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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:FOXO3

Protein Summary

check button Gene summary
Gene name: FOXO3
ASpdb.0 ID: 2309
Gene
Gene symbol

FOXO3

Gene ID

2309

Gene nameforkhead box O3
SynonymsAF6q21|FKHRL1|FKHRL1P2|FOXO2|FOXO3A
Cytomap

6q21

Type of geneprotein-coding
Descriptionforkhead box protein O3FOXO3A-forkhead box O3Aforkhead homolog (rhabdomyosarcoma) like 1forkhead in rhabdomyosarcoma-like 1forkhead, Drosophila, homolog of, in rhabdomyosarcoma-like 1
Modification date20240416
UniProtAcc

O43524


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneFOXO3

GO:0000122

negative regulation of transcription by RNA polymerase II

18393360|20371612|21621563

GeneFOXO3

GO:0001227

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

20371612

GeneFOXO3

GO:0003677

DNA binding

21329882

GeneFOXO3

GO:0003700

DNA-binding transcription factor activity

14734530|30513302

GeneFOXO3

GO:0005634

nucleus

10102273|15084260|16751106|18393360|21329882|22761832|23283301|23640897|25327288

GeneFOXO3

GO:0005654

nucleoplasm

-

GeneFOXO3

GO:0005737

cytoplasm

10102273|15084260|16751106|20371612|21329882|23283301

GeneFOXO3

GO:0005739

mitochondrion

23283301

GeneFOXO3

GO:0005741

mitochondrial outer membrane

29445193

GeneFOXO3

GO:0005759

mitochondrial matrix

29445193

GeneFOXO3

GO:0005829

cytosol

23640897

GeneFOXO3

GO:0006417

regulation of translation

21329882

GeneFOXO3

GO:0032991

protein-containing complex

23283301|29445193

GeneFOXO3

GO:0042149

cellular response to glucose starvation

29445193

GeneFOXO3

GO:0043065

positive regulation of apoptotic process

20371612

GeneFOXO3

GO:0043565

sequence-specific DNA binding

10102273

GeneFOXO3

GO:0045591

positive regulation of regulatory T cell differentiation

30513302

GeneFOXO3

GO:0045648

positive regulation of erythrocyte differentiation

14734530

GeneFOXO3

GO:0045893

positive regulation of DNA-templated transcription

10102273|15084260

GeneFOXO3

GO:0045944

positive regulation of transcription by RNA polymerase II

14734530

GeneFOXO3

GO:0045944

positive regulation of transcription by RNA polymerase II

10102273

GeneFOXO3

GO:1990837

sequence-specific double-stranded DNA binding

28473536



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
O43524-1O43524-1_2uzk_A.pdb2UZKX-ray2.7A158253

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
O43524FOXO3O43524-1O43524-26734531220Deletionnonenone00

check buttonMultiple sequence alignment of our canonical and alternatively spliced FOXO3

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of FOXO3
UniProt-idENSGENSTENSP
O43524-1ENSG00000118689.15ENST00000343882.10ENSP00000339527.6
O43524-1ENSG00000118689.15ENST00000406360.2ENSP00000385824.1
O43524-2ENSG00000118689.15ENST00000540898.1ENSP00000446316.1

UniProt-idNM IDNP ID
O43524-1NM_001455.3NP_001446.1
O43524-1NM_201559.2NP_963853.1
O43524-2XM_017010586.1XP_016866075.1

check buttonAmino acid sequences of our canonical and alternatively spliced FOXO3
accession_idProtein sequence
O43524-1MAEAPASPAPLSPLEVELDPEFEPQSRPRSCTWPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGRAGSAMAIGGGGGSGTLGS
GLLLEDSARVLAPGGQDPGSGPATAAGGLSGGTQALLQPQQPLPPPQPGAAGGSGQPRKCSSRRNAWGNLSYADLITRAIESSPDKRLTL
SQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWIINPDGGKSGKAPRRRAVSMDNSNKYTKSRGRAAKK
KAALQTAPESADDSPSQLSKWPGSPTSRSSDELDAWTDFRSRTNSNASTVSGRLSPIMASTELDEVQDDDAPLSPMLYSSSASLSPSVSK
PCTVELPRLTDMAGTMNLNDGLTENLMDDLLDNITLPPSQPSPTGGLMQRSSSFPYTTKGSGLGSPTSSFNSTVFGPSSLNSLRQSPMQT
IQENKPATFSSMSHYGNQTLQDLLTSDSLSHSDVMMTQSDPLMSQASTAVSAQNSRRNVMLRNDPMMSFAAQPNQGSLVNQNLLHHQHQT
QGALGGSRALSNSVSNMGLSESSSLGSAKHQQQSPVSQSMQTLSDSLSGSSLYSTSANLPVMGHEKFPSDLDLDMFNGSLECDMESIIRS
O43524-2MRVQNEGTGKSSWWIINPDGGKSGKAPRRRAVSMDNSNKYTKSRGRAAKKKAALQTAPESADDSPSQLSKWPGSPTSRSSDELDAWTDFR
SRTNSNASTVSGRLSPIMASTELDEVQDDDAPLSPMLYSSSASLSPSVSKPCTVELPRLTDMAGTMNLNDGLTENLMDDLLDNITLPPSQ
PSPTGGLMQRSSSFPYTTKGSGLGSPTSSFNSTVFGPSSLNSLRQSPMQTIQENKPATFSSMSHYGNQTLQDLLTSDSLSHSDVMMTQSD
PLMSQASTAVSAQNSRRNVMLRNDPMMSFAAQPNQGSLVNQNLLHHQHQTQGALGGSRALSNSVSNMGLSESSSLGSAKHQQQSPVSQSM
QTLSDSLSGSSLYSTSANLPVMGHEKFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDSLISTQNVVGLNVGNFTGAKQASSQSW

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
FOXO3 (go to UniProt):O43524

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
O43524DNA binding157251Note=Fork-head;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00089Type=Deletion;Start=1;End=220
O43524Region1153Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=1;End=220
O43524Region80108Note=Required for mitochondrial import;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23283301;Dbxref=PMID:23283301Type=Deletion;Start=1;End=220
O43524Compositional bias5569Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=1;End=220


Gene Isoform Structures and Expression Levels for FOXO3

check buttonGene structures of our canonical and alternative spliced genes of FOXO3
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of FOXO3

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 O43524-1
3D view using mol* of O43524-2


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 O43524-1
all structure
pLDDT distribution across the protein length of O43524-2
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 O43524-1
all structure
Ramachandran plot of O43524-2
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
O43524-10.585100.53255.2230.7780.6821.0761.4540.5362.7140.763170,171,176,236,238,242
O43524-20.663460.53265.5130.6320.5470.8020.0661.3290.0490.496337,338,339,340,341,403,406,407,410,411

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 O43524-1_O43524-1_2uzk_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 O43524-1_2uzk_A_O43524-2.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 O43524-1_O43524-2.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/O43524-1_vs_O43524-2.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/O43524-1_vs_O43524-2.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 FOXO3


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

Related Diseases to FOXO3


check button Previous studies relating to the alternative splicing of FOXO3 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term


Clinically important variants in FOXO3


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