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SMAD4 SMAD family member 4 [ Homo sapiens (human) ]

Gene ID: 4089, updated on 20-Dec-2019

Summary

Official Symbol
SMAD4provided by HGNC
Official Full Name
SMAD family member 4provided by HGNC
Primary source
HGNC:HGNC:6770
See related
Ensembl:ENSG00000141646 MIM:600993
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
JIP; DPC4; MADH4; MYHRS
Summary
This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasng blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Aug 2017]
Expression
Ubiquitous expression in thyroid (RPKM 12.0), endometrium (RPKM 10.8) and 25 other tissues See more
Orthologs

Genomic context

See SMAD4 in Genome Data Viewer
Location:
18q21.2
Exon count:
12
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 18 NC_000018.10 (51030213..51085042)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (48556583..48611412)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985152 Neighboring gene elaC ribonuclease Z 1 Neighboring gene Sharpr-MPRA regulatory region 5267 Neighboring gene uncharacterized LOC105372117 Neighboring gene serine and arginine rich splicing factor 10 pseudogene 1 Neighboring gene uncharacterized LOC105372118 Neighboring gene mex-3 RNA binding family member C

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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2012-04-19)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2012-04-19)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
A genome-wide association study of host genetic determinants of the antibody response to Anthrax Vaccine Adsorbed.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat-treated pulmonary arterial smooth muscle cells downregulate levels of phosphorylated SMAD2/3 proteins and SMAD2/3-SMAD4 protein complex, which are repressed by cocaine exposure PubMed
tat HIV-1 Tat-treated pulmonary arterial smooth muscle cells modulate levels of phosphorylated SMAD1/5/8 proteins and SMAD1/5/8-SMAD4 protein complex, which are repressed by cocaine exposure PubMed
tat HIV-1 Tat proteins from different clades modulate differently Pur-alpha and SMAD4 to bind the JCV non-coding control region and affect differently on SMAD4 localization to the nucleus PubMed
tat HIV-1 Tat enhances binding of SMAD2, -3 and -4 and their binding partner Fast1 to the JCV DNA control region (CR) to stimulate JCV gene transcription in living cells PubMed
tat Smad-4 inhibits Smad-3 and HIV-1 Tat-induced transcription from the HIV-1 LTR promoter and the MCP promoter through a direct association with amino acids 1-40 of Tat PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Potential readthrough

Included gene: ELAC1

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription activator activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific NAS
Non-traceable Author Statement
more info
PubMed 
I-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
R-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II transcription factor binding IEA
Inferred from Electronic Annotation
more info
 
chromatin binding IEA
Inferred from Electronic Annotation
more info
 
collagen binding IEA
Inferred from Electronic Annotation
more info
 
identical protein binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
molecular function regulator IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
proximal promoter sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
sulfate binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
transcription coregulator activity IDA
Inferred from Direct Assay
more info
PubMed 
transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
transforming growth factor beta receptor, common-partner cytoplasmic mediator activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
BMP signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
BMP signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
BMP signaling pathway TAS
Traceable Author Statement
more info
 
SMAD protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
SMAD protein signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
atrioventricular canal development ISS
Inferred from Sequence or Structural Similarity
more info
 
atrioventricular valve formation ISS
Inferred from Sequence or Structural Similarity
more info
 
axon guidance IEA
Inferred from Electronic Annotation
more info
 
brainstem development IEA
Inferred from Electronic Annotation
more info
 
branching involved in ureteric bud morphogenesis IEA
Inferred from Electronic Annotation
more info
 
cell proliferation IEA
Inferred from Electronic Annotation
more info
 
cellular iron ion homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to BMP stimulus NAS
Non-traceable Author Statement
more info
PubMed 
developmental growth IEA
Inferred from Electronic Annotation
more info
 
embryonic digit morphogenesis IEA
Inferred from Electronic Annotation
more info
 
endocardial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
endothelial cell activation IEA
Inferred from Electronic Annotation
more info
 
epithelial to mesenchymal transition involved in endocardial cushion formation IEA
Inferred from Electronic Annotation
more info
 
female gonad morphogenesis IEA
Inferred from Electronic Annotation
more info
 
formation of anatomical boundary IEA
Inferred from Electronic Annotation
more info
 
gastrulation with mouth forming second IEA
Inferred from Electronic Annotation
more info
 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
interleukin-6-mediated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
intracellular signal transduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
left ventricular cardiac muscle tissue morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
mesendoderm development IEA
Inferred from Electronic Annotation
more info
 
metanephric mesenchyme morphogenesis IEA
Inferred from Electronic Annotation
more info
 
negative regulation of ERK1 and ERK2 cascade ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of cardiac muscle hypertrophy ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of cardiac myofibril assembly ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of cell death IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell growth IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 
negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
nephrogenic mesenchyme morphogenesis IEA
Inferred from Electronic Annotation
more info
 
neural crest cell differentiation IEA
Inferred from Electronic Annotation
more info
 
neuron fate commitment IEA
Inferred from Electronic Annotation
more info
 
outflow tract septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
ovarian follicle development IEA
Inferred from Electronic Annotation
more info
 
positive regulation of BMP signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of SMAD protein signal transduction ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cell proliferation involved in heart valve morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of epithelial to mesenchymal transition ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of follicle-stimulating hormone secretion IEA
Inferred from Electronic Annotation
more info
 
positive regulation of histone H3-K4 methylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of histone H3-K9 acetylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of luteinizing hormone secretion IEA
Inferred from Electronic Annotation
more info
 
positive regulation of pathway-restricted SMAD protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 
positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus TAS
Traceable Author Statement
more info
PubMed 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
pri-miRNA transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
protein deubiquitination TAS
Traceable Author Statement
more info
 
protein homotrimerization IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of binding IEA
Inferred from Electronic Annotation
more info
 
regulation of hair follicle development IEA
Inferred from Electronic Annotation
more info
 
regulation of transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of transforming growth factor beta2 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to hypoxia IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to transforming growth factor beta IDA
Inferred from Direct Assay
more info
PubMed 
sebaceous gland development IEA
Inferred from Electronic Annotation
more info
 
secondary palate development ISS
Inferred from Sequence or Structural Similarity
more info
 
seminiferous tubule development IEA
Inferred from Electronic Annotation
more info
 
single fertilization IEA
Inferred from Electronic Annotation
more info
 
somatic stem cell population maintenance TAS
Traceable Author Statement
more info
 
somite rostral/caudal axis specification IEA
Inferred from Electronic Annotation
more info
 
spermatogenesis IEA
Inferred from Electronic Annotation
more info
 
transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
transforming growth factor beta receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
uterus development IEA
Inferred from Electronic Annotation
more info
 
ventricular septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
SMAD protein complex IDA
Inferred from Direct Assay
more info
PubMed 
SMAD protein complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
activin responsive factor complex IDA
Inferred from Direct Assay
more info
PubMed 
cell IEA
Inferred from Electronic Annotation
more info
 
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
 
nuclear chromatin IDA
Inferred from Direct Assay
more info
PubMed 
nuclear chromatin ISA
Inferred from Sequence Alignment
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 
transcription factor complex IDA
Inferred from Direct Assay
more info
PubMed 
transcription factor complex IPI
Inferred from Physical Interaction
more info
PubMed 

General protein information

Preferred Names
mothers against decapentaplegic homolog 4
Names
MAD homolog 4
SMAD, mothers against DPP homolog 4
deleted in pancreatic carcinoma locus 4
deletion target in pancreatic carcinoma 4
mothers against decapentaplegic, Drosophila, homolog of, 4

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_013013.2 RefSeqGene

    Range
    67174..122003
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_318

mRNA and Protein(s)

  1. NM_005359.6NP_005350.1  mothers against decapentaplegic homolog 4

    See identical proteins and their annotated locations for NP_005350.1

    Status: REVIEWED

    Source sequence(s)
    AC091551, AU120224, BC002379, BM701399
    Consensus CDS
    CCDS11950.1
    UniProtKB/Swiss-Prot
    Q13485
    UniProtKB/TrEMBL
    A0A024R274
    Related
    ENSP00000341551.3, ENST00000342988.7
    Conserved Domains (3) summary
    pfam05539
    Location:176281
    Pneumo_att_G; Pneumovirinae attachment membrane glycoprotein G
    cd10492
    Location:14138
    MH1_SMAD_4; N-terminal Mad Homology 1 (MH1) domain in SMAD4
    cd10498
    Location:320541
    MH2_SMAD_4; C-terminal Mad Homology 2 (MH2) domain in SMAD4

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p13 Primary Assembly

    Range
    51030213..51085042
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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