Version 5.4
Bos taurus Gene: SMAD4
Summary
InnateDB Gene IDBG-644730.3
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol SMAD4
Gene Name mothers against decapentaplegic homolog 4
Synonyms
Species Bos taurus
Ensembl Gene ENSBTAG00000006919
Encoded Proteins
IDBP-697390
mothers against decapentaplegic homolog 4
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation from Orthologs
Summary
PMID 25410655
[Homo sapiens] TGF-β signalling upregulates MIR181A2 expression through SMAD3/4-dependent promoter activation.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000141646:
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 24:50993949-51045661
Strand Forward strand
Band
Transcripts
ENSBTAT00000009081 ENSBTAP00000009081
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 205 interaction(s) predicted by orthology.
Predicted by orthology
Total 205 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0000988 protein binding transcription factor activity
GO:0001076 RNA polymerase II transcription factor binding transcription factor activity
GO:0001085 RNA polymerase II transcription factor binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0005515 protein binding
GO:0005518 collagen binding
GO:0030616 transforming growth factor beta receptor, common-partner cytoplasmic mediator activity
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0070411 I-SMAD binding
GO:0070412 R-SMAD binding
Biological Process
GO:0001658 branching involved in ureteric bud morphogenesis
GO:0001666 response to hypoxia
GO:0001701 in utero embryonic development
GO:0001702 gastrulation with mouth forming second
GO:0001822 kidney development
GO:0003190 atrioventricular valve formation
GO:0003198 epithelial to mesenchymal transition involved in endocardial cushion formation
GO:0003251 positive regulation of cell proliferation involved in heart valve morphogenesis
GO:0003279 cardiac septum development
GO:0003360 brainstem development
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007183 SMAD protein complex assembly
GO:0007369 gastrulation
GO:0007411 axon guidance
GO:0007492 endoderm development
GO:0007498 mesoderm development
GO:0008283 cell proliferation
GO:0008285 negative regulation of cell proliferation
GO:0009952 anterior/posterior pattern specification
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0014033 neural crest cell differentiation
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0030308 negative regulation of cell growth
GO:0030509 BMP signaling pathway
GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
GO:0030513 positive regulation of BMP signaling pathway
GO:0032525 somite rostral/caudal axis specification
GO:0032909 regulation of transforming growth factor beta2 production
GO:0035556 intracellular signal transduction
GO:0036302 atrioventricular canal development
GO:0042118 endothelial cell activation
GO:0042127 regulation of cell proliferation
GO:0042177 negative regulation of protein catabolic process
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048589 developmental growth
GO:0048663 neuron fate commitment
GO:0048729 tissue morphogenesis
GO:0048733 sebaceous gland development
GO:0048859 formation of anatomical boundary
GO:0051098 regulation of binding
GO:0051797 regulation of hair follicle development
GO:0060021 palate development
GO:0060391 positive regulation of SMAD protein import into nucleus
GO:0060395 SMAD protein signal transduction
GO:0060548 negative regulation of cell death
GO:0060956 endocardial cell differentiation
GO:0071559 response to transforming growth factor beta
GO:0072133 metanephric mesenchyme morphogenesis
GO:0072134 nephrogenic mesenchyme morphogenesis
Cellular Component
GO:0000790 nuclear chromatin
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0032444 activin responsive factor complex
GO:0071141 SMAD protein complex
Orthologs
Species
Homo sapiens
Mus musculus
Gene ID
Gene Order
ENSG00000141646
View Gene Order
ENSMUSG00000024515
View Gene Order
Pathway Predictions based on Human Orthology Data
NETPATH
NetPath_7
TGF_beta_Receptor pathway
REACTOME
REACT_120850
TGF-beta receptor signaling activates SMADs pathway
REACT_121111
Downregulation of SMAD2/3:SMAD4 transcriptional activity pathway
REACT_120734
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway
REACT_150238
Signaling by Activin pathway
REACT_12034
Signaling by BMP pathway
REACT_12627
Generic Transcription Pathway pathway
REACT_111057
Signaling by NODAL pathway
REACT_169107
SMAD4 MH2 Domain Mutants in Cancer pathway
REACT_111045
Developmental Biology pathway
REACT_200812
Transcriptional regulation of pluripotent stem cells pathway
REACT_169219
Loss of Function of SMAD4 in Cancer pathway
REACT_169398
Loss of Function of SMAD2/3 in Cancer pathway
REACT_169122
Signaling by TGF-beta Receptor Complex in Cancer pathway
REACT_169192
TGFBR2 MSI Frameshift Mutants in Cancer pathway
REACT_111102
Signal Transduction pathway
REACT_121061
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer pathway
REACT_169165
SMAD2/3 MH2 Domain Mutants in Cancer pathway
REACT_169435
Loss of Function of TGFBR2 in Cancer pathway
REACT_169103
SMAD2/3 Phosphorylation Motif Mutants in Cancer pathway
REACT_169263
TGFBR1 KD Mutants in Cancer pathway
REACT_169311
Loss of Function of TGFBR1 in Cancer pathway
REACT_169445
TGFBR1 LBD Mutants in Cancer pathway
REACT_169440
TGFBR2 Kinase Domain Mutants in Cancer pathway
REACT_71
Gene Expression pathway
REACT_116125
Disease pathway
REACT_6844
Signaling by TGF-beta Receptor Complex pathway
REACT_217958
SMAD2/3 Phosphorylation Motif Mutants in Cancer pathway
REACT_189085
Disease pathway
REACT_215068
Loss of Function of SMAD4 in Cancer pathway
REACT_213336
Signaling by TGF-beta Receptor Complex in Cancer pathway
REACT_220505
Signaling by BMP pathway
REACT_224217
TGFBR1 LBD Mutants in Cancer pathway
REACT_203510
TGF-beta receptor signaling activates SMADs pathway
REACT_220566
Downregulation of SMAD2/3:SMAD4 transcriptional activity pathway
REACT_220645
Signaling by NODAL pathway
REACT_204241
Loss of Function of TGFBR2 in Cancer pathway
REACT_216222
Transcriptional regulation of pluripotent stem cells pathway
REACT_216258
Signaling by Activin pathway
REACT_216792
SMAD2/3 MH2 Domain Mutants in Cancer pathway
REACT_224787
TGFBR2 Kinase Domain Mutants in Cancer pathway
REACT_233572
Gene Expression pathway
REACT_188576
Developmental Biology pathway
REACT_223317
Loss of Function of TGFBR1 in Cancer pathway
REACT_209370
TGFBR2 MSI Frameshift Mutants in Cancer pathway
REACT_202264
SMAD4 MH2 Domain Mutants in Cancer pathway
REACT_206529
Generic Transcription Pathway pathway
REACT_188257
Signal Transduction pathway
REACT_224802
TGFBR1 KD Mutants in Cancer pathway
REACT_212101
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer pathway
REACT_225428
Signaling by TGF-beta Receptor Complex pathway
REACT_226256
Loss of Function of SMAD2/3 in Cancer pathway
REACT_203903
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway
KEGG
hsa05210
Colorectal cancer pathway
hsa04310
Wnt signaling pathway pathway
hsa04350
TGF-beta signaling pathway pathway
hsa04110
Cell cycle pathway
hsa04520
Adherens junction pathway
hsa05220
Chronic myeloid leukemia pathway
hsa05212
Pancreatic cancer pathway
hsa05200
Pathways in cancer pathway
mmu04350
TGF-beta signaling pathway pathway
mmu04310
Wnt signaling pathway pathway
mmu05210
Colorectal cancer pathway
mmu04110
Cell cycle pathway
mmu04520
Adherens junction pathway
mmu05220
Chronic myeloid leukemia pathway
mmu05212
Pancreatic cancer pathway
mmu05200
Pathways in cancer pathway
INOH
INOH website
Wnt signaling pathway pathway
INOH website
LIF signaling pathway
INOH website
TGF-beta signaling pathway
INOH website
BMP2 signaling pathway
INOH website
Wnt signaling pathway pathway
INOH website
LIF signaling pathway
INOH website
BMP2 signaling pathway
INOH website
TGF-beta signaling pathway
PID NCI
alk2pathway
ALK2 signaling events
bmppathway
BMP receptor signaling
era_genomic_pathway
Validated nuclear estrogen receptor alpha network
alk1pathway
ALK1 signaling events
myc_represspathway
Validated targets of C-MYC transcriptional repression
myc_activpathway
Validated targets of C-MYC transcriptional activation
lkb1_pathway
LKB1 signaling events
smad2_3nuclearpathway
Regulation of nuclear SMAD2/3 signaling
hif1_tfpathway
HIF-1-alpha transcription factor network
tgfbrpathway
TGF-beta receptor signaling
smad2_3pathway
Regulation of cytoplasmic and nuclear SMAD2/3 signaling
Cross-References
SwissProt
TrEMBL B0JYL0
UniProt Splice Variant
Entrez Gene 540248
UniGene Bt.109310 Bt.13220 Bt.70601
RefSeq NM_001076209 XM_005224250
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL BC151330 DAAA02057034
GenPept AAI51331
RNA Seq Atlas 540248

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

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Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca