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

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; AllianceGenome:HGNC:6773
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: mouse all
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Genomic context

Location:: 18q21.1

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (48919853..48950965, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (49115112..49146228, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (46446223..46477335, complement)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Knockdown of YAP1 Reduces YTHDF3 to Stabilize SMAD7 and thus Inhibit Bladder Cancer Stem Cell Stemness.
Title: Knockdown of YAP1 Reduces YTHDF3 to Stabilize SMAD7 and thus Inhibit Bladder Cancer Stem Cell Stemness.
UHRF1 inhibition mitigates vascular endothelial cell injury and ameliorates atherosclerosis in mice via regulating the SMAD7/YAP1 axis.
Title: UHRF1 inhibition mitigates vascular endothelial cell injury and ameliorates atherosclerosis in mice via regulating the SMAD7/YAP1 axis.
Circular RNA circWNK1 inhibits the progression of gastric cancer via regulating the miR-21-3p/SMAD7 axis.
Title: Circular RNA circWNK1 inhibits the progression of gastric cancer via regulating the miR-21-3p/SMAD7 axis.
SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors.
Title: SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors.
SMAD7 gene polymorphisms and their influence on patients with colorectal cancer.
Title: SMAD7 gene polymorphisms and their influence on patients with colorectal cancer.
Circular RNA sirtuin-1 restrains the malignant phenotype of non-small cell lung cancer cells via the microRNA-510-5p/SMAD family member 7 axis.
Title: Circular RNA sirtuin-1 restrains the malignant phenotype of non-small cell lung cancer cells via the microRNA-510-5p/SMAD family member 7 axis.
Identification and characterization of colorectal-cancer-associated SNPs on the SMAD7 locus.
Title: Identification and characterization of colorectal-cancer-associated SNPs on the SMAD7 locus.
[Silencing of SMAD family member 3 promotes M2 polarization of macrophages and the expression of SMAD7 in rheumatoid arthritis].
Title: [Silencing of SMAD family member 3 promotes M2 polarization of macrophages and the expression of SMAD7 in rheumatoid arthritis].
TGF-beta1 signaling and Smad7 control T-cell responses in health and immune-mediated disorders.
Title: TGF-β1 signaling and Smad7 control T-cell responses in health and immune-mediated disorders.
CircMACF1 alleviates myocardial fibrosis after acute myocardial infarction by suppressing cardiac fibroblast activation via the miR-16-5p/SMAD7 axis.
Title: CircMACF1 alleviates myocardial fibrosis after acute myocardial infarction by suppressing cardiac fibroblast activation via the miR-16-5p/SMAD7 axis.

Submit: New GeneRIF Correction See all GeneRIFs (302)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:482050

SHGC-148875 (e-PCR)
- UniSTS:176659

SHGC-147306 (e-PCR)
- UniSTS:175735

Smad7 (e-PCR), detects polymorphism
- UniSTS:466574

PMC193708P1 (e-PCR)
- UniSTS:271759

PMC193708P2 (e-PCR)
- UniSTS:271760

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables I-SMAD binding	IBA Inferred from Biological aspect of Ancestor more info
enables I-SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
enables activin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables beta-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables collagen binding	IEA Inferred from Electronic Annotation 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 corepressor activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription regulator inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables transcription regulator inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables type I transforming growth factor beta receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-like ligase-substrate adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in SMAD protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in adherens junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in anatomical structure morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in artery morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in beta-catenin destruction complex disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of SMAD protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of SMAD protein signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of T cell cytokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of T-helper 17 cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of T-helper 17 type immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of activin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell migration	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of chondrocyte proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of epithelial to mesenchymal transition	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of ossification	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by competitive promoter binding	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell-cell adhesion mediated by cadherin	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chondrocyte hypertrophy	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in protein stabilization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein-containing complex disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in protein-containing complex localization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cardiac muscle contraction	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of epithelial to mesenchymal transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of ventricular cardiac muscle cell membrane depolarization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in response to laminar fluid shear stress	IEP Inferred from Expression Pattern more info	PubMed
involved_in transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in ureteric bud development	IEA Inferred from Electronic Annotation more info
involved_in ventricular cardiac muscle tissue morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in ventricular septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
colocalizes_with adherens junction	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in fibrillar center	IDA Inferred from Direct Assay more info
part_of heteromeric SMAD protein complex	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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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)

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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

NG_023330.1 RefSeqGene

Range

4747..35859

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001190821.2 → NP_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

Consensus CDS

CCDS59317.1

UniProtKB/Swiss-Prot

O15105

Related

ENSP00000467621.1, ENST00000589634.1

Conserved Domains (2) summary

cd10494
Location:60 → 205

MH1_SMAD_7; N-terminal Mad Homology 1 (MH1) domain in SMAD7

cd10500
Location:253 → 423

MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7
NM_001190822.2 → NP_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, ENST00000591805.5

Conserved Domains (1) summary

cd10500
Location:39 → 209

MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7
NM_001190823.2 → NP_001177752.1 mothers against decapentaplegic homolog 7 isoform 4 precursor

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/TrEMBL

B3KYA8

Related

ENST00000545051.2

Conserved Domains (1) summary

cd10500
Location:66 → 236

MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7
NM_005904.4 → NP_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

Consensus CDS

CCDS11936.1

UniProtKB/Swiss-Prot

B7Z773, K7EQ10, O14740, O15105, Q6DK23

Related

ENSP00000262158.2, ENST00000262158.8

Conserved Domains (2) summary

cd10494
Location:60 → 205

MH1_SMAD_7; N-terminal Mad Homology 1 (MH1) domain in SMAD7

cd10500
Location:254 → 424

MH2_SMAD_7; C-terminal Mad Homology 2 (MH2) domain in SMAD7