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Aliases for SMAD3 Gene

Aliases for SMAD3 Gene

  • SMAD Family Member 3 2 3 4 5
  • Mothers Against DPP Homolog 3 3 4
  • MAD Homolog 3 3 4
  • JV15-2 3 4
  • HMAD-3 3 4
  • HSMAD3 3 4
  • MADH3 3 4
  • Mad3 3 4
  • MAD, Mothers Against Decapentaplegic Homolog 3 (Drosophila) 2
  • SMAD, Mothers Against DPP Homolog 3 (Drosophila) 2
  • MAD, Mothers Against Decapentaplegic Homolog 3 3
  • Mothers Against Decapentaplegic Homolog 3 3
  • SMAD, Mothers Against DPP Homolog 3 3
  • SMA- And MAD-Related Protein 3 3
  • Mad Protein Homolog 3
  • Mad Homolog JV15-2 3
  • HsT17436 3
  • HSPC193 3
  • SMAD 3 4
  • LDS1C 3
  • Smad3 4
  • LDS3 3

External Ids for SMAD3 Gene

Previous HGNC Symbols for SMAD3 Gene

  • MADH3

Previous GeneCards Identifiers for SMAD3 Gene

  • GC15P065075
  • GC15P065145
  • GC15P067358
  • GC15P044193

Summaries for SMAD3 Gene

Entrez Gene Summary for SMAD3 Gene

  • The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions as a transcriptional modulator activated by transforming growth factor-beta and is thought to play a role in the regulation of carcinogenesis. [provided by RefSeq, Apr 2009]

GeneCards Summary for SMAD3 Gene

SMAD3 (SMAD Family Member 3) is a Protein Coding gene. Diseases associated with SMAD3 include Loeys-Dietz Syndrome 3 and Cutaneous Polyarteritis Nodosa. Among its related pathways are Gene Expression and Endometrial cancer. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is SMAD2.

UniProtKB/Swiss-Prot for SMAD3 Gene

  • Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.

Gene Wiki entry for SMAD3 Gene

Additional gene information for SMAD3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SMAD3 Gene

Genomics for SMAD3 Gene

GeneHancer (GH) Regulatory Elements for SMAD3 Gene

Promoters and enhancers for SMAD3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15J067060 Promoter/Enhancer 2.5 EPDnew Ensembl ENCODE dbSUPER 661.9 +2.4 2390 11 CLOCK MLX FEZF1 DMAP1 IRF4 YY1 ZNF213 ZNF416 ZNF263 SP3 SMAD3 LOC102723493 PIR44207 ENSG00000260773 SKOR1 ENSG00000259202 ENSG00000259410 MAP2K5 IQCH-AS1 PIAS1
GH15J067129 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 665.5 +77.5 77458 23 HDGF PKNOX1 FOXA2 SMAD1 MLX ARID4B SIN3A FEZF1 DMAP1 ZNF2 SMAD3 PIR53240 SNORD16 AAGAB IQCH ENSG00000260773 ENSG00000259202 PIR54457
GH15J067113 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 665.4 +57.7 57742 15.9 HDGF PKNOX1 CLOCK FOXA2 MLX ARID4B SIN3A YY1 ZNF143 FOS SMAD3 AAGAB IQCH DIS3L GC15P069965 PIR54457
GH15J067037 Enhancer 1.4 Ensembl ENCODE dbSUPER 19 -22.0 -21985 7.6 ARID4B SIN3A ZNF2 ZNF207 FOS DEK ZC3H11A ZNF662 REST ZNF592 ENSG00000260773 IQCH-AS1 TIPIN SKOR1 SMAD3 ENSG00000259202 ENSG00000259410 RPL35AP32 ZWILCH SNAPC5
GH15J067171 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 12.7 +112.7 112744 10.4 PKNOX1 ATF1 ARNT ZFP64 SIN3A TCF12 GATA2 FOS ATF7 RUNX3 ENSG00000260773 SNORD16 IQCH RPL35AP32 SMAD3 ZWILCH SNAPC5 TIPIN AAGAB IQCH-AS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SMAD3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SMAD3 gene promoter:
  • ATF-2
  • C/EBPalpha
  • Sp1
  • C/EBPbeta
  • N-Myc
  • GATA-1
  • PPAR-alpha
  • Egr-3
  • NF-AT
  • NF-AT1

Genomic Locations for SMAD3 Gene

Genomic Locations for SMAD3 Gene
chr15:67,063,763-67,195,195
(GRCh38/hg38)
Size:
131,433 bases
Orientation:
Plus strand
chr15:67,356,101-67,487,533
(GRCh37/hg19)
Size:
131,433 bases
Orientation:
Plus strand

Genomic View for SMAD3 Gene

Genes around SMAD3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMAD3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMAD3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMAD3 Gene

Proteins for SMAD3 Gene

  • Protein details for SMAD3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P84022-SMAD3_HUMAN
    Recommended name:
    Mothers against decapentaplegic homolog 3
    Protein Accession:
    P84022
    Secondary Accessions:
    • A8K4B6
    • B7Z4Z5
    • B7Z6M9
    • B7Z9Q2
    • F5H383
    • O09064
    • O09144
    • O14510
    • O35273
    • Q92940
    • Q93002
    • Q9GKR4

    Protein attributes for SMAD3 Gene

    Size:
    425 amino acids
    Molecular mass:
    48081 Da
    Quaternary structure:
    • Monomer; in the absence of TGF-beta. Homooligomer; in the presence of TGF-beta. Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex. Interacts with TGFBR1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PML, PRDM16, HGS, WWP1 and SNW1. Interacts (via MH2 domain) with CITED2 (via C-terminus). Interacts with NEDD4L; the interaction requires TGF-beta stimulation. Interacts (via the MH2 domain) with ZFYVE9. Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and TGFB1I1. Interacts with DACH1; the interaction inhibits the TGF-beta signaling. Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta. Found in a complex with SMAD3, RAN and XPO4. Interacts in the complex directly with XPO4. Interacts (via the MH2 domain) with LEMD3; the interaction represses SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus. Interacts with RBPMS. Interacts (via MH2 domain) with MECOM. Interacts with WWTR1 (via its coiled-coil domain). Interacts (via the linker region) with EP300 (C-terminal); the interaction promotes SMAD3 acetylation and is enhanced by TGF-beta phosphorylation in the C-terminal of SMAD3. This interaction can be blocked by competitive binding of adenovirus oncoprotein E1A to the same C-terminal site on EP300, which then results in partially inhibited SMAD3/SMAD4 transcriptional activity. Interacts with SKI; the interaction represses SMAD3 transcriptional activity. Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. Interacts (via an N-terminal domain) with JUN (via its basic DNA binding and leucine zipper domains); this interaction is essential for DNA binding and cooperative transcriptional activity in response to TGF-beta. Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling. Interacts (dephosphorylated form via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling. Interacts with MEN1. Interacts with IL1F7. Interaction with CSNK1G2. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation and protein levels. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts with PMEPA1. Interacts with ZC3H3 (By similarity). Interacts with ZNF451 (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts with ZFHX3. Interacts weakly with ZNF8 (PubMed:12370310). Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD3 inhibitors (By similarity). Interacts with STUB1, HSPA1A, HSPA1B, HSP90AA1 and HSP90AB1 (PubMed:24613385).

    Three dimensional structures from OCA and Proteopedia for SMAD3 Gene

    Alternative splice isoforms for SMAD3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SMAD3 Gene

Post-translational modifications for SMAD3 Gene

  • Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated by PDPK1.
  • Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.
  • Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.
  • Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding (PubMed:21947082). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082). Ubiquitinated by RNF111, leading to its degradation: only SMAD3 proteins that are in use are targeted by RNF111, RNF111 playing a key role in activating SMAD3 and regulating its turnover (By similarity). Undergoes STUB1-mediated ubiquitination and degradation (PubMed:24613385).
  • Ubiquitination at posLast=8181 and posLast=3333
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for SMAD3 Gene

Domains & Families for SMAD3 Gene

Gene Families for SMAD3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Graphical View of Domain Structure for InterPro Entry

P84022

UniProtKB/Swiss-Prot:

SMAD3_HUMAN :
  • The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding.
  • Belongs to the dwarfin/SMAD family.
Domain:
  • The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding.
  • The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.
  • The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.
Family:
  • Belongs to the dwarfin/SMAD family.
genes like me logo Genes that share domains with SMAD3: view

Function for SMAD3 Gene

Molecular function for SMAD3 Gene

UniProtKB/Swiss-Prot Function:
Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.

Phenotypes From GWAS Catalog for SMAD3 Gene

Gene Ontology (GO) - Molecular Function for SMAD3 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 IDA 21947082
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding NAS 19274049
GO:0000983 transcription factor activity, RNA polymerase II core promoter sequence-specific DNA binding IDA,IMP 26311719
GO:0000987 proximal promoter sequence-specific DNA binding IDA 18832382
genes like me logo Genes that share ontologies with SMAD3: view
genes like me logo Genes that share phenotypes with SMAD3: view

Human Phenotype Ontology for SMAD3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SMAD3 Gene

MGI Knock Outs for SMAD3:

Animal Model Products

Targeted motifs for SMAD3 Gene
HOMER Transcription Factor Regulatory Elements motif SMAD3
  • Consensus sequence: TWGTCTGV Submotif: canonical Cell Type: NPC GEO ID: GSE36673

Clone Products

  • Addgene plasmids for SMAD3

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targets for SMAD3 Gene

Localization for SMAD3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMAD3 Gene

Cytoplasm. Nucleus. Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 (PubMed:15799969). Through the action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1 (PubMed:16751101, PubMed:19289081). Co-localizes with LEMD3 at the nucleus inner membrane (PubMed:15601644). MAPK-mediated phosphorylation appears to have no effect on nuclear import (PubMed:19218245). PDPK1 prevents its nuclear translocation in response to TGF-beta (PubMed:17327236). {ECO:0000269 PubMed:15601644, ECO:0000269 PubMed:15799969, ECO:0000269 PubMed:16751101, ECO:0000269 PubMed:17327236, ECO:0000269 PubMed:19218245, ECO:0000269 PubMed:19289081}.

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 SMAD3 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 4
extracellular 3
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SMAD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 21828274
GO:0005622 intracellular IEA --
GO:0005634 nucleus IDA,IEA 9311995
GO:0005637 nuclear inner membrane IDA 15647271
GO:0005654 nucleoplasm IDA,TAS --
genes like me logo Genes that share ontologies with SMAD3: view

Pathways & Interactions for SMAD3 Gene

genes like me logo Genes that share pathways with SMAD3: view

Gene Ontology (GO) - Biological Process for SMAD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II TAS --
GO:0001501 skeletal system development IEA --
GO:0001649 osteoblast differentiation IEA --
GO:0001657 ureteric bud development IEA --
GO:0001666 response to hypoxia IMP 12411310
genes like me logo Genes that share ontologies with SMAD3: view

Drugs & Compounds for SMAD3 Gene

(21) Drugs for SMAD3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(19) Additional Compounds for SMAD3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SMAD3: view

Transcripts for SMAD3 Gene

Unigene Clusters for SMAD3 Gene

SMAD family member 3:
Representative Sequences:

Clone Products

  • Addgene plasmids for SMAD3

Alternative Splicing Database (ASD) splice patterns (SP) for SMAD3 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11a · 11b · 11c ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15a · 15b ^ 16 ^ 17
SP1: - - - - - - - - - -
SP2: - - - -
SP3: - - -
SP4: - - - - - -
SP5: - - - -
SP6: - - -
SP7: -
SP8: - - - - - - - - - - - - - - -
SP9:
SP10:
SP11: - - -

Relevant External Links for SMAD3 Gene

GeneLoc Exon Structure for
SMAD3
ECgene alternative splicing isoforms for
SMAD3

Expression for SMAD3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SMAD3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SMAD3 Gene

This gene is overexpressed in Breast (23.8) and Pancreas (7.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SMAD3 Gene



NURSA nuclear receptor signaling pathways regulating expression of SMAD3 Gene:

SMAD3

SOURCE GeneReport for Unigene cluster for SMAD3 Gene:

Hs.727986

Evidence on tissue expression from TISSUES for SMAD3 Gene

  • Nervous system(4.8)
  • Pancreas(4.6)
  • Lung(4.2)
  • Kidney(3.6)
  • Intestine(3.4)
  • Muscle(3.3)
  • Liver(3.1)
  • Skin(2.9)
  • Blood(2.8)
  • Heart(2.6)
  • Bone marrow(2.1)
  • Eye(2.1)
  • Lymph node(2)
  • Thyroid gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SMAD3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • meninges
  • mouth
  • neck
  • pharynx
  • skull
  • tooth
Thorax:
  • aorta
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • abdominal wall
  • intestine
Pelvis:
  • pelvis
  • uterus
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with SMAD3: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for SMAD3 Gene

Orthologs for SMAD3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMAD3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SMAD2 34
  • 100 (a)
OneToOne
SMAD3 33
  • 99.69 (n)
oppossum
(Monodelphis domestica)
Mammalia SMAD3 34
  • 99 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SMAD3 34
  • 99 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SMAD3 34 33
  • 94.2 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SMAD3 34 33
  • 94.12 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Smad3 16 34 33
  • 93.02 (n)
rat
(Rattus norvegicus)
Mammalia Smad3 33
  • 92.31 (n)
chicken
(Gallus gallus)
Aves SMAD3 34 33
  • 86.75 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 84 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia smad3 33
  • 83.25 (n)
African clawed frog
(Xenopus laevis)
Amphibia madh3-A 33
zebrafish
(Danio rerio)
Actinopterygii smad3a 34
  • 97 (a)
OneToMany
smad3b 34 33
  • 81 (n)
OneToMany
madh3b 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1591 33
fruit fly
(Drosophila melanogaster)
Insecta Smox 34 33
  • 67.22 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009777 33
  • 62.78 (n)
worm
(Caenorhabditis elegans)
Secernentea sma-2 34
  • 50 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 69 (a)
ManyToMany
-- 34
  • 51 (a)
ManyToMany
Species where no ortholog for SMAD3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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)
  • wheat (Triticum aestivum)

Evolution for SMAD3 Gene

ENSEMBL:
Gene Tree for SMAD3 (if available)
TreeFam:
Gene Tree for SMAD3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SMAD3: view image

Paralogs for SMAD3 Gene

Paralogs for SMAD3 Gene

(9) SIMAP similar genes for SMAD3 Gene using alignment to 9 proteins:

  • SMAD3_HUMAN
  • H0YKE2_HUMAN
  • H0YL71_HUMAN
  • H0YMP2_HUMAN
  • H0YMY0_HUMAN
  • H0YNV1_HUMAN
  • H3BP09_HUMAN
  • H3BQ00_HUMAN
  • H3BVD1_HUMAN
genes like me logo Genes that share paralogs with SMAD3: view

Variants for SMAD3 Gene

Sequence variations from dbSNP and Humsavar for SMAD3 Gene

SNP ID Clin Chr 15 pos Variation AA Info Type
rs1008630676 uncertain-significance, Loeys-Dietz syndrome, Thoracic aortic aneurysm and aortic dissection 67,192,355(+) C/T 3_prime_UTR_variant
rs1057518977 likely-pathogenic, Aneurysm 67,164,969(+) G/T 5_prime_UTR_variant, coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, upstream_transcript_variant
rs1060500764 uncertain-significance, Thoracic aortic aneurysm and aortic dissection 67,181,363(+) A/G coding_sequence_variant, missense_variant
rs1060500765 uncertain-significance, Thoracic aortic aneurysm and aortic dissection 67,190,448(+) A/G/T coding_sequence_variant, missense_variant
rs1060500766 uncertain-significance, Thoracic aortic aneurysm and aortic dissection 67,187,473(+) G/A coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for SMAD3 Gene

Variant ID Type Subtype PubMed ID
dgv457e199 CNV deletion 23128226
esv1009806 CNV deletion 20482838
esv1476959 CNV deletion 17803354
esv2749799 CNV deletion 23290073
esv3552596 CNV deletion 23714750
nsv1112279 CNV deletion 24896259
nsv1147295 CNV deletion 26484159
nsv457187 CNV loss 19166990
nsv507785 OTHER sequence alteration 20534489
nsv512399 CNV loss 21212237
nsv569796 CNV loss 21841781
nsv569797 CNV loss 21841781
nsv569798 CNV loss 21841781
nsv94737 CNV deletion 16902084
nsv958804 CNV deletion 24416366

Variation tolerance for SMAD3 Gene

Residual Variation Intolerance Score: 17.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.57; 44.65% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SMAD3 Gene

Human Gene Mutation Database (HGMD)
SMAD3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMAD3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMAD3 Gene

Disorders for SMAD3 Gene

MalaCards: The human disease database

(33) MalaCards diseases for SMAD3 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
loeys-dietz syndrome 3
  • aos
cutaneous polyarteritis nodosa
  • cutaneous pan
renal fibrosis
aortic aneurysm
  • abdominal aortic aneurysm, ruptured
aneurysm
  • aneurysms
- elite association - COSMIC cancer census association via MalaCards
Search SMAD3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SMAD3_HUMAN
  • Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269 PubMed:16959974}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
  • Loeys-Dietz syndrome 3 (LDS3) [MIM:613795]: An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation. {ECO:0000269 PubMed:21217753, ECO:0000269 PubMed:21778426}. Note=The disease is caused by mutations affecting the gene represented in this entry. SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:21778426). This phenotype is distinguised from LDS3 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit aneurysms of other arteries, including abdominal aorta, iliac, and/or intracranial arteries (PubMed:21778426), they have been classified as LDS3 by the OMIM resource. {ECO:0000269 PubMed:21778426}.

Additional Disease Information for SMAD3

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 SMAD3: view

No data available for Genatlas for SMAD3 Gene

Publications for SMAD3 Gene

  1. Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk. (PMID: 19255064) Ahn J … Prostate, Lung, Colorectal and Ovarian Trial Project Team (Carcinogenesis 2009) 3 22 44 58
  2. Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling. (PMID: 18794808) Guo X … Wang XF (Oncogene 2008) 3 4 22 58
  3. The mechanism of nuclear export of Smad3 involves exportin 4 and Ran. (PMID: 16449645) Kurisaki A … Moustakas A (Molecular and cellular biology 2006) 3 4 22 58
  4. Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. (PMID: 16156666) Matsuura I … Liu F (Biochemistry 2005) 3 4 22 58
  5. Novel function of androgen receptor-associated protein 55/Hic-5 as a negative regulator of Smad3 signaling. (PMID: 15561701) Wang H … Danielpour D (The Journal of biological chemistry 2005) 3 4 22 58

Products for SMAD3 Gene