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SMAD6 SMAD family member 6 [ Homo sapiens (human) ]

Gene ID: 4091, updated on 19-Jul-2014
Official Symbol
SMAD6provided by HGNC
Official Full Name
SMAD family member 6provided by HGNC
Primary source
HGNC:6772
See related
Ensembl:ENSG00000137834; HPRD:04240; MIM:602931; Vega:OTTHUMG00000133218
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
AOVD2; MADH6; MADH7; HsT17432
Summary
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 encoding different isoforms have been found for this gene.[provided by RefSeq, May 2009]
See SMAD6 in Epigenomics, MapViewer
Location:
15q21-q22
Exon count:
6
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 15 NC_000015.10 (66702336..66782000)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (66994674..67074338)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA, C/D box 18A Neighboring gene zwilch kinetochore protein Neighboring gene ribosomal protein L4 Neighboring gene lactase-like Neighboring gene leucine zipper-EF-hand containing transmembrane protein 1, pseudogene 1 Neighboring gene uncharacterized LOC102723481

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Aortic valve disease 2
MedGen: CN143724 OMIM: 614823 GeneReviews: Not available
not available

NHGRI GWAS Catalog

Description
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Tat tat SMAD6 expression and its phosphorylation, in response to bone morphogenetic protein-2 (BMP2) treatment, is downregulated by HIV-1 Tat treatment in the macrophage cell line U937 PubMed

Go to the HIV-1, Human Protein Interaction Database

  • BMP receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
    BMP receptor signaling, organism-specific biosystem
    BMP receptor signaling
  • BMP signalling and regulation, organism-specific biosystem (from WikiPathways)
    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...
  • Endocytosis, organism-specific biosystem (from KEGG)
    Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endocytosis, conserved biosystem (from KEGG)
    Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • 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...
  • 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 BMP, organism-specific biosystem (from REACTOME)
    Signaling by BMP, 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...
  • TGF Beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TGF Beta Signaling Pathway, 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 Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TGF-beta Receptor Signaling Pathway, organism-specific biosystem"The TGF beta receptors TGFBR1 and TGFBR2 belong to a subfamily of membrane-bound serine/threonine kinases which are designated as Type I or II based on their structural and functional properties. Th...
  • 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...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
I-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
R-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
chromatin binding IDA
Inferred from Direct Assay
more info
PubMed 
co-SMAD 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 
sequence-specific DNA binding transcription factor activity IEA
Inferred from Electronic Annotation
more info
 
transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity IDA
Inferred from Direct Assay
more info
PubMed 
transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
type I activin receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
type I transforming growth factor beta receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
BMP signaling pathway IDA
Inferred from Direct Assay
more info
 
BMP signaling pathway TAS
Traceable Author Statement
more info
 
cell-substrate adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
fat cell differentiation IDA
Inferred from Direct Assay
more info
 
immune response IMP
Inferred from Mutant Phenotype
more info
PubMed 
intracellular signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
intracellular signal transduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of BMP signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of SMAD protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of pathway-restricted SMAD protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of pathway-restricted SMAD protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to estrogen IEA
Inferred from Electronic Annotation
more info
 
response to laminar fluid shear stress IEP
Inferred from Expression Pattern
more info
PubMed 
transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
transforming growth factor beta receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
ureteric bud development IEA
Inferred from Electronic Annotation
more info
 
zygotic specification of dorsal/ventral axis IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cytoplasm TAS
Traceable Author Statement
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
protein complex IDA
Inferred from Direct Assay
more info
 
transcription factor complex IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
mothers against decapentaplegic homolog 6
Names
mothers against decapentaplegic homolog 6
SMAD 6
hSMAD6
MAD homolog 6
mothers against DPP homolog 6
SMAD, mothers against DPP homolog 6
Mothers against decapentaplegic, drosophila, homolog of, 6

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_012244.1 

    Range
    5001..84665
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001142861.2NP_001136333.1  mothers against decapentaplegic homolog 6 isoform 2

    See proteins identical to NP_001136333.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant uses a different exon at the 5' terminus, compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus with a truncated Mad homolog (MH)-1 domain, compared to isoform 1. The variant is also known as SMAD6s.
    Source sequence(s)
    AC013564, CN314453, U59914
    Consensus CDS
    CCDS45287.1
    UniProtKB/Swiss-Prot
    O43541
    Related
    ENSP00000345054, ENST00000338426
    Conserved Domains (1) summary
    cd10499
    Location:61233
    Blast Score: 966
    MH2_SMAD_6; C-terminal Mad Homology 2 (MH2) domain in SMAD6
  2. NM_005585.4NP_005576.3  mothers against decapentaplegic homolog 6 isoform 1

    See proteins identical to NP_005576.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AF035528, BC012986, BC029288, CA406301, CN314453, CN314455, U59914
    Consensus CDS
    CCDS10221.1
    UniProtKB/Swiss-Prot
    O43541
    Related
    ENSP00000288840, OTTHUMP00000164291, ENST00000288840, OTTHUMT00000256953
    Conserved Domains (2) summary
    cd10493
    Location:160273
    Blast Score: 518
    MH1_SMAD_6; N-terminal Mad Homology 1 (MH1) domain in SMAD6
    cd10499
    Location:322494
    Blast Score: 972
    MH2_SMAD_6; C-terminal Mad Homology 2 (MH2) domain in SMAD6

RNA

  1. NR_027654.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), also known as SMAD6B, includes an alternate exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF035528, AM909653, BC029288, CA406301, CN314453, CN314455, U59914

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000015.10 

    Range
    66702336..66782000
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000147.1 

    Range
    43830247..43909482
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018926.2 

    Range
    67112770..67192414
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)