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Center for Computational Systems Medicine
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Protein Summary

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AS Summary

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Protein Functional Features

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Gene Isoform Structures and Expression Levels

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Protein Structures

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pLDDT Score Distribution

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Ramachandran Plot of Protein Structures

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Potential Active Site Information

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Protein Structure and Feature Comparision

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Protein-Protein Interaction

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Related Drugs

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Related Diseases

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Clinically Important Variants

Protein:SMAD3

Protein Summary

check button Gene summary
Gene name: SMAD3
ASpdb.0 ID: 4088
Gene
Gene symbol

SMAD3

Gene ID

4088

Gene nameSMAD family member 3
SynonymsHSPC193|HsT17436|JV15-2|LDS1C|LDS3|MADH3|hMAD-3|hSMAD3|mad3
Cytomap

15q22.33

Type of geneprotein-coding
Descriptionmothers against decapentaplegic homolog 3MAD homolog 3MAD, mothers against decapentaplegic homolog 3SMA- and MAD-related protein 3SMAD, mothers against DPP homolog 3mad homolog JV15-2mad protein homologmothers against DPP homolog 3
Modification date20240416
UniProtAcc

P84022


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneSMAD3

GO:0000122

negative regulation of transcription by RNA polymerase II

8774881|28467929

GeneSMAD3

GO:0000785

chromatin

21828274

GeneSMAD3

GO:0000976

transcription cis-regulatory region binding

9732876

GeneSMAD3

GO:0000978

RNA polymerase II cis-regulatory region sequence-specific DNA binding

18832382|21947082|24378993|31582430

GeneSMAD3

GO:0000981

DNA-binding transcription factor activity, RNA polymerase II-specific

21947082

GeneSMAD3

GO:0000987

cis-regulatory region sequence-specific DNA binding

21947082

GeneSMAD3

GO:0001217

DNA-binding transcription repressor activity

28467929

GeneSMAD3

GO:0001228

DNA-binding transcription activator activity, RNA polymerase II-specific

24378993|25605017

GeneSMAD3

GO:0003677

DNA binding

28467929

GeneSMAD3

GO:0003700

DNA-binding transcription factor activity

9111321

GeneSMAD3

GO:0003700

DNA-binding transcription factor activity

9732876|10823886|21947082

GeneSMAD3

GO:0005634

nucleus

9311995|12446380|16007207|21145499|21947082|25893292

GeneSMAD3

GO:0005637

nuclear inner membrane

15647271

GeneSMAD3

GO:0005654

nucleoplasm

-

GeneSMAD3

GO:0005667

transcription regulator complex

21947082

GeneSMAD3

GO:0005737

cytoplasm

9311995|12446380|21145499|21947082

GeneSMAD3

GO:0005829

cytosol

-

GeneSMAD3

GO:0006355

regulation of DNA-templated transcription

25060702

GeneSMAD3

GO:0006357

regulation of transcription by RNA polymerase II

21947082

GeneSMAD3

GO:0007179

transforming growth factor beta receptor signaling pathway

9311995|9732876|10823886|18548003|21947082|28467929

GeneSMAD3

GO:0008270

zinc ion binding

12686552

GeneSMAD3

GO:0010628

positive regulation of gene expression

21307346

GeneSMAD3

GO:0010718

positive regulation of epithelial to mesenchymal transition

21307346

GeneSMAD3

GO:0030308

negative regulation of cell growth

8774881

GeneSMAD3

GO:0043130

ubiquitin binding

18794808

GeneSMAD3

GO:0043565

sequence-specific DNA binding

10823886

GeneSMAD3

GO:0045429

positive regulation of nitric oxide biosynthetic process

27038547

GeneSMAD3

GO:0045599

negative regulation of fat cell differentiation

19816956

GeneSMAD3

GO:0045893

positive regulation of DNA-templated transcription

9111321|9311995|9732876

GeneSMAD3

GO:0045944

positive regulation of transcription by RNA polymerase II

8774881|18832382

GeneSMAD3

GO:0051481

negative regulation of cytosolic calcium ion concentration

27038547

GeneSMAD3

GO:0060395

SMAD protein signal transduction

9111321|9311995|9732876|10823886

GeneSMAD3

GO:0071141

SMAD protein complex

18832382|21947082

GeneSMAD3

GO:0071144

heteromeric SMAD protein complex

21828274

GeneSMAD3

GO:0071560

cellular response to transforming growth factor beta stimulus

12902338

GeneSMAD3

GO:1901203

positive regulation of extracellular matrix assembly

21307346

GeneSMAD3

GO:1902895

positive regulation of miRNA transcription

24378993



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
P84022-1P84022-1_1u7f_A.pdb1U7FX-ray2.6A228424

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
P84022SMAD3P84022-1P84022-2425381168SubstitutionMSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPMSCLHPRQTWKGAALVHRKAWWMG124
P84022SMAD3P84022-1P84022-34253201105Deletionnonenone00
P84022SMAD3P84022-1P84022-44252301195Deletionnonenone00

check buttonMultiple sequence alignment of our canonical and alternatively spliced SMAD3

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of SMAD3
UniProt-idENSGENSTENSP
P84022-1ENSG00000166949.17ENST00000327367.9ENSP00000332973.4
P84022-2ENSG00000166949.17ENST00000439724.7ENSP00000401133.3
P84022-3ENSG00000166949.17ENST00000540846.6ENSP00000437757.2
P84022-3ENSG00000166949.17ENST00000558739.2ENSP00000453684.2
P84022-3ENSG00000166949.17ENST00000559460.6ENSP00000453082.2
P84022-3ENSG00000166949.17ENST00000679624.1ENSP00000505445.1
P84022-3ENSG00000166949.17ENST00000681239.1ENSP00000505641.1
P84022-4ENSG00000166949.17ENST00000537194.6ENSP00000445348.2
P84022-4ENSG00000166949.17ENST00000558428.6ENSP00000454165.2
P84022-4ENSG00000166949.17ENST00000558827.2ENSP00000452767.2

UniProt-idNM IDNP ID
P84022-1NM_005902.3NP_005893.1
P84022-2NM_001145103.1NP_001138575.1
P84022-3NM_001145102.1NP_001138574.1
P84022-4NM_001145104.1NP_001138576.1

check buttonAmino acid sequences of our canonical and alternatively spliced SMAD3
accession_idProtein sequence
P84022-1MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRSLDGRLQVSHRKGLPHVIYCR
LWRWPDLHSHHELRAMELCEFAFNMKKDEVCVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETP
PPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFC
LGLLSNVNRNAAVELTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGF
P84022-2MSCLHPRQTWKGAALVHRKAWWMGRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEVCVNPYHYQRVETPV
LPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETPPPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPV
TYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIGGEVFAECLSDSAIF
VQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPL
P84022-3MELCEFAFNMKKDEVCVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETPPPGYLSEDGETSDHQ
MNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVEL
TRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMS
P84022-4MNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVEL
TRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMS

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
SMAD3 (go to UniProt):P84022

check buttonRetention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
Accession_idSubsectionStartEndFuncitonal featureSplicing information
P84022Domain10136Note=MH1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00438Type=Substitution;Start=1;End=68
P84022Domain10136Note=MH1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00438Type=Deletion;Start=1;End=105
P84022Domain10136Note=MH1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00438Type=Deletion;Start=1;End=195
P84022Region137231Note=LinkerType=Deletion;Start=1;End=195
P84022Region165208Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=1;End=195


Gene Isoform Structures and Expression Levels for SMAD3

check buttonGene structures of our canonical and alternative spliced genes of SMAD3
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of SMAD3

check button Expression levels of gene isoforms across GTEx.
gtex expression

check button Expression levels of gene isoforms across TCGA.
tcga expression


Protein Structures

check button PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
3D view using mol* of P84022-1
3D view using mol* of P84022-2
3D view using mol* of P84022-3
3D view using mol* of P84022-4


pLDDT Score Distribution

check button pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
pLDDT distribution across the protein length of P84022-1
all structure
pLDDT distribution across the protein length of P84022-2
all structure
pLDDT distribution across the protein length of P84022-3
all structure
pLDDT distribution across the protein length of P84022-4
all structure


Ramachandran Plot of Protein Structures


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.
Ramachandran plot of P84022-1
all structure
Ramachandran plot of P84022-2
all structure
Ramachandran plot of P84022-3
all structure

Potential Active Site Information


check button The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
UniProt-idSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
P84022-11.0351381.063471.9680.5730.7280.940.7370.9620.7670.665153,154,155,156,157,159,160,161,164,166,316,318,32
2,328,329,351,355,358,361,362,364,365,366,367,368,
369,371,373
P84022-21.0212551.011785.1270.5190.730.9830.471.1270.4170.79633,36,38,39,41,42,43,46,54,55,56,57,58,59,60,61,69
,70,83,85,86,87,88,89,90,91,92,93,181,182,183,184,
185,186,187,188,207,209,254,255,256,257,301,362
P84022-31.0192991.037935.0180.5390.7250.9550.6481.0370.6250.49848,49,50,51,52,54,55,56,57,58,59,60,61,62,131,133,
136,211,213,217,222,223,224,225,226,246,249,250,25
3,254,256,257,259,260,261,262,263,264,266,267,268,
275,276,277,278,279,282,283,284,285,290,292,294
P84022-40.963771.033182.4760.6090.6240.8631.6420.5123.2071.47525,26,27,28,29,154,157,158,161,211,215,218,219

Protein Structure and Feature Comparision


check button Protein Structure Comparision Using Template Modeling Scores (TM-score).
all structure

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
3D view using mol* of P84022-1_P84022-1_1u7f_A.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P84022-1_1u7f_A_P84022-2.pdb
3D view using mol* of P84022-1_1u7f_A_P84022-3.pdb
3D view using mol* of P84022-1_1u7f_A_P84022-4.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P84022-1_P84022-2.pdb
3D view using mol* of P84022-1_P84022-3.pdb
3D view using mol* of P84022-1_P84022-4.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/P84022-1_vs_P84022-2.png
all structure<
./stats/secondary_structure/figure/P84022-1_vs_P84022-3.png
all structure<
./stats/secondary_structure/figure/P84022-1_vs_P84022-4.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/P84022-1_vs_P84022-2.png
all structure<
./stats/relative_asa/P84022-1_vs_P84022-3.png
all structure<
./stats/relative_asa/P84022-1_vs_P84022-4.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to SMAD3


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions

Related Diseases to SMAD3


check button Previous studies relating to the alternative splicing of SMAD3 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term


Clinically important variants in SMAD3


check button (ClinVar, 04/20/2024)
accession_iduniprot_idgene_nameTypeVariantClinical_significance