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

Gene ID: 4089, updated on 30-Jun-2015
Official Symbol
SMAD4provided by HGNC
Official Full Name
SMAD family member 4provided by HGNC
Primary source
HGNC:HGNC:6770
See related
Ensembl:ENSG00000141646; HPRD:02995; MIM:600993; Vega:OTTHUMG00000132696
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 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 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, Oct 2009]
Orthologs
See SMAD4 in Epigenomics, MapViewer
Location:
18q21.1
Exon count:
12
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 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 elaC ribonuclease Z 1 Neighboring gene uncharacterized LOC105372117 Neighboring gene serine/arginine-rich splicing factor 10 pseudogene 1 Neighboring gene uncharacterized LOC105372118 Neighboring gene mex-3 RNA binding family member C

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Carcinoma of pancreas
MedGen: C0235974 OMIM: 260350 GeneReviews: Not available
not available
Juvenile polyposis syndrome
MedGen: C0345893 OMIM: 174900 GeneReviews: Juvenile Polyposis Syndrome
not available
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome not available
Myhre syndrome
MedGen: C0796081 OMIM: 139210 GeneReviews: Not available
not available

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

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

Products Interactant Other Gene Complex Source Pubs Description

Markers

Potential readthrough

Included gene: ELAC1

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to DNA binding IDA
Inferred from Direct Assay
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 core promoter proximal region sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II transcription factor binding IEA
Inferred from Electronic Annotation
more info
 
RNA polymerase II transcription factor binding transcription factor activity 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
 
core promoter proximal region sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
identical protein 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 
contributes_to protein binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
protein heterodimerization activity IEA
Inferred from Electronic Annotation
more info
 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to sequence-specific DNA binding transcription factor 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 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 IEA
Inferred from Electronic Annotation
more info
 
atrioventricular valve formation IEA
Inferred from Electronic Annotation
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
 
cardiac septum development IEA
Inferred from Electronic Annotation
more info
 
cell proliferation IEA
Inferred from Electronic Annotation
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 IEA
Inferred from Electronic Annotation
more info
 
endoderm development IEA
Inferred from Electronic Annotation
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
 
formation of anatomical boundary IEA
Inferred from Electronic Annotation
more info
 
gastrulation with mouth forming second IEA
Inferred from Electronic Annotation
more info
 
gene expression TAS
Traceable Author Statement
more info
 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
intracellular signal transduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
mesoderm development IEA
Inferred from Electronic Annotation
more info
 
metanephric mesenchyme morphogenesis IEA
Inferred from Electronic Annotation
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 protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription from RNA polymerase II promoter 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
 
palate development ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of BMP signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of SMAD protein import into nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cell proliferation involved in heart valve morphogenesis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of epithelial to mesenchymal transition ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of pathway-restricted SMAD protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription from RNA polymerase II promoter 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 
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
 
somatic stem cell maintenance TAS
Traceable Author Statement
more info
 
somite rostral/caudal axis specification IEA
Inferred from Electronic Annotation
more info
 
transcription initiation from RNA polymerase II promoter TAS
Traceable Author Statement
more info
 
transcription, DNA-templated TAS
Traceable Author Statement
more info
 
transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
SMAD protein complex IDA
Inferred from Direct Assay
more info
PubMed 
activin responsive factor complex 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 TAS
Traceable Author Statement
more info
 
nuclear chromatin IDA
Inferred from Direct Assay
more info
PubMed 
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 
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

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_005359.5NP_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/TrEMBL
    A0A024R274
    UniProtKB/Swiss-Prot
    Q13485
    Related
    ENSP00000341551, ENST00000342988
    Conserved Domains (2) summary
    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 Annotation Release 107

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p2 Primary Assembly

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

Alternate CHM1_1.1

Genomic

  1. NC_018929.2 Alternate CHM1_1.1

    Range
    48551997..48606836
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)