JUN
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Also known as c-JunAP-1
Summary
JUN (Jun proto-oncogene, AP-1 transcription factor subunit, HGNC:6204) is a protein-coding gene on chromosome 1p32.1, encoding Transcription factor Jun (P05412). Transcription factor that recognizes and binds to the AP-1 consensus motif 5’-TGA[GC]TCA-3’. In precision oncology, JUN Overexpression confers sensitivity to Irbesartan in Colorectal Adenocarcinoma (CIViC Level C). It is a selective cancer dependency (DepMap: 18.8% of cell lines).
This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a protein which is highly similar to the viral protein, and which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.
Source: NCBI Gene 3725 — RefSeq curated summary.
At a glance
- GWAS associations: 3
- Clinical variants (ClinVar): 23 total — 1 pathogenic
- Druggable target: yes — 3 molecules with ChEMBL bioactivity
- Precision-oncology evidence (CIViC): 1 curated variant–drug association
- Cancer dependency (DepMap): dependent in 18.8% of screened cell lines
- Transcription factor: yes — 715 downstream targets (CollecTRI)
- MANE Select transcript:
NM_002228
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:6204 |
| Approved symbol | JUN |
| Name | Jun proto-oncogene, AP-1 transcription factor subunit |
| Location | 1p32.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | c-Jun, AP-1 |
| Ensembl gene | ENSG00000177606 |
| Ensembl biotype | protein_coding |
| OMIM | 165160 |
| Entrez | 3725 |
Gene structure
Transcript identifiers
Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay
ENST00000371222, ENST00000678696, ENST00000710273
RefSeq mRNA: 1 — MANE Select: NM_002228
NM_002228
CCDS: CCDS610
Canonical transcript exons
ENST00000371222 — 1 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001454665 | 58780791 | 58784047 |
Expression profiles
Bgee: expression breadth ubiquitous, 290 present calls, max score 99.72.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.8828 / max 3246.6283, expressed in 1814 samples.
FANTOM5 promoters (5 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 12576 | 53.9170 | 1802 |
| 12577 | 14.8868 | 1709 |
| 12575 | 8.5526 | 1418 |
| 12574 | 2.1078 | 841 |
| 201526 | 0.4187 | 203 |
Top tissues by expression
294 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| vena cava | UBERON:0004087 | 99.72 | gold quality |
| mucosa of stomach | UBERON:0001199 | 99.66 | gold quality |
| cardia of stomach | UBERON:0001162 | 99.61 | gold quality |
| mammary duct | UBERON:0001765 | 99.50 | gold quality |
| saphenous vein | UBERON:0007318 | 99.50 | gold quality |
| epithelium of mammary gland | UBERON:0003244 | 99.49 | gold quality |
| seminal vesicle | UBERON:0000998 | 99.48 | gold quality |
| pericardium | UBERON:0002407 | 99.37 | gold quality |
| parotid gland | UBERON:0001831 | 99.28 | gold quality |
| endothelial cell | CL:0000115 | 99.23 | gold quality |
| pylorus | UBERON:0001166 | 99.19 | gold quality |
| nipple | UBERON:0002030 | 99.18 | gold quality |
| urethra | UBERON:0000057 | 99.09 | gold quality |
| left uterine tube | UBERON:0001303 | 99.09 | gold quality |
| ventricular zone | UBERON:0003053 | 99.06 | gold quality |
| trigeminal ganglion | UBERON:0001675 | 98.96 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 98.95 | gold quality |
| penis | UBERON:0000989 | 98.90 | gold quality |
| pancreatic ductal cell | CL:0002079 | 98.72 | gold quality |
| right ovary | UBERON:0002118 | 98.71 | gold quality |
| omental fat pad | UBERON:0010414 | 98.71 | gold quality |
| peritoneum | UBERON:0002358 | 98.69 | gold quality |
| blood vessel layer | UBERON:0004797 | 98.65 | gold quality |
| mucosa of paranasal sinus | UBERON:0005030 | 98.64 | gold quality |
| cervix squamous epithelium | UBERON:0006922 | 98.62 | gold quality |
| ectocervix | UBERON:0012249 | 98.60 | gold quality |
| synovial joint | UBERON:0002217 | 98.51 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 98.50 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 98.47 | gold quality |
| body of stomach | UBERON:0001161 | 98.42 | gold quality |
Single-cell (SCXA)
Detected in 43 experiment(s), a significant marker in 32.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-9841 | yes | 9455.45 |
| E-GEOD-137537 | yes | 6219.91 |
| E-CURD-122 | yes | 6060.66 |
| E-MTAB-9543 | yes | 5435.22 |
| E-MTAB-8142 | yes | 5175.35 |
| E-MTAB-10885 | yes | 4936.86 |
| E-GEOD-134144 | yes | 4729.31 |
| E-MTAB-9467 | yes | 4159.65 |
| E-GEOD-139324 | yes | 3689.31 |
| E-CURD-53 | yes | 3209.84 |
| E-HCAD-5 | yes | 2826.56 |
| E-HCAD-4 | yes | 2488.78 |
| E-GEOD-106540 | yes | 1408.48 |
| E-MTAB-7052 | yes | 1241.42 |
| E-MTAB-7037 | yes | 1119.79 |
Regulation
Is transcription factor: yes
Downstream targets (CollecTRI)
715 targets.
| Target | Regulation |
|---|---|
| A2M | |
| AANAT | Unknown |
| ABCB1 | Activation |
| ABCC1 | |
| ABCC3 | |
| ABCC8 | |
| ABL1 | |
| ACE | |
| ACHE | |
| ACOT11 | |
| ACTA1 | Unknown |
| ACTB | |
| ACTG1 | Activation |
| ADAM2 | |
| ADARB1 | |
| ADCYAP1 | |
| ADH7 | |
| AFF2 | |
| AFP | |
| AGT | Unknown |
| AKR1B10 | Unknown |
| AKR1B15 | |
| AKT1 | |
| ALAS2 | |
| ALDOA | Activation |
| ALOX12 | Unknown |
| ANKRD1 | |
| AP1 | Activation |
| APC | |
| APOC3 | Activation |
JASPAR motifs
| Motif | Name | Family |
|---|---|---|
| MA0099.2 | FOS::JUN | Fos-related::Jun-related |
| MA0099.3 | FOS::JUN | Fos-related::Jun-related |
| MA0099.4 | FOS::JUN | Fos-related::Jun-related |
| MA0462.1 | BATF::JUN | B-ATF-related factors::Jun-related |
| MA0462.2 | BATF::JUN | B-ATF-related factors::Jun-related |
| MA0462.3 | BATF::JUN | B-ATF-related factors::Jun-related |
| MA0488.1 | JUN | Jun-related |
| MA0488.2 | JUN | Jun-related |
| MA0489.1 | JUN | Jun-related |
| MA1126.1 | FOS::JUN | Fos-related::Jun-related |
| MA1126.2 | FOS::JUN | Fos-related::Jun-related |
| MA1127.1 | FOSB::JUN | Fos-related::Jun-related |
| MA1128.1 | FOSL1::JUN | Fos-related::Jun-related |
| MA1128.2 | FOSL1::JUN | Fos-related::Jun-related |
| MA1129.1 | FOSL1::JUN | Fos-related::Jun-related |
| MA1130.1 | FOSL2::JUN | Fos-related::Jun-related |
| MA1130.2 | FOSL2::JUN | Fos-related::Jun-related |
| MA1131.1 | FOSL2::JUN | Fos-related::Jun-related |
| MA1131.2 | FOSL2::JUN | Fos-related::Jun-related |
| MA1132.1 | JUN::JUNB | Jun-related |
| MA1132.2 | JUN::JUNB | Jun-related |
| MA1133.1 | JUN::JUNB | Jun-related |
| MA1133.2 | JUN::JUNB | Jun-related |
JASPAR matrix evidence (PMIDs): PMID:17916232, PMID:11988758, PMID:22992523, PMID:21703547, PMID:15240010
Upstream regulators (CollecTRI, top): ABL1, AHR, AP1, AR, ARNT, ATF1, ATF2, ATF3, BMAL1, CEBPA, CEBPG, CLOCK, CREB1, CREM, CTCF, CTNNB1, CUX1, E2F1, E2F4, EGR1, EGR2, EGR3, ELK3, ENO1, ERF, ESR1, ESR2, ETS1, FOS, FOXO1, GLI1, GLI2, HDAC3, HDAC4, HES1, HIF1A, HLX, HMGA2, HNF4A, HSF1
miRNA regulators (miRDB)
66 targeting JUN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-200B-3P | 100.00 | 73.31 | 2693 |
| HSA-MIR-200C-3P | 100.00 | 73.35 | 2685 |
| HSA-MIR-429 | 100.00 | 73.44 | 2698 |
| HSA-MIR-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-190A-3P | 100.00 | 80.35 | 5520 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-1277-5P | 100.00 | 73.95 | 5056 |
| HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 |
| HSA-MIR-524-5P | 99.98 | 73.43 | 4882 |
| HSA-MIR-4803 | 99.98 | 71.99 | 3117 |
| HSA-MIR-493-5P | 99.96 | 72.47 | 2382 |
| HSA-MIR-495-3P | 99.96 | 72.81 | 4197 |
| HSA-MIR-5688 | 99.96 | 73.23 | 4504 |
| HSA-MIR-6721-5P | 99.93 | 68.92 | 2981 |
| HSA-MIR-498-3P | 99.91 | 71.27 | 1114 |
| HSA-MIR-139-5P | 99.80 | 69.50 | 1399 |
| HSA-MIR-374C-5P | 99.80 | 72.06 | 2910 |
| HSA-MIR-655-3P | 99.80 | 72.19 | 2909 |
| HSA-MIR-6817-3P | 99.79 | 68.35 | 2126 |
| HSA-MIR-1299 | 99.77 | 71.24 | 2389 |
| HSA-MIR-3156-3P | 99.76 | 66.72 | 939 |
| HSA-MIR-8084 | 99.73 | 69.57 | 1760 |
| HSA-MIR-12129 | 99.72 | 67.45 | 1311 |
| HSA-MIR-3714 | 99.71 | 70.74 | 2671 |
| HSA-MIR-4677-5P | 99.70 | 70.09 | 1940 |
| HSA-MIR-4729 | 99.69 | 72.18 | 4233 |
| HSA-MIR-580-3P | 99.67 | 69.23 | 1841 |
| HSA-MIR-298 | 99.63 | 67.56 | 1916 |
| HSA-MIR-12123 | 99.52 | 71.79 | 2990 |
| HSA-MIR-513C-5P | 99.50 | 68.42 | 1730 |
Functional genomics
DepMap (CRISPR cell-line fitness): dependent in 18.8% of screened cell lines.
Literature-anchored findings (GeneRIF, showing 40)
- c-Jun regulates vascular smooth muscle cell growth and neointima formation after arterial injury (PMID:11891228)
- Bombesin antagonists inhibit growth of MDA-MB-435 estrogen-independent breast cancers and decrease the expression of the ErbB-2/HER-2 oncoprotein and c-jun and c-fos oncogenes (PMID:11891317)
- An alternative model of H ferritin promoter transactivation by c-Jun (H ferritin, also called isoferritin) (PMID:11903046)
- Analysis of heterophilic and homophilic interactions of cadherins using the c-Jun/c-Fos dimerization domains (PMID:11909859)
- Functional role of ERK1/2 activation in phorbol ester-induced promoter activation of human 12(S)-lipoxygenase gene. (PMID:11914583)
- Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1. (PMID:11956220)
- c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity (PMID:12034730)
- Kip1 inhibits Jab1 mediated c-Jun dependent transcription (PMID:12119282)
- Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. (PMID:12145210)
- Review.AP1 plays a crucial role during human papillomavirus (HPV) early gene expression, in particular of the expression of E6 and E7 oncoproteins. (PMID:12183893)
- Epstein-Barr virus latent membrane protein 2A may exploit MAPK kinases and affect both the phosphorylation and stability of c-Jun protein (PMID:12186939)
- structurally distinct modes of recognition of the KIX domain of CBP by CREB and this protein (PMID:12437352)
- results suggest strongly that human amylin induces apoptosis in pancreatic islet beta-cells through stimulation of expression and activation of c-Jun (PMID:12441106)
- studies suggest that the cooperative interaction of the estrogen receptor with Fos and Jun proteins helps confer estrogen responsiveness to the endogenous progesterone receptor gene (PMID:12446585)
- Tumor promoter arsenite stimulates histone H3 phosphoacetylation of c-fos and this proto-oncogene chromatin in diploid fibroblasts. (PMID:12547826)
- Phosphorylation of c-jun was induced by TPA only. On the other hand, expression of proto-oncogene c-jun was induced by TPA and Saikosaponin a during 30 min to 6 h of treatment. (PMID:12592382)
- conclude that Ras regulates TNF-alpha-induced chemokine expression by activating the AP-1 pathway and enhancing transcriptional function of NF-kappaB, whereas MEKK1 activates both the AP-1 and NF-kappaB pathways (PMID:12600818)
- AP-1 (c-Jun & FosB) binds to a site in the 5’ untranslated region of the CD95L gene. Transdominant negative Jun mutants reduce CD95L promoter activity. FosB dimerized with c-Jun has an important role in TCR/CD3-mediated activation-induced cell death. (PMID:12618758)
- Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16. (PMID:12682910)
- data demonstratre that c-Jun physically and functionally interacts with JCV major early regulatory protein large T-Ag and that this interaction modulates JCV transcription and replication in glial cells (PMID:12692226)
- c-Jun has an important functional role in the induction of cell cycle arrest and proliferation arrest of myeloid leukemia cells because of the ligation of the cell surface adhesion receptor CD44 by anti-CD44 antibody. (PMID:12700665)
- The expression of c-Jun protein and c-jun mRNA is significantly increased in the cerebellar vermis of patients with schizophrenia; no significant differences are found in the expression of Jun B or Jun D proteins. (PMID:12799614)
- activator protein 1 and ERKs play crucial roles in FGF2-stimulated premature cranial suture closure (PMID:12815619)
- The AP1 transcription factor c-jun is the prototypical nuclear effector of the JNK signal transduction pathway. (PMID:12853483)
- Data suggest that overexpression and binding of JunB to the AP-1 site may relieve the repression of the core promoter by CD30 in Hodgkin-Redd Sternberg cells, which provide one basis for the constitutive overexpression of CD30 in Hodgkin’s lymphoma (PMID:12875982)
- The Ca2+-mediated increase in AP-1 binding may play an important role in upregulating AP-1-responsive gene expression, in stimulating pulmonary vascular cell proliferation and in pulmonary vascular remodeling in hypoxia-mediated pulmonary hypertension. (PMID:12909593)
- transcription factors Sp1 and c-Jun have roles in regulation of keratin 16 gene expression by epidermal growth factor (PMID:12954631)
- JUN has a role in androgen stimulation which blocks p53-dependent transactivation of the Fas gene, which can be blocked by androgen stimulation during radiation-induced Fas sensitization in prostate cancer cells (PMID:12963547)
- c-Jun fails to act as a negative regulator for the cell survival of pancreatic cancer cells (PMID:12963995)
- Findings strongly suggest that the AP-1/JNK signaling pathway has little or no impact on the generation of inflammatory mediators in neutrophils. (PMID:14500675)
- c-fos and AP-1 are regulated by JNK and p38 MAPK (PMID:14511403)
- NF-kappa B and AP-1 are required for basal MAT2A expression in HepG2 cells and mediate the increase in MAT2A expression in response to TNF-alpha (PMID:14530285)
- 15d-PGJ2 covalently modifies c-Jun and directly inhibits the DNA binding activity of AP-1. In addition, 15d-PGJ2 can promote the oligomerization of a fraction of c-Jun through the formation of intermolecular disulfide bonds or 15d-PGJ2-bonded dimers. (PMID:14532268)
- c-Jun activity is modified by the estrogen receptor in the stress response (PMID:14638681)
- activator protein-1 is repressed by Notch-1 with C promoter-binding factor 1 (PMID:14645224)
- findings demonstrate that activator protein-1 activation in human smooth muscle cells in response to angiotensin II and platelet-derived growth factor-AA is mediated via generation of p22phox-dependent reactive oxygen species (PMID:14652666)
- An inverse correlation between JUN and p27(Kip1) expression levels in breast cancer. (PMID:14654548)
- DET1 promotes ubiquitination and degradation of c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1 (PMID:14739464)
- AP1 and CHOP are induced by MEKK3 and have roles in TRAF7-related apoptosis (PMID:15001576)
- Results suggest that in human HL60 cells the presence of the AP-1 signal acts as a survival factor that determines the outcome of myc-induced proliferation or apoptosis. (PMID:15034932)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | jun | ENSDARG00000043531 |
| mus_musculus | Jun | ENSMUSG00000052684 |
| rattus_norvegicus | Jun | ENSRNOG00000026293 |
| drosophila_melanogaster | Jra | FBGN0001291 |
| caenorhabditis_elegans | WBGENE00008945 |
Paralogs (2): JUND (ENSG00000130522), JUNB (ENSG00000171223)
Protein
Protein identifiers
Transcription factor Jun — P05412 (reviewed: P05412)
Alternative names: Activator protein 1, Proto-oncogene c-Jun, Transcription factor AP-1 subunit Jun, V-jun avian sarcoma virus 17 oncogene homolog, p39
All UniProt accessions (2): A0AA34QVR9, P05412
UniProt curated annotations — full annotation on UniProt →
Function. Transcription factor that recognizes and binds to the AP-1 consensus motif 5’-TGA[GC]TCA-3’. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5’-TGA[GC]TCA-3’ and enhancing its transcriptional activity. Together with FOSB, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells. Binds to the USP28 promoter in colorectal cancer (CRC) cells. (Microbial infection) Upon Epstein-Barr virus (EBV) infection, binds to viral BZLF1 Z promoter and activates viral BZLF1 expression.
Subunit / interactions. Heterodimer with either BATF3 or ATF7. Heterodimer with FOS. Heterodimer with FOSB isoform 1 and 2. Component of an AP-1 transcription factor complex composed of JUN-FOS heterodimers. As part of the AP-1 transcription factor complex, forms heterodimers with FOSB, thereby binding to the AP-1 consensus sequence and stimulating transcription. Interacts with FOS and FOSB isoform 1 and 2. The ATF7/JUN heterodimer is essential for ATF7 transactivation activity. Interacts with TSC22D3 (via N-terminus); the interaction inhibits the binding of active AP1 to its target DNA. Interacts with HIVEP3 and MYBBP1A. Interacts with SP1, SPIB and TCF20. Interacts with COPS5; the interaction leads indirectly to its phosphorylation. Component of the SMAD3/SMAD4/JUN/FOS/complex which forms at the AP1 promoter site. The SMAD3/SMAD4 heterodimer acts synergistically with the JUN/FOS heterodimer to activate transcription in response to TGF-beta. Interacts (via its basic DNA binding and leucine zipper domains) with SMAD3 (via an N-terminal domain); the interaction is required for TGF-beta-mediated transactivation of the SMAD3/SMAD4/JUN/FOS/complex. Interacts with methylated RNF187. Binds to HIPK3. Interacts (when phosphorylated) with FBXW7. Found in a complex with PRR7 and FBXW7. Interacts with PRR7 and FBXW7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity. Interacts with RBM39. Interacts with PAGE4. Interacts with ARK2N and CSNK2B; the interaction with ARK2N is mediated by CSNK2B.
Subcellular location. Nucleus.
Tissue specificity. Expressed in the developing and adult prostate and prostate cancer cells.
Post-translational modifications. Ubiquitinated by the SCF(FBXW7), leading to its degradation. Ubiquitination takes place following phosphorylation, that promotes interaction with FBXW7. Phosphorylated by CaMK4 and PRKDC; phosphorylation enhances the transcriptional activity. Phosphorylated by HIPK3. Phosphorylated by DYRK2 at Ser-243; this primes the protein for subsequent phosphorylation by GSK3B at Thr-239. Phosphorylated at Thr-239, Ser-243 and Ser-249 by GSK3B; phosphorylation reduces its ability to bind DNA. Phosphorylated by PAK2 at Thr-2, Thr-8, Thr-89, Thr-93 and Thr-286 thereby promoting JUN-mediated cell proliferation and transformation. Phosphorylated by PLK3 following hypoxia or UV irradiation, leading to increase DNA-binding activity. Phosphorylated by VRK1. Acetylated at Lys-271 by EP300.
Similarity. Belongs to the bZIP family. Jun subfamily.
RefSeq proteins (1): NP_002219* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR002112 | Leuzip_Jun | Family |
| IPR004827 | bZIP | Domain |
| IPR005643 | JNK | Domain |
| IPR008917 | TF_DNA-bd_sf | Homologous_superfamily |
| IPR046347 | bZIP_sf | Homologous_superfamily |
| IPR050946 | AP-1_TF_bZIP | Family |
Pfam: PF00170, PF03957
UniProt features (43 total): modified residue 14, mutagenesis site 12, cross-link 5, sequence conflict 4, region of interest 3, chain 1, domain 1, sequence variant 1, helix 1, site 1
Structure
Experimental structures (PDB)
10 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 6Y3V | X-RAY DIFFRACTION | 1.5 |
| 5T01 | X-RAY DIFFRACTION | 1.89 |
| 5FV8 | X-RAY DIFFRACTION | 1.99 |
| 1JNM | X-RAY DIFFRACTION | 2.2 |
| 8SOS | X-RAY DIFFRACTION | 2.33 |
| 1A02 | X-RAY DIFFRACTION | 2.7 |
| 1T2K | X-RAY DIFFRACTION | 3 |
| 1FOS | X-RAY DIFFRACTION | 3.05 |
| 1S9K | X-RAY DIFFRACTION | 3.1 |
| 1JUN | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P05412-F1 | 62.45 | 0.22 |
Antibody-complex structures (SAbDab): 1 — 8SOS
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1): 272 (necessary for synergistic transcriptional activity with smad3)
Post-translational modifications (19): 63, 73, 89, 91, 93, 239, 243, 249, 271, 286, 35, 50, 56, 70, 226, 2, 8, 56, 58
Mutagenesis-validated functional residues (12):
| Position | Phenotype |
|---|---|
| 2 | complete loss of pak2-mediated phosphorylation; when associated with a-8; a-89; a-93; and a-286. |
| 6–194 | abolishes activation of faslg/cd95l transcription. |
| 8 | complete loss of pak2-mediated phosphorylation; when associated with a-2; a-89; a-93; and a-286. |
| 63 | greatly reduced atf7-mediated transcriptional activity; when associated with a-73. abolishes interaction with fbxw7; whe |
| 73 | greatly reduced atf7-mediated transcriptional activity; when associated with a-63. abolishes interaction with fbxw7; whe |
| 89 | complete loss of pak2-mediated phosphorylation; when associated with a-2; a-8; a-93; and a-286. |
| 91 | abolishes interaction with fbxw7; when associated with a-63; a-73 and a-93. |
| 93 | abolishes interaction with fbxw7; when associated with a-63; a-73 and a-91. |
| 93 | complete loss of pak2-mediated phosphorylation; when associated with a-2; a-8; a-89; and a-286. |
| 243 | abolishes phosphorylation by dyrk2. abolishes phosphorylation by gsk3b at thr-239. |
| 272 | abolishes the synergistic activity with smad3 to activate tgf-beta-mediated transcription. |
| 286 | complete loss of pak2-mediated phosphorylation; when associated with a-2; a-8; a-89; and a-93. |
Function
Pathways and Gene Ontology
Reactome pathways
67 pathways
| ID | Pathway |
|---|---|
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation |
| R-HSA-2559580 | Oxidative Stress Induced Senescence |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) |
| R-HSA-2871796 | FCERI mediated MAPK activation |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogenesis |
| R-HSA-5687128 | MAPK6/MAPK4 signaling |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models |
| R-HSA-8943724 | Regulation of PTEN gene transcription |
| R-HSA-9018519 | Estrogen-dependent gene expression |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription |
| R-HSA-9976102 | Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells) |
| R-HSA-1257604 | PIP3 activates AKT signaling |
| R-HSA-1266738 | Developmental Biology |
| R-HSA-1280215 | Cytokine Signaling in Immune system |
| R-HSA-157118 | Signaling by NOTCH |
| R-HSA-162582 | Signal Transduction |
| R-HSA-1643685 | Disease |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane |
| R-HSA-166166 | MyD88-independent TLR4 cascade |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade |
MSigDB gene sets: 938 (showing top):
PID_BCR_5PATHWAY, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, REACTOME_SIGNALING_BY_NOTCH, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GRUETZMANN_PANCREATIC_CANCER_DN, PID_TELOMERASE_PATHWAY, HARRIS_HYPOXIA
GO Biological Process (43): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), microglial cell activation (GO:0001774), liver development (GO:0001889), positive regulation of endothelial cell proliferation (GO:0001938), outflow tract morphogenesis (GO:0003151), regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), transforming growth factor beta receptor signaling pathway (GO:0007179), JNK cascade (GO:0007254), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), positive regulation of epithelial cell migration (GO:0010634), release from viral latency (GO:0019046), monocyte differentiation (GO:0030224), axon regeneration (GO:0031103), response to endoplasmic reticulum stress (GO:0034976), leading edge cell differentiation (GO:0035026), response to muscle stretch (GO:0035994), regulation of cell population proliferation (GO:0042127), negative regulation of DNA binding (GO:0043392), negative regulation of neuron apoptotic process (GO:0043524), host-mediated suppression of viral transcription (GO:0043922), host-mediated activation of viral transcription (GO:0043923), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of fibroblast proliferation (GO:0048146), response to steroid hormone (GO:0048545), regulation of cell cycle (GO:0051726), SMAD protein signal transduction (GO:0060395), eyelid development in camera-type eye (GO:0061029), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to calcium ion (GO:0071277), cellular response to anisomycin (GO:0072740), integrated stress response signaling (GO:0140467), positive regulation of miRNA transcription (GO:1902895), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), positive regulation of DNA-templated transcription initiation (GO:2000144)
GO Molecular Function (21): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), RNA binding (GO:0003723), GTPase activator activity (GO:0005096), enzyme binding (GO:0019899), ubiquitin protein ligase binding (GO:0031625), cAMP response element binding (GO:0035497), identical protein binding (GO:0042802), ubiquitin-like protein ligase binding (GO:0044389), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), R-SMAD binding (GO:0070412), general transcription initiation factor binding (GO:0140296), sequence-specific double-stranded DNA binding (GO:1990837), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515)
GO Cellular Component (9): nuclear chromosome (GO:0000228), chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), transcription repressor complex (GO:0017053), transcription factor AP-1 complex (GO:0035976), RNA polymerase II transcription regulator complex (GO:0090575)
Reactome top-level categories
Rollup of top-17 pathways:
| Category | Pathways |
|---|---|
| Cellular Senescence | 2 |
| Pre-NOTCH Expression and Processing | 1 |
| Fc epsilon receptor (FCERI) signaling | 1 |
| MAPK targets/ Nuclear events mediated by MAP kinases | 1 |
| Activation of HOX genes during differentiation | 1 |
| MAPK family signaling cascades | 1 |
| Transcriptional Regulation by TP53 | 1 |
| Neurodegenerative Diseases | 1 |
| PTEN Regulation | 1 |
| ESR-mediated signaling | 1 |
| Killing mechanisms | 1 |
| Signaling by ALK in cancer | 1 |
| Regulation of PD-L1(CD274) expression | 1 |
| Differentiation of T cells | 1 |
| Intracellular signaling by second messengers | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| RNA polymerase II transcription regulatory region sequence-specific DNA binding | 4 |
| regulation of transcription by RNA polymerase II | 2 |
| transcription by RNA polymerase II | 2 |
| regulation of DNA-templated transcription | 2 |
| chromatin | 2 |
| DNA-binding transcription factor activity, RNA polymerase II-specific | 2 |
| nucleic acid binding | 2 |
| protein binding | 2 |
| chromosome | 2 |
| nuclear lumen | 2 |
| cellular anatomical structure | 2 |
| transcription regulator complex | 2 |
| negative regulation of DNA-templated transcription | 1 |
| blood vessel morphogenesis | 1 |
| anatomical structure formation involved in morphogenesis | 1 |
| leukocyte activation involved in inflammatory response | 1 |
| macrophage activation | 1 |
| glial cell activation | 1 |
| gland development | 1 |
| hepaticobiliary system development | 1 |
| endothelial cell proliferation | 1 |
| regulation of endothelial cell proliferation | 1 |
| positive regulation of epithelial cell proliferation | 1 |
| heart morphogenesis | 1 |
| anatomical structure morphogenesis | 1 |
| programmed cell death | 1 |
| apoptotic signaling pathway | 1 |
| execution phase of apoptosis | 1 |
| cellular response to transforming growth factor beta stimulus | 1 |
| transforming growth factor beta receptor superfamily signaling pathway | 1 |
| MAPK cascade | 1 |
| cellular process | 1 |
| cell population proliferation | 1 |
| regulation of cell population proliferation | 1 |
| negative regulation of cellular process | 1 |
| response to chemical | 1 |
| epithelial cell migration | 1 |
| regulation of epithelial cell migration | 1 |
| positive regulation of cell migration | 1 |
| viral process | 1 |
Protein interactions and networks
STRING
10838 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| JUN | FOSL2 | P15408 | 999 |
| JUN | FOS | P01100 | 999 |
| JUN | FOSB | P53539 | 998 |
| JUN | CREB1 | P16220 | 997 |
| JUN | FOSL1 | P15407 | 996 |
| JUN | ATF3 | P18847 | 996 |
| JUN | COPS5 | Q92905 | 995 |
| JUN | ESR1 | P03372 | 995 |
| JUN | STAT3 | P40763 | 994 |
| JUN | BATF | Q16520 | 993 |
| JUN | MAF | O75444 | 993 |
| JUN | NFKB1 | P19838 | 992 |
| JUN | EP300 | Q09472 | 992 |
| JUN | TP53 | P04637 | 992 |
| JUN | IRF3 | Q14653 | 992 |
IntAct
464 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| JUN | FOS | psi-mi:“MI:2364”(proximity) | 0.980 |
| JUN | FOS | psi-mi:“MI:0407”(direct interaction) | 0.980 |
| FOS | JUN | psi-mi:“MI:0914”(association) | 0.980 |
| FOS | JUN | psi-mi:“MI:0407”(direct interaction) | 0.980 |
| FOS | JUN | psi-mi:“MI:2364”(proximity) | 0.980 |
| JUN | FOS | psi-mi:“MI:0915”(physical association) | 0.980 |
| ATF2 | JUN | psi-mi:“MI:0407”(direct interaction) | 0.950 |
| JUN | ATF2 | psi-mi:“MI:0407”(direct interaction) | 0.950 |
| JUN | ATF2 | psi-mi:“MI:0914”(association) | 0.950 |
| ATF2 | JUN | psi-mi:“MI:0914”(association) | 0.950 |
| JUN | ATF2 | psi-mi:“MI:0915”(physical association) | 0.950 |
| JUN | FOSL2 | psi-mi:“MI:0407”(direct interaction) | 0.930 |
| FOSL2 | JUN | psi-mi:“MI:0407”(direct interaction) | 0.930 |
| JUN | FOSL2 | psi-mi:“MI:0915”(physical association) | 0.930 |
| JUN | BATF3 | psi-mi:“MI:0407”(direct interaction) | 0.870 |
| BATF3 | JUN | psi-mi:“MI:0407”(direct interaction) | 0.870 |
| JUN | FOSL1 | psi-mi:“MI:2364”(proximity) | 0.850 |
| JUN | ATF3 | psi-mi:“MI:0407”(direct interaction) | 0.850 |
| MAPK8 | JUN | psi-mi:“MI:0407”(direct interaction) | 0.850 |
| FOSL1 | JUN | psi-mi:“MI:0914”(association) | 0.850 |
| JUN | MAPK8 | psi-mi:“MI:0217”(phosphorylation reaction) | 0.850 |
| MAPK10 | JUN | psi-mi:“MI:0407”(direct interaction) | 0.760 |
| MAPK10 | JUN | psi-mi:“MI:0217”(phosphorylation reaction) | 0.760 |
| JUN | JUN | psi-mi:“MI:0407”(direct interaction) | 0.740 |
BioGRID (926): JUN (Biochemical Activity), JUN (Biochemical Activity), JUN (Affinity Capture-Western), JUN (Biochemical Activity), JUN (Biochemical Activity), PPP3CA (Affinity Capture-Western), PPP3CA (Reconstituted Complex), SP1 (Reconstituted Complex), SP1 (Affinity Capture-Western), JUN (Affinity Capture-Western), JUN (Affinity Capture-Western), JUN (Reconstituted Complex), JUN (Affinity Capture-Western), JUN (Co-fractionation), JUN (Co-localization)
ESM2 similar proteins: A0JMF8, A2RSY1, A6QLW9, B1WAV2, B2GV50, O60271, O75069, O77627, P05412, P05627, P0C090, P17325, P22670, P48377, P48378, P48379, P48380, P48381, P56432, Q0V989, Q0V9K5, Q16656, Q32NR3, Q3KR73, Q499B3, Q49GP3, Q4R3I8, Q4R3Z4, Q4V872, Q4VGL6, Q58A65, Q5EAP5, Q5EY87, Q5RDR2, Q5RJA1, Q5TC82, Q62739, Q66IV1, Q6NRE7, Q6NUC6
Diamond homologs: A0A0A2J9B3, A7YY54, B8NLU5, O77627, O93602, P05411, P05412, P05627, P09450, P11939, P12981, P15066, P15336, P16951, P17275, P17325, P17535, P17544, P18870, P23050, P24898, P27921, P52890, P52909, P54864, P56432, P78962, P79703, Q00969, Q02100, Q02930, Q09771, Q09926, Q0VBZ5, Q2U616, Q4WVQ7, Q59VR1, Q5R9C9, Q8K1L0, Q8R0S1
SIGNOR signaling
129 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| PELI3 | up-regulates | JUN | |
| VRK1 | up-regulates | JUN | phosphorylation |
| JUN | up-regulates | TCF4 | binding |
| GSK3A | down-regulates | JUN | phosphorylation |
| PP2B | up-regulates | JUN | dephosphorylation |
| PLK3 | up-regulates | JUN | phosphorylation |
| RELA | up-regulates | JUN | binding |
| MAPK10 | up-regulates | JUN | phosphorylation |
| PAK2 | up-regulates | JUN | phosphorylation |
| DVL1 | up-regulates | JUN | binding |
| CDK3 | up-regulates | JUN | phosphorylation |
| MAPK9 | up-regulates | JUN | phosphorylation |
| (-)-anisomycin | up-regulates | JUN | “chemical activation” |
| DYRK2 | down-regulates | JUN | phosphorylation |
| CSNK2A1 | down-regulates | JUN | phosphorylation |
| JUN | up-regulates | Brown_adipogenesis | |
| MAPK1 | “up-regulates activity” | JUN | phosphorylation |
| NfKb-p65/p50 | up-regulates | JUN | binding |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 104 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| MAPK targets/ Nuclear events mediated by MAP kinases | 6 | 44.1× | 1e-06 |
| NGF-stimulated transcription | 7 | 27.0× | 1e-06 |
| MAP kinase activation | 6 | 25.0× | 6e-06 |
| FCERI mediated MAPK activation | 5 | 23.4× | 5e-05 |
| Interleukin-17 signaling | 6 | 20.6× | 1e-05 |
| Toll Like Receptor 10 (TLR10) Cascade | 7 | 20.4× | 5e-06 |
| Toll Like Receptor 5 (TLR5) Cascade | 7 | 20.4× | 5e-06 |
| MyD88 cascade initiated on plasma membrane | 7 | 19.3× | 6e-06 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| integrated stress response signaling | 7 | 53.4× | 2e-08 |
| osteoclast differentiation | 5 | 18.7× | 1e-03 |
| positive regulation of gene expression | 12 | 5.0× | 9e-04 |
Disease & clinical
Cancer significance
Clinical variants and AI predictions
ClinVar
23 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 0 |
| Uncertain significance | 20 |
| Likely benign | 1 |
| Benign | 1 |
Top pathogenic / likely-pathogenic (1)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1706623 | NM_002228.4(JUN):c.659del (p.Pro220fs) | Pathogenic |
SpliceAI
41 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:58783059:CTT:C | acceptor_gain | 0.7600 |
| 1:58783060:TTT:T | acceptor_gain | 0.7600 |
| 1:58783893:TCTGG:T | acceptor_gain | 0.5200 |
| 1:58783902:T:TC | acceptor_gain | 0.4700 |
| 1:58783913:G:GC | acceptor_gain | 0.4700 |
| 1:58783006:T:TG | acceptor_gain | 0.4600 |
| 1:58783061:T:G | acceptor_gain | 0.4600 |
| 1:58783913:G:C | acceptor_gain | 0.4400 |
| 1:58783061:T:C | acceptor_gain | 0.3800 |
| 1:58783894:C:CC | acceptor_gain | 0.3300 |
| 1:58783895:TGG:T | acceptor_gain | 0.3300 |
| 1:58783896:GGG:G | acceptor_gain | 0.3300 |
| 1:58783900:A:T | acceptor_gain | 0.3300 |
| 1:58783891:GCTC:G | acceptor_gain | 0.3100 |
| 1:58783894:C:G | acceptor_gain | 0.3100 |
| 1:58783892:CT:C | acceptor_gain | 0.3000 |
| 1:58783902:T:C | acceptor_gain | 0.2900 |
| 1:58783931:TTGC:T | acceptor_gain | 0.2800 |
| 1:58783588:T:TA | donor_gain | 0.2700 |
| 1:58783897:GGC:G | acceptor_gain | 0.2500 |
| 1:58783901:GTT:G | acceptor_gain | 0.2500 |
| 1:58783892:CTCT:C | acceptor_gain | 0.2400 |
| 1:58783933:G:GT | acceptor_gain | 0.2400 |
| 1:58783938:TCGG:T | acceptor_gain | 0.2400 |
| 1:58783890:AGCTC:A | acceptor_gain | 0.2300 |
| 1:58783899:CAGT:C | acceptor_gain | 0.2300 |
| 1:58783889:TAGCT:T | acceptor_loss | 0.2200 |
| 1:58783892:CTC:C | acceptor_loss | 0.2200 |
| 1:58783893:TCT:T | acceptor_loss | 0.2200 |
| 1:58783894:CTGG:C | acceptor_loss | 0.2200 |
AlphaMissense
2166 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:58782106:A:G | L322P | 1.000 |
| 1:58782106:A:T | L322H | 1.000 |
| 1:58782111:G:C | C320W | 1.000 |
| 1:58782112:C:A | C320F | 1.000 |
| 1:58782112:C:G | C320S | 1.000 |
| 1:58782112:C:T | C320Y | 1.000 |
| 1:58782113:A:G | C320R | 1.000 |
| 1:58782113:A:T | C320S | 1.000 |
| 1:58782115:C:A | G319V | 1.000 |
| 1:58782115:C:T | G319E | 1.000 |
| 1:58782116:C:A | G319W | 1.000 |
| 1:58782116:C:G | G319R | 1.000 |
| 1:58782116:C:T | G319R | 1.000 |
| 1:58782124:A:T | V316D | 1.000 |
| 1:58782126:G:C | H315Q | 1.000 |
| 1:58782126:G:T | H315Q | 1.000 |
| 1:58782127:T:A | H315L | 1.000 |
| 1:58782127:T:C | H315R | 1.000 |
| 1:58782127:T:G | H315P | 1.000 |
| 1:58782128:G:A | H315Y | 1.000 |
| 1:58782128:G:C | H315D | 1.000 |
| 1:58782128:G:T | H315N | 1.000 |
| 1:58782136:A:G | V312A | 1.000 |
| 1:58782136:A:T | V312D | 1.000 |
| 1:58782137:C:A | V312F | 1.000 |
| 1:58782142:T:G | Q310P | 1.000 |
| 1:58782144:T:A | K309N | 1.000 |
| 1:58782144:T:G | K309N | 1.000 |
| 1:58782145:T:A | K309I | 1.000 |
| 1:58782146:T:C | K309E | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000134509 (1:58784735 C>A,T), RS1002236220 (1:58781981 T>C), RS1002522831 (1:58783476 C>G,T), RS1002553932 (1:58783248 C>T), RS1002673759 (1:58781801 A>G,T), RS1002685861 (1:58783474 C>G,T), RS1003231149 (1:58783666 G>A), RS1004097773 (1:58781904 T>G), RS1004199037 (1:58781293 G>A), RS1004415465 (1:58781834 A>G), RS1004536812 (1:58782991 C>A,T), RS1004757670 (1:58783226 C>T), RS1006088100 (1:58783411 C>A,T), RS1006143902 (1:58784143 G>T), RS1006521447 (1:58785303 C>T)
Disease associations
OMIM: gene MIM:165160 | disease phenotypes:
GenCC curated gene-disease
Mondo (1): breast neoplasm (MONDO:0021100)
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
3 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST000477_4 | Cognitive performance | 5.000000e-06 |
| GCST003542_175 | Night sleep phenotypes | 8.000000e-06 |
| GCST90011899_102 | Aspartate aminotransferase levels | 2.000000e-10 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0003926 | neuropsychological test |
| EFO:0004736 | aspartate aminotransferase measurement |
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D001943 | Breast Neoplasms | C04.588.180; C17.800.090.500 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL2111421 (PROTEIN COMPLEX), CHEMBL4977 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 94,323 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL140 | CURCUMIN | 3 | 93,882 |
| CHEMBL17205 | CYCLOVALONE | 2 | 348 |
| CHEMBL129857 | AS-602868 | 1 | 93 |
Clinical evidence (CIViC)
Drug × variant × indication: 1 predictive associations from 1 curated evidence items.
| Variant | Therapy | Indication | Effect | Level | CIViC |
|---|---|---|---|---|---|
| JUN Overexpression | Irbesartan | Colorectal Adenocarcinoma | Sensitivity/Response | CIViC C | EID1633 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
Binding affinities (BindingDB)
9 measured of 9 human assays (9 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| (1E,4E)-1,5-dipyridin-3-ylpenta-1,4-dien-3-one | IC50 | 3400 nM | US-9187397: Therapeutic curcumin derivatives |
| (1E,4E)-1,5-dipyridin-4-ylpenta-1,4-dien-3-one | IC50 | 3500 nM | US-9187397: Therapeutic curcumin derivatives |
| (1E,4E)-1,5-bis(2-hydroxyphenyl)penta-1,4-dien-3-one | IC50 | 4200 nM | US-9187397: Therapeutic curcumin derivatives |
| 2,6-Bis-[1-(4-hydroxy-3-methoxy-phenyl)-meth-(E)-ylidene]-cyclohexanone | IC50 | 4200 nM | US-9187397: Therapeutic curcumin derivatives |
| [4-[(1E,4E)-5-(4-acetyloxy-3-methoxyphenyl)-3-oxopenta-1,4-dienyl]-2-methoxyphenyl] acetate | IC50 | 5400 nM | US-9187397: Therapeutic curcumin derivatives |
| (1E,4E)-1,5-bis(2,5-dimethoxyphenyl)penta-1,4-dien-3-one | IC50 | 6400 nM | US-9187397: Therapeutic curcumin derivatives |
| (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-methylhepta-1,4,6-trien-3-one | IC50 | 6700 nM | US-9187397: Therapeutic curcumin derivatives |
| (1E,4Z,6E)-4-benzyl-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one | IC50 | 7600 nM | US-9187397: Therapeutic curcumin derivatives |
| (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one | IC50 | 8200 nM | US-9187397: Therapeutic curcumin derivatives |
ChEMBL bioactivities
190 potent at pChembl≥5 of 210 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.52 | IC50 | 3 | nM | CHEMBL337665 |
| 8.16 | IC50 | 6.9 | nM | CURCUMIN |
| 8.10 | IC50 | 8 | nM | AS-602868 |
| 8.10 | IC50 | 7.9 | nM | NORDIHYDROGUAIARETIC ACID |
| 7.70 | IC50 | 20 | nM | CHEMBL132495 |
| 7.70 | IC50 | 20 | nM | CHEMBL43549 |
| 7.70 | IC50 | 20 | nM | CHEMBL1761563 |
| 7.50 | IC50 | 32 | nM | AILANTHINONE |
| 7.46 | IC50 | 35 | nM | CHEMBL85822 |
| 7.40 | IC50 | 40 | nM | GLAUCARUBINONE |
| 7.40 | IC50 | 40 | nM | CHEMBL1761561 |
| 7.40 | IC50 | 40 | nM | CHEMBL1761582 |
| 7.40 | IC50 | 40 | nM | CHEMBL1761583 |
| 7.35 | IC50 | 45 | nM | CHEMBL86615 |
| 7.30 | IC50 | 50 | nM | CHEMBL336546 |
| 7.30 | IC50 | 50 | nM | CHEMBL1761584 |
| 7.19 | IC50 | 65 | nM | TYLOPHORINIDINE |
| 7.17 | IC50 | 68 | nM | CHEMBL250474 |
| 7.15 | IC50 | 71 | nM | CHEMBL564009 |
| 7.01 | IC50 | 98 | nM | CHEMBL315804 |
| 7.00 | IC50 | 100 | nM | CHEMBL131006 |
| 7.00 | IC50 | 100 | nM | CHEMBL42952 |
| 7.00 | IC50 | 100 | nM | CHEMBL3341912 |
| 7.00 | IC50 | 100 | nM | CHEMBL1761577 |
| 7.00 | IC50 | 100 | nM | CHEMBL43610 |
| 6.96 | IC50 | 110 | nM | TYLOPHORININE |
| 6.92 | IC50 | 120 | nM | CHEMBL1761555 |
| 6.89 | EC50 | 130 | nM | NOTHOSPONDIN |
| 6.89 | IC50 | 130 | nM | CHEMBL1761581 |
| 6.89 | EC50 | 130 | nM | GLAUCARUBINONE |
| 6.80 | IC50 | 160 | nM | CHEMBL1761579 |
| 6.70 | IC50 | 200 | nM | CHEMBL340779 |
| 6.70 | IC50 | 200 | nM | CHEMBL1761569 |
| 6.70 | IC50 | 200 | nM | CHEMBL44525 |
| 6.70 | IC50 | 200 | nM | CHEMBL295192 |
| 6.70 | IC50 | 200 | nM | CHEMBL295508 |
| 6.70 | IC50 | 200 | nM | CHEMBL42650 |
| 6.70 | IC50 | 200 | nM | CHEMBL43534 |
| 6.68 | IC50 | 210 | nM | CHEMBL87274 |
| 6.68 | IC50 | 210 | nM | DIHYDROGUAIARETIC ACID |
| 6.60 | IC50 | 250 | nM | CHEMBL1761565 |
| 6.54 | IC50 | 290 | nM | CHEMBL1761562 |
| 6.52 | IC50 | 300 | nM | CHEMBL339462 |
| 6.52 | IC50 | 300 | nM | CHEMBL337656 |
| 6.52 | IC50 | 300 | nM | CHEMBL87433 |
| 6.52 | IC50 | 300 | nM | CHEMBL296695 |
| 6.52 | IC50 | 300 | nM | CHEMBL45261 |
| 6.52 | IC50 | 300 | nM | CHEMBL296202 |
| 6.52 | IC50 | 300 | nM | CHEMBL43259 |
| 6.52 | IC50 | 300 | nM | CHEMBL42204 |
PubChem BioAssay actives
184 with measured affinity, of 540 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| [(1S,4S,5R,6R,7S,8R,11R,13S,17S,18S,19R)-4,5,17-trihydroxy-6,14,18-trimethyl-9,16-dioxo-3,10-dioxapentacyclo[9.8.0.01,7.04,19.013,18]nonadec-14-en-8-yl] acetate | 422099: Inhibition of TPA-induced AP1 transfected in HEK293 cells assessed as inhibition of beta-lactamase reporter activity treated 1 hr before TPA stimulation measured after 18 hrs by luciferase reporter gene assay | ic50 | <0.0001 | uM |
| methyl (1S,2R,3R,4S,5R,8R,9S,10R,13R,15S,16S)-10-acetyloxy-3,4-dihydroxy-1,16-dimethyl-11,19-dioxo-6,12,20-trioxahexacyclo[13.7.0.02,8.05,9.08,13.017,21]docosa-17,21-diene-5-carboxylate | 422099: Inhibition of TPA-induced AP1 transfected in HEK293 cells assessed as inhibition of beta-lactamase reporter activity treated 1 hr before TPA stimulation measured after 18 hrs by luciferase reporter gene assay | ic50 | <0.0001 | uM |
| [(1S,4S,5R,7S,8R,11R,13S,17S,18S,19R)-4,5,17-trihydroxy-14,18-dimethyl-6-methylidene-9,16-dioxo-3,10-dioxapentacyclo[9.8.0.01,7.04,19.013,18]nonadec-14-en-8-yl] (E)-dodec-3-enoate | 422099: Inhibition of TPA-induced AP1 transfected in HEK293 cells assessed as inhibition of beta-lactamase reporter activity treated 1 hr before TPA stimulation measured after 18 hrs by luciferase reporter gene assay | ic50 | <0.0001 | uM |
| methyl (1R,2S,3R,6R,8R,13S,14R,15R,16S,17S)-3-[(E)-3,4-dimethylpent-2-enoyl]oxy-10,15,16-trihydroxy-9,13-dimethyl-4,11-dioxo-5,18-dioxapentacyclo[12.5.0.01,6.02,17.08,13]nonadec-9-ene-17-carboxylate | 422099: Inhibition of TPA-induced AP1 transfected in HEK293 cells assessed as inhibition of beta-lactamase reporter activity treated 1 hr before TPA stimulation measured after 18 hrs by luciferase reporter gene assay | ic50 | <0.0001 | uM |
| 1-[(6-methoxy-2-thiophen-2-ylquinazolin-4-yl)amino]-3-methylpyrrole-2,5-dione | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0030 | uM |
| 4-[4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol | 1178344: Inhibition of Fos-Jun dimer formation (unknown origin) | ic50 | 0.0079 | uM |
| 1-[(5-methoxy-2-thiophen-2-ylquinazolin-4-yl)amino]-3-methylpyrrole-2,5-dione | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0080 | uM |
| N-[3,5-bis(trifluoromethyl)phenyl]-2-chloro-4-methylpyrimidine-5-carboxamide | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0200 | uM |
| 8-(6-methyl-3-pyridinyl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.0200 | uM |
| ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-2-ylpyrimidine-5-carboxylate | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0200 | uM |
| [(1S,4S,5R,6R,7S,8R,11R,13S,17S,18S,19R)-4,5,17-trihydroxy-6,14,18-trimethyl-9,16-dioxo-3,10-dioxapentacyclo[9.8.0.01,7.04,19.013,18]nonadec-14-en-8-yl] 2-methylbutanoate | 422099: Inhibition of TPA-induced AP1 transfected in HEK293 cells assessed as inhibition of beta-lactamase reporter activity treated 1 hr before TPA stimulation measured after 18 hrs by luciferase reporter gene assay | ic50 | 0.0320 | uM |
| ethyl 4-ethyl-2-[methyl-(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0350 | uM |
| [(1S,4R,5R,6R,7S,8R,11R,13S,17S,18S,19R)-4,5,17-trihydroxy-6,14,18-trimethyl-9,16-dioxo-3,10-dioxapentacyclo[9.8.0.01,7.04,19.013,18]nonadec-14-en-8-yl] (2S)-2-hydroxy-2-methylbutanoate | 422099: Inhibition of TPA-induced AP1 transfected in HEK293 cells assessed as inhibition of beta-lactamase reporter activity treated 1 hr before TPA stimulation measured after 18 hrs by luciferase reporter gene assay | ic50 | 0.0400 | uM |
| 7,8-bis(1-methylpyrazol-4-yl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.0400 | uM |
| 7-(1-methylpyrazol-4-yl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]-8-phenylquinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.0400 | uM |
| N-[4-[3-(6-methyl-3-pyridinyl)-1,2,4-triazol-1-yl]phenyl]-7-(1H-pyrazol-4-yl)quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.0400 | uM |
| ethyl 2-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-4-(5-methylthiophen-2-yl)pyrimidine-5-carboxylate | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0450 | uM |
| 8-methoxy-7-(1-methylpyrazol-4-yl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.0500 | uM |
| N-[3,5-bis(trifluoromethyl)phenyl]-2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxamide | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0500 | uM |
| (13aS,14S)-3,7-dimethoxy-9,11,12,13,13a,14-hexahydrophenanthro[10,9-f]indolizine-6,14-diol | 308180: Inhibition of AP1-mediated gene transcription in HepG2 cells by luciferase reporter gene assay | ic50 | 0.0650 | uM |
| (13aR)-3,7-dimethoxy-9,11,12,13,13a,14-hexahydrophenanthro[10,9-f]indolizin-6-ol | 308180: Inhibition of AP1-mediated gene transcription in HepG2 cells by luciferase reporter gene assay | ic50 | 0.0680 | uM |
| [(1S,4S,5R,6R,7S,11S,12R,13S,16S,17S,18S,19R)-4,5,16,17-tetrahydroxy-6,14,18-trimethyl-9-oxo-3,10-dioxapentacyclo[9.8.0.01,7.04,19.013,18]nonadec-14-en-12-yl] 3-methylbut-2-enoate | 422099: Inhibition of TPA-induced AP1 transfected in HEK293 cells assessed as inhibition of beta-lactamase reporter activity treated 1 hr before TPA stimulation measured after 18 hrs by luciferase reporter gene assay | ic50 | 0.0710 | uM |
| 1-[[5-benzoyl-4-(trifluoromethyl)pyrimidin-2-yl]amino]-3-methylpyrrole-2,5-dione | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.0980 | uM |
| 2-chloro-8-(trifluoromethyl)-6H-pyrimido[4,5-b][1,5]benzothiazepin-5-one | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.1000 | uM |
| N-[3,5-bis(trifluoromethyl)phenyl]-2-fluoro-4-(trifluoromethyl)pyrimidine-5-carboxamide | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.1000 | uM |
| ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-phenylpyrimidine-5-carboxylate | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.1000 | uM |
| ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-3-ylpyrimidine-5-carboxylate | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.1000 | uM |
| 8-chloro-7-(1-methylpyrazol-4-yl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.1000 | uM |
| (13aS,14R)-3,6,7-trimethoxy-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizin-14-ol | 308180: Inhibition of AP1-mediated gene transcription in HepG2 cells by luciferase reporter gene assay | ic50 | 0.1100 | uM |
| N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]-7-(1H-pyrazol-4-yl)quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.1200 | uM |
| (1S,2S,4S,5R,6S,7S,9R,13R,17S)-4,5-dihydroxy-15-methoxy-2,6,14,17-tetramethyl-10-oxatetracyclo[7.7.1.02,7.013,17]heptadec-14-ene-3,11,16-trione | 1178347: Inhibition of AP-1 (unknown origin) by FRET assay | ec50 | 0.1300 | uM |
| 8-cyclopropyl-7-(1-methylpyrazol-4-yl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.1300 | uM |
| 8-methyl-7-(1-methylpyrazol-4-yl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.1600 | uM |
| N-[3,5-bis(trifluoromethyl)phenyl]-2,4-dichloropyrimidine-5-carboxamide | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.2000 | uM |
| 3-methyl-1-[[5-(4-methyl-1,3-oxazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.2000 | uM |
| 3-methyl-1-[[5-(2-methyltetrazol-5-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.2000 | uM |
| ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-(5-methylthiophen-2-yl)pyrimidine-5-carboxylate | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.2000 | uM |
| 1-[[5-(4,5-dihydro-1,3-oxazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]-3-methylpyrrole-2,5-dione | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.2000 | uM |
| ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-methylsulfanylpyrimidine-5-carboxylate | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.2000 | uM |
| N-[4-(3-methyl-1,2,4-triazol-1-yl)phenyl]-8-(1,3-thiazol-2-yl)quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.2000 | uM |
| 4-[4-(4-hydroxy-3-methoxyphenyl)-2,3-dimethylbutyl]-2-methoxyphenol | 1178344: Inhibition of Fos-Jun dimer formation (unknown origin) | ic50 | 0.2100 | uM |
| tert-butyl 2-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-4-(trifluoromethyl)pyrimidine-5-carboxylate | 1178333: Inhibition of AP-1-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay | ic50 | 0.2100 | uM |
| 8-(3-fluoro-4-methoxyphenyl)-N-[4-(3-morpholin-4-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.2500 | uM |
| 7-(1-methylpyrazol-4-yl)-N-[4-(3-pyridin-2-yl-1,2,4-triazol-1-yl)phenyl]quinazolin-2-amine | 589356: Inhibition of c-Jun | ic50 | 0.2900 | uM |
| N-[3,5-bis(trifluoromethyl)phenyl]-2-chloropyrimidine-5-carboxamide | 31747: Concentration required to inhibit activator protein-1(AP-1) mediated transcriptional activation in human Jurkat T-cells | ic50 | 0.3000 | uM |
| N-[3,5-bis(trifluoromethyl)phenyl]-2-chloro-4-ethylpyrimidine-5-carboxamide | 31747: Concentration required to inhibit activator protein-1(AP-1) mediated transcriptional activation in human Jurkat T-cells | ic50 | 0.3000 | uM |
| ethyl 2-(5-chlorothiophen-2-yl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.3000 | uM |
| ethyl 2-(3,5-dichlorophenyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.3000 | uM |
| 3-methyl-1-[[5-(3-methyl-1,2-oxazol-5-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.3000 | uM |
| 3-methyl-1-[[5-(5-methyl-1,3,4-oxadiazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione | 95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | ic50 | 0.3000 | uM |
CTD chemical–gene interactions
524 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| pyrazolanthrone | affects localization, increases phosphorylation, increases expression, increases activity, increases reaction (+5 more) | 51 |
| Tetradecanoylphorbol Acetate | increases localization, increases activity, increases expression, affects cotreatment, increases phosphorylation (+7 more) | 30 |
| sodium arsenite | affects cotreatment, affects expression, increases localization, decreases reaction, increases expression (+8 more) | 27 |
| Arsenic Trioxide | decreases reaction, increases phosphorylation, increases activity, increases reaction, affects response to substance (+7 more) | 26 |
| Resveratrol | affects binding, increases reaction, affects cotreatment, decreases expression, decreases phosphorylation (+4 more) | 18 |
| Acetylcysteine | increases phosphorylation, affects cotreatment, increases reaction, increases activity, decreases activity (+2 more) | 18 |
| Quercetin | affects cotreatment, increases reaction, decreases activity, affects binding, increases expression (+5 more) | 16 |
| Estradiol | increases reaction, affects cotreatment, increases expression, increases phosphorylation, affects binding (+4 more) | 14 |
| Hydrogen Peroxide | increases localization, decreases reaction, increases expression, increases phosphorylation, increases reaction (+3 more) | 14 |
| Cadmium Chloride | increases expression, affects cotreatment, increases reaction, decreases expression, increases abundance (+3 more) | 14 |
| Particulate Matter | affects reaction, increases secretion, decreases expression, increases reaction, increases abundance (+5 more) | 13 |
| U 0126 | decreases reaction, increases expression, increases localization, decreases activity, decreases localization (+5 more) | 12 |
| Benzo(a)pyrene | affects activity, increases phosphorylation, increases expression, increases methylation, decreases reaction | 12 |
| Lipopolysaccharides | increases activity, affects localization, increases localization, affects cotreatment, increases expression (+5 more) | 12 |
| Cisplatin | decreases reaction, affects cotreatment, decreases expression, increases reaction, affects reaction (+3 more) | 11 |
| 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one | increases activity, affects cotreatment, affects localization, decreases reaction, increases phosphorylation (+1 more) | 10 |
| Cadmium | increases expression, increases phosphorylation, affects binding, increases reaction, affects cotreatment (+2 more) | 9 |
| Bortezomib | decreases expression, increases activity, increases phosphorylation, increases expression, decreases reaction (+1 more) | 8 |
| Tetrachlorodibenzodioxin | affects reaction, increases activity, increases reaction, affects localization, decreases reaction (+3 more) | 8 |
| Acetaminophen | increases expression, increases phosphorylation, affects cotreatment, increases reaction, decreases reaction (+2 more) | 7 |
| Air Pollutants | increases expression, affects cotreatment, decreases expression, increases abundance, affects expression (+1 more) | 7 |
| Copper | increases reaction, affects cotreatment, decreases reaction, increases phosphorylation, affects binding (+2 more) | 7 |
| Curcumin | increases expression, increases phosphorylation, affects cotreatment, increases activity, decreases activity (+2 more) | 7 |
| Tobacco Smoke Pollution | affects expression, decreases expression, increases expression | 7 |
| Tretinoin | decreases reaction, affects cotreatment, increases reaction, affects binding, increases phosphorylation (+4 more) | 7 |
| Benzene | affects expression, decreases expression, increases expression | 6 |
| Doxorubicin | decreases reaction, increases phosphorylation, affects binding, affects cotreatment, increases expression (+3 more) | 6 |
| Silicon Dioxide | increases response to substance, decreases reaction, increases phosphorylation, decreases expression, increases reaction (+2 more) | 6 |
| Valproic Acid | affects expression, affects cotreatment, increases expression | 6 |
| Luteolin | affects reaction, decreases reaction, increases expression, affects localization, affects binding (+6 more) | 6 |
ChEMBL screening assays
88 unique, capped per target: 87 binding, 1 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL3223401 | Binding | Inhibition of c-FOS/AP1 (unknown origin) | Small-molecule inhibitors of dimeric transcription factors: Antagonism of proteinprotein and proteinDNA interactions — Medchemcomm |
| CHEMBL705832 | Functional | Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells | Novel inhibitors of AP-1 and NF-kappaB mediated gene expression: structure-activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)++ +pyrimidi ne-5-carboxylate. — Bioorg Med Chem Lett |
Cellosaurus cell lines
14 cell lines: 6 cancer cell line, 4 transformed cell line, 3 embryonic stem cell, 1 telomerase immortalized cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_1454 | NCI-H1092 | Cancer cell line | Male |
| CVCL_A3J5 | SEES3-1V human JUN, clone1 | Embryonic stem cell | Male |
| CVCL_A3J6 | SEES3-1V human JUN, clone2 | Embryonic stem cell | Male |
| CVCL_A3J7 | SEES3-1V human JUN, clone3 | Embryonic stem cell | Male |
| CVCL_B0YG | Abcam HEK293 JUN KO | Transformed cell line | Female |
| CVCL_C3KA | N/Tert-1 JUN | Telomerase immortalized cell line | Male |
| CVCL_D7GN | Ubigene HEK293T JUN KO | Transformed cell line | Female |
| CVCL_D9HT | Ubigene HEK293 JUN KO | Transformed cell line | Female |
| CVCL_E0FX | Ubigene HeLa JUN KO | Cancer cell line | Female |
| CVCL_E9C1 | HEI-286 F-GFP JUN KO | Transformed cell line | Male |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00092183 | PHASE4 | COMPLETED | An Investigational Drug for the Prevention of Chemotherapy-Induced Nausea and Vomiting (MK-0869-071) |
| NCT00128778 | PHASE4 | COMPLETED | Maintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients |
| NCT00302120 | PHASE4 | UNKNOWN | The MONET - Study: MR Mammography of Nonpalpable Breast Tumors |
| NCT00307606 | PHASE4 | UNKNOWN | Does a Single Steroid Injection Reduce the Formation of Postmastectomy Seroma |
| NCT00370240 | PHASE4 | COMPLETED | Chlorhydrate of Ropivacaine and Breast Cancer Surgery |
| NCT00375752 | PHASE4 | TERMINATED | Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer |
| NCT00575354 | PHASE4 | COMPLETED | Comparison of Sevoflurane and Isoflurane Anesthesia for Benign Breast Tumor Excision |
| NCT00604968 | PHASE4 | TERMINATED | Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059) |
| NCT00616135 | PHASE4 | COMPLETED | Study of Autologous Fat Enhanced w/ Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy |
| NCT00649090 | PHASE4 | COMPLETED | A Study to Evaluate the Safety of Adjuvant Treatment With Exemestane Following Previous Treatment With Tamoxifen in Postmenopausal Women With Estrogen Sensitive Primary Breast Cancer |
| NCT00779285 | PHASE4 | TERMINATED | Safety Study of CAELYX in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines (Study P04057)(TERMINATED) |
| NCT01176916 | PHASE4 | COMPLETED | Aromasin® Interventional Study Of Early Invasive Breast Cancer Patients In China |
| NCT01427400 | PHASE4 | UNKNOWN | The Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction |
| NCT01849380 | PHASE4 | UNKNOWN | Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer |
| NCT01859936 | PHASE4 | COMPLETED | Will Preoperative MRI Breast in Women Under 56 Years With Breast Cancer Change Primary Treatment |
| NCT01948960 | PHASE4 | COMPLETED | Influence of Exceptional Patient Characteristics on Everolimus Exposure |
| NCT01961544 | PHASE4 | COMPLETED | Eribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer |
| NCT01975064 | PHASE4 | COMPLETED | Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia |
| NCT02004834 | PHASE4 | ACTIVE_NOT_RECRUITING | Levobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine |
| NCT02372305 | PHASE4 | WITHDRAWN | Comparison of FlexHD and Alloderm Outcomes in Breast Reconstructive Surgery |
| NCT02479347 | PHASE4 | COMPLETED | Wound Infections in Breast Cancer Surgery After Preoperative Skin Preparation With Chlorhexidine vs. Povidone-iodine |
| NCT02549677 | PHASE4 | COMPLETED | Epirubicin Versus Docetaxel Plus Cyclophosphamide in Lymph Node Negative, ER-positive, Her2-negative Breast Cancer |
| NCT02612870 | PHASE4 | UNKNOWN | Sienna+® Injection Time Study 4 Arms |
| NCT02627560 | PHASE4 | COMPLETED | The Effect of Topical Tranexamic Acid on Bleeding and Seroma Formation in After Undergoing Mastectomy |
| NCT02661932 | PHASE4 | COMPLETED | Fertility Preservation in Breast Cancer Patients |
| NCT02781259 | PHASE4 | UNKNOWN | Selective Lymph Node Dissection Using Fluorescent Dye in Node-positive Breast Cancer |
| NCT02819921 | PHASE4 | TERMINATED | Desvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen |
| NCT03220178 | PHASE4 | TERMINATED | Impact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy |
| NCT03583944 | PHASE4 | COMPLETED | A Study to Evaluate Safety, Tolerability and Efficacy of Eribulin Mesylate in Treating Adult Females With Locally Advanced or Metastatic Breast Cancer |
| NCT03586154 | PHASE4 | COMPLETED | Combined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain |
| NCT04707196 | PHASE4 | COMPLETED | A Study of Abemaciclib in Indian Women With Advanced Breast Cancer |
| NCT04931615 | PHASE4 | COMPLETED | ARTISS a Single-centre Randomised Control Study |
| NCT05033769 | PHASE4 | UNKNOWN | Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer |
| NCT05036005 | PHASE4 | UNKNOWN | Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON) |
| NCT05452213 | PHASE4 | RECRUITING | Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients |
| NCT05465031 | PHASE4 | RECRUITING | Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM) |
| NCT05949333 | PHASE4 | UNKNOWN | Reducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy |
| NCT07158164 | PHASE4 | RECRUITING | DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment |
| NCT07162259 | PHASE4 | NOT_YET_RECRUITING | Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer |
| NCT00000611 | PHASE3 | COMPLETED | Women’s Health Initiative (WHI) |
Related Atlas pages
- Associated diseases: colorectal adenocarcinoma
- Biomarker drugs (CIViC) (drugs whose response is associated with variants in this gene — CIViC predictive evidence, not targeting): Irbesartan
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): breast neoplasm, colorectal adenocarcinoma