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Aliases for SMAD6 Gene

Aliases for SMAD6 Gene

  • SMAD Family Member 6 2 3 4
  • MADH6 3 4 6
  • MAD Homolog 6 3 4
  • AOVD2 3 6
  • MAD, Mothers Against Decapentaplegic Homolog 6 (Drosophila) 2
  • Mothers Against Decapentaplegic, Drosophila, Homolog Of, 6 3
  • SMAD, Mothers Against DPP Homolog 6 (Drosophila) 2
  • Mothers Against Decapentaplegic Homolog 6 3
  • SMAD, Mothers Against DPP Homolog 6 3
  • Mothers Against DPP Homolog 6 4
  • HsT17432 3
  • SMAD 6 4
  • HSMAD6 4
  • MADH7 3
  • Smad6 4

External Ids for SMAD6 Gene

Previous HGNC Symbols for SMAD6 Gene

  • MADH7
  • MADH6

Previous GeneCards Identifiers for SMAD6 Gene

  • GC15P064681
  • GC15P064781
  • GC15P066994
  • GC15P043830

Summaries for SMAD6 Gene

Entrez Gene Summary for SMAD6 Gene

  • The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]

GeneCards Summary for SMAD6 Gene

SMAD6 (SMAD Family Member 6) is a Protein Coding gene. Diseases associated with SMAD6 include aortic valve disease 2 and familial bicuspid aortic valve. Among its related pathways are Signaling by GPCR and ERK Signaling. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and transcription regulatory region DNA binding. An important paralog of this gene is SMAD1.

UniProtKB/Swiss-Prot for SMAD6 Gene

  • Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions.

Gene Wiki entry for SMAD6 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SMAD6 Gene

Genomics for SMAD6 Gene

Regulatory Elements for SMAD6 Gene

Transcription factor binding sites by QIAGEN in the SMAD6 gene promoter:

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for SMAD6 Gene

Start:
66,702,228 bp from pter
End:
66,782,848 bp from pter
Size:
80,621 bases
Orientation:
Plus strand

Genomic View for SMAD6 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SMAD6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMAD6 Gene

Proteins for SMAD6 Gene

  • Protein details for SMAD6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43541-SMAD6_HUMAN
    Recommended name:
    Mothers against decapentaplegic homolog 6
    Protein Accession:
    O43541
    Secondary Accessions:
    • A9J6M5
    • O43654
    • Q15799
    • Q7Z7L4
    • Q96E31
    • Q9UKZ3

    Protein attributes for SMAD6 Gene

    Size:
    496 amino acids
    Molecular mass:
    53497 Da
    Quaternary structure:
    • Interacts with NEDD4L (By similarity). Interacts with WWP1 (By similarity). Interacts with STAMBP and PRKX. Interacts with RNF111 and AXIN1. Interacts with TGF-beta type I receptor superfamily members, including ACVR1B, BMPR1B and TGFBR1. In response to BMP2, but not to TGFB treatment, interacts with SMAD1, but not with SMAD2, nor with SMAD4; this interaction may inhibit SMAD1 binding to SMAD4. Interacts with HOXC8 and HOXC9. Interacts with PELI1; this interaction interferes with PELI1 complex formation with TRAF6, IRAK1, IRAK4 and MYD88 in response to IL1B and hence negatively regulates IL1R-TLR signaling.

    Alternative splice isoforms for SMAD6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SMAD6 Gene

Proteomics data for SMAD6 Gene at MOPED

Post-translational modifications for SMAD6 Gene

  • Arginine methylation by PRMT1, which is recruited by BMPR2, initiates BMP-Induced signaling and induces dissociation from the BMPR1B receptor at the cell surface leading to derepress downstream Smad1/Smad5 signaling.
  • Phosphorylated by BMP type 1 receptor kinase and by PRKX.
  • Ubiquitinated by WWP1 (By similarity). Monoubiquitinated at Lys-173 by the E2/E3 hybrid ubiquitin-protein ligase UBE2O, leading to reduced binding affinity for the activated BMP type I receptor ACVR1/ALK2, thereby enhancing BMP7 and regulating adipocyte differentiation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SMAD6 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for SMAD6 Gene

Domains for SMAD6 Gene

Gene Families for SMAD6 Gene

HGNC:

Suggested Antigen Peptide Sequences for SMAD6 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O43541

UniProtKB/Swiss-Prot:

SMAD6_HUMAN :
  • O43541
Domain:
  • Contains 1 MH1 (MAD homology 1) domain.
  • Contains 1 MH2 (MAD homology 2) domain.
Family:
  • Belongs to the dwarfin/SMAD family.
genes like me logo Genes that share domains with SMAD6: view

Function for SMAD6 Gene

Molecular function for SMAD6 Gene

UniProtKB/Swiss-Prot Function:
Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions.

Gene Ontology (GO) - Molecular Function for SMAD6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA 16491121
GO:0003682 chromatin binding IDA 16491121
GO:0003700 sequence-specific DNA binding transcription factor activity IEA --
GO:0005515 protein binding IPI 11483516
GO:0030617 transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity IMP 19047146
genes like me logo Genes that share ontologies with SMAD6: view
genes like me logo Genes that share phenotypes with SMAD6: view

Animal Model Products

miRNA for SMAD6 Gene

miRTarBase miRNAs that target SMAD6

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SMAD6

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targeting and HOMER Transcription for SMAD6 Gene

Localization for SMAD6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMAD6 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SMAD6 Gene COMPARTMENTS Subcellular localization image for SMAD6 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 2
extracellular 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for SMAD6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular --
GO:0005634 nucleus IDA 16491121
GO:0005667 transcription factor complex IEA --
GO:0005737 cytoplasm TAS 19018011
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with SMAD6: view

Pathways for SMAD6 Gene

genes like me logo Genes that share pathways with SMAD6: view

PCR Array Products

Gene Ontology (GO) - Biological Process for SMAD6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001657 ureteric bud development IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated --
GO:0006955 immune response IMP 16886151
GO:0007179 transforming growth factor beta receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with SMAD6: view

Compounds for SMAD6 Gene

(4) ApexBio Compounds for SMAD6 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]

(2) Novoseek inferred chemical compound relationships for SMAD6 Gene

Compound -log(P) Hits PubMed IDs
tgf beta1 45.8 1
tyrosine 0 1
genes like me logo Genes that share compounds with SMAD6: view

Transcripts for SMAD6 Gene

Unigene Clusters for SMAD6 Gene

SMAD family member 6:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SMAD6

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SMAD6 Gene

No ASD Table

Relevant External Links for SMAD6 Gene

GeneLoc Exon Structure for
SMAD6
ECgene alternative splicing isoforms for
SMAD6

Expression for SMAD6 Gene

mRNA expression in normal human tissues for SMAD6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SMAD6 Gene

This gene is overexpressed in Heart - Atrial Appendage (5.8) and Lung (4.7).

Protein differential expression in normal tissues for SMAD6 Gene

This gene is overexpressed in Liver (60.5).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SMAD6 Gene

SOURCE GeneReport for Unigene cluster for SMAD6 Gene Hs.153863

mRNA Expression by UniProt/SwissProt for SMAD6 Gene

O43541-SMAD6_HUMAN
Tissue specificity: Ubiquitous in various organs, with higher levels in lung. Isoform B is up-regulated in diseased heart tissue
genes like me logo Genes that share expressions with SMAD6: view

Expression partners for SMAD6 Gene

In Situ Assay Products

Orthologs for SMAD6 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMAD6 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia SMAD6 35
  • 95.36 (n)
  • 95.77 (a)
SMAD6 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SMAD6 35
  • 94.02 (n)
  • 94.35 (a)
SMAD6 36
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Smad6 35
  • 91.12 (n)
  • 93.09 (a)
Smad6 16
Smad6 36
  • 94 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia SMAD6 35
  • 99.26 (n)
  • 99.4 (a)
SMAD6 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Smad6 35
  • 90.9 (n)
  • 93.17 (a)
oppossum
(Monodelphis domestica)
Mammalia SMAD6 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SMAD6 36
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves SMAD6 35
  • 76.97 (n)
  • 79.15 (a)
SMAD6 36
  • 85 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SMAD6 36
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.2540 35
African clawed frog
(Xenopus laevis)
Amphibia Xl.2593 35
zebrafish
(Danio rerio)
Actinopterygii LOC564395 35
  • 67.44 (n)
  • 66.38 (a)
wufk08g05 35
smad6a 36
  • 59 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Dad 36
  • 24 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea daf-3 36
  • 13 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9437 36
  • 33 (a)
OneToMany
Species with no ortholog for SMAD6:
  • 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)
  • rainbow trout (Oncorhynchus mykiss)
  • 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)

Evolution for SMAD6 Gene

ENSEMBL:
Gene Tree for SMAD6 (if available)
TreeFam:
Gene Tree for SMAD6 (if available)

Paralogs for SMAD6 Gene

Paralogs for SMAD6 Gene

Selected SIMAP similar genes for SMAD6 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with SMAD6: view

Variants for SMAD6 Gene

Sequence variations from dbSNP and Humsavar for SMAD6 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type MAF
rs755450 -- 66,742,815(-) CAGTC(C/T)AAGCA intron-variant
rs755451 -- 66,742,613(-) AGAGC(G/T)ACCAA intron-variant
rs755452 -- 66,742,580(-) AGACC(C/T)CATGG intron-variant
rs893900 -- 66,722,190(+) GATCA(C/T)ACCTG intron-variant
rs893901 -- 66,722,392(+) ATCTG(A/G)GTGAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SMAD6 Gene

Variant ID Type Subtype PubMed ID
nsv904325 CNV Loss 21882294
nsv827370 CNV Gain 20364138

Relevant External Links for SMAD6 Gene

HapMap Linkage Disequilibrium report
SMAD6
Human Gene Mutation Database (HGMD)
SMAD6
Locus Specific Mutation Databases (LSDB)
SMAD6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMAD6 Gene

Disorders for SMAD6 Gene

MalaCards: The human disease database

MalaCards: The human disease database.

Search for SMAD6 Gene in MalaCards »

(2) Diseases for SMAD6 Gene including...

(1) OMIM Diseases for SMAD6 Gene (602931)

UniProtKB/Swiss-Prot

SMAD6_HUMAN
  • Aortic valve disease 2 (AOVD2) [MIM:614823]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. {ECO:0000269 PubMed:22275001}. Note=The disease is caused by mutations affecting the gene represented in this entry. SMAD6 variants may contribute to increased risk of congenital cardiovascular malformations (CVM). CVM is a major cause of mortality and morbidity in childhood. In most sporadic cases that cannot be attributed to particular malformation syndromes or teratogenic exposures, there remains a substantial excess familial risk, indicating a significant genetic contribution to disease susceptibility (PubMed:22275001). {ECO:0000269 PubMed:22275001}.

(5) Novoseek inferred disease relationships for SMAD6 Gene

Disease -log(P) Hits PubMed IDs
pancreatic cancer 14.8 1
carcinoma squamous cell 0 2
renal disease 0 1
hepatocellular carcinoma 0 1
tumors 0 2

Relevant External Links for SMAD6

Genetic Association Database (GAD)
SMAD6
Human Genome Epidemiology (HuGE) Navigator
SMAD6
genes like me logo Genes that share disorders with SMAD6: view

No data available for University of Copenhagen DISEASES and Genatlas for SMAD6 Gene

Publications for SMAD6 Gene

  1. Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members. (PMID: 9712726) Afrakhte M. … ten Dijke P. (Biochem. Biophys. Res. Commun. 1998) 3 4 23
  2. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. (PMID: 9256479) Topper J.N. … Falb D. (Proc. Natl. Acad. Sci. U.S.A. 1997) 2 3 23
  3. Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. (PMID: 11483516) Itoh F. … Itoh S. (EMBO J. 2001) 3 4 23
  4. A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. (PMID: 19211612) Shintani M. … Matsuoka R. (J. Med. Genet. 2009) 3 23 48
  5. Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1. (PMID: 16951688) Choi K.C. … Park S.H. (Nat. Immunol. 2006) 3 4 23

Products for SMAD6 Gene

  • Addgene plasmids for SMAD6

Sources for SMAD6 Gene

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