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SMAD7 SMAD family member 7 [ Homo sapiens (human) ]

Gene ID: 4092, updated on 4-Nov-2018

Summary

Official Symbol
SMAD7provided by HGNC
Official Full Name
SMAD family member 7provided by HGNC
Primary source
HGNC:HGNC:6773
See related
Ensembl:ENSG00000101665 MIM:602932; Vega:OTTHUMG00000132655
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
CRCS3; MADH7; MADH8
Summary
The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
Expression
Ubiquitous expression in lung (RPKM 15.3), placenta (RPKM 11.2) and 25 other tissues See more
Orthologs

Genomic context

See SMAD7 in Genome Data Viewer
Location:
18q21.1
Exon count:
5
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 18 NC_000018.10 (48919853..48950711, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (46446223..46477081, complement)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene cap binding complex dependent translation initiation factor Neighboring gene uncharacterized LOC105372106 Neighboring gene uncharacterized LOC105372105 Neighboring gene uncharacterized LOC105372108 Neighboring gene uncharacterized LOC105372109

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Colorectal cancer 3
MedGen: C2677123 OMIM: 612229 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
NHGRI GWA Catalog
A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk.
NHGRI GWA Catalog
Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.
NHGRI GWA Catalog
Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians.
NHGRI GWA Catalog
GWAS of dental caries patterns in the permanent dentition.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
NHGRI GWA Catalog
Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
NHGRI GWA Catalog
Meta-analysis of new genome-wide association studies of colorectal cancer risk.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of SMAD family member 7 (SMAD7) in human B cells PubMed
env HIV-1 gp120-induced apoptosis in human proximal renal tubular cells is significantly enhanced by p300, and Smad7 and an anti-TGF-beta antibody inhibit this effect of p300 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • ALK1 signaling events, organism-specific biosystem (from Pathway Interaction Database)
    ALK1 signaling events, organism-specific biosystem
    ALK1 signaling events
  • Apoptosis-related network due to altered Notch3 in ovarian cancer, organism-specific biosystem (from WikiPathways)
    Apoptosis-related network due to altered Notch3 in ovarian cancer, organism-specific biosystemResults of pathway analysis of apoptosis-related genes in OVCAR3 cells treated with Notch3 siRNA or control siRNA.
  • BMP receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
    BMP receptor signaling, organism-specific biosystem
    BMP receptor signaling
  • Deubiquitination, organism-specific biosystem (from REACTOME)
    Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
  • Downregulation of TGF-beta receptor signaling, organism-specific biosystem (from REACTOME)
    Downregulation of TGF-beta receptor signaling, organism-specific biosystemTGF-beta receptor signaling is downregulated by proteasome and lysosome-mediated degradation of ubiquitinated TGFBR1, SMAD2 and SMAD3, as well as by dephosphorylation of TGFBR1, SMAD2 and SMAD3. In t...
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • Hfe effect on hepcidin production, organism-specific biosystem (from WikiPathways)
    Hfe effect on hepcidin production, organism-specific biosystemnew pathway, converted from mouse WP3673
  • Hippo signaling pathway, organism-specific biosystem (from KEGG)
    Hippo signaling pathway, organism-specific biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
  • Hippo signaling pathway, conserved biosystem (from KEGG)
    Hippo signaling pathway, conserved biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
  • IFN-gamma pathway, organism-specific biosystem (from Pathway Interaction Database)
    IFN-gamma pathway, organism-specific biosystem
    IFN-gamma pathway
  • 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...
  • Lung fibrosis, organism-specific biosystem (from WikiPathways)
    Lung fibrosis, organism-specific biosystemLung fibrosis pathway linked to events (molecular initiating event, key events and associative events) in a putative Adverse Outcome Pathway for lung fibrosis.
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Post-translational protein modification, organism-specific biosystem (from REACTOME)
    Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
  • Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
    Regulation of nuclear SMAD2/3 signaling
  • SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystem (from REACTOME)
    SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystemAfter phosphorylated SMAD2 and/or SMAD3 form a heterotrimer with SMAD4, SMAD2/3:SMAD4 complex translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003). In the nucleus, lin...
  • 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 biosystemBone morphogenetic proteins (BMPs) have many biological activities in various tissues, including bone, cartilage, blood vessels, heart, kidney, neurons, liver and lung. They are members of the Transf...
  • Signaling by TGF-beta Receptor Complex, organism-specific biosystem (from REACTOME)
    Signaling by TGF-beta Receptor Complex, organism-specific biosystemThe TGF-beta/BMP pathway incorporates several signaling pathways that share most, but not all, components of a central signal transduction engine. The general signaling scheme is rather simple: upon ...
  • Signaling events mediated by HDAC Class I, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by HDAC Class I, organism-specific biosystem
    Signaling events mediated by HDAC Class I
  • TGF-beta Receptor Signaling, organism-specific biosystem (from WikiPathways)
    TGF-beta Receptor Signaling, 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 Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TGF-beta Signaling Pathway, organism-specific biosystemThe signal transduction mechanisms underlying the pathophysiological activities of transforming growth factor-? (TGF-?) have been extensively studied since its discovery nearly 30 years ago. TGF-? li...
  • TGF-beta receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
    TGF-beta receptor signaling, organism-specific biosystem
    TGF-beta receptor signaling
  • TGF-beta receptor signaling activates SMADs, organism-specific biosystem (from REACTOME)
    TGF-beta receptor signaling activates SMADs, organism-specific biosystemBinding of transforming growth factor beta 1 (TGF beta 1, i.e. TGFB1) to TGF beta receptor type 2 (TGFBR2) activates TGF beta receptor signaling cascade. TGFB1 is posttranslationally processed by fur...
  • 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...
  • Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystem (from REACTOME)
    Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystemIn the nucleus, SMAD2/3:SMAD4 heterotrimer complex acts as a transcriptional regulator. The activity of SMAD2/3 complex is regulated both positively and negatively by association with other transcrip...
  • UCH proteinases, organism-specific biosystem (from REACTOME)
    UCH proteinases, organism-specific biosystemDUBs of the Ub C-terminal Hydrolase (UCH) family are thiol proteases that have an N-terminal catalytic domain sometimes followed by C-terminal extensions that mediate protein-protein interactions. Hu...
  • Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
    Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ16482

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
I-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
activin binding IPI
Inferred from Physical Interaction
more info
PubMed 
beta-catenin binding IPI
Inferred from Physical Interaction
more info
PubMed 
collagen binding IEA
Inferred from Electronic Annotation
more info
 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
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 
type I transforming growth factor beta receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
BMP signaling pathway TAS
Traceable Author Statement
more info
 
adherens junction assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
artery morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular protein-containing complex localization IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to leukemia inhibitory factor IEA
Inferred from Electronic Annotation
more info
 
cellular response to transforming growth factor beta stimulus 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 DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of T cell cytokine production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of T-helper 17 cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of T-helper 17 type immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of cell migration TAS
Traceable Author Statement
more info
PubMed 
negative regulation of epithelial to mesenchymal transition IC
Inferred by Curator
more info
PubMed 
negative regulation of epithelial to mesenchymal transition TAS
Traceable Author Statement
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 TAS
Traceable Author Statement
more info
PubMed 
negative regulation of peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of peptidyl-threonine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription by competitive promoter binding IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
negative regulation of ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
pathway-restricted SMAD protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cell-cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of proteasomal ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 
protein deubiquitination TAS
Traceable Author Statement
more info
 
protein stabilization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of activin receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cardiac muscle contraction ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of epithelial to mesenchymal transition IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of transforming growth factor beta receptor signaling pathway IC
Inferred by Curator
more info
PubMed 
regulation of ventricular cardiac muscle cell membrane depolarization IC
Inferred by Curator
more info
PubMed 
response to laminar fluid shear stress IEP
Inferred from Expression Pattern
more info
PubMed 
transforming growth factor beta receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
ureteric bud development IEA
Inferred from Electronic Annotation
more info
 
ventricular cardiac muscle tissue morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
ventricular septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
colocalizes_with catenin complex IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with cell-cell adherens junction IDA
Inferred from Direct Assay
more info
PubMed 
centrosome IDA
Inferred from Direct Assay
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
fibrillar center IDA
Inferred from Direct Assay
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 
transcription factor complex IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
mothers against decapentaplegic homolog 7
Names
MAD (mothers against decapentaplegic, Drosophila) homolog 7
MAD homolog 8
Mothers against decapentaplegic, drosophila, homolog of, 7
SMAD, mothers against DPP homolog 7
hSMAD7
mothers against DPP homolog 8

NCBI Reference Sequences (RefSeq)

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_023330.1 RefSeqGene

    Range
    5001..35859
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001190821.1NP_001177750.1  mothers against decapentaplegic homolog 7 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 aa shorter compared to isoform 1.
    Source sequence(s)
    AC114684, AF010193, DA882147
    Consensus CDS
    CCDS59317.1
    UniProtKB/Swiss-Prot
    O15105
    Related
    ENSP00000467621.1, OTTHUMP00000263158, ENST00000589634.1, OTTHUMT00000448901
    Conserved Domains (2) summary
    cd10494
    Location:60205
    MH1_SMAD_7; N-terminal Mad Homology 1 (MH1) domain in SMAD7
    cd10500
    Location:253423
    MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7
  2. NM_001190822.1NP_001177751.1  mothers against decapentaplegic homolog 7 isoform 3

    See identical proteins and their annotated locations for NP_001177751.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC114684, AF010193, AK301535
    Consensus CDS
    CCDS54186.1
    UniProtKB/Swiss-Prot
    O15105
    Related
    ENSP00000466902.1, OTTHUMP00000262928, ENST00000591805.5, OTTHUMT00000448898
    Conserved Domains (1) summary
    cd10500
    Location:39209
    MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7
  3. NM_001190823.1NP_001177752.1  mothers against decapentaplegic homolog 7 isoform 4

    See identical proteins and their annotated locations for NP_001177752.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (4) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC114684, AF010193, AK301535, BP363832
    UniProtKB/Swiss-Prot
    O15105
    UniProtKB/TrEMBL
    B3KYA8
    Conserved Domains (1) summary
    cd10500
    Location:66236
    MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7
  4. NM_005904.3NP_005895.1  mothers against decapentaplegic homolog 7 isoform 1

    See identical proteins and their annotated locations for NP_005895.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC114684, AF010193
    Consensus CDS
    CCDS11936.1
    UniProtKB/Swiss-Prot
    O15105
    Related
    ENSP00000262158.2, OTTHUMP00000163490, ENST00000262158.7, OTTHUMT00000255906
    Conserved Domains (2) summary
    cd10494
    Location:60205
    MH1_SMAD_7; N-terminal Mad Homology 1 (MH1) domain in SMAD7
    cd10500
    Location:254424
    MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p12 Primary Assembly

    Range
    48919853..48950711 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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