Protein:STAT3 |
Protein Summary |
 Gene summary |
| Gene name: STAT3 | ASpdb.0 ID: 6774 | Gene | Gene symbol | STAT3 | Gene ID | 6774 |
| Gene name | signal transducer and activator of transcription 3 |
| Synonyms | ADMIO|ADMIO1|APRF|HIES |
| Cytomap | 17q21.2 |
| Type of gene | protein-coding |
| Description | signal transducer and activator of transcription 3DNA-binding protein APRFacute-phase response factor |
| Modification date | 20240416 |
| UniProtAcc | P40763 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | STAT3 | GO:0000785 | chromatin | 16835372 |
| Gene | STAT3 | GO:0000976 | transcription cis-regulatory region binding | 17324931 |
| Gene | STAT3 | GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | 19390056 |
| Gene | STAT3 | GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | 17344214|32929201 |
| Gene | STAT3 | GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | 16835372 |
| Gene | STAT3 | GO:0003700 | DNA-binding transcription factor activity | 7568001|9535918|15653507|16285960|17344214|18782771|28781374 |
| Gene | STAT3 | GO:0004879 | nuclear receptor activity | 17324931 |
| Gene | STAT3 | GO:0005634 | nucleus | 12743296|15653507|16285960|17344214 |
| Gene | STAT3 | GO:0005634 | nucleus | 12444102|17324931|17360477|18234692|22783022|24846175|28065600|31899195 |
| Gene | STAT3 | GO:0005654 | nucleoplasm | - |
| Gene | STAT3 | GO:0005667 | transcription regulator complex | 24429361 |
| Gene | STAT3 | GO:0005737 | cytoplasm | 15653507|16285960|17360477|18234692|22783022|31899195 |
| Gene | STAT3 | GO:0005829 | cytosol | - |
| Gene | STAT3 | GO:0006355 | regulation of DNA-templated transcription | 15664994|17344214 |
| Gene | STAT3 | GO:0006606 | protein import into nucleus | 18234692 |
| Gene | STAT3 | GO:0007259 | cell surface receptor signaling pathway via JAK-STAT | 8272873 |
| Gene | STAT3 | GO:0010507 | negative regulation of autophagy | 26962683 |
| Gene | STAT3 | GO:0010628 | positive regulation of gene expression | 23820254 |
| Gene | STAT3 | GO:0010629 | negative regulation of gene expression | 23820254 |
| Gene | STAT3 | GO:0030154 | cell differentiation | 28781374 |
| Gene | STAT3 | GO:0030522 | intracellular receptor signaling pathway | 17324931 |
| Gene | STAT3 | GO:0031490 | chromatin DNA binding | 17344214 |
| Gene | STAT3 | GO:0032355 | response to estradiol | 12552091 |
| Gene | STAT3 | GO:0032870 | cellular response to hormone stimulus | 12552091 |
| Gene | STAT3 | GO:0033210 | leptin-mediated signaling pathway | 17344214 |
| Gene | STAT3 | GO:0035723 | interleukin-15-mediated signaling pathway | 7568001 |
| Gene | STAT3 | GO:0038110 | interleukin-2-mediated signaling pathway | 7568005 |
| Gene | STAT3 | GO:0038113 | interleukin-9-mediated signaling pathway | 9535918 |
| Gene | STAT3 | GO:0038154 | interleukin-11-mediated signaling pathway | 28781374 |
| Gene | STAT3 | GO:0042803 | protein homodimerization activity | 15653507 |
| Gene | STAT3 | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 27830702 |
| Gene | STAT3 | GO:0044320 | cellular response to leptin stimulus | 17344214 |
| Gene | STAT3 | GO:0044321 | response to leptin | 17344214 |
| Gene | STAT3 | GO:0045893 | positive regulation of DNA-templated transcription | 19390056 |
| Gene | STAT3 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 17324931|27050391 |
| Gene | STAT3 | GO:0051726 | regulation of cell cycle | 17344214 |
| Gene | STAT3 | GO:0060396 | growth hormone receptor signaling pathway | 10925297 |
| Gene | STAT3 | GO:0060397 | growth hormone receptor signaling pathway via JAK-STAT | 12552091 |
| Gene | STAT3 | GO:0070102 | interleukin-6-mediated signaling pathway | 12359225|12552091|16285960|17324931|24429361 |
| Gene | STAT3 | GO:0072538 | T-helper 17 type immune response | 31899195 |
| Gene | STAT3 | GO:0106015 | negative regulation of inflammatory response to wounding | 27830702 |
| Gene | STAT3 | GO:0140610 | RNA sequestering activity | 31507089 |
| Gene | STAT3 | GO:1902895 | positive regulation of miRNA transcription | 19390056|23820254 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P40763-1 | P40763-1_6qhd_A.pdb | 6QHD | X-ray | 2.85 | A | 136 | 715 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P40763 | STAT3 | P40763-1 | P40763-2 | 770 | 769 | 701 | 701 | Deletion | none | none | 700 | 700 |
| P40763 | STAT3 | P40763-1 | P40763-3 | 770 | 722 | 716 | 722 | Substitution | TTCSNTI | FIDAVWK | 716 | 722 |
| P40763 | STAT3 | P40763-1 | P40763-3 | 770 | 722 | 723 | 770 | Deletion | none | none | 722 | 722 |
| Multiple sequence alignment of our canonical and alternatively spliced STAT3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of STAT3 |
| UniProt-id | ENSG | ENST | ENSP |
| P40763-1 | ENSG00000168610.16 | ENST00000264657.10 | ENSP00000264657.4 |
| P40763-1 | ENSG00000168610.16 | ENST00000588969.5 | ENSP00000467985.1 |
| P40763-1 | ENSG00000168610.16 | ENST00000678044.1 | ENSP00000503102.1 |
| P40763-1 | ENSG00000168610.16 | ENST00000678906.1 | ENSP00000504184.1 |
| P40763-1 | ENSG00000168610.16 | ENST00000678960.1 | ENSP00000503181.1 |
| P40763-2 | ENSG00000168610.16 | ENST00000404395.3 | ENSP00000384943.3 |
| P40763-2 | ENSG00000168610.16 | ENST00000677723.1 | ENSP00000503574.1 |
| P40763-2 | ENSG00000168610.16 | ENST00000679014.1 | ENSP00000503237.1 |
| P40763-3 | ENSG00000168610.16 | ENST00000585517.5 | ENSP00000467000.1 |
| P40763-3 | ENSG00000168610.16 | ENST00000677030.1 | ENSP00000503662.1 |
| P40763-3 | ENSG00000168610.16 | ENST00000678827.1 | ENSP00000503634.1 |
| UniProt-id | NM ID | NP ID |
| P40763-1 | NM_139276.2 | NP_644805.1 |
| P40763-2 | NM_003150.3 | NP_003141.2 |
| P40763-3 | NM_213662.1 | NP_998827.1 |
| Amino acid sequences of our canonical and alternatively spliced STAT3 |
| accession_id | Protein sequence |
| P40763-1 | MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNLLGEIDQQYSRFLQESNVLYQHNLRRIKQFL QSRYLEKPMEIARIVARCLWEESRLLQTAATAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLK SQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEELADWKRRQQIACIGGPPNICLDRLENWITSL AESQLQTRQQIKKLEELQQKVSYKGDPIVQHRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNY QLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGNGGRANCDASLIVTEELHLITFETEVYHQGL KIDLETHSLPVVVISNICQMPNAWASILWYNMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYS GCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDISG KTQIQSVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSN |
| P40763-2 | MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNLLGEIDQQYSRFLQESNVLYQHNLRRIKQFL QSRYLEKPMEIARIVARCLWEESRLLQTAATAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLK SQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEELADWKRRQQIACIGGPPNICLDRLENWITSL AESQLQTRQQIKKLEELQQKVSYKGDPIVQHRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNY QLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGNGGRANCDASLIVTEELHLITFETEVYHQGL KIDLETHSLPVVVISNICQMPNAWASILWYNMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYS GCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDISG KTQIQSVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGAAPYLKTKFICVTPTTCSNT |
| P40763-3 | MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNLLGEIDQQYSRFLQESNVLYQHNLRRIKQFL QSRYLEKPMEIARIVARCLWEESRLLQTAATAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLK SQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEELADWKRRQQIACIGGPPNICLDRLENWITSL AESQLQTRQQIKKLEELQQKVSYKGDPIVQHRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNY QLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGNGGRANCDASLIVTEELHLITFETEVYHQGL KIDLETHSLPVVVISNICQMPNAWASILWYNMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYS GCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDISG KTQIQSVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPFIDAV |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| STAT3 (go to UniProt):P40763 |
| Retention 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 * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
Gene Isoform Structures and Expression Levels for STAT3 |
| Gene structures of our canonical and alternative spliced genes of STAT3 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| 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 P40763-1 |
| 3D view using mol* of P40763-2 |
| 3D view using mol* of P40763-3 |
pLDDT Score Distribution |
| 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 P40763-1 |
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| pLDDT distribution across the protein length of P40763-2 |
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| pLDDT distribution across the protein length of P40763-3 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P40763-1 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P40763-1 | 1.039 | 172 | 0.965 | 347.459 | 0.456 | 0.757 | 1.108 | 0.47 | 1.318 | 0.356 | 0.883 | 369,372,373,374,375,377,378,379,380,381,382,383,38 4,416,417,418,419,421,423,428,429,430,431,432,434, 435,436,437,438,490,491,493 |
| P40763-2 | 1.022 | 148 | 1.005 | 297.724 | 0.448 | 0.731 | 1.026 | 0.419 | 1.145 | 0.366 | 0.777 | 369,372,373,377,378,379,380,381,382,383,415,416,41 7,418,419,420,421,422,423,429,430,434,435,436,437, 438,490,491,492,493 |
| P40763-3 | 1.005 | 313 | 0.994 | 691.488 | 0.548 | 0.706 | 0.932 | 0.338 | 1.135 | 0.298 | 0.853 | 236,240,241,242,243,244,245,247,248,318,319,321,32 2,323,326,369,370,371,372,373,375,376,377,378,379, 380,381,382,383,415,416,417,418,419,421,422,423,42 9,430,431,432,434,435,436,437,438,440,455,456,457, 459,485,487,488,490,491,492,493 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P40763-1_P40763-1_6qhd_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P40763-1_6qhd_A_P40763-2.pdb |
| 3D view using mol* of P40763-1_6qhd_A_P40763-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P40763-1_P40763-2.pdb |
| 3D view using mol* of P40763-1_P40763-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P40763-1_vs_P40763-2.png |
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| ./stats/secondary_structure/figure/P40763-1_vs_P40763-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P40763-1_vs_P40763-2.png |
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| ./stats/relative_asa/P40763-1_vs_P40763-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to STAT3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P40763 | STAT3 | DB05959 | ENMD-1198 | investigational | |
| P40763 | STAT3 | DB16630 | OPB-111077 | investigational | inhibitor |
Related Diseases to STAT3 |
| Previous studies relating to the alternative splicing of STAT3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| STAT3 | 25984943 | Ratios of Four STAT3 Splice Variants in Human Eosinophils and Diffuse Large B Cell Lymphoma Cells. | "Signal transducer and activator of transcription 3 (STAT3) is a key mediator of leukocyte differentiation and proliferation. The 3' end of STAT3 transcripts is subject to two alternative splicing events. One results in either full-length STAT3α or in STAT3β, which lacks part of the C-terminal transactivation domain. The other is at a tandem donor (5') splice site and results in the codon for Ser-701 being included (S) or excluded (ΔS). Despite the proximity of Ser-701 to the site of activating phosphorylation at Tyr-705, ΔS/S splicing has barely been studied. Sequencing of cDNA from purified eosinophils revealed the presence of four transcripts (S-α, ΔS-α, S-β, and ΔS-β) rather than the three reported in publically available databases from which ΔS-β is missing. To gain insight into regulation of the two alternative splicing events, we developed a quantitative(q) PCR protocol to compare transcript ratios in eosinophils in which STAT3 is upregulated by cytokines, activated B cell diffuse large B cell Lymphoma (DLBCL) cells in which STAT3 is dysregulated, and in germinal center B cell-like DLBCL cells in which it is not. With the exception of one line of activated B cell DLCBL cells, the four variants were found in roughly the same ratios despite differences in total levels of STAT3 transcripts. S-α was the most abundant, followed by S-β. ΔS-α and ΔS-β together comprised 15.6 ± 4.0 % (mean ± SD, n = 21) of the total. The percentage of STAT3β variants that were ΔS was 1.5-fold greater than of STAT3α variants that were ΔS. Inspection of Illumina's ""BodyMap"" RNA-Seq database revealed that the ΔS variant accounts for 10-26 % of STAT3 transcripts across 16 human tissues, with less variation than three other genes with the identical tandem donor splice site sequence. Thus, it seems likely that all cells contain the S-α, ΔS-α, S-β, and ΔS-β variants of STAT3." | D016403 | Lymphoma, Large B-Cell, Diffuse |
Clinically important variants in STAT3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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