Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
We will be switching to the new UniProt website soon. Please explore and share your feedback. Take me to the new website.

UniProtKB - P84022 (SMAD3_HUMAN)

Entry version 197 (23 Feb 2022)
Sequence version 1 (05 Jul 2004)
Previous versions | rss
Add a publicationFeedback
Protein

Mothers against decapentaplegic homolog 3

Gene

SMAD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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.

11 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei40Required for trimerization1
Sitei41Required for interaction with DNA and JUN and for functional cooperation with JUN1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi64Zinc1
Metal bindingi109Zinc1
Metal bindingi121Zinc1
Metal bindingi126Zinc1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDNA-binding
Biological processHost-virus interaction, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P84022

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1181150, Signaling by NODAL
R-HSA-1502540, Signaling by Activin
R-HSA-2173788, Downregulation of TGF-beta receptor signaling
R-HSA-2173789, TGF-beta receptor signaling activates SMADs
R-HSA-2173795, Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173796, SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-3304356, SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-3311021, SMAD4 MH2 Domain Mutants in Cancer
R-HSA-3315487, SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-3656532, TGFBR1 KD Mutants in Cancer
R-HSA-5689880, Ub-specific processing proteases
R-HSA-8941855, RUNX3 regulates CDKN1A transcription
R-HSA-8952158, RUNX3 regulates BCL2L11 (BIM) transcription
R-HSA-9008059, Interleukin-37 signaling
R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription
R-HSA-9615017, FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9617828, FOXO-mediated transcription of cell cycle genes

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P84022

SIGNOR Signaling Network Open Resource

More...SIGNORi		P84022

Protein family/group databases

MoonDB Database of extreme multifunctional and moonlighting proteins

More...MoonDBi		P84022, Predicted

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 3
Short name:
MAD homolog 3
Short name:
Mad3
Short name:
Mothers against DPP homolog 3
Short name:
hMAD-3
Alternative name(s):
JV15-2
SMAD family member 3
Short name:
SMAD 3
Short name:
Smad3
Short name:
hSMAD3
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SMAD3
Synonyms:MADH3
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 15

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:6769, SMAD3

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603109, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P84022

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000166949

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Colorectal cancer (CRC)1 Publication
The disease may be caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Loeys-Dietz syndrome 3 (LDS3)2 Publications
The disease is caused by variants 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.1 Publication
Disease descriptionAn 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_067051112A → V in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906854EnsemblClinVar.1
Natural variantiVAR_067047239E → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906853EnsemblClinVar.1
Natural variantiVAR_065578261T → I in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906851EnsemblClinVar.1
Natural variantiVAR_067048279R → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906852EnsemblClinVar.1
Natural variantiVAR_065579287R → W in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906850EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi8T → V: Reduced phosphorylation, increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-179 and A-213. 1 Publication1
Mutagenesisi33K → R: Slightly decreased monoubiquitination. 1 Publication1
Mutagenesisi40K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-41; A-43 and A-44. 1 Publication1
Mutagenesisi41K → A: Greatly reduced interaction with DNA and JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-44 and A-43. 1 Publication1
Mutagenesisi43K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-41 and A-44. 1 Publication1
Mutagenesisi44K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with JUN; when associated with A-40; A-41 and A-43. 1 Publication1
Mutagenesisi53K → R: Slightly decreased monoubiquitination. 1 Publication1
Mutagenesisi74R → D: Reduced interaction with JUN. Loss of transcriptional activity and cooperation with JUN. 1 Publication1
Mutagenesisi81K → R: Decreased monoubiquitination. 1 Publication1
Mutagenesisi179T → V: Reduced phosphorylation, increased transcriptional and increased antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and A-213. 3 Publications1
Mutagenesisi204S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. 3 Publications1
Mutagenesisi208S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. 3 Publications1
Mutagenesisi213S → A: Reduced phosphorylation. Increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and V-179. 1 Publication1
Mutagenesisi333K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-341; R-378 and R-409. 1 Publication1
Mutagenesisi341K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-378 and R-409. 1 Publication1
Mutagenesisi378K → Q: Increased transcriptional activity. No further increase in transcriptional activity with EP300. 1 Publication1
Mutagenesisi378K → R: Greatly reduced acetylation and 85% reduction in transcriptional activity. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-409. 1 Publication1
Mutagenesisi409K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-378. 1 Publication1
Mutagenesisi418S → A: Increased constitutive activity. 1 Publication1
Mutagenesisi418S → D: Decreased activity. 1 Publication1
Mutagenesisi422 – 425SSVS → AAVA: Does not abolish protein nuclear export. Abolishes almost completely acetylation. 3 Publications4
Mutagenesisi422 – 425SSVS → EEVE: Forms heterotrimers. 3 Publications4
Mutagenesisi422 – 425SSVS → RRVR: Diminishes cargo protein export. 3 Publications4

Keywords - Diseasei

Aortic aneurysm, Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		4088

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		SMAD3

MalaCards human disease database

More...MalaCardsi		SMAD3
MIMi114500, phenotype
613795, phenotype

Open Targets

More...OpenTargetsi		ENSG00000166949

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		284984, Aneurysm-osteoarthritis syndrome
91387, Familial thoracic aortic aneurysm and aortic dissection

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA30526

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P84022, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1293258

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		SMAD3

Domain mapping of disease mutations (DMDM)

More...DMDMi		51338669

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000908562 – 425Mothers against decapentaplegic homolog 3Add BLAST424

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylserineCombined sources1
Modified residuei8Phosphothreonine; by CDK2 and CDK41 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki81Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei179Phosphothreonine; by CDK2, CDK4 and MAPK3 Publications1
Modified residuei204Phosphoserine; by GSK3 and MAPKPROSITE-ProRule annotation3 Publications1
Modified residuei208Phosphoserine; by MAPKPROSITE-ProRule annotation3 Publications1
Modified residuei213Phosphoserine; by CDK2 and CDK4PROSITE-ProRule annotation1 Publication1
Modified residuei378N6-acetyllysine1 Publication1
Modified residuei416PhosphoserineCombined sources1
Modified residuei418Phosphoserine; by CK1PROSITE-ProRule annotation1 Publication1
Modified residuei422Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1
Modified residuei423Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1
Modified residuei425Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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 G1/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 PDPK1.10 Publications
Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.1 Publication
Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.1 Publication
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).By similarity2 Publications

Keywords - PTMi

Acetylation, ADP-ribosylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P84022

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P84022

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P84022

MaxQB - The MaxQuant DataBase

More...MaxQBi		P84022

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P84022

PeptideAtlas

More...PeptideAtlasi		P84022

PRoteomics IDEntifications database

More...PRIDEi		P84022

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		26192
57743 [P84022-1]
57744 [P84022-2]
57745 [P84022-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P84022

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P84022

SwissPalm database of S-palmitoylation events

More...SwissPalmi		P84022

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000166949, Expressed in amniotic fluid and 242 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P84022, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P84022, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000166949, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer; in the absence of TGF-beta (PubMed:9670020). Homooligomer; in the presence of TGF-beta (PubMed:9670020). 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 (PubMed:9670020, PubMed:11224571, PubMed:15799969, PubMed:15350224).

Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:9892009).

Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta (PubMed:16751102).

Found in a complex composed of SMAD3, RAN and XPO4; within the complex interacts directly with XPO4 (PubMed:16449645).

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 (PubMed:9732876, PubMed:10995748).

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 (PubMed:9732876, PubMed:10995748).

Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267).

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 (PubMed:16751101).

Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (PubMed:16777850).

Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD3 inhibitors (PubMed:9311995).

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 (PubMed:19289081).

Interacts (via 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 (PubMed:15601644, PubMed:15647271).

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 (PubMed:9843571, PubMed:15588252). 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 (PubMed:9843571, PubMed:15588252).

Interacts with TGFBR1 (PubMed:9311995).

Interacts with TGFB1I1 (PubMed:15561701).

Interacts with PRDM16 (PubMed:19049980).

Interacts with SNW1 (PubMed:11278756).

Interacts (via MH2 domain) with ZFYVE9 (PubMed:9865696, PubMed:12154125).

Interacts with HDAC1 (PubMed:19049980).

Interacts with TGIF2 (PubMed:11427533).

Interacts with SKOR1 (PubMed:17292623).

Interacts with SKOR2 (PubMed:16200078).

Interacts with DACH1; the interaction inhibits the TGF-beta signaling (PubMed:14525983).

Interacts with RBPMS (PubMed:17099224).

Interacts (via MH2 domain) with MECOM (PubMed:9665135, PubMed:15897867).

Interacts with WWTR1 (via its coiled-coil domain) (PubMed:18568018).

Interacts with SKI; the interaction represses SMAD3 transcriptional activity (PubMed:19049980).

Interacts with MEN1 (PubMed:11274402).

Interacts with IL1F7 (PubMed:20935647). Interaction with CSNK1G2 (PubMed:18794808).

Interacts with PDPK1 (via PH domain) (PubMed:17327236).

Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation (PubMed:11387212).

Interacts with USP15 (PubMed:21947082).

Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation and protein levels (PubMed:22781750).

Interacts with LDLRAD4 (via the SMAD interaction motif) (PubMed:24627487).

Interacts with PMEPA1 (PubMed:20129061).

Interacts with ZNF451 (PubMed:24324267).

Interacts with ZFHX3 (PubMed:25105025).

Interacts weakly with ZNF8 (PubMed:12370310).

Interacts with STUB1, HSPA1A, HSPA1B, HSP90AA1 and HSP90AB1 (PubMed:24613385).

Interacts with YAP1 (when phosphorylated at 'Ser-127') (By similarity).

Interacts with AIP1 (By similarity).

Interacts (via MH2 domain) with CITED2 (via C-terminus) (By similarity).

Interacts with HGS (By similarity).

Interacts with WWP1 (By similarity).

Interacts with TTRAP (By similarity).

Interacts with FOXL2 (By similarity).

Interacts with PML (By similarity).

Interacts with NEDD4L; the interaction requires TGF-beta stimulation (By similarity).

Interacts with ZC3H3 (By similarity).

Interacts with TGIF.

Interacts with CREBBP.

Interacts with ATF2.

By similarity43 Publications

(Microbial infection) Interacts with SARS-CoV nucleoprotein.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

P84022
With#Exp.IntAct
APLP2 - isoform 5 [Q06481-5]3EBI-347161,EBI-25646567
APP [P05067]3EBI-347161,EBI-77613
BLZF1 [Q9H2G9]9EBI-347161,EBI-2548012
CAMK2A [Q9UQM7]3EBI-347161,EBI-1383687
CASP1 - isoform Gamma [P29466-3]3EBI-347161,EBI-12248206
CCDC198 [E9PSE9]3EBI-347161,EBI-11748295
CCDC33 [Q8N5R6]4EBI-347161,EBI-11522976
CHRD [Q9H2X0]2EBI-347161,EBI-947551
CPSF7 [Q8N684]3EBI-347161,EBI-746909
CPSF7 - isoform 3 [Q8N684-3]3EBI-347161,EBI-11523759
CRX [O43186]3EBI-347161,EBI-748171
CSMD1 [Q96PZ7]3EBI-347161,EBI-766158
CSNK1D - isoform 2 [P48730-2]3EBI-347161,EBI-9087876
DAB2 [P98082]3EBI-347161,EBI-1171238
DDX5 [P17844]2EBI-347161,EBI-351962
DOCK9 [Q9BZ29]3EBI-347161,EBI-2695893
FAM90A1 [Q86YD7]3EBI-347161,EBI-6658203
FLI1 [Q01543]3EBI-347161,EBI-2271018
FOXH1 [O75593]4EBI-347161,EBI-1759806
FOXO3 [O43524]5EBI-347161,EBI-1644164
GLI2 [P10070]4EBI-347161,EBI-10821567
HIF1A [Q16665]6EBI-347161,EBI-447269
IPO8 [O15397]2EBI-347161,EBI-358808
JPH3 [Q8WXH2]3EBI-347161,EBI-1055254
MEOX2 [P50222]6EBI-347161,EBI-748397
MTMR4 [Q9NYA4]2EBI-347161,EBI-1052346
MYD88 [Q99836]3EBI-347161,EBI-447677
NEDD4 - isoform 3 [P46934-3]3EBI-347161,EBI-11980721
PCK2 [Q16822]2EBI-347161,EBI-2825219
PHC2 [Q8IXK0]3EBI-347161,EBI-713786
PHC2 - isoform 5 [Q8IXK0-5]3EBI-347161,EBI-11527347
PIK3R1 - isoform 2 [P27986-2]3EBI-347161,EBI-9090282
PPP1R12C [Q9BZL4]2EBI-347161,EBI-721802
PRKACA [P17612]3EBI-347161,EBI-476586
PSMB1 [P20618]3EBI-347161,EBI-372273
RNF31 [Q96EP0]2EBI-347161,EBI-948111
SBK3 [P0C264]3EBI-347161,EBI-17181801
SETD2 [Q9BYW2]2EBI-347161,EBI-945869
SKI [P12755]8EBI-347161,EBI-347281
SMAD2 [Q15796]2EBI-347161,EBI-1040141
itself3EBI-347161,EBI-347161
SMAD4 [Q13485]35EBI-347161,EBI-347263
SMURF2 [Q9HAU4]8EBI-347161,EBI-396727
SNW1 [Q13573]5EBI-347161,EBI-632715
SQSTM1 [Q13501]3EBI-347161,EBI-307104
TEKT4 [Q8WW24]3EBI-347161,EBI-750487
TGIF1 [Q15583]3EBI-347161,EBI-714215
TLE5 [Q08117]4EBI-347161,EBI-717810
TLE5 - isoform 2 [Q08117-2]3EBI-347161,EBI-11741437
TSC22D4 [Q9Y3Q8]2EBI-347161,EBI-739485
USP7 [Q93009]2EBI-347161,EBI-302474
WWP1 [Q9H0M0]9EBI-347161,EBI-742157
WWP2 [O00308]7EBI-347161,EBI-743923
ZC3H12A [Q5D1E8]2EBI-347161,EBI-747793
ZFYVE9 [O95405]5EBI-347161,EBI-296817
ZNF774 [Q6NX45]3EBI-347161,EBI-10251462
Tgfbr1 [Q64729] from Mus musculus.6EBI-347161,EBI-2899393
Core protein precursor (PRO_0000278742) from Hepatitis C virus genotype 1b (strain HC-J4).6EBI-347161,EBI-9213553

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		110263, 388 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-1, SMAD2-SMAD3-SMAD4 complex
CPX-12, SMAD3 homotrimer
CPX-3252, SMAD3-SMAD4 complex
CPX-6062, SMAD3-TTF-1 complex

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P84022

Database of interacting proteins

More...DIPi		DIP-29720N

Protein interaction database and analysis system

More...IntActi		P84022, 211 interactors

Molecular INTeraction database

More...MINTi		P84022

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000332973

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P84022

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P84022, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P84022

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P84022

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini10 – 136MH1PROSITE-ProRule annotationAdd BLAST127
Domaini232 – 425MH2PROSITE-ProRule annotationAdd BLAST194

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni137 – 231LinkerAdd BLAST95
Regioni165 – 208DisorderedSequence analysisAdd BLAST44
Regioni271 – 324Sufficient for interaction with XPO41 PublicationAdd BLAST54

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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.

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3701, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000153499

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_026736_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P84022

Identification of Orthologs from Complete Genome Data

More...OMAi		MGSPNIR

Database for complete collections of gene phylogenies

More...PhylomeDBi		P84022

TreeFam database of animal gene trees

More...TreeFami		TF314923

Family and domain databases

Database of protein disorder

More...DisProti		DP01648

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.60.200.10, 1 hit
3.90.520.10, 1 hit

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...IDEALi		IID00113

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR013790, Dwarfin
IPR003619, MAD_homology1_Dwarfin-type
IPR013019, MAD_homology_MH1
IPR017855, SMAD-like_dom_sf
IPR001132, SMAD_dom_Dwarfin-type
IPR008984, SMAD_FHA_dom_sf
IPR036578, SMAD_MH1_sf

The PANTHER Classification System

More...PANTHERi		PTHR13703, PTHR13703, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF03165, MH1, 1 hit
PF03166, MH2, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00523, DWA, 1 hit
SM00524, DWB, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF49879, SSF49879, 1 hit
SSF56366, SSF56366, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51075, MH1, 1 hit
PS51076, MH2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P84022-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE 
        60         70         80         90        100
LEKAITTQNV NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH 
       110        120        130        140        150
HELRAMELCE FAFNMKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF 
       160        170        180        190        200
PPLDDYSHSI PENTNFPAGI EPQSNIPETP PPGYLSEDGE TSDHQMNHSM 
       210        220        230        240        250
DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL NQRVGETFHA 
       260        270        280        290        300
SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG 
       310        320        330        340        350
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA 
       360        370        380        390        400
LLAQSVNQGF EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL 
       410        420 
NGPLQWLDKV LTQMGSPSIR CSSVS
Length:425
Mass (Da):48,081
Last modified:July 5, 2004 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i46DF5E8B371321AC
GO
Isoform 2 (identifier: P84022-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: MSSILPFTPP...NVNTKCITIP → MSCLHPRQTWKGAALVHRKAWWMG

Show »
Length:381
Mass (Da):43,237
Checksum:iD436B607B2677761
GO
Isoform 3 (identifier: P84022-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.

Show »
Length:320
Mass (Da):35,895
Checksum:iCB3D9B2D53AAC9E9
GO
Isoform 4 (identifier: P84022-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-195: Missing.

Show »
Length:230
Mass (Da):25,722
Checksum:iAFC64318B5EC08D1
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BVD1H3BVD1_HUMAN
Mothers against decapentaplegic hom...
SMAD3
213Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BP09H3BP09_HUMAN
Mothers against decapentaplegic hom...
SMAD3
114Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YNV1H0YNV1_HUMAN
Mothers against decapentaplegic hom...
SMAD3
84Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YKE2H0YKE2_HUMAN
Mothers against decapentaplegic hom...
SMAD3
112Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YL71H0YL71_HUMAN
Mothers against decapentaplegic hom...
SMAD3
92Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YMP2H0YMP2_HUMAN
Mothers against decapentaplegic hom...
SMAD3
63Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BQ00H3BQ00_HUMAN
Mothers against decapentaplegic hom...
SMAD3
156Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YMY0H0YMY0_HUMAN
Mothers against decapentaplegic hom...
SMAD3
96Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti178E → EVGTWAAQAGL in BAA22032 (PubMed:9464505).Curated1
Sequence conflicti360F → L in BAH13315 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067051112A → V in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906854EnsemblClinVar.1
Natural variantiVAR_052021170I → V. Corresponds to variant dbSNP:rs35874463EnsemblClinVar.1
Natural variantiVAR_067047239E → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906853EnsemblClinVar.1
Natural variantiVAR_065578261T → I in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906851EnsemblClinVar.1
Natural variantiVAR_067048279R → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906852EnsemblClinVar.1
Natural variantiVAR_065579287R → W in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906850EnsemblClinVar.1
Natural variantiVAR_036474393P → L in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0453481 – 195Missing in isoform 4. 1 PublicationAdd BLAST195
Alternative sequenceiVSP_0437931 – 105Missing in isoform 3. 1 PublicationAdd BLAST105
Alternative sequenceiVSP_0429001 – 68MSSIL…CITIP → MSCLHPRQTWKGAALVHRKA WWMG in isoform 2. 1 PublicationAdd BLAST68

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
U68019 mRNA Translation: AAB80960.1
U76622 mRNA Translation: AAB18967.1
AB004930 Genomic DNA Translation: BAA22032.1
AF025300 AF025299 Genomic DNA Translation: AAL68976.1
AK290881 mRNA Translation: BAF83570.1
AK298139 mRNA Translation: BAH12731.1
AK300614 mRNA Translation: BAH13315.1
AK316017 mRNA Translation: BAH14388.1
AC012568 Genomic DNA No translation available.
AC087482 Genomic DNA No translation available.
CH471082 Genomic DNA Translation: EAW77788.1
BC050743 mRNA Translation: AAH50743.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS10222.1 [P84022-1]
CCDS45288.1 [P84022-2]
CCDS53950.1 [P84022-3]
CCDS53951.1 [P84022-4]

Protein sequence database of the Protein Information Resource

More...PIRi		S71798

NCBI Reference Sequences

More...RefSeqi		NP_001138574.1, NM_001145102.1 [P84022-3]
NP_001138575.1, NM_001145103.1 [P84022-2]
NP_001138576.1, NM_001145104.1 [P84022-4]
NP_005893.1, NM_005902.3 [P84022-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000327367; ENSP00000332973; ENSG00000166949
ENST00000439724; ENSP00000401133; ENSG00000166949 [P84022-2]
ENST00000537194; ENSP00000445348; ENSG00000166949 [P84022-4]
ENST00000540846; ENSP00000437757; ENSG00000166949 [P84022-3]
ENST00000679624; ENSP00000505445; ENSG00000166949 [P84022-3]
ENST00000681239; ENSP00000505641; ENSG00000166949 [P84022-3]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		4088

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:4088

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000327367.9; ENSP00000332973.4; NM_005902.4; NP_005893.1

UCSC genome browser

More...UCSCi		uc002aqj.4, human [P84022-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68019 mRNA Translation: AAB80960.1
U76622 mRNA Translation: AAB18967.1
AB004930 Genomic DNA Translation: BAA22032.1
AF025300 AF025299 Genomic DNA Translation: AAL68976.1
AK290881 mRNA Translation: BAF83570.1
AK298139 mRNA Translation: BAH12731.1
AK300614 mRNA Translation: BAH13315.1
AK316017 mRNA Translation: BAH14388.1
AC012568 Genomic DNA No translation available.
AC087482 Genomic DNA No translation available.
CH471082 Genomic DNA Translation: EAW77788.1
BC050743 mRNA Translation: AAH50743.1
CCDSiCCDS10222.1 [P84022-1]
CCDS45288.1 [P84022-2]
CCDS53950.1 [P84022-3]
CCDS53951.1 [P84022-4]
PIRiS71798
RefSeqiNP_001138574.1, NM_001145102.1 [P84022-3]
NP_001138575.1, NM_001145103.1 [P84022-2]
NP_001138576.1, NM_001145104.1 [P84022-4]
NP_005893.1, NM_005902.3 [P84022-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MHDX-ray2.80A/B1-132[»]
1MJSX-ray1.91A229-425[»]
1MK2X-ray2.74A220-425[»]
1OZJX-ray2.40A/B1-144[»]
1U7FX-ray2.60A/C228-425[»]
2LAJNMR-B202-211[»]
2LB2NMR-B178-189[»]
5OD6X-ray2.00A/B11-135[»]
5ODGX-ray2.12A/B11-135[»]
5XOCX-ray2.40A220-416[»]
6YIBX-ray1.70P417-425[»]
6ZMNX-ray2.33A/B10-136[»]
SMRiP84022
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi110263, 388 interactors
ComplexPortaliCPX-1, SMAD2-SMAD3-SMAD4 complex
CPX-12, SMAD3 homotrimer
CPX-3252, SMAD3-SMAD4 complex
CPX-6062, SMAD3-TTF-1 complex
CORUMiP84022
DIPiDIP-29720N
IntActiP84022, 211 interactors
MINTiP84022
STRINGi9606.ENSP00000332973

Chemistry databases

BindingDBiP84022
ChEMBLiCHEMBL1293258

Protein family/group databases

MoonDBiP84022, Predicted

PTM databases

iPTMnetiP84022
PhosphoSitePlusiP84022
SwissPalmiP84022

Genetic variation databases

BioMutaiSMAD3
DMDMi51338669

Proteomic databases

EPDiP84022
jPOSTiP84022
MassIVEiP84022
MaxQBiP84022
PaxDbiP84022
PeptideAtlasiP84022
PRIDEiP84022
ProteomicsDBi26192
57743 [P84022-1]
57744 [P84022-2]
57745 [P84022-3]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		P84022, 2 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		26224, 2368 antibodies from 44 providers

The DNASU plasmid repository

More...DNASUi		4088

Genome annotation databases

EnsembliENST00000327367; ENSP00000332973; ENSG00000166949
ENST00000439724; ENSP00000401133; ENSG00000166949 [P84022-2]
ENST00000537194; ENSP00000445348; ENSG00000166949 [P84022-4]
ENST00000540846; ENSP00000437757; ENSG00000166949 [P84022-3]
ENST00000679624; ENSP00000505445; ENSG00000166949 [P84022-3]
ENST00000681239; ENSP00000505641; ENSG00000166949 [P84022-3]
GeneIDi4088
KEGGihsa:4088
MANE-SelectiENST00000327367.9; ENSP00000332973.4; NM_005902.4; NP_005893.1
UCSCiuc002aqj.4, human [P84022-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		4088
DisGeNETi4088

GeneCards: human genes, protein and diseases

More...GeneCardsi		SMAD3
GeneReviewsiSMAD3
HGNCiHGNC:6769, SMAD3
HPAiENSG00000166949, Low tissue specificity
MalaCardsiSMAD3
MIMi114500, phenotype
603109, gene
613795, phenotype
neXtProtiNX_P84022
OpenTargetsiENSG00000166949
Orphaneti284984, Aneurysm-osteoarthritis syndrome
91387, Familial thoracic aortic aneurysm and aortic dissection
PharmGKBiPA30526
VEuPathDBiHostDB:ENSG00000166949

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3701, Eukaryota
GeneTreeiENSGT00940000153499
HOGENOMiCLU_026736_0_0_1
InParanoidiP84022
OMAiMGSPNIR
PhylomeDBiP84022
TreeFamiTF314923

Enzyme and pathway databases

PathwayCommonsiP84022
ReactomeiR-HSA-1181150, Signaling by NODAL
R-HSA-1502540, Signaling by Activin
R-HSA-2173788, Downregulation of TGF-beta receptor signaling
R-HSA-2173789, TGF-beta receptor signaling activates SMADs
R-HSA-2173795, Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173796, SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-3304356, SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-3311021, SMAD4 MH2 Domain Mutants in Cancer
R-HSA-3315487, SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-3656532, TGFBR1 KD Mutants in Cancer
R-HSA-5689880, Ub-specific processing proteases
R-HSA-8941855, RUNX3 regulates CDKN1A transcription
R-HSA-8952158, RUNX3 regulates BCL2L11 (BIM) transcription
R-HSA-9008059, Interleukin-37 signaling
R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription
R-HSA-9615017, FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9617828, FOXO-mediated transcription of cell cycle genes
SignaLinkiP84022
SIGNORiP84022

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		4088, 9 hits in 1072 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		SMAD3, human
EvolutionaryTraceiP84022

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Mothers_against_decapentaplegic_homolog_3

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		4088
PharosiP84022, Tbio

Protein Ontology

More...PROi		PR:P84022
RNActiP84022, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000166949, Expressed in amniotic fluid and 242 other tissues
ExpressionAtlasiP84022, baseline and differential
GenevisibleiP84022, HS

Family and domain databases

DisProtiDP01648
Gene3Di2.60.200.10, 1 hit
3.90.520.10, 1 hit
IDEALiIID00113
InterProiView protein in InterPro
IPR013790, Dwarfin
IPR003619, MAD_homology1_Dwarfin-type
IPR013019, MAD_homology_MH1
IPR017855, SMAD-like_dom_sf
IPR001132, SMAD_dom_Dwarfin-type
IPR008984, SMAD_FHA_dom_sf
IPR036578, SMAD_MH1_sf
PANTHERiPTHR13703, PTHR13703, 1 hit
PfamiView protein in Pfam
PF03165, MH1, 1 hit
PF03166, MH2, 1 hit
SMARTiView protein in SMART
SM00523, DWA, 1 hit
SM00524, DWB, 1 hit
SUPFAMiSSF49879, SSF49879, 1 hit
SSF56366, SSF56366, 1 hit
PROSITEiView protein in PROSITE
PS51075, MH1, 1 hit
PS51076, MH2, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSMAD3_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P84022
Secondary accession number(s): A8K4B6
, B7Z4Z5, B7Z6M9, B7Z9Q2, F5H383, O09064, O09144, O14510, O35273, Q92940, Q93002, Q9GKR4
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: July 5, 2004
Last modified: February 23, 2022
This is version 197 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again