Pancreas(2.9)
- Lymph node(2.6)
- Heart(2.5)
- Kidney(2.5)
- Skin(2.5)
- Stomach(2.5)
- Thyroid gland(2.3)
- Blood(2.1)
- Gall bladder(2.1)
Phenotype-based relationships between genes and organs from Gene ORGANizer for SMAD4 Gene
Germ Layers:
- ectoderm
- endoderm
- mesoderm
Systems:
- cardiovascular
- digestive
- endocrine
- immune
- integumentary
- nervous
- reproductive
- respiratory
- skeletal muscle
- skeleton
- urinary
Regions:
Head and neck:
- brain
- cheek
- cranial nerve
- ear
- epiglottis
- eye
- eyelid
- face
- forehead
- head
- jaw
- larynx
- lip
- mandible
- maxilla
- mouth
- neck
- nose
- outer ear
- salivary gland
- skull
- tongue
- tooth
- vocal cord
Thorax:
- aorta
- breast
- chest wall
- clavicle
- esophagus
- heart
- heart valve
- lung
- rib
- rib cage
- trachea
Abdomen:
- appendix
- duodenum
- intestine
- kidney
- large intestine
- liver
- pancreas
- small intestine
- spleen
- stomach
Pelvis:
- anus
- pelvis
- rectum
- testicle
Limb:
- ankle
- arm
- digit
- elbow
- femur
- fibula
- finger
- foot
- forearm
- hand
- hip
- humerus
- knee
- lower limb
- nail
- radius
- shin
- shoulder
- thigh
- tibia
- toe
- ulna
- upper limb
- wrist
General:
- blood
- blood vessel
- coagulation system
- hair
- peripheral nerve
- peripheral nervous system
- red blood cell
- skin
- spinal column
- spinal cord
- vertebrae
- white blood cell
Primer Products
-
OriGene qPCR primer pairs for SMAD4
-
OriGene qPCR primer pairs and template standards for SMAD4
No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for SMAD4 Gene
Orthologs for SMAD4 Gene
This gene was present in the common ancestor of animals.
| Organism | Taxonomy | Gene | Similarity | Type | Details |
|---|---|---|---|---|---|
| chimpanzee (Pan troglodytes) |
Mammalia | SMAD4 34 33 |
|
OneToOne | |
| dog (Canis familiaris) |
Mammalia | MADH4 34 |
|
OneToOne | |
| SMAD4 33 |
|
||||
| platypus (Ornithorhynchus anatinus) |
Mammalia | -- 34 |
|
OneToMany | |
| -- 34 |
|
OneToMany | |||
| cow (Bos Taurus) |
Mammalia | SMAD4 33 34 |
|
||
| oppossum (Monodelphis domestica) |
Mammalia | -- 34 |
|
OneToMany | |
| -- 34 |
|
OneToMany | |||
| mouse (Mus musculus) |
Mammalia | Smad4 16 34 33 |
|
||
| rat (Rattus norvegicus) |
Mammalia | Smad4 33 |
|
||
| chicken (Gallus gallus) |
Aves | SMAD7A 34 |
|
ManyToMany | |
| lizard (Anolis carolinensis) |
Reptilia | SMAD4 34 |
|
OneToOne | |
| tropical clawed frog (Silurana tropicalis) |
Amphibia | smad4.1 33 |
|
||
| Str.8149 33 |
|
||||
| African clawed frog (Xenopus laevis) |
Amphibia | Xl.885 33 |
|
||
| zebrafish (Danio rerio) |
Actinopterygii | smad4 34 |
|
OneToMany | |
| SMAD4 (6 of 6) 34 |
|
OneToMany | |||
| SMAD4 (5 of 6) 34 |
|
OneToMany | |||
| zmp:0000000768 33 |
|
||||
| CT955987.1 34 |
|
OneToMany | |||
| SMAD4 (3 of 6) 34 |
|
OneToMany | |||
| SMAD4 (4 of 6) 34 |
|
OneToMany | |||
| madh4 33 |
|
||||
| rainbow trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.2009 33 |
|
||
| fruit fly (Drosophila melanogaster) |
Insecta | Med 33 34 |
|
||
| worm (Caenorhabditis elegans) |
Secernentea | sma-4 34 |
|
OneToOne | |
| sea squirt (Ciona savignyi) |
Ascidiacea | CSA.8788 34 |
|
OneToOne |
- Species where no ortholog for SMAD4 was found in the sources mined by GeneCards:
-
- A. gosspyii yeast (Ashbya gossypii)
- Actinobacteria (Mycobacterium tuberculosis)
- African malaria mosquito (Anopheles gambiae)
- Alicante grape (Vitis vinifera)
- alpha proteobacteria (Wolbachia pipientis)
- amoeba (Dictyostelium discoideum)
- Archea (Pyrococcus horikoshii)
- baker's yeast (Saccharomyces cerevisiae)
- barley (Hordeum vulgare)
- beta proteobacteria (Neisseria meningitidis)
- bread mold (Neurospora crassa)
- Chromalveolata (Phytophthora infestans)
- common water flea (Daphnia pulex)
- corn (Zea mays)
- E. coli (Escherichia coli)
- filamentous fungi (Aspergillus nidulans)
- Firmicute bacteria (Streptococcus pneumoniae)
- fission yeast (Schizosaccharomyces pombe)
- green algae (Chlamydomonas reinhardtii)
- honey bee (Apis mellifera)
- K. lactis yeast (Kluyveromyces lactis)
- loblloly pine (Pinus taeda)
- malaria parasite (Plasmodium falciparum)
- medicago trunc (Medicago Truncatula)
- moss (Physcomitrella patens)
- orangutan (Pongo pygmaeus)
- pig (Sus scrofa)
- rice (Oryza sativa)
- rice blast fungus (Magnaporthe grisea)
- schistosome parasite (Schistosoma mansoni)
- sea anemone (Nematostella vectensis)
- sea urchin (Strongylocentrotus purpuratus)
- sorghum (Sorghum bicolor)
- soybean (Glycine max)
- stem rust fungus (Puccinia graminis)
- sugarcane (Saccharum officinarum)
- thale cress (Arabidopsis thaliana)
- tomato (Lycopersicon esculentum)
- toxoplasmosis (Toxoplasma gondii)
- Trichoplax (Trichoplax adhaerens)
- wheat (Triticum aestivum)
Paralogs for SMAD4 Gene
(5) SIMAP similar genes for SMAD4 Gene using alignment to 13 proteins:
Variants for SMAD4 Gene
| SNP ID | Clin | Chr 18 pos | Variation | AA Info | Type |
|---|---|---|---|---|---|
| rs1010877617 | uncertain-significance, Hereditary cancer-predisposing syndrome | 51,067,038(+) | G/A | coding_sequence_variant, missense_variant | |
| rs1033291618 | uncertain-significance, Myhre syndrome, Juvenile Polyposis, Osler hemorrhagic telangiectasia syndrome | 51,082,310(+) | G/A | 3_prime_UTR_variant | |
| rs10470 | likely-benign, Myhre syndrome, Juvenile Polyposis, Osler hemorrhagic telangiectasia syndrome | 51,079,646(+) | T/C | 3_prime_UTR_variant | |
| rs1051119571 | uncertain-significance, Myhre syndrome, Osler hemorrhagic telangiectasia syndrome, Juvenile Polyposis | 51,030,256(+) | C/G | 5_prime_UTR_variant | |
| rs1053158497 | likely-benign, Juvenile polyposis syndrome | 51,047,206(+) | T/C | coding_sequence_variant, synonymous_variant |
| Variant ID | Type | Subtype | PubMed ID |
|---|---|---|---|
| esv3583062 | CNV | loss | 25503493 |
| esv3342561 | CNV | insertion | 20981092 |
Residual Variation Intolerance Score:
23.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score:
0.54;
11.75% of all genes are more intolerant (likely to be disease-causing)
Additional Variant Information for SMAD4 Gene
No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMAD4 Gene
Disorders for SMAD4 Gene
(43) MalaCards diseases for SMAD4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards
| Disorder | Aliases | PubMed IDs |
|---|---|---|
| juvenile polyposis syndrome |
|
|
| myhre syndrome |
|
|
| juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome |
|
|
| pancreatic cancer |
|
|
| hereditary hemorrhagic telangiectasia |
|
|
Search SMAD4 in MalaCards
View complete list of genes associated with diseases
UniProtKB/Swiss-Prot
SMAD4_HUMAN- Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269 PubMed:16959974}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
- Juvenile polyposis syndrome (JPS) [MIM:174900]: Autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers. {ECO:0000269 PubMed:12417513, ECO:0000269 PubMed:9811934}. Note=The disease is caused by mutations affecting the gene represented in this entry.
- Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT) [MIM:175050]: JP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic etiology of this association is unknown. {ECO:0000269 PubMed:15031030}. Note=The disease is caused by mutations affecting the gene represented in this entry.
- Myhre syndrome (MYHRS) [MIM:139210]: A syndrome characterized by pre- and postnatal growth deficiency, mental retardation, generalized muscle hypertrophy and striking muscular build, decreased joint mobility, cryptorchidism, and unusual facies. Dysmorphic facial features include microcephaly, midface hypoplasia, prognathism, and blepharophimosis. Typical skeletal anomalies are short stature, square body shape, broad ribs, iliac hypoplasia, brachydactyly, flattened vertebrae, and thickened calvaria. Other features, such as congenital heart disease, may also occur. {ECO:0000269 PubMed:22158539, ECO:0000269 PubMed:22243968}. Note=The disease is caused by mutations affecting the gene represented in this entry.
- Note=SMAD4 variants may be associated with susceptibility to pulmonary hypertension, a disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. {ECO:0000269 PubMed:21898662}.
- Pancreatic cancer (PNCA) [MIM:260350]: A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. {ECO:0000269 PubMed:8553070}. Note=The gene represented in this entry may be involved in disease pathogenesis.
Additional Disease Information for SMAD4
- Genetic Association Database
- (GAD)
- Human Genome Epidemiology Navigator
- (HuGE)
- ATLAS of Genetics and Cytogenetics in Oncology and Haematology
No data available for Genatlas for SMAD4 Gene
Publications for SMAD4 Gene
- The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis. (PMID: 18823382) Calva-Cerqueira D … Howe JR (Clinical genetics 2009) 3 22 44 58
- A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). (PMID: 15031030) Gallione CJ … Marchuk DA (Lancet (London, England) 2004) 3 4 22 58
- Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation. (PMID: 11818334) Wan M … Cao X (EMBO reports 2002) 3 4 22 58
- Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. (PMID: 12417513) Sayed MG … Howe JR (Annals of surgical oncology 2002) 3 4 44 58
- Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. (PMID: 9811934) Houlston R … Tomlinson I (Human molecular genetics 1998) 3 4 22 58
Products for SMAD4 Gene
- R&D Systems Antibodies for SMAD4 (Smad4)
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- Invitrogen Antibodies for SMAD4
- Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat
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- Mammalian expression: PiggyBac
- Mammalian Tet-on expression: plasmid
- Mammalian conditional (Cre-Lox): plasmid and PiggyBac
- Mammalian shRNA knockdown: lentiviral, adenoviral, AAV, and PiggyBac
- CRISPR: plasmid gRNA, lentiviral gRNA, and donor plasmid
- Bacterial expression: pET, pBAD, and pCS
- Yeast expression
- Addgene plasmids for SMAD4
- antibodies-online: Search results for 190 available SMAD4 Antibodies ranked by validation data
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- GeneTex SMAD4 antibody for SMAD4
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- ViGene Biosciences adenoviral particle packaged cDNA for SMAD4 gene
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- genomics-online: cdna clones - Search results for 98 available SMAD4 gene related products
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Sources for SMAD4 Gene
- (1) GeneCards
- (2) HGNC
- (3) EntrezGene
- (4) Swiss-Prot
- (5) Ensembl
- (6) OMIM
- (7) GeneLoc
- (8) Gene Wiki
- (9) UCSC
- (10) PhosphoSitePlus
- (11) GO
- (12) TrEMBL
- (13) InterPro
- (14) ProtoNet
- (15) Blocks
- (16) MGI
- (17) IUBMB
- (18) KEGG
- (19) MINT
- (20) STRING
- (21) IntAct
- (22) Novoseek
- (23) PharmGKB
- (24) DrugBank
- (25) HMDB
- (26) UniGene
- (27) AceView
- (28) ASD
- (29) ECgene
- (30) GeneAnnot
- (31) CGAP SAGE
- (32) SOURCE
- (33) HomoloGene
- (34) PanEnsembl
- (35) euGenes
- (36) SGD
- (37) FlyBase
- (38) WormBase
- (39) Pseudogene
- (40) DGV