Smad3 SMAD family member 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Smad3provided by MGI
Official Full Name: SMAD family member 3provided by MGI
Primary source: MGI:MGI:1201674
See related: Ensembl:ENSMUSG00000032402 AllianceGenome:MGI:1201674
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Madh3
Summary: Enables several functions, including DNA binding activity; DNA-binding transcription activator activity, RNA polymerase II-specific; and promoter-specific chromatin binding activity. Involved in several processes, including JNK cascade; negative regulation of osteoblast proliferation; and positive regulation of chondrocyte differentiation. Acts upstream of or within several processes, including animal organ development; regulation of transcription by RNA polymerase II; and transmembrane receptor protein serine/threonine kinase signaling pathway. Located in cytoplasm; nucleus; and plasma membrane. Is expressed in several structures, including alimentary system; early conceptus; genitourinary system; limb; and nervous system. Used to study osteoarthritis. Human ortholog(s) of this gene implicated in Loeys-Dietz syndrome 3; Lynch syndrome; and pancreatic cancer. Orthologous to human SMAD3 (SMAD family member 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in ovary adult (RPKM 18.8), limb E14.5 (RPKM 18.2) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 C; 9 34.22 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (63554048..63665276, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (63646766..63757994, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction.
Title: A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction.
Integrin beta8 prevents pericyte-myofibroblast transition and renal fibrosis through inhibiting the TGF-beta1/TGFBR1/Smad3 pathway in diabetic kidney disease.
Title: Integrin β8 prevents pericyte-myofibroblast transition and renal fibrosis through inhibiting the TGF-β1/TGFBR1/Smad3 pathway in diabetic kidney disease.
miR-129-2-3p mediates LPS-induced macrophage polarization and ferroptosis by targeting the SMAD3-GPX4 axis.
Title: miR-129-2-3p mediates LPS-induced macrophage polarization and ferroptosis by targeting the SMAD3-GPX4 axis.
Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition.
Title: Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition.
circEIF3I facilitates the recruitment of SMAD3 to early endosomes to promote TGF-beta signalling pathway-mediated activation of MMPs in pancreatic cancer.
Title: circEIF3I facilitates the recruitment of SMAD3 to early endosomes to promote TGF-β signalling pathway-mediated activation of MMPs in pancreatic cancer.
Tsp-1[+] microglia attenuate retinal neovascularization by maintaining the expression of Smad3 in endothelial cells through exosomes with decreased miR-27a-5p.
Title: Tsp-1(+) microglia attenuate retinal neovascularization by maintaining the expression of Smad3 in endothelial cells through exosomes with decreased miR-27a-5p.
Smad3 Mediates Diabetic Dyslipidemia and Fatty Liver in db/db Mice by Targeting PPARdelta.
Title: Smad3 Mediates Diabetic Dyslipidemia and Fatty Liver in db/db Mice by Targeting PPARδ.
CTRP3 regulates NF-kappaB and TGFbeta1/Smad3 pathways to alleviate airway inflammation and remodeling in asthmatic mice induced by OVA.
Title: CTRP3 regulates NF-κB and TGFβ1/Smad3 pathways to alleviate airway inflammation and remodeling in asthmatic mice induced by OVA.
Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC.
Title: Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC.
Estrogen receptor beta attenuates renal fibrosis by suppressing the transcriptional activity of Smad3.
Title: Estrogen receptor β attenuates renal fibrosis by suppressing the transcriptional activity of Smad3.

Submit: New GeneRIF Correction See all GeneRIFs (417)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (5) 1 citation
Endonuclease-mediated (7)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Smad3 (e-PCR), detects polymorphism
- UniSTS:480349

Smad3 (e-PCR), detects polymorphism
- UniSTS:466571

RH138729 (e-PCR)
- UniSTS:220816

AU022421 (e-PCR)
- UniSTS:159888

Madh3 (e-PCR), detects polymorphism
- UniSTS:143810

Madh3 (e-PCR), detects polymorphism
- UniSTS:143811

Madh3 (e-PCR), detects polymorphism
- UniSTS:143812

NoName (e-PCR)
- UniSTS:548548

Madh3 (e-PCR), detects polymorphism
- UniSTS:143813

Madh3 (e-PCR), detects polymorphism
- UniSTS:143814

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DEAD/H-box RNA helicase binding	ISO Inferred from Sequence Orthology more info
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IPI Inferred from Physical Interaction more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription repressor activity	ISO Inferred from Sequence Orthology more info
enables I-SMAD binding	IBA Inferred from Biological aspect of Ancestor more info
enables R-SMAD binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables bHLH transcription factor binding	ISO Inferred from Sequence Orthology more info
enables beta-catenin binding	ISO Inferred from Sequence Orthology more info
enables chromatin DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables co-SMAD binding	ISO Inferred from Sequence Orthology more info
enables collagen binding	IPI Inferred from Physical Interaction more info	PubMed
enables double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nuclear glucocorticoid receptor binding	ISO Inferred from Sequence Orthology more info
enables nuclear mineralocorticoid receptor binding	ISO Inferred from Sequence Orthology more info
enables nuclear receptor binding	ISO Inferred from Sequence Orthology more info
enables phosphatase binding	ISO Inferred from Sequence Orthology more info
enables promoter-specific chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables sterol response element binding	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info
enables transcription coactivator binding	ISO Inferred from Sequence Orthology more info
enables transcription corepressor binding	ISO Inferred from Sequence Orthology more info
enables transforming growth factor beta receptor binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in SMAD protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within SMAD protein signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of SMAD protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in SMAD protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in T cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in activin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in activin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in activin receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in adrenal gland development	ISO Inferred from Sequence Orthology more info
involved_in anatomical structure morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell-cell junction organization	ISO Inferred from Sequence Orthology more info
involved_in cellular response to transforming growth factor beta stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to virus	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within developmental growth	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic cranial skeleton morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic foregut morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic pattern specification	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within endoderm development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in extrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within gastrulation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within heart looping	IGI Inferred from Genetic Interaction more info	PubMed
involved_in immune response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within immune system development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within in utero embryonic development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within lens fiber cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within liver development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within mesoderm formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cardiac muscle hypertrophy in response to stress	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cytosolic calcium ion concentration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of fat cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of lung blood pressure	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of miRNA transcription	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of osteoblast differentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of osteoblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of wound healing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nodal signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within osteoblast development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within paraxial mesoderm morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pericardium development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of bone mineralization	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chondrocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of epithelial to mesenchymal transition	ISO Inferred from Sequence Orthology more info
acts_upstream_of positive regulation of extracellular matrix assembly	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of focal adhesion assembly	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-1 beta production	ISO Inferred from Sequence Orthology more info
acts_upstream_of positive regulation of miRNA transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of nitric oxide biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of positive chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of stress fiber assembly	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transforming growth factor beta3 production	ISO Inferred from Sequence Orthology more info
involved_in protein stabilization	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within regulation of binding	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of immune response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of striated muscle tissue development	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in regulation of transforming growth factor beta2 production	ISO Inferred from Sequence Orthology more info
acts_upstream_of response to angiotensin	ISO Inferred from Sequence Orthology more info
involved_in response to hypoxia	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to transforming growth factor beta	IGI Inferred from Genetic Interaction more info	PubMed
involved_in signal transduction involved in regulation of gene expression	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within skeletal system development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within somitogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within thyroid gland development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in transdifferentiation	ISO Inferred from Sequence Orthology more info
involved_in transforming growth factor beta receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in transforming growth factor beta receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in ureteric bud development	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
part_of SMAD protein complex	ISO Inferred from Sequence Orthology more info
part_of chromatin	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
part_of heteromeric SMAD protein complex	IBA Inferred from Biological aspect of Ancestor more info
part_of heteromeric SMAD protein complex	ISO Inferred from Sequence Orthology more info
part_of heteromeric SMAD protein complex	NAS Non-traceable Author Statement more info	PubMed
located_in nuclear inner membrane	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	ISO Inferred from Sequence Orthology more info
part_of transcription regulator complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: mothers against decapentaplegic homolog 3

Names: MAD homolog 3; Smad 3; mMad3; mad3; mothers against DPP homolog 3

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_016769.4 → NP_058049.3 mothers against decapentaplegic homolog 3

See identical proteins and their annotated locations for NP_058049.3

Status: VALIDATED

Source sequence(s)

AC158515, AK048626, AK083158

Consensus CDS

CCDS23272.1

UniProtKB/Swiss-Prot

Q8BUN5, Q8BX84

UniProtKB/TrEMBL

Q3V3E0

Related

ENSMUSP00000034973.4, ENSMUST00000034973.10

Conserved Domains (2) summary

cd10491
Location:8 → 132

MH1_SMAD_2_3; N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3

cd10985
Location:224 → 414

MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

63554048..63665276 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006510819.4 → XP_006510882.3 mothers against decapentaplegic homolog 3 isoform X1

UniProtKB/TrEMBL

Q3V3E0

Conserved Domains (2) summary

cd10985
Location:192 → 382

MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3

cl00055
Location:37 → 100

MH1; N-terminal Mad Homology 1 (MH1) domain
XM_006510821.5 → XP_006510884.1 mothers against decapentaplegic homolog 3 isoform X2

See identical proteins and their annotated locations for XP_006510884.1

Conserved Domains (1) summary

cd10985
Location:29 → 219

MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3