NCOA1

Summary

NCOA1 (nuclear receptor coactivator 1, HGNC:7668) is a protein-coding gene on chromosome 2p23.3, encoding Nuclear receptor coactivator 1 (Q15788). Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion.

The protein encoded by this gene acts as a transcriptional coactivator for steroid and nuclear hormone receptors. It is a member of the p160/steroid receptor coactivator (SRC) family and like other family members has histone acetyltransferase activity and contains a nuclear localization signal, as well as bHLH and PAS domains. The product of this gene binds nuclear receptors directly and stimulates the transcriptional activities in a hormone-dependent fashion. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 8648 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 431 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): ambiguous (mixed evidence) across 1 cancer types
• Transcription factor: yes — 97 downstream targets (CollecTRI)
• MANE Select transcript: NM_003743

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7668
Approved symbol	NCOA1
Name	nuclear receptor coactivator 1
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	SRC1, F-SRC-1, NCoA-1, KAT13A, RIP160, bHLHe74
Ensembl gene	ENSG00000084676
Ensembl biotype	protein_coding
OMIM	602691
Entrez	8648

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 25 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000288599, ENST00000348332, ENST00000395856, ENST00000405141, ENST00000406961, ENST00000407230, ENST00000469850, ENST00000483904, ENST00000486198, ENST00000493773, ENST00000496333, ENST00000856014, ENST00000918340, ENST00000918341, ENST00000918342, ENST00000918343, ENST00000918344, ENST00000918345, ENST00000950148, ENST00000950149, ENST00000950150, ENST00000950151, ENST00000950152, ENST00000950153, ENST00000950154, ENST00000950155, ENST00000950156, ENST00000950157, ENST00000950158, ENST00000950159

RefSeq mRNA: 7 — MANE Select: NM_003743 NM_001362950, NM_001362952, NM_001362954, NM_001362955, NM_003743, NM_147223, NM_147233

CCDS: CCDS1712, CCDS1713, CCDS42660

Canonical transcript exons

ENST00000348332 — 23 exons

Exon	Start	End
ENSE00000726392	24739432	24739533
ENSE00000726395	24741784	24742186
ENSE00000726401	24757973	24758156
ENSE00000726404	24762687	24762776
ENSE00000808887	24710931	24711111
ENSE00000808888	24726589	24726706
ENSE00000808889	24728308	24728476
ENSE00000808890	24729501	24729815
ENSE00000808891	24751982	24752156
ENSE00001070983	24665749	24665915
ENSE00001070985	24706568	24707888
ENSE00001070992	24697658	24697798
ENSE00001070993	24691481	24691660
ENSE00001070995	24693252	24693347
ENSE00001071000	24705086	24705233
ENSE00001353786	24643966	24644122
ENSE00001547784	24584476	24584560
ENSE00001556688	24564295	24564430
ENSE00003475744	24673366	24673463
ENSE00003508610	24682951	24683128
ENSE00003580489	24658661	24658766
ENSE00003626454	24768221	24770702
ENSE00003921648	24491254	24491602

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 97.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7035 / max 495.3932, expressed in 1774 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19185	12.9903	1731
19183	2.3461	959
19186	0.7603	323
202114	0.6316	329
19184	0.4341	251
19196	0.4152	135
202113	0.1258	53

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	97.26	gold quality
middle frontal gyrus	UBERON:0002702	96.78	gold quality
paraflocculus	UBERON:0005351	95.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.76	gold quality
entorhinal cortex	UBERON:0002728	95.70	gold quality
tibialis anterior	UBERON:0001385	95.49	gold quality
postcentral gyrus	UBERON:0002581	95.13	gold quality
frontal pole	UBERON:0002795	94.99	gold quality
endothelial cell	CL:0000115	94.88	gold quality
parietal lobe	UBERON:0001872	94.66	gold quality
CA1 field of hippocampus	UBERON:0003881	94.63	gold quality
calcaneal tendon	UBERON:0003701	94.62	gold quality
superior frontal gyrus	UBERON:0002661	94.51	gold quality
olfactory bulb	UBERON:0002264	94.42	silver quality
Brodmann (1909) area 46	UBERON:0006483	94.19	gold quality
cortical plate	UBERON:0005343	94.01	gold quality
deltoid	UBERON:0001476	93.85	gold quality
lateral globus pallidus	UBERON:0002476	93.68	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.19	gold quality
biceps brachii	UBERON:0001507	93.05	gold quality
primary visual cortex	UBERON:0002436	93.04	gold quality
orbitofrontal cortex	UBERON:0004167	93.04	gold quality
occipital lobe	UBERON:0002021	92.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.90	gold quality
jejunal mucosa	UBERON:0000399	92.78	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	92.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.36	gold quality
secondary oocyte	CL:0000655	92.27	gold quality
inferior olivary complex	UBERON:0002127	92.23	gold quality
temporal lobe	UBERON:0001871	92.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

97 targets.

Target	Regulation
ABCA1	Activation
ADIPOQ	Activation
ADRB1
AGT
ALDOB	Activation
APOA5	Activation
APOC3	Activation
AR	Activation
BGLAP
C3
CARM1
CCNA2
CCND1
CD24
CD74
CDK2
CDKN1A	Activation
CRABP2	Activation
CREBBP
CRH
CSF1	Activation
CSN2
CXCL8	Unknown
CYP11A1
CYP2B6
CYP2C9
CYP3A4
CYP4F12
CYP7A1	Activation
DIO1

Upstream regulators (CollecTRI, top): ESR1, NR3C1

miRNA regulators (miRDB)

199 targeting NCOA1, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 40)

• CBP/p300 and NcoA/SRC1a may function in a common pathway to regulate STAT3 transcriptional activity. (PMID:11773079)
• Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERalpha transcriptional activity and MCF-7 proliferation (PMID:11818499)
• CAR antagonizes ER-mediated transcriptional activity by squelching limiting amounts of p160 coactivators, such as SRC-1 and GRIP-1. (PMID:12114525)
• mutation of the AF2 transactivation domain on Glucocorticoid Receptors disrupts the direct interaction of GR with steroid receptor coactivator 1 (SRC-1) (PMID:12118039)
• STAT6 has a protein binding motif that controls the interaction with NcoA-1 in transcriptional activation (PMID:12138096)
• Data show that steroid receptor coactivator-1 (SRC-1) enhanced ligand-independent activation of the AR by IL-6 to the same magnitude as that obtained via ligand-dependent activation, and that activation required MAPK. (PMID:12163482)
• Overexpression of SRC-1 (NCOA1) and TIF-2 (NCOA2) increases estrogen-induced gene expression. (PMID:12403846)
• our results indicate an important role for Mediator, as well as its functional interplay with p300/CBP-SRC, in the enhancement of ERalpha-dependent transcription with chromatin templates (PMID:12482985)
• Sumoylation was shown to increase progesterone receptor-SRC-1 interaction and to prolong SRC-1 retention in the nucleus. (PMID:12529333)
• is a coactivator of MHC class II genes that stimulates their interferon gamma (IFNgamma) and class II transactivator (CIITA)-mediated expression. (PMID:12933903)
• NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the alpha-helical region of the STAT5 transactivation domain (PMID:12954634)
• differential recruitment of steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors by estrogen receptor-alpha and beta in breast cancer may be central to the response of the tumor to endocrine treatment (PMID:14715875)
• surface complementarity between the hydrophobic faces of the STAT6 fragment and of the NCoA-1 PAS-B domain almost exclusively defines the binding specificity between the two proteins (PMID:14757047)
• TNF-alpha impairs progesterone-stimulated PR-B-mediated transactivation, and these effects appear to be due, in part, to reduced expression of SRC-1 and -2 (PMID:15231721)
• A novel translocation t(2;2)(q35;p23), which generates a fusion protein composed of PAX3 and the NCOA1was identified in rhabdomyosarcoma. (PMID:15313887)
• Data show that steroid receptor coactivator-1 (SRC-1) overexpressing cells are more responsive to Po mRNA induction by dihydroprogesterone (DHP) than SRC-1-deficient cells, and that DHP treatment increases not only Po but also SRC-1 mRNA levels. (PMID:15456935)
• The conserved STAT3 region from 752 to 761, called STAT3 CR2, plays critical roles in STAT3-dependent transcription by recruiting SRC-1 and allowing Ser727 phosphorylation. (PMID:15530426)
• The SRC-1 has been shown to be involved in HIF-1alpha-mediated activation of transcription. (PMID:15615775)
• SRC-1 and SMRT content change in a tissue-specific manner in the rat brain during the estrous cycle. (PMID:15862975)
• ASXL1 is a novel coactivator of RAR that cooperates with SRC-1 (PMID:16606617)
• SRC1-deficient P19 cells showed severely compromised retinoid-induced responses, in agreement with the supposed role of SRC1 as a retinoic acid recepetor coactivator. (PMID:16723356)
• HPV E7 proteins dysregulate hormone-dependent gene expression by association with and relocalization of SRC-1. (PMID:16775354)
• These results establish the importance of coactivators PGC1alpha and SRC1 for the hepatic expression of human P450s and uncover a new HNF4alpha-dependent regulatory mechanism to constitutively control the CYP1A1/2 cluster. (PMID:16882880)
• Binding and dissociation of full-length steroid receptor coactivator-1a (SRC1a) from full-length estrogen receptor alpha or beta. (PMID:17135255)
• not only the Q158K variant found in Chinese, but also in native pregnane X receptor variants in other ethnic groups (D163G, A370T, R381W, and I403V) affect CYP3A4 induction by altering steroid receptor coactivator-1 recruitment (PMID:17429319)
• Expression of androgen receptor co-regulators in the testes of men with azoospermia. (PMID:17919607)
• The main transactivation function of the androgen receptor interacts with both the C-terminal domain of coactivator SRC-1a and the general transcription factor RAP74/TFIIF large subunit. (PMID:18284209)
• important role for androgen receptor-associated coactivators in urothelial carcinoma of the bladder (PMID:18845648)
• The small interfering RNA depletion of SRC-1 did not inhibited growth of MCF-7 cells as well as a reduction in ERalpha transcriptional activity. (PMID:19095746)
• STAT3 transactivates its target genes by the recruitment of CBP/p300 co-activators and this process generally does not require the contribution of SRC-1. (PMID:19203349)
• SRC-1 is a strong independent predictor of reduced disease free survival, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment. (PMID:19276281)
• Age-induced loss of PPARgamma/SRC-1 interactions increased the binding of PPARgamma to the promoter of the adipogenic gene aP2. (PMID:19485965)
• describes in detail the BRET(2) assay as it is used to examine the physical interaction between the nuclear receptor ERalpha and the transcriptional coactivator SRC-1 (PMID:19763509)
• Clomiphene citrate may inhibit E2-induced endometrial epithelial cell proliferation and ERE transactivation by inhibiting the recruitment of SRC-1 to ER alpha. (PMID:19934375)
• Studies expand knowledge of PAX3 variant translocations in rhabdomyossarcoma with identification of a novel PAX3-NCOA2 fusion. (PMID:19953635)
• HOXC11 and SRC-1 cooperate to regulate expression of the calcium-binding protein S100beta in resistant breast cancer cells. (PMID:20145129)
• NR box-2 and -3 are the essential binding targets for the SRC-1-induced stimulation of LXR transactivity; the competitive in vitro binding of NR box-2 and -3 to LXR was observed. (PMID:20682316)
• Distinctive functions of p160 steroid receptor coactivators in proliferation of an estrogen-independent, tamoxifen-resistant breast cancer cell line. (PMID:21059860)
• The induced AF1 conformation facilitates its interaction with SRC-1, and subsequent AF1-mediated transcriptional activity. (PMID:21760925)
• findings suggest that SRC-1 switches steroid-responsive tumors to a steroid-resistant state in which the SRC-1 target gene ADAM22 has a critical role (PMID:22072566)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncoa1	ENSDARG00000018257
mus_musculus	Ncoa1	ENSMUSG00000020647
rattus_norvegicus	Ncoa1	ENSRNOG00000004068
drosophila_melanogaster	tai	FBGN0041092

Paralogs (2): NCOA3 (ENSG00000124151), NCOA2 (ENSG00000140396)

Protein

Protein identifiers

Nuclear receptor coactivator 1 — Q15788 (reviewed: Q15788)

Alternative names: Class E basic helix-loop-helix protein 74, Protein Hin-2, RIP160, Renal carcinoma antigen NY-REN-52, Steroid receptor coactivator 1

All UniProt accessions (2): Q15788, B5MCN7

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.

Subunit / interactions. Interacts with PPARA; the interaction is direct. Interacts with PPARG; the interaction is direct. Interacts with ESRRG; the interaction is direct. Interacts with STAT5A (via FDL motif). Interacts with STAT5B (via FDL motif). Interacts with STAT6 (via LXXLL motif). Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif). Interacts with ASXL1. Interacts with the methyltransferase CARM1. Interacts with COPS5. Interacts with the histone acetyltransferase CREBBP. Interacts with DDX5. Interacts with the histone acetyltransferase EP300. Interacts with ESR1. Interacts with GCCR. Interacts with the basal transcription factor GTF2B. Interacts with NCOA6. Interacts with NCOA2. Interacts with NR3C1. Interacts with NR4A1/Nur77. Interacts with NR4A3. Interacts with PCAF. Interacts with PGR. Interacts with PRMT2. Interacts with PRMT6. Interacts with PSMB9. Interacts with RXRA, the interaction is ligand-dependent. Interacts with STAT3 following IL-6 stimulation. Interacts with TRA. Interacts with TRIP4. Interacts with TTLL5/STAMP. Interacts with UBE2L3; they functionally interact to regulate progesterone receptor transcriptional activity. Interacts with VDR.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Post-translational modifications. Sumoylated; sumoylation increases its interaction with PGR and prolongs its retention in the nucleus. It does not prevent its ubiquitination and does not exert a clear effect on the stability of the protein. Ubiquitinated; leading to proteasome-mediated degradation. Ubiquitination and sumoylation take place at different sites.

Disease relevance. A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.

Domain organisation. The C-terminal (1107-1441) part mediates the histone acetyltransferase (HAT) activity. Contains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motifs 3, 4 and 5 are essential for the association with nuclear receptors. LXXLL motif 7, which is not present in isoform 2, increases the affinity for steroid receptors in vitro.

Miscellaneous. Major form. Contains a domain at its C-terminus (1241-1399) that is able to mediate transactivation.

Similarity. Belongs to the SRC/p160 nuclear receptor coactivator family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15788-1	1, SRC-1A, SRC1a	yes
Q15788-2	2, SRC-1E, SRC1e
Q15788-3	3, SRC-1 (-Q)

RefSeq proteins (7): NP_001349879, NP_001349881, NP_001349883, NP_001349884, NP_003734, NP_671756, NP_671766 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR009110	Nuc_rcpt_coact	Homologous_superfamily
IPR010011	NCO_DUF1518	Domain
IPR011598	bHLH_dom	Domain
IPR013767	PAS_fold	Domain
IPR014920	Nuc_rcpt_coact_Ncoa-typ	Domain
IPR014935	SRC/p160_LXXLL	Domain
IPR017426	Nuclear_rcpt_coactivator	Family
IPR028819	NCOA1_bHLH	Domain
IPR035965	PAS-like_dom_sf	Homologous_superfamily
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR037077	Nuc_rcpt_coact_Ncoa_int_sf	Homologous_superfamily
IPR056193	bHLH_NCOA1-3	Domain

Pfam: PF00989, PF07469, PF08815, PF08832, PF14598, PF16665, PF23172

Enzyme classification (BRENDA):

• EC 2.3.1.48 — histone acetyltransferase (BRENDA: 41 organisms, 681 substrates, 1134 inhibitors, 140 Km, 96 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–0.046	51
HISTONE H3	0.007–2.09	23
HISTONE H4	—	11
HISTONE H4 PEPTIDE	0.0208–0.197	7
HISTONE	0.075–1.4	6
HISTONE H3 TAIL PEPTIDE	0.044–0.112	4
PICCOLONUA4 PEPTIDE	0.135–0.372	4
3-AZIDOPROPIONYL-COA	0.0002–0.0086	3
4-PENTYNOYL-COA	0.0009–0.0859	3
SPERMIDINE	0.18–0.27	3
5-HEXYNOYL-COA	0.0006–0.0117	2
6-HEPTYNOYL-COA	0.0003–0.0237	2
HISTONE H3-PEPTIDE	0.05–0.49	2
PROTEIN P53	1.28–4.63	2
3-AZIDOPROPANOYL-COA	0.0103	1

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)

UniProt features (98 total): modified residue 16, region of interest 11, compositionally biased region 11, helix 11, sequence variant 10, mutagenesis site 8, strand 8, short sequence motif 7, sequence conflict 4, cross-link 3, domain 2, splice variant 2, turn 2, initiator methionine 1, chain 1, site 1

Structure

Experimental structures (PDB)

301 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9GC7	X-RAY DIFFRACTION	1.46
1NQ7	X-RAY DIFFRACTION	1.5
3OLL	X-RAY DIFFRACTION	1.5
7BQ2	X-RAY DIFFRACTION	1.52
7BQ1	X-RAY DIFFRACTION	1.52
6GEV	X-RAY DIFFRACTION	1.54
7XVY	X-RAY DIFFRACTION	1.54
3UUD	X-RAY DIFFRACTION	1.6
6W9I	X-RAY DIFFRACTION	1.61
7BQ4	X-RAY DIFFRACTION	1.62
7KXD	X-RAY DIFFRACTION	1.62
8HUQ	X-RAY DIFFRACTION	1.65
5HJS	X-RAY DIFFRACTION	1.72
5MWY	X-RAY DIFFRACTION	1.75
7BQ0	X-RAY DIFFRACTION	1.77
2P54	X-RAY DIFFRACTION	1.79
3KMR	X-RAY DIFFRACTION	1.8
4MGA	X-RAY DIFFRACTION	1.8
5Q0K	X-RAY DIFFRACTION	1.8
5Q0P	X-RAY DIFFRACTION	1.8
6GG8	X-RAY DIFFRACTION	1.8
6L6K	X-RAY DIFFRACTION	1.8
5MWP	X-RAY DIFFRACTION	1.82
5L7H	X-RAY DIFFRACTION	1.84
4MG8	X-RAY DIFFRACTION	1.85
4MGB	X-RAY DIFFRACTION	1.85
4TV1	X-RAY DIFFRACTION	1.85
5GTN	X-RAY DIFFRACTION	1.85
5Q14	X-RAY DIFFRACTION	1.85
5Q1E	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15788-F1	47.53	0.10

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): 867–868 (breakpoint for translocation to form pax3-ncoa1 oncogene)

Post-translational modifications (19): 2, 22, 372, 395, 517, 558, 569, 698, 1033, 1073, 1091, 1124, 1131, 1179, 1185, 1372, 732, 774, 846

Mutagenesis-validated functional residues (8):

Position	Phenotype
636–637	slightly affects interactions with steroid receptors. abolishes interactions with steroid receptors; when associated wit
693–694	slightly affects interactions with steroid receptors. abolishes interactions with steroid receptors; when associated wit
732	abolishes sumoylation; when associated with r-774.
752–753	slightly affects interactions with steroid receptors. abolishes interactions with steroid receptors; when associated wit
774	abolishes sumoylation; when associated with r-732.
800	does not affect sumoylation of the protein.
846	does not affect sumoylation of the protein.
1378	does not affect sumoylation of the protein.

Function

Pathways and Gene Ontology

Reactome pathways

55 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-159418	Recycling of bile acids and salts
R-HSA-192105	Synthesis of bile acids and bile salts
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781	PPARA activates gene expression
R-HSA-211976	Endogenous sterols
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-3214847	HATs acetylate histones
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-9623433	NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression
R-HSA-1266738	Developmental Biology
R-HSA-1368082
R-HSA-1430728	Metabolism
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-162582	Signal Transduction
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-194068	Bile acid and bile salt metabolism

MSigDB gene sets: 473 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GCACCTT_MIR18A_MIR18B, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_METENCEPHALON_DEVELOPMENT, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ESTRADIOL, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION

GO Biological Process (30): positive regulation of transcription from RNA polymerase II promoter by galactose (GO:0000435), regulation of thyroid hormone receptor signaling pathway (GO:0002155), lactation (GO:0007595), male gonad development (GO:0008584), cerebellum development (GO:0021549), hippocampus development (GO:0021766), hypothalamus development (GO:0021854), cerebral cortex development (GO:0021987), estrogen receptor signaling pathway (GO:0030520), response to estradiol (GO:0032355), response to retinoic acid (GO:0032526), response to progesterone (GO:0032570), cellular response to hormone stimulus (GO:0032870), peroxisome proliferator activated receptor signaling pathway (GO:0035357), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of apoptotic process (GO:0043065), estrous cycle (GO:0044849), positive regulation of neuron differentiation (GO:0045666), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of female receptivity (GO:0045925), positive regulation of transcription by RNA polymerase II (GO:0045944), progesterone receptor signaling pathway (GO:0050847), male mating behavior (GO:0060179), labyrinthine layer morphogenesis (GO:0060713), regulation of cellular response to insulin stimulus (GO:1900076), cellular response to Thyroglobulin triiodothyronine (GO:1904017), positive regulation of adipose tissue development (GO:1904179), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), response to hormone (GO:0009725)

GO Molecular Function (16): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), nuclear receptor binding (GO:0016922), nuclear estrogen receptor binding (GO:0030331), protein-containing complex binding (GO:0044877), nuclear retinoid X receptor binding (GO:0046965), protein dimerization activity (GO:0046983), protein-lysine-acetyltransferase activity (GO:0061733), DNA binding (GO:0003677), histone acetyltransferase activity (GO:0004402), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), nuclear retinoic acid receptor binding (GO:0042974), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Bile acid and bile salt metabolism	2
Synthesis of bile acids and bile salts	2
NR1H2 and NR1H3-mediated signaling	2
Circadian clock	1
Regulation of lipid metabolism by PPARalpha	1
Cytochrome P450 - arranged by substrate type	1
Mitochondrial biogenesis	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Chromatin modifying enzymes	1
Adipogenesis	1
SUMO E3 ligases SUMOylate target proteins	1
Metabolism of lipids	1
ESR-mediated signaling	1
Cellular response to chemical stress	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	4
binding	3
cellular anatomical structure	3
pallium development	2
limbic system development	2
response to lipid	2
response to oxygen-containing compound	2
nuclear receptor binding	2
positive regulation of transcription by galactose	1
regulation of transcription from RNA polymerase II promoter by galactose	1
carbon catabolite activation of transcription from RNA polymerase II promoter	1
thyroid hormone receptor signaling pathway	1
regulation of intracellular signal transduction	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
gonad development	1
development of primary male sexual characteristics	1
metencephalon development	1
diencephalon development	1
nuclear receptor-mediated steroid hormone signaling pathway	1
response to steroid hormone	1
response to ketone	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
nuclear receptor-mediated signaling pathway	1
transcription by RNA polymerase II	1
mRNA transcription	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
ovulation cycle	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of female receptivity	1

Protein interactions and networks

STRING

1930 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCOA1	CREBBP	Q92793	992
NCOA1	EP300	Q09472	991
NCOA1	ESR1	P03372	986
NCOA1	ESR2	Q92731	946
NCOA1	KAT2B	Q92831	942
NCOA1	PPARGC1A	Q9UBK2	936
NCOA1	PGR	P06401	924
NCOA1	CARM1	Q86X55	923
NCOA1	PPARG	P37231	908
NCOA1	NCOA2	Q15596	902
NCOA1	AR	P10275	888
NCOA1	NR1I2	O75469	883
NCOA1	STAT6	P42226	872
NCOA1	NCOA3	Q9Y6Q9	863
NCOA1	MED1	Q15648	827

IntAct

152 interactions, top by confidence:

A	B	Type	Score
RARA	NCOA1	psi-mi:“MI:0407”(direct interaction)	0.870
NCOA1	RARA	psi-mi:“MI:0915”(physical association)	0.870
RARA	NCOA1	psi-mi:“MI:0915”(physical association)	0.870
RXRA	NCOA1	psi-mi:“MI:0407”(direct interaction)	0.860
NCOA1	RXRA	psi-mi:“MI:0407”(direct interaction)	0.860
NCOA1	RXRA	psi-mi:“MI:0915”(physical association)	0.860
ESR1	NCOA1	psi-mi:“MI:0914”(association)	0.840
ESR1	NCOA1	psi-mi:“MI:0915”(physical association)	0.840
NCOA1	ESR1	psi-mi:“MI:0915”(physical association)	0.840
ESR1	NCOA1	psi-mi:“MI:2364”(proximity)	0.840
NCOA1	NR1H3	psi-mi:“MI:0915”(physical association)	0.690
NR1H3	NCOA1	psi-mi:“MI:0915”(physical association)	0.690
NR1H3	NCOA1	psi-mi:“MI:0407”(direct interaction)	0.690
NCOA1	NR1H3	psi-mi:“MI:0407”(direct interaction)	0.690
CREBBP	NCOA1	psi-mi:“MI:0915”(physical association)	0.670
NCOA1	CREBBP	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (423): PPARG (Reconstituted Complex), NR1I2 (Two-hybrid), NCOA1 (Affinity Capture-Western), PPARG (Co-crystal Structure), NCOA1 (Protein-peptide), NCOA1 (Reconstituted Complex), NCOA1 (Reconstituted Complex), NCOA1 (Two-hybrid), PPARG (Reconstituted Complex), NCOA1 (Two-hybrid), NCOA1 (Reconstituted Complex), NCOA1 (Reconstituted Complex), NCOA1 (Reconstituted Complex), NCOA1 (Two-hybrid), PPARG (Reconstituted Complex)

ESM2 similar proteins: A0A0G2JTY4, A2VD01, A5PMU4, A8E4V2, D2HNW6, E1BEQ5, O54972, O95644, P16236, P59281, P70365, P97305, Q12968, Q13191, Q13469, Q13905, Q15788, Q1LY51, Q2VPU4, Q3LRZ1, Q3TTA7, Q3U182, Q4PJW2, Q4VCS5, Q60591, Q61122, Q66IV1, Q68FF7, Q6DFR2, Q6GQL0, Q6NYU6, Q6ZNC4, Q80TM6, Q80VG1, Q8HWS3, Q8IXK0, Q8IY63, Q8K4S7, Q8N228, Q8VHG2

Diamond homologs: A1YFY6, A2T6X9, A9YTQ3, E7FFX1, O02747, O09000, O44712, O57539, O61734, P30561, P35869, P41738, P70365, P81133, P90953, P97459, Q0VBL6, Q14190, Q15788, Q24119, Q2VPD4, Q3U1U7, Q4PJW2, Q61045, Q61079, Q75NT5, Q8R4S2, Q8R4S4, Q8R4S5, Q8R4S6, Q8R4S7, Q95LD9, Q98SJ5, Q99742, Q9JHS2, Q9WVS9, Q9Y2N7, B5DE09, O15945, Q15596

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
NCOA1	up-regulates	STAT5A	binding
NCOA1	up-regulates	STAT5B	binding
NR3C1	“up-regulates quantity by expression”	NCOA1	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	ALDOB	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	OTC	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	CYP7A1	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	APOA5	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	APOC3	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	PCK2	“transcriptional regulation”
NCOA1	“up-regulates activity”	ASXL1	binding
ASXL1	“up-regulates activity”	NCOA1	binding
NCOA1	“up-regulates quantity by expression”	RARA	“transcriptional regulation”
PTMS	“up-regulates activity”	NCOA1	binding
Gbeta	up-regulates	NCOA1	phosphorylation
ERK1/2	up-regulates	NCOA1	phosphorylation
NCOA1	“up-regulates quantity by expression”	Aldolase	“transcriptional regulation”
NCOA1	up-regulates	ESR1	binding
NCOA1	up-regulates	PGR
MAPK1	up-regulates	NCOA1	phosphorylation
MAPK3	up-regulates	NCOA1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
SUMOylation of intracellular receptors	15	76.3×	2e-23
Nuclear Receptor transcription pathway	20	60.7×	3e-29
R-HSA-1368082	5	54.1×	6e-07
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	7	43.3×	1e-08
Activation of HOX genes during differentiation	6	39.9×	2e-07
BMAL1:CLOCK,NPAS2 activates circadian expression	6	38.5×	2e-07
R-HSA-400253	6	31.5×	7e-07
Expression of BMAL (ARNTL), CLOCK, and NPAS2	7	31.1×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
intracellular receptor signaling pathway	9	122.2×	3e-15
retinoic acid receptor signaling pathway	6	53.3×	2e-07
negative regulation of miRNA transcription	5	42.8×	8e-06
mRNA transcription by RNA polymerase II	7	31.7×	3e-07
hormone-mediated signaling pathway	5	27.5×	7e-05
negative regulation of inflammatory response	7	13.1×	7e-05
cholesterol homeostasis	5	10.7×	4e-03
gene expression	6	6.6×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: ambiguous (mixed evidence) across 1 cancer types — PAAD.

Clinical variants and AI predictions

ClinVar

431 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	278
Likely benign	121
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4900 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24564394:G:GT	donor_gain	1.0000
2:24584471:TTCA:T	acceptor_loss	1.0000
2:24584472:TCA:T	acceptor_loss	1.0000
2:24584473:CAGGT:C	acceptor_loss	1.0000
2:24584474:AGGT:A	acceptor_loss	1.0000
2:24584558:AGGGT:A	donor_loss	1.0000
2:24584559:GG:G	donor_gain	1.0000
2:24584559:GGGT:G	donor_loss	1.0000
2:24584560:GG:G	donor_gain	1.0000
2:24584560:GGTA:G	donor_loss	1.0000
2:24584561:G:C	donor_loss	1.0000
2:24584562:TAAGT:T	donor_loss	1.0000
2:24643962:CTA:C	acceptor_loss	1.0000
2:24643963:TA:T	acceptor_loss	1.0000
2:24643964:AG:A	acceptor_loss	1.0000
2:24643964:AGTT:A	acceptor_gain	1.0000
2:24643965:GTT:G	acceptor_gain	1.0000
2:24643965:GTTG:G	acceptor_gain	1.0000
2:24644118:CCCAG:C	donor_loss	1.0000
2:24644119:CCAG:C	donor_loss	1.0000
2:24644120:CAG:C	donor_loss	1.0000
2:24644121:AG:A	donor_loss	1.0000
2:24644122:GG:G	donor_loss	1.0000
2:24644123:G:GA	donor_loss	1.0000
2:24644124:T:G	donor_loss	1.0000
2:24658655:GTTTA:G	acceptor_loss	1.0000
2:24658656:TTTA:T	acceptor_loss	1.0000
2:24658657:TTAGG:T	acceptor_loss	1.0000
2:24658658:TA:T	acceptor_loss	1.0000
2:24658660:G:GA	acceptor_loss	1.0000

AlphaMissense

9478 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:24665796:T:A	L46Q	1.000
2:24665796:T:C	L46P	1.000
2:24665868:T:C	L70S	1.000
2:24665889:T:C	I77T	1.000
2:24682999:T:C	F135L	1.000
2:24683001:T:A	F135L	1.000
2:24683001:T:G	F135L	1.000
2:24693323:T:C	F262L	1.000
2:24693324:T:C	F262S	1.000
2:24693324:T:G	F262C	1.000
2:24693325:T:A	F262L	1.000
2:24693325:T:G	F262L	1.000
2:24693334:G:C	K265N	1.000
2:24693334:G:T	K265N	1.000
2:24693336:A:C	Q266P	1.000
2:24693339:A:T	D267V	1.000
2:24693347:G:C	G270R	1.000
2:24693347:G:T	G270C	1.000
2:24697658:G:A	G270D	1.000
2:24697658:G:T	G270V	1.000
2:24697664:T:A	I272N	1.000
2:24697664:T:C	I272T	1.000
2:24697664:T:G	I272S	1.000
2:24697669:T:C	S274P	1.000
2:24697673:T:A	I275N	1.000
2:24697673:T:G	I275S	1.000
2:24697711:T:A	W288R	1.000
2:24697711:T:C	W288R	1.000
2:24697715:A:T	E289V	1.000
2:24697724:T:A	V292E	1.000

dbSNP variants (sampled 300 via entrez): RS1000007042 (2:24720902 C>T), RS1000035282 (2:24636889 G>A), RS1000050691 (2:24541230 T>C), RS1000064433 (2:24547610 T>C), RS1000102313 (2:24668168 A>G), RS1000102963 (2:24567199 A>G), RS1000105960 (2:24657817 G>C), RS1000108960 (2:24591194 A>C,G), RS1000126573 (2:24759876 T>C), RS1000150966 (2:24637194 T>C,G), RS1000158772 (2:24547441 T>G), RS1000161086 (2:24734338 C>T), RS1000168983 (2:24603542 T>C), RS1000172523 (2:24694467 A>G), RS1000176343 (2:24592895 C>T)

Disease associations

OMIM: gene MIM:602691 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST002636_1	Diffuse large B cell lymphoma	4.000000e-08
GCST002929_19	Chromium levels	7.000000e-06
GCST004077_5	Cognitive function	1.000000e-07
GCST004562_83	Waist circumference adjusted for body mass index	2.000000e-08
GCST004563_60	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	7.000000e-07
GCST004744_20	Lung adenocarcinoma	9.000000e-06
GCST004748_78	Lung cancer	4.000000e-06
GCST004748_79	Lung cancer	2.000000e-06
GCST004749_90	Lung cancer in ever smokers	6.000000e-06
GCST004749_91	Lung cancer in ever smokers	4.000000e-06
GCST005075_2	Breast Cancer in BRCA1 mutation carriers	3.000000e-07
GCST005077_5	Breast cancer	1.000000e-08
GCST005212_4	Asthma	2.000000e-07
GCST005830_89	Hand grip strength	1.000000e-08
GCST005950_4	Body mass index x sex x age interaction (4df test)	5.000000e-26
GCST005951_195	Body mass index	3.000000e-24
GCST005952_4	Body mass index (age>50)	5.000000e-09
GCST005953_10	Body mass index (age <50)	6.000000e-20
GCST007293_13	Body fat distribution (arm fat ratio)	2.000000e-39
GCST007293_41	Body fat distribution (arm fat ratio)	5.000000e-22
GCST007293_5	Body fat distribution (arm fat ratio)	2.000000e-21
GCST007294_128	Body fat distribution (trunk fat ratio)	7.000000e-06
GCST007294_94	Body fat distribution (trunk fat ratio)	9.000000e-10
GCST90020025_1585	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020027_1594	Waist-hip index	9.000000e-10
GCST90020028_425	Hip circumference adjusted for BMI	3.000000e-09
GCST90020029_645	Waist circumference adjusted for body mass index	5.000000e-09
GCST90020029_646	Waist circumference adjusted for body mass index	4.000000e-08
GCST90020029_647	Waist circumference adjusted for body mass index	8.000000e-09
GCST90020029_648	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0006941	grip strength measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004341	body fat distribution
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1615387 (SINGLE PROTEIN), CHEMBL2095162 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195556 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 542,892 (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
CHEMBL44657	ETOPOSIDE	4	226,069
CHEMBL803	CYTARABINE	4	202,889
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4	113,934

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1804645	Toxicity	3	tamoxifen	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1804645	NCOA1	3	1.00	1	tamoxifen

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.3.1.48 Histone acetyltransferases (HATs)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 26 [PMID: 21733693]	Inhibition	8.0	pIC50

Binding affinities (BindingDB)

97 measured of 339 human assays (349 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-(benzylsulfanyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile	IC50	25.4 nM
2,5-bis(chloranyl)-3-[2-(dimethylamino)-1,3-thiazol-5-yl]-6-pyrrolidin-1-yl-cyclohexa-2,5-diene-1,4-dione	EC50	210 nM
4-amino-3-(4-methylphenyl)-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazole-2(3H)-thione	IC50	250 nM
3,4-dimethyl-N-(5-thiophen-2-yl-1,3,4-thiadiazol-2-yl)benzamide	EC50	786 nM
5-bromanyl-N-(4-piperidin-1-ylphenyl)pyridine-3-carboxamide	EC50	1020 nM
1-[[1-(4-methoxyphenyl)-3-pyrrolidinyl]methyl]-3-phenylurea	IC50	2580 nM
2-(2-Adamantan-1-yl-2-oxo-ethylsulfanyl)-6-amino-4-(4-chloro-phenyl)-pyridine-3,5-dicarbonitrile	EC50	2940 nM
4-[(2-benzoxybenzyl)amino]phenol	EC50	2980 nM
MLS000107751	EC50	3570 nM
2-(4-chloranyl-3-methyl-phenoxy)-N-[2-methyl-5-(3-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)phenyl]ethanamide	IC50	4880 nM
MLS000560834	EC50	6080 nM
(7-Cyano-[1,3]dioxolo[4,5-g]quinolin-6-ylsulfanyl)-acetic acid methyl ester	EC50	7890 nM
2-[(3,4-dimethoxyphenyl)-oxomethyl]imino-3,4-dimethyl-5-thiazolecarboxylic acid ethyl ester	EC50	8100 nM
MLS000040305	EC50	8460 nM
2-[[1-(3,5-dimethoxyphenyl)-1,2,3,4-tetrazol-5-yl]sulfanyl]-N-(4-ethanoylphenyl)ethanamide	EC50	8560 nM
3-[(5-bromothiophene-2-carbonyl)amino]thiophene-2-carboxylic acid methyl ester	EC50	8670 nM
4-bromanyl-N-(1-propylbenzimidazol-2-yl)benzamide	EC50	8960 nM
2-[2-(2-chlorophenyl)-4-phenyl-1,3-thiazol-5-yl]-N-phenyl-ethanamide	EC50	10000 nM
2-[3-Cyano-6-(4-methoxy-phenyl)-4-thiophen-2-yl-pyridin-2-ylsulfanyl]-N-(2-methoxy-benzyl)-acetamide	EC50	10300 nM
10-methoxy-5H-[1]benzothiolo[2,3-c]quinolin-6-one	EC50	11000 nM
2-[(6-amino-3,5-dicyano-4-p-phenetyl-2-pyridyl)thio]acetic acid butyl ester	IC50	11000 nM
2-[(3-methoxyphenyl)-oxomethyl]imino-3,4-dimethyl-5-thiazolecarboxylic acid ethyl ester	EC50	11000 nM
2-[2-(3-chlorobenzothiophene-2-carbonyl)imino-6-sulfamoyl-1,3-benzothiazol-3-yl]acetic acid ethyl ester	EC50	11200 nM
3-(4-Chloro-phenyl)-1-cyclopropyl-1-(7-ethyl-1,2,3,9b-tetraaza-cyclopenta[a]naphthalen-4-ylmethyl)-thiourea	EC50	11500 nM
(7-Cyano-[1,3]dioxolo[4,5-g]quinolin-6-ylsulfanyl)-acetic acid isopropyl ester	EC50	11900 nM
5-[[4-(4-methylpiperidino)sulfonylbenzoyl]oxymethyl]furan-2-carboxylic acid methyl ester	EC50	12600 nM
2-[[5-(1-benzofuran-2-yl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-N-(3-bromophenyl)acetamide	EC50	13300 nM
2,5-bis(chloranyl)-N-[3-(2-ethoxyethyl)-6-sulfamoyl-1,3-benzothiazol-2-ylidene]thiophene-3-carboxamide	EC50	13400 nM
2-[4-(1,3-benzothiazol-2-yl)-1-piperazinyl]-4-methoxy-1,3-benzothiazole	EC50	13400 nM
2-({5-[2-(4-bromophenyl)-2-oxoethyl]-3-cyano-4,6-dimethyl-2-pyridinyl}sulfanyl)-N-(4-fluorophenyl)acetamide	EC50	13800 nM
MLS000543203	EC50	14400 nM
2-[2-oxidanylidene-2-(2-oxidanylidenechromen-3-yl)ethyl]sulfanyl-6-phenyl-pyridine-3-carbonitrile	EC50	15500 nM
4-[[4-(4-chlorophenyl)-3-cyano-6-phenyl-2-pyridinyl]thio]-3-oxobutanoic acid ethyl ester	EC50	16400 nM
N-(4-(4-(azepan-1-ylsulfonyl)phenyl)thiazol-2-yl)thiophene-2-carboxamide	EC50	16500 nM
6-(4-fluorophenyl)-3-methyl-N-(6-methyl-2-pyridinyl)-2-imidazo[2,1-b]thiazolecarboxamide	EC50	16800 nM
2-(1,3-benzoxazol-2-ylsulfanyl)-1-(3,4,5-trimethoxyphenyl)ethanone	EC50	16900 nM
4-[4-(2,4-dichlorophenyl)-1,3-thiazol-2-yl]-N-prop-2-enyl-benzamide	EC50	17100 nM
4-fluoranyl-N-(2-phenylquinazolin-4-yl)benzamide	EC50	17200 nM
5-bromanyl-N-(phenylcarbamothioyl)furan-2-carboxamide	EC50	17600 nM
4-methyl-N-(4-pyrrolidin-1-ylphenyl)benzamide	IC50	17900 nM
2-(4-isopropoxybenzoyl)imino-3,4-dimethyl-4-thiazoline-5-carboxylic acid ethyl ester	EC50	18300 nM
6-amino-5-[1-(4-chlorophenyl)-3-methyl-thieno[2,3-c]pyrazole-5-carbonyl]-1,3-dimethyl-pyrimidine-2,4-quinone	EC50	18400 nM
5-chloranyl-N-(4-methoxy-3-prop-2-ynyl-1,3-benzothiazol-2-ylidene)thiophene-2-carboxamide	EC50	18400 nM
2-[3-cyano-6-(4-methoxyphenyl)-4-thiophen-2-yl-pyridin-2-yl]sulfanyl-N-(phenylmethyl)ethanamide	EC50	18800 nM
2-(3-Cyano-6-methyl-quinolin-2-ylsulfanyl)-N-thiophen-2-ylmethyl-acetamide	EC50	19000 nM
2-(3-bromophenyl)-4-quinolinecarboxylic acid [2-[3-(dimethylsulfamoyl)anilino]-2-oxoethyl] ester	EC50	19100 nM
3,6-bis(chloranyl)-1-[2-[[3-chloranyl-5-(trifluoromethyl)pyridin-2-yl]amino]ethyl]quinoxalin-2-one	EC50	19800 nM
1-(1,3-benzodioxol-5-ylmethyl)-3-(2,1,3-benzothiadiazol-5-yl)urea	EC50	20400 nM
4-(4-{[4-cyclohexyl-3-(2-hydroxyethyl)piperazin-1-yl]methyl}phenyl)-2-methylbut-3-yn-2-ol	IC50	21200 nM
3-chloro-1-benzothiophene-2-carboxylic acid [2-[(3,5-dichloro-2-pyridinyl)amino]-2-oxoethyl] ester	EC50	21600 nM

ChEMBL bioactivities

138 potent at pChembl≥5 of 433 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	CHEMBL1808264
6.02	EC50	958	nM	METHYLENE BLUE ANHYDROUS
6.00	EC50	1003	nM	CHEMBL1471189
5.94	IC50	1153	nM	ETOPOSIDE
5.79	EC50	1607	nM	CHEMBL1331930
5.74	EC50	1811	nM	CHEMBL1386916
5.71	EC50	1972	nM	CHEMBL1388589
5.70	EC50	2003	nM	CHEMBL1427926
5.69	EC50	2045	nM	CHEMBL1613238
5.64	EC50	2284	nM	CHEMBL1349621
5.61	IC50	2442	nM	CHEMBL1610875
5.57	EC50	2680	nM	CHEMBL1579464
5.57	EC50	2718	nM	CHEMBL1538790
5.56	EC50	2751	nM	CHEMBL3198000
5.55	IC50	2843	nM	CHEMBL1418980
5.54	EC50	2864	nM	CHEMBL1556161
5.53	EC50	2941	nM	CHEMBL1539280
5.49	EC50	3267	nM	CHEMBL1416266
5.48	EC50	3335	nM	CHEMBL1589567
5.47	IC50	3371	nM	CHEMBL1469670
5.46	IC50	3449	nM	CHEMBL1705854
5.44	EC50	3596	nM	CHEMBL1587976
5.43	EC50	3685	nM	CHEMBL1426003
5.43	EC50	3671	nM	CHEMBL1374054
5.43	EC50	3685	nM	CHEMBL1331978
5.43	IC50	3715	nM	CHEMBL2373711
5.42	EC50	3802	nM	CHEMBL1380232
5.41	IC50	3871	nM	CHEMBL1564670
5.40	EC50	4018	nM	CHEMBL1547257
5.40	IC50	3973	nM	CHEMBL1528507
5.39	EC50	4027	nM	CHEMBL1604975
5.39	EC50	4060	nM	CHEMBL1417231
5.37	EC50	4261	nM	CHEMBL1452524
5.37	IC50	4256	nM	CHEMBL1307972
5.34	EC50	4590	nM	CHEMBL3193785
5.32	EC50	4797	nM	CHEMBL1416815
5.32	IC50	4813	nM	CHEMBL1383315
5.31	EC50	4858	nM	CHEMBL1365146
5.31	IC50	4943	nM	CHEMBL1985479
5.30	EC50	4998	nM	CHEMBL1510408
5.29	IC50	5184	nM	CHEMBL1996281
5.28	EC50	5233	nM	CHEMBL3197060
5.28	IC50	5220	nM	CHEMBL533226
5.27	IC50	5399	nM	CHEMBL1461035
5.27	IC50	5315	nM	CHEMBL1398705
5.25	EC50	5577	nM	CHEMBL1978236
5.25	IC50	5694	nM	CHEMBL1969300
5.25	IC50	5695	nM	CHEMBL1306377
5.23	EC50	5852	nM	CHEMBL1426930
5.23	EC50	5908	nM	CHEMBL1580375

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
2,6-difluoro-N-[2-fluoro-5-[5-[2-[(6-morpholin-4-yl-3-pyridinyl)amino]pyrimidin-4-yl]-2-propan-2-yl-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	609679: Inhibition of Src1	ic50	0.0100	uM

CTD chemical–gene interactions

141 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, increases response to substance, affects binding, affects reaction, increases reaction (+3 more)	24
Rifampin	increases reaction, increases expression, decreases expression, increases activity, decreases reaction (+3 more)	15
bisphenol A	increases expression, decreases expression, decreases methylation, affects binding, affects reaction (+6 more)	11
Calcitriol	affects binding, increases reaction, increases activity, increases response to substance, decreases reaction	6
Ketoconazole	affects binding, decreases reaction, increases reaction	6
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	increases reaction, affects cotreatment, decreases reaction, affects binding, increases activity	5
Benzo(a)pyrene	decreases expression, affects methylation	5
Diethylstilbestrol	affects binding, increases reaction	5
Tamoxifen	affects binding, increases response to substance, affects cotreatment, decreases expression, decreases reaction (+1 more)	5
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects binding, increases activity, increases reaction (+2 more)	5
Genistein	affects binding, increases reaction	4
Fulvestrant	decreases reaction, increases reaction, increases expression, affects cotreatment, increases methylation (+1 more)	3
Troglitazone	affects localization, increases activity, increases reaction, decreases reaction, decreases response to substance (+2 more)	3
Chenodeoxycholic Acid	decreases reaction, affects binding, increases reaction	3
Lithocholic Acid	increases reaction, affects binding	3
Dihydrotestosterone	affects binding, increases reaction, decreases reaction, increases expression, increases activity	3
Raloxifene Hydrochloride	affects cotreatment, decreases expression, affects binding, increases reaction, increases expression	3
daidzein	increases expression, affects binding, increases reaction	2
pirinixic acid	increases activity, increases reaction, affects binding	2
GW 4064	affects binding, increases reaction	2
T0901317	increases reaction, affects binding, decreases reaction, increases activity	2
bisphenol AF	affects binding, affects folding, affects reaction, decreases reaction	2
Alitretinoin	affects binding, affects cotreatment, increases reaction, increases activity	2
Cadmium	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
Clotrimazole	affects binding, increases reaction	2
Dexamethasone	affects cotreatment, increases activity, increases expression	2
Mitotane	affects binding, increases reaction	2
Valproic Acid	affects expression, decreases methylation	2
Metribolone	increases activity, affects binding, affects folding, increases reaction, decreases reaction	2
Aflatoxin B1	increases methylation, decreases expression	2

ChEMBL screening assays

5 unique, capped per target: 3 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1811523	Binding	Inhibition of Src1	Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup. — Bioorg Med Chem Lett
CHEMBL1963838	Functional	PUBCHEM_BIOASSAY: Luminescence-based cell-based high throughput dose response assay for inhibitors of the Steroid Receptor Coactivator 1 (SRC1; NCOA1). (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8L9	Abcam HCT 116 NCOA1 KO	Cancer cell line	Male
CVCL_B8ZD	Abcam MCF-7 NCOA1 KO	Cancer cell line	Female
CVCL_B9NF	Abcam A-549 NCOA1 KO	Cancer cell line	Male
CVCL_BW95	ES-R1 CAG-S-hSRC-1	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.