Smad6 SMAD family member 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Smad6provided by MGI
Official Full Name: SMAD family member 6provided by MGI
Primary source: MGI:MGI:1336883
See related: Ensembl:ENSMUSG00000036867 AllianceGenome:MGI:1336883
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Madh6; b2b390Clo
Summary: Predicted to enable several functions, including SMAD binding activity; signaling receptor binding activity; and transcription regulator inhibitor activity. Involved in heart development; negative regulation of ossification; and positive regulation of pri-miRNA transcription by RNA polymerase II. Acts upstream of or within circulatory system development and ureteric bud development. Predicted to be located in Golgi apparatus; cytosol; and nuclear body. Predicted to be part of heteromeric SMAD protein complex. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; heart; and sensory organ. Human ortholog(s) of this gene implicated in aortic valve disease 2; craniosynostosis; and radioulnar synostosis. Orthologous to human SMAD6 (SMAD family member 6). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in lung adult (RPKM 141.3), stomach adult (RPKM 37.6) and 11 other tissues See more
Orthologs: human all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 9; 9 C

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (63860358..63929374, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (63953076..64022085, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Nuclear IL-33/SMAD signaling axis promotes cancer development in chronic inflammation.
Title: Nuclear IL-33/SMAD signaling axis promotes cancer development in chronic inflammation.
A complex form of acute rheumatic heart disease with tissue hardening is seen in the absence of either Smad-6 (or NKX2-5).
Title: Functional role of NKX2-5 and Smad6 expression in developing rheumatic heart disease.
These results indicate that PRIP is implicated in BMP-induced osteoblast differentiation by the negative regulation of Smad phosphorylation, through the methylation of inhibitory Smad6
Title: Involvement of PRIP (Phospholipase C-Related But Catalytically Inactive Protein) in BMP-Induced Smad Signaling in Osteoblast Differentiation.
These findings suggest that TNF-alpha induces valvular and vascular cell calcification, in part, by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6.
Title: Protective Role of Smad6 in Inflammation-Induced Valvular Cell Calcification.
The Smad6 is a novel target of Arkadia, and that Arkadia positively regulates BMP signalling via degradation of Smad6, Smad7 and c-Ski/SnoN.
Title: Arkadia enhances BMP signalling through ubiquitylation and degradation of Smad6.
Smad6 inhibits non-canonical TGF-beta1 signaling by recruiting the deubiquitinase A20 to TRAF6.
Title: Smad6 inhibits non-canonical TGF-β1 signalling by recruiting the deubiquitinase A20 to TRAF6.
monoubiquitinated SMAD6 impairs the binding affinity of non-modified SMAD6 to the BMP type I receptor. Moreover, UBE2O and SMAD6 cooperated in the regulation of BMP7-induced adipogenesis
Title: Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6.
Hepcidin, Smad6 and Smad7 mRNA expression is coordinated in a way that it correlates with the activity of the Bmp/Smad signaling pathway.
Title: Smad6 and Smad7 are co-regulated with hepcidin in mouse models of iron overload.
Sema7A positively regulates the production of transforming growth factor (TGF)-beta1 and Smad6 to facilitate West Nile virus pathogenesis in mice.
Title: Semaphorin 7A contributes to West Nile virus pathogenesis through TGF-β1/Smad6 signaling.
Results indicate that peptidyl-prolyl isomerase Pin1 Associates with Smad3 and Smad6.
Title: Pin1 protein regulates Smad protein signaling and pulmonary fibrosis.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Variation

Go to the top of the page Help

Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1)
Targeted (1) 1 citation
Chemically induced (ENU) (1)
Endonuclease-mediated (1)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

Smad6 (e-PCR), detects polymorphism
- UniSTS:516410

Smad6 (e-PCR), detects polymorphism
- UniSTS:516411

D9Mit144 (e-PCR), detects polymorphism
- UniSTS:131696

D9Mit144.2 (e-PCR), detects polymorphism
- UniSTS:131697

Smad5 (e-PCR), detects polymorphism
- UniSTS:466573

NoName (e-PCR)
- UniSTS:548550

Homology

Homologs of the Smad6 gene: The Smad6 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 499 organisms have orthologs with human gene Smad6
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables I-SMAD binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables I-SMAD binding	ISO Inferred from Sequence Orthology more info
enables R-SMAD binding	ISO Inferred from Sequence Orthology more info
enables chromatin binding	ISO Inferred from Sequence Orthology more info
enables co-SMAD binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info
enables transcription regulator inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables transcription regulator inhibitor activity	ISO Inferred from Sequence Orthology more info
enables type I activin receptor binding	ISO Inferred from Sequence Orthology more info
enables type I transforming growth factor beta receptor binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in BMP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in BMP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in SMAD protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in anatomical structure morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within aorta development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in aortic valve morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in cardiac vascular smooth muscle cell development	TAS Traceable Author Statement more info	PubMed
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cell-substrate adhesion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within coronary vasculature development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in coronary vasculature morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in fat cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within heart valve development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune response	ISO Inferred from Sequence Orthology more info
involved_in mitral valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of BMP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of SMAD protein complex assembly	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ossification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of osteoblast differentiation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of pathway-restricted SMAD protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in outflow tract septum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of miRNA transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of vasoconstriction	TAS Traceable Author Statement more info	PubMed
involved_in pulmonary valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in transforming growth factor beta receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in ureteric bud development	IEP Inferred from Expression Pattern more info	PubMed
involved_in vasoconstriction	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within ventricular septum development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in zygotic specification of dorsal/ventral axis	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
part_of heteromeric SMAD protein complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info	PubMed
part_of transcription regulator complex	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: mothers against decapentaplegic homolog 6

Names: MAD homolog 6; Smad 6; mad homolog 7; mothers against DPP homolog 6

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.

mRNA and Protein(s)

NM_008542.3 → NP_032568.3 mothers against decapentaplegic homolog 6

See identical proteins and their annotated locations for NP_032568.3

Status: VALIDATED

Source sequence(s)

AC114674, AC135672, AI415735, AK046602

Consensus CDS

CCDS23273.1

UniProtKB/Swiss-Prot

O35182, Q9CW62

Related

ENSMUSP00000036285.6, ENSMUST00000041029.6

Conserved Domains (2) summary

cd10493
Location:161 → 274

MH1_SMAD_6; N-terminal Mad Homology 1 (MH1) domain in SMAD6

cd10499
Location:323 → 493

MH2_SMAD_6; C-terminal Mad Homology 2 (MH2) domain in SMAD6

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 109 details...

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

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

63860358..63929374 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006510822.4 → XP_006510885.1 mothers against decapentaplegic homolog 6 isoform X1

See identical proteins and their annotated locations for XP_006510885.1

UniProtKB/Swiss-Prot

O35182, Q9CW62

Conserved Domains (2) summary

cd10493
Location:161 → 274

MH1_SMAD_6; N-terminal Mad Homology 1 (MH1) domain in SMAD6

cd10499
Location:323 → 493

MH2_SMAD_6; C-terminal Mad Homology 2 (MH2) domain in SMAD6