The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided b... See more...

Aliases for SMAD5 Gene

Aliases for SMAD5 Gene

  • SMAD Family Member 5 2 3 4 5
  • Mothers Against Decapentaplegic Homolog 5 3 4
  • MADH5 3 4
  • JV5-1 3 4
  • MAD, Mothers Against Decapentaplegic Homolog 5 (Drosophila) 2
  • Mothers Against Decapentaplegic, Drosophila, Homolog Of, 5 3
  • SMAD, Mothers Against DPP Homolog 5 (Drosophila) 2
  • MAD, Mothers Against Decapentaplegic Homolog 5 3
  • SMAD, Mothers Against DPP Homolog 5 3
  • SMA- And MAD-Related Protein 5 3
  • Mothers Against DPP Homolog 5 4
  • MAD Homolog 5 4
  • SMAD 5 4
  • HSmad5 4
  • Smad5 4
  • DWFC 3

External Ids for SMAD5 Gene

Previous HGNC Symbols for SMAD5 Gene

  • MADH5

Previous GeneCards Identifiers for SMAD5 Gene

  • GC05P135545
  • GC05P135496
  • GC05P130657
  • GC05P135470

Summaries for SMAD5 Gene

Entrez Gene Summary for SMAD5 Gene

  • The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

GeneCards Summary for SMAD5 Gene

SMAD5 (SMAD Family Member 5) is a Protein Coding gene. Diseases associated with SMAD5 include Fibrodysplasia Ossificans Progressiva and Deafness, Autosomal Dominant 52. Among its related pathways are Th1 Differentiation Pathway and ERK Signaling. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II core promoter sequence-specific DNA binding. An important paralog of this gene is SMAD1.

UniProtKB/Swiss-Prot Summary for SMAD5 Gene

  • Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).

Gene Wiki entry for SMAD5 Gene

Additional gene information for SMAD5 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SMAD5 Gene

Genomics for SMAD5 Gene

GeneHancer (GH) Regulatory Elements for SMAD5 Gene

Promoters and enhancers for SMAD5 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SMAD5 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SMAD5

Top Transcription factor binding sites by QIAGEN in the SMAD5 gene promoter:
  • AML1a
  • FOXD3
  • FOXJ2
  • FOXJ2 (long isoform)
  • FOXO4
  • Ik-2
  • IRF-7A
  • Nkx6-1

Genomic Locations for SMAD5 Gene

Genomic Locations for SMAD5 Gene
chr5:136,132,845-136,188,747
(GRCh38/hg38)
Size:
55,903 bases
Orientation:
Plus strand
chr5:135,468,534-135,524,435
(GRCh37/hg19)
Size:
55,902 bases
Orientation:
Plus strand

Genomic View for SMAD5 Gene

Genes around SMAD5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMAD5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMAD5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMAD5 Gene

Proteins for SMAD5 Gene

  • Protein details for SMAD5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99717-SMAD5_HUMAN
    Recommended name:
    Mothers against decapentaplegic homolog 5
    Protein Accession:
    Q99717
    Secondary Accessions:
    • O14688
    • Q15798
    • Q9UQA1

    Protein attributes for SMAD5 Gene

    Size:
    465 amino acids
    Molecular mass:
    52258 Da
    Quaternary structure:
    • May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1. Interacts with TMEM119 (By similarity). Interacts with ZNF8 (PubMed:12370310). Interacts with RANBP3L (PubMed:25755279).

    Three dimensional structures from OCA and Proteopedia for SMAD5 Gene

neXtProt entry for SMAD5 Gene

Post-translational modifications for SMAD5 Gene

  • Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.
  • Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for SMAD5 Gene

Domains & Families for SMAD5 Gene

Gene Families for SMAD5 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for SMAD5 Gene

Suggested Antigen Peptide Sequences for SMAD5 Gene

GenScript: Design optimal peptide antigens:
  • MADH5 protein (Q6I9T1_HUMAN)
  • SMAD family member 5 (SMAD5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99717

UniProtKB/Swiss-Prot:

SMAD5_HUMAN :
  • Belongs to the dwarfin/SMAD family.
Family:
  • Belongs to the dwarfin/SMAD family.
genes like me logo Genes that share domains with SMAD5: view

Function for SMAD5 Gene

Molecular function for SMAD5 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).

Phenotypes From GWAS Catalog for SMAD5 Gene

Gene Ontology (GO) - Molecular Function for SMAD5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IEA --
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA --
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IEA --
genes like me logo Genes that share ontologies with SMAD5: view
genes like me logo Genes that share phenotypes with SMAD5: view

Animal Models for SMAD5 Gene

MGI Knock Outs for SMAD5:

Animal Model Products

CRISPR Products

miRNA for SMAD5 Gene

miRTarBase miRNAs that target SMAD5

Clone Products

  • Addgene plasmids for SMAD5

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SMAD5 Gene

Localization for SMAD5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMAD5 Gene

Cytoplasm. Nucleus. Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SMAD5 gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 3
mitochondrion 3
plasma membrane 2
cytoskeleton 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SMAD5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005622 intracellular IEA --
GO:0005634 nucleus NAS,TAS 19018011
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IEA --
genes like me logo Genes that share ontologies with SMAD5: view

Pathways & Interactions for SMAD5 Gene

PathCards logo

SuperPathways for SMAD5 Gene

SuperPathway Contained pathways
1 DREAM Repression and Dynorphin Expression
.44
.01
2 Human Embryonic Stem Cell Pluripotency
.50
.50
3 TGF-Beta Pathway
.60
.57
4 Signaling by BMP
5 Wnt / Hedgehog / Notch
genes like me logo Genes that share pathways with SMAD5: view

Pathways by source for SMAD5 Gene

2 R&D Systems pathways for SMAD5 Gene
8 Qiagen pathways for SMAD5 Gene
  • BMP Pathway
  • Cardiomyocyte Differentiation through BMP Receptors
  • Factors Promoting Cardiogenesis in Vertebrates
  • Human Embryonic Stem Cell Pluripotency
  • JAK-STAT Pathway
1 Cell Signaling Technology pathway for SMAD5 Gene
1 GeneTex pathway for SMAD5 Gene

SIGNOR curated interactions for SMAD5 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for SMAD5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0001503 ossification IEA --
GO:0001657 ureteric bud development IEA --
GO:0001880 Mullerian duct regression IEA --
GO:0002051 osteoblast fate commitment IEA --
genes like me logo Genes that share ontologies with SMAD5: view

Drugs & Compounds for SMAD5 Gene

(2) Drugs for SMAD5 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with SMAD5: view

Transcripts for SMAD5 Gene

mRNA/cDNA for SMAD5 Gene

3 REFSEQ mRNAs :
22 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for SMAD5

Alternative Splicing Database (ASD) splice patterns (SP) for SMAD5 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8 ^ 9a · 9b
SP1: -
SP2:
SP3: - - - - - - - - - -
SP4: -
SP5: -
SP6:
SP7: - -

Relevant External Links for SMAD5 Gene

GeneLoc Exon Structure for
SMAD5

Expression for SMAD5 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SMAD5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SMAD5 Gene

This gene is overexpressed in Fetal heart (23.5), Ovary (21.3), Placenta (8.2), and Colon (7.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SMAD5 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SMAD5

SOURCE GeneReport for Unigene cluster for SMAD5 Gene:

Hs.167700

mRNA Expression by UniProt/SwissProt for SMAD5 Gene:

Q99717-SMAD5_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for SMAD5 Gene

  • Nervous system(3.6)
  • Muscle(2.4)
  • Heart(2.2)
  • Liver(2.2)
  • Bone(2.1)
genes like me logo Genes that share expression patterns with SMAD5: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SMAD5 Gene

Orthologs for SMAD5 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMAD5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SMAD5 30
  • 100 (n)
oppossum
(Monodelphis domestica)
Mammalia SMAD5 31
  • 98 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SMAD5 31
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SMAD5 31 30
  • 95.77 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SMAD5 31 30
  • 95.63 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Smad5 17 31 30
  • 91.68 (n)
rat
(Rattus norvegicus)
Mammalia Smad5 30
  • 89.32 (n)
chicken
(Gallus gallus)
Aves SMAD5 31 30
  • 85.52 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SMAD5 31
  • 90 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii smad5 31 30
  • 77.14 (n)
OneToOne
madh5 30
fruit fly
(Drosophila melanogaster)
Insecta Mad 31
  • 64 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea sma-2 31
  • 56 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea Cin.3946 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.3946 30
Species where no ortholog for SMAD5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for SMAD5 Gene

ENSEMBL:
Gene Tree for SMAD5 (if available)
TreeFam:
Gene Tree for SMAD5 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SMAD5: view image

Paralogs for SMAD5 Gene

Paralogs for SMAD5 Gene

(9) SIMAP similar genes for SMAD5 Gene using alignment to 7 proteins:

  • SMAD5_HUMAN
  • D6R9D4_HUMAN
  • D6RBB4_HUMAN
  • D6RIZ9_HUMAN
  • F5GWU7_HUMAN
  • H0YAK7_HUMAN
  • H0YAM3_HUMAN
genes like me logo Genes that share paralogs with SMAD5: view

Variants for SMAD5 Gene

Additional dbSNP identifiers (rs#s) for SMAD5 Gene

Structural Variations from Database of Genomic Variants (DGV) for SMAD5 Gene

Variant ID Type Subtype PubMed ID
esv2759380 CNV loss 17122850
nsv508381 CNV deletion 20534489
nsv819700 CNV loss 19587683

Variation tolerance for SMAD5 Gene

Gene Damage Index Score: 0.17; 3.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SMAD5 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMAD5

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SMAD5 Gene

Disorders for SMAD5 Gene

MalaCards: The human disease database

(4) MalaCards diseases for SMAD5 Gene - From: DISEASES and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search SMAD5 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SMAD5

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SMAD5: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SMAD5 Gene

Publications for SMAD5 Gene

  1. A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. (PMID: 19211612) Shintani M … Matsuoka R (Journal of medical genetics 2009) 3 23 41 54
  2. Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway modulate HFE hemochromatosis penetrance. (PMID: 17847004) Milet J … Mosser J (American journal of human genetics 2007) 3 23 41 54
  3. Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression. (PMID: 15107829) Frontelo P … Lechleider RJ (Oncogene 2004) 3 4 23 54
  4. Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. (PMID: 9442019) Nishimura R … Yoneda T (The Journal of biological chemistry 1998) 3 4 23 54
  5. Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60. (PMID: 9264367) Zavadil J … Michalová K (Leukemia 1997) 3 4 23 54

Products for SMAD5 Gene

Sources for SMAD5 Gene