MAP3K1

Summary

MAP3K1 (mitogen-activated protein kinase kinase kinase 1, HGNC:6848) is a protein-coding gene on chromosome 5q11.2, encoding Mitogen-activated protein kinase kinase kinase 1 (Q13233). Component of a protein kinase signal transduction cascade.

The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus.

Source: NCBI Gene 4214 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 46,XY sex reversal 6 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 92
• Clinical variants (ClinVar): 338 total — 10 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes — 31 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 10 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6848
Approved symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MEKK, MAPKKK1
Ensembl gene	ENSG00000095015
Ensembl biotype	protein_coding
OMIM	600982
Entrez	4214

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000399503, ENST00000469188, ENST00000872824, ENST00000872825, ENST00000948659

RefSeq mRNA: 1 — MANE Select: NM_005921 NM_005921

CCDS: CCDS43318

Canonical transcript exons

ENST00000399503 — 20 exons

Exon	Start	End
ENSE00000745951	56859715	56859915
ENSE00000745995	56864734	56864934
ENSE00000746124	56871910	56872031
ENSE00000746182	56872641	56872722
ENSE00000746259	56872825	56873005
ENSE00000746337	56875032	56875310
ENSE00000746373	56878980	56879101
ENSE00000746405	56880711	56880802
ENSE00000746427	56881083	56881272
ENSE00000746594	56883527	56883679
ENSE00000746613	56884664	56884826
ENSE00000746632	56885932	56886063
ENSE00000746658	56887378	56887520
ENSE00000746681	56888226	56888357
ENSE00000815243	56865340	56865456
ENSE00001085022	56856600	56856750
ENSE00001179087	56865829	56865977
ENSE00001538733	56881570	56882866
ENSE00001538799	56815549	56816055
ENSE00003569597	56893531	56896152

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 97.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1259 / max 271.6326, expressed in 1543 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56505	9.3451	1519
56506	0.6237	239
56504	0.3713	205
56503	0.3423	142
56507	0.2629	121
56502	0.1805	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.84	gold quality
upper leg skin	UBERON:0004262	97.53	gold quality
skin of hip	UBERON:0001554	97.48	gold quality
parotid gland	UBERON:0001831	97.36	gold quality
corpus epididymis	UBERON:0004359	95.50	gold quality
monocyte	CL:0000576	95.30	gold quality
mononuclear cell	CL:0000842	95.13	gold quality
leukocyte	CL:0000738	94.98	gold quality
mammalian vulva	UBERON:0000997	94.58	gold quality
oral cavity	UBERON:0000167	94.48	gold quality
esophagus squamous epithelium	UBERON:0006920	94.24	gold quality
mammary duct	UBERON:0001765	94.05	gold quality
gingiva	UBERON:0001828	93.79	gold quality
trabecular bone tissue	UBERON:0002483	93.60	gold quality
nipple	UBERON:0002030	93.52	gold quality
pigmented layer of retina	UBERON:0001782	93.43	gold quality
palpebral conjunctiva	UBERON:0001812	93.36	gold quality
gingival epithelium	UBERON:0001949	93.17	gold quality
epithelium of nasopharynx	UBERON:0001951	93.04	gold quality
germinal epithelium of ovary	UBERON:0001304	92.97	gold quality
renal medulla	UBERON:0000362	92.53	gold quality
penis	UBERON:0000989	92.39	gold quality
caput epididymis	UBERON:0004358	92.39	gold quality
endothelial cell	CL:0000115	91.81	gold quality
blood	UBERON:0000178	91.11	gold quality
seminal vesicle	UBERON:0000998	91.06	gold quality
parietal pleura	UBERON:0002400	90.84	gold quality
tonsil	UBERON:0002372	90.80	gold quality
bone marrow	UBERON:0002371	90.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.36	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.89
E-MTAB-6075	no	1328.29
E-ENAD-17	no	571.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, EGR1, JUN, MYC, SP1, SP3, TP53

miRNA regulators (miRDB)

262 targeting MAP3K1, 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-3613-3P	100.00	76.36	7965
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-9-5P	100.00	72.28	2361
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
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-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-6077	99.99	68.04	2299
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Modulation of human cytomegalovirus immediate early gene enhancer and promoter activity by MEKK1 is under the control of the NFkappaB/rel sites. (PMID:11746500)
• MEK kinase 1 induces mitochondrial permeability transition leading to apoptosis (PMID:11756439)
• caspase cleavage of MEKK1 is a dynamic regulatory mechanism that alters the subcellular distribution of MEKK1, changing its function to pro-apoptotic signaling (PMID:11782455)
• Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the CD28 responsive element in T-cells (PMID:11903060)
• Results suggest that the conserved AR acetylation site contributes to a pathway governing prostate cancer cellular survival, as AR acetylation mutants are defective in MEKK1-induced apoptosis. (PMID:11971970)
• Results show that oncogenic ras provokes premature senescence by sequentially activating the MEK-ERK and MKK3/6-p38 pathways in normal, primary cells. (PMID:11971971)
• the NOx-induced cell proliferation via activation of MEKK1 might contribute to lung tissue damage caused by NOx (PMID:12079429)
• The difference of suppression in pancreatic cancer cells and non-pancreatic cancer cells suggested that the MEKK1 pathway mainly contributes to cell survival in pancreatic cancer cells (PMID:12185592)
• mechanism by which the MEKK1-dependent JNK/SAPK pathway is negatively regulated by PAK through phosphorylation of serine 67 (PMID:12228228)
• Ubiquitylation of MEKK1 inhibits its phosphorylation of MKK1 and MKK4 and activation of the ERK1/2 and JNK pathways (PMID:12456688)
• MEKK1 is activated by GSK3beta (PMID:12584189)
• 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)
• Axin utilizes distinct regions for competitive MEKK1 and MEKK4 binding and JNK activation. (PMID:12878610)
• subdomain VIII of MEKK1 is involved not only in binding to, but also in discrimination of, protein substrates (PMID:14500727)
• coexpression of constitutive-active MEKK1 inhibited orphan receptor TR3 transcriptional activity and TR3-induced proliferation in lung cancer cells (PMID:14612408)
• The G(i)-Ras-MEKK1 signaling pathway mediates lysophosphatidic acid-stimulated ovarian cancer cell migration by facilitating focal adhesion kinase redistribution to focal contacts. (PMID:15205333)
• glutathione s-transferaase Mu suppresses MEKK1-mediated apoptosis and functions as a negative regulator of MEKK1. (PMID:15299005)
• MEKK1 plays a key role in Bcr-Abl-induced STAT3 activation and in ES cells’ capacity for LIF-independent self-renewal and may thus be involved in Bcr-Abl-mediated leukemogenesis in stem cells (PMID:16044153)
• Galpha13-induced VASP phosphorylation that involves activation of RhoA and MEKK1, phosphorylation and degradation of IkappaB, release of PKA catalytic subunit from the complex with IkappaB and NF-kappaB, and subsequent phosphorylation of VASP (PMID:16046415)
• Induction of Nur77 nuclear export by MEKK1 required a prolonged MEKK1 activation and was attenuated by Akt activation. Expression of constitutively active Akt prevented MEKK1-induced Nur77 nuclear export. (PMID:16434970)
• Pge2 abolished the MEKK1-induced MMP-1 promoter luciferase activity. (PMID:16714289)
• MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in Extracellular Matrix homeostasis, epithelial cell migration, and wound reepithelialization. (PMID:16760432)
• Caspase-3 and the p38alpha MAP kinase were activated during TIMP-1-induced UT-7 cells erythroid differentiation. (PMID:17301822)
• The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. (PMID:17397260)
• A pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor. (PMID:17889508)
• Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. (PMID:17997823)
• reduction of upstream MEKK1 signals uncovers analogous but differential roles of JNK1 and JNK2 in a biological process (PMID:18032450)
• MEK functions to enhance GCN2-dependent eIF2alpha phosphorylation rather than suppressing dephosphorylation (PMID:18287093)
• Signaling pathways that augment or diminish beta-cell MEKK-1 activity may aid in the generation of novel therapeutic strategies in the treatment of type 1 diabetes. (PMID:18308848)
• The differences in the effects of the FGFR2 and MAP3K1 SNPs between BRCA1 and BRCA2 carriers point to differences in the biology of BRCA1 and BRCA2 breast cancer tumors and confirm the distinct nature of breast cancer in BRCA1 mutation carriers. (PMID:18355772)
• MEKK-1 mediates cytokine-induced JNK- and NF-kappaB activation, and this event is necessary for iNOS expression and cell death in pancreatic islet cells. (PMID:18420486)
• MAP3K1 protects against acute lung injury induced by nickel. (PMID:18467339)
• The activation of TORC1 through MEKK1-mediated phosphorylation, is reported. (PMID:18784253)
• IPS-1 requires TRAF6 and MEKK1 to activate NF-kappaB and mitogen-activated protein kinases that are critical for the optimal induction of type I interferons (PMID:18984593)
• FGFR2 and MAP3K1 are involved in breast cancer susceptibility and confer their effects primarily in ER+ and PR+ tumors. (PMID:19028704)
• Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation (PMID:19289468)
• MEKK1 may be a potential target for development of anti-invasion and metastasis drugs. (PMID:19513748)
• These results of MAP3K1, previously reported as an Axin1 inter-actor in c-Jun NH(2)-terminal kinase pathway, is also involved in the canonical Wnt signalling pathway and positively regulates expression of Wnt target genes. (PMID:20128690)
• MAP3K1 rs889312 polymorphism is associated with increased risk of breast cancer in BRCA1 mutation carriers (PMID:20809358)
• MAP/ERK kinase kinase 1 (MEKK1) mediates transcriptional repression by interacting with polycystic kidney disease-1 (PKD1) promoter-bound p53 tumor suppressor protein (PMID:20923779)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	map3k1	ENSDARG00000098405
mus_musculus	Map3k1	ENSMUSG00000021754
rattus_norvegicus	Map3k1	ENSRNOG00000013177

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Mitogen-activated protein kinase kinase kinase 1 — Q13233 (reviewed: Q13233)

Alternative names: MAPK/ERK kinase kinase 1

All UniProt accessions (1): Q13233

UniProt curated annotations — full annotation on UniProt →

Function. Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. May phosphorylate the MAPK8/JNK1 kinase. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway.

Subunit / interactions. Binds both upstream activators and downstream substrates in multimolecular complexes through its N-terminus. Oligomerizes after binding MAP2K4 or TRAF2. Interacts with AXIN1. Interacts (via the kinase catalytic domain) with STK38. Interacts with GRIPAP1.

Post-translational modifications. Autophosphorylated.

Disease relevance. 46,XY sex reversal 6 (SRXY6) [MIM:613762] A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by autophosphorylation on Thr-1400 and Thr-1412 following oligomerization.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

RefSeq proteins (1): NP_005912* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001841	Znf_RING	Domain
IPR007527	Znf_SWIM	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050538	MAP_kinase_kinase_kinase	Family

Pfam: PF00069, PF04434, PF21040

Enzyme classification (BRENDA):

• EC 2.7.11.25 — mitogen-activated protein kinase kinase kinase (BRENDA: 30 organisms, 191 substrates, 74 inhibitors, 12 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MEK	0.0002–0.0004	6
ATP	0.02–0.394	5

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (86 total): helix 18, modified residue 17, compositionally biased region 12, sequence conflict 11, region of interest 8, sequence variant 8, turn 4, binding site 2, zinc finger region 2, initiator methionine 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6WHB	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13233-F1	59.80	0.18

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): 1369 (proton acceptor)

Ligand- & substrate-binding residues (2): 1249–1257; 1272

Post-translational modifications (17): 2, 21, 35, 137, 154, 275, 285, 292, 297, 300, 507, 531, 923, 1018, 1043, 1400, 1412

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975871	MyD88 cascade initiated on plasma membrane
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) 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
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-975155	MyD88 dependent cascade initiated on endosome

MSigDB gene sets: 520 (showing top): PID_BCR_5PATHWAY, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, BIOCARTA_TNFR2_PATHWAY, BIOCARTA_FMLP_PATHWAY, REACTOME_INNATE_IMMUNE_SYSTEM, BIOCARTA_MAL_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, PID_NFAT_3PATHWAY, MORF_RAD51L3, BIOCARTA_IL1R_PATHWAY, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (5): protein phosphorylation (GO:0006468), Fc-epsilon receptor signaling pathway (GO:0038095), cellular response to mechanical stimulus (GO:0071260), MAPK cascade (GO:0000165), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (13): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), MAP kinase kinase kinase activity (GO:0004709), ATP binding (GO:0005524), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), ubiquitin protein ligase activity (GO:0061630), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), tight junction (GO:0070160)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Toll-like Receptor Cascades	6
Innate Immune System	3
Toll Like Receptor 2 (TLR2) Cascade	2
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Fc epsilon receptor (FCERI) signaling	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
MyD88 dependent cascade initiated on endosome	1
Toll Like Receptor 10 (TLR10) Cascade	1
Toll Like Receptor 5 (TLR5) Cascade	1
Immune System	1
Toll Like Receptor 9 (TLR9) Cascade	1
Toll Like Receptor 7/8 (TLR7/8) Cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
Fc receptor signaling pathway	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
intracellular signaling cassette	1
signal transduction	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
MAPK cascade	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
kinase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
cell-cell junction	1

Protein interactions and networks

STRING

4000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP3K1	BIRC2	Q13490	839
MAP3K1	TOX3	O15405	833
MAP3K1	BRCA1	P38398	771
MAP3K1	LSP1	P33241	760
MAP3K1	TRAF3	Q13114	747
MAP3K1	JUN	P05412	746
MAP3K1	TNFRSF1A	P19438	738
MAP3K1	UBE2N	P61088	737
MAP3K1	TAB1	Q15750	734
MAP3K1	TP53	P04637	727
MAP3K1	AXIN1	O15169	720
MAP3K1	DCAF7	P61962	716
MAP3K1	IKBKG	Q9Y6K9	709
MAP3K1	BIRC3	Q13489	695
MAP3K1	PTEN	P60484	676

IntAct

167 interactions, top by confidence:

A	B	Type	Score
AXIN1	APC	psi-mi:“MI:0914”(association)	0.850
MAP3K1	DCAF7	psi-mi:“MI:0915”(physical association)	0.710
MAP3K1	DCAF7	psi-mi:“MI:0914”(association)	0.710
MAP3K1	DCAF7	psi-mi:“MI:0407”(direct interaction)	0.710
DCAF7	MAP3K1	psi-mi:“MI:0403”(colocalization)	0.710
YWHAE	MAP3K1	psi-mi:“MI:0915”(physical association)	0.710
MAP3K1	YWHAE	psi-mi:“MI:0403”(colocalization)	0.710
MAP3K1	BRAF	psi-mi:“MI:0217”(phosphorylation reaction)	0.610
MAP3K1	BRAF	psi-mi:“MI:0915”(physical association)	0.610
MAP2K4	MAP3K1	psi-mi:“MI:0915”(physical association)	0.600
MAP3K1	MAP2K4	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
MAP3K1	MAP2K4	psi-mi:“MI:0915”(physical association)	0.600
MAP3K1	TRAF2	psi-mi:“MI:2364”(proximity)	0.540
MAP3K1	HSPA1L	psi-mi:“MI:2364”(proximity)	0.540
MAP3K1	TRAF2	psi-mi:“MI:0915”(physical association)	0.540
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
FLNB	RAC1	psi-mi:“MI:0914”(association)	0.500
FLNB	MAP3K1	psi-mi:“MI:0915”(physical association)	0.500
MAP3K1		psi-mi:“MI:0915”(physical association)	0.500
MAP3K1	ARRB2	psi-mi:“MI:2364”(proximity)	0.480
MAP3K1	ESR1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MAP3K1	IKBKB	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MAP3K1	HNRNPK	psi-mi:“MI:0915”(physical association)	0.400
MAP3K1	MAP4K2	psi-mi:“MI:0915”(physical association)	0.400
MAP4K2	MAP3K1	psi-mi:“MI:0915”(physical association)	0.400
MAP3K1	MAP2K7	psi-mi:“MI:0915”(physical association)	0.400
MAP3K1	MAP2K1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (247): RHOA (Affinity Capture-Western), FRAT1 (Affinity Capture-Western), MAPK1 (Biochemical Activity), MAPK3 (Biochemical Activity), AXIN1 (Affinity Capture-Luminescence), FRAT1 (Affinity Capture-Luminescence), BAP1 (Biochemical Activity), FKBP6 (Biochemical Activity), NPLOC4 (Biochemical Activity), ASCC2 (Biochemical Activity), UBE2V1 (Biochemical Activity), UBAC1 (Biochemical Activity), DNAJB6 (Biochemical Activity), TOM1L2 (Biochemical Activity), CUEDC1 (Biochemical Activity)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, A1A5B6, A4D2P6, D7PF45, F1LXF1, O15357, O60346, O75808, P11274, P49796, P52734, P53349, P59672, P70268, P78524, P98174, Q0QWG9, Q13233, Q13905, Q16825, Q3MII6, Q50H33, Q5RDA9, Q62925, Q63433, Q6NS60, Q6P549, Q6PDJ6, Q6WVG3, Q7Z5H3, Q8BL80, Q8BUP8, Q8N2R8, Q8TF61, Q8VHK2, Q8WXD9, Q924W7, Q92625, Q96CX2

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0XXN8, B5VNQ3, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, O08648, O14047, O14299, O22040, O22042, O35099, O54748, O61122, O74304, O81472, O95382, P23561, P25390, P28829, P41892, P53349, P53599, Q01389, Q03497

SIGNOR signaling

35 interactions.

A	Effect	B	Mechanism
RIPK1	“up-regulates activity”	MAP3K1	phosphorylation
RIPK1	up-regulates	MAP3K1	phosphorylation
MAP3K1	“down-regulates activity”	FADD	phosphorylation
TRAF2	up-regulates	MAP3K1	binding
MAP3K1	up-regulates	CRTC1	phosphorylation
PAK1	“up-regulates activity”	MAP3K1	phosphorylation
MAP3K1	“up-regulates activity”	STAT3	phosphorylation
MAP3K1	“up-regulates activity”	MAP2K4	phosphorylation
GRIPAP1	“up-regulates activity”	MAP3K1	binding
Ub:E2	“up-regulates activity”	MAP3K1	ubiquitination
MAP3K1	“down-regulates quantity by destabilization”	ERK1/2	polyubiquitination
MAP3K1	“up-regulates activity”	MAP2K7	phosphorylation
hsa-miR-23b-3p	“down-regulates quantity by repression”	MAP3K1	“post transcriptional regulation”
MAP3K1	“up-regulates activity”	SMAD2	phosphorylation
MAP3K1	“up-regulates activity”	IKBKB	phosphorylation
MAP3K1	“down-regulates activity”	NOTCH1	phosphorylation
ABL1	“up-regulates activity”	MAP3K1	phosphorylation
KRAS	up-regulates	MAP3K1	binding
MAP4K1	up-regulates	MAP3K1	phosphorylation
MAP4K4	up-regulates	MAP3K1	phosphorylation
MAP3K1	up-regulates	MAP2K7	phosphorylation
MAP4K5	up-regulates	MAP3K1
MAP3K1	up-regulates	MAP2K6	phosphorylation
MAP4K2	up-regulates	MAP3K1	binding
MAP4K3	up-regulates	MAP3K1	phosphorylation
SMAD7	down-regulates	MAP3K1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 148 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
Formation of tubulin folding intermediates by CCT/TriC	12	39.4×	2e-15
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	12	37.9×	4e-15
Prefoldin mediated transfer of substrate to CCT/TriC	12	36.6×	6e-15
RHO GTPases activate IQGAPs	11	29.5×	1e-12
Gap junction trafficking and regulation	8	29.5×	3e-09
Gap junction trafficking	8	29.5×	3e-09
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	7	29.5×	3e-08
Transport of connexons to the plasma membrane	7	29.5×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	8	41.9×	2e-09
cytoplasmic translation	24	31.8×	8e-27
protein refolding	7	31.2×	3e-07
Fc-epsilon receptor signaling pathway	5	26.2×	1e-04
translation	25	18.4×	6e-22
binding of sperm to zona pellucida	6	18.1×	1e-04
ribosomal small subunit biogenesis	11	17.9×	5e-09
ribosomal large subunit biogenesis	5	15.8×	9e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 10 cancer types — BRCA, CCRCC, CEAD, COAD, COADREAD, GBM, HCC, PCM, UCEC, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	7
Uncertain significance	155
Likely benign	61
Benign	51

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
2745804	NM_005921.2(MAP3K1):c.1348A>G (p.Met450Val)	Pathogenic
30144	NM_005921.2(MAP3K1):c.634-8T>A	Pathogenic
30146	NM_005921.2(MAP3K1):c.566T>C (p.Leu189Pro)	Pathogenic
30147	NM_005921.2(MAP3K1):c.566T>G (p.Leu189Arg)	Pathogenic
430732	NM_005921.2(MAP3K1):c.1760T>A (p.Leu587His)	Pathogenic
471688	NM_005921.2(MAP3K1):c.1016G>A (p.Arg339Gln)	Pathogenic
634713	NM_005921.2(MAP3K1):c.2627_2642del (p.Thr876fs)	Pathogenic
634716	NM_005921.2(MAP3K1):c.4369_4373del (p.His1457fs)	Pathogenic
634720	NM_005921.2(MAP3K1):c.2111C>G (p.Ser704Ter)	Pathogenic
634799	NM_005921.2(MAP3K1):c.1408del (p.His470fs)	Pathogenic
2507001	NM_005921.2(MAP3K1):c.3964T>G (p.Phe1322Val)	Likely pathogenic
268092	NM_005921.2(MAP3K1):c.1923G>A (p.Met641Ile)	Likely pathogenic
4281633	NM_005921.2(MAP3K1):c.565C>G (p.Leu189Val)	Likely pathogenic
430731	NM_005921.2(MAP3K1):c.566T>A (p.Leu189Gln)	Likely pathogenic
4538420	NM_005921.2(MAP3K1):c.2370-1G>C	Likely pathogenic
634727	NM_005921.2(MAP3K1):c.2512_2523del (p.Leu838_Leu841del)	Likely pathogenic
988563	NM_005921.2(MAP3K1):c.2273T>C (p.Leu758Pro)	Likely pathogenic

SpliceAI

2851 predictions. Top by Δscore:

Variant	Effect	Δscore
5:56856586:T:A	acceptor_gain	1.0000
5:56856590:T:A	acceptor_gain	1.0000
5:56856593:A:AG	acceptor_gain	1.0000
5:56856594:T:G	acceptor_gain	1.0000
5:56856597:TA:T	acceptor_loss	1.0000
5:56856598:A:AG	acceptor_gain	1.0000
5:56856598:AGTC:A	acceptor_gain	1.0000
5:56856599:G:GG	acceptor_gain	1.0000
5:56856599:GT:G	acceptor_gain	1.0000
5:56856599:GTC:G	acceptor_gain	1.0000
5:56856599:GTCG:G	acceptor_gain	1.0000
5:56856599:GTCGT:G	acceptor_gain	1.0000
5:56856708:G:GT	donor_gain	1.0000
5:56856721:TTGGA:T	donor_gain	1.0000
5:56856747:TGTGG:T	donor_loss	1.0000
5:56856748:GTG:G	donor_gain	1.0000
5:56856748:GTGGT:G	donor_loss	1.0000
5:56856749:TGGTA:T	donor_loss	1.0000
5:56856750:GGTA:G	donor_loss	1.0000
5:56856751:G:C	donor_loss	1.0000
5:56856751:G:GG	donor_gain	1.0000
5:56856752:TAAGT:T	donor_loss	1.0000
5:56859883:GGA:G	donor_gain	1.0000
5:56859884:GAG:G	donor_gain	1.0000
5:56859886:G:GG	donor_gain	1.0000
5:56871906:A:AG	acceptor_gain	1.0000
5:56871907:T:G	acceptor_gain	1.0000
5:56871908:A:AG	acceptor_gain	1.0000
5:56871908:A:G	acceptor_loss	1.0000
5:56871909:G:GA	acceptor_gain	1.0000

AlphaMissense

9845 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:56871935:T:A	C443S	1.000
5:56871935:T:C	C443R	1.000
5:56871936:G:A	C443Y	1.000
5:56871936:G:C	C443S	1.000
5:56871937:T:G	C443W	1.000
5:56871944:T:C	C446R	1.000
5:56871945:G:A	C446Y	1.000
5:56871946:C:G	C446W	1.000
5:56871983:T:A	C459S	1.000
5:56871983:T:C	C459R	1.000
5:56871984:G:A	C459Y	1.000
5:56871984:G:C	C459S	1.000
5:56871985:T:G	C459W	1.000
5:56871995:T:A	C463S	1.000
5:56871995:T:C	C463R	1.000
5:56871996:G:C	C463S	1.000
5:56871997:C:G	C463W	1.000
5:56872008:T:C	L467P	1.000
5:56872010:C:G	H468D	1.000
5:56872019:T:C	C471R	1.000
5:56872020:G:A	C471Y	1.000
5:56872021:C:G	C471W	1.000
5:56872031:T:A	W475R	1.000
5:56872031:T:C	W475R	1.000
5:56872642:G:C	W475C	1.000
5:56872642:G:T	W475C	1.000
5:56872679:T:A	C488S	1.000
5:56872679:T:C	C488R	1.000
5:56872679:T:G	C488G	1.000
5:56872680:G:A	C488Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000042047 (5:56824790 C>G), RS1000097153 (5:56818757 A>G), RS1000114612 (5:56835268 A>G), RS1000201153 (5:56886938 T>G), RS1000205012 (5:56882700 A>G), RS1000257277 (5:56882986 C>A,G,T), RS1000259925 (5:56852892 TATAC>T,TATACATAC), RS1000277936 (5:56830358 C>A), RS1000285625 (5:56894375 A>C,T), RS1000413312 (5:56889508 C>A), RS1000427637 (5:56846448 A>G,T), RS1000435664 (5:56888693 C>T), RS1000520625 (5:56824430 A>T), RS1000541608 (5:56863218 C>T), RS1000551858 (5:56824279 G>T)

Disease associations

OMIM: gene MIM:600982 | disease phenotypes: MIM:613762

GenCC curated gene-disease

Disease	Classification	Inheritance
46,XY sex reversal 6	Definitive	Autosomal dominant
breast cancer	Moderate	Autosomal dominant
46,XY complete gonadal dysgenesis	Supportive	Autosomal dominant
46,XY partial gonadal dysgenesis	Supportive	Autosomal dominant

Mondo (7): 46,XY sex reversal 6 (MONDO:0013410), hereditary neoplastic syndrome (MONDO:0015356), hearing loss disorder (MONDO:0005365), ovarian neoplasm (MONDO:0021068), 46,XY complete gonadal dysgenesis (MONDO:0010765), 46,XY partial gonadal dysgenesis (MONDO:0016674), breast cancer (MONDO:0007254)

Orphanet (2): Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000037	Male pseudohermaphroditism
HP:0000041	Chordee
HP:0000044	Hypogonadotropic hypogonadism
HP:0000045	Abnormal scrotum morphology
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000062	Ambiguous genitalia
HP:0000100	Nephrotic syndrome
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000147	Polycystic ovaries
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000812	Abnormal internal genitalia
HP:0000815	Hypergonadotropic hypogonadism
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000846	Adrenal insufficiency
HP:0000868	Decreased fertility in females
HP:0000939	Osteoporosis
HP:0001007	Hirsutism
HP:0002215	Sparse axillary hair
HP:0002225	Sparse pubic hair

GWAS associations

92 associations (top):

Study	Trait	p-value
GCST000035_5	Breast cancer	7.000000e-20
GCST000365_1	Breast cancer	5.000000e-07
GCST000678_1	Breast cancer	5.000000e-09
GCST000758_30	Triglycerides	1.000000e-10
GCST001759_2	Type 2 diabetes	4.000000e-06
GCST001937_2	Breast cancer	3.000000e-36
GCST002063_5	Sexual dimorphism in anthropometric traits	8.000000e-07
GCST002137_1	Waist circumference	1.000000e-07
GCST002216_35	Triglycerides	3.000000e-16
GCST002248_13	Fasting insulin (dietary factor interaction)	9.000000e-07
GCST002253_2	Homeostasis model assessment of insulin resistance (dietary factor interaction)	1.000000e-06
GCST002346_1	Breast cancer (early onset)	9.000000e-14
GCST002346_10	Breast cancer (early onset)	2.000000e-09
GCST002346_11	Breast cancer (early onset)	1.000000e-08
GCST002346_14	Breast cancer (early onset)	1.000000e-14
GCST002346_2	Breast cancer (early onset)	2.000000e-12
GCST002346_3	Breast cancer (early onset)	4.000000e-12
GCST002346_4	Breast cancer (early onset)	5.000000e-12
GCST002346_5	Breast cancer (early onset)	5.000000e-12
GCST002346_6	Breast cancer (early onset)	4.000000e-11
GCST002346_7	Breast cancer (early onset)	6.000000e-11
GCST002346_8	Breast cancer (early onset)	7.000000e-11
GCST002346_9	Breast cancer (early onset)	3.000000e-10
GCST002782_24	Waist-to-hip ratio adjusted for body mass index	6.000000e-12
GCST002782_25	Waist-to-hip ratio adjusted for body mass index	9.000000e-09
GCST002782_26	Waist-to-hip ratio adjusted for body mass index	8.000000e-12
GCST002782_27	Waist-to-hip ratio adjusted for body mass index	2.000000e-08
GCST002782_63	Waist-to-hip ratio adjusted for body mass index	4.000000e-12
GCST002782_64	Waist-to-hip ratio adjusted for body mass index	7.000000e-08
GCST002782_65	Waist-to-hip ratio adjusted for body mass index	5.000000e-12

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005951	sexual dimorphism
EFO:0008111	diet measurement
EFO:0004501	HOMA-IR
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004343	waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008434	initial pursuit acceleration
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004314	forced expiratory volume
EFO:0003924	hair color
EFO:0004346	neuroimaging measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006061	Gonadal Dysgenesis, 46,XY	C12.050.351.875.253.096.687; C12.050.351.875.253.309.388; C12.200.706.316.096.687; C12.200.706.316.309.388; C12.800.316.096.687; C12.800.316.309.388; C16.131.939.316.096.687; C16.131.939.316.309.388; C19.391.119.096.687; C19.391.119.309.388
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3956 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

31 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 295,629 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL2087361	ICOTINIB	3	2,802
CHEMBL3544983	TESEVATINIB	3	2,819
CHEMBL603469	LESTAURTINIB	3
CHEMBL230011	TG100-115	2	1,504
CHEMBL2386889	SCH-900776	2	740
CHEMBL253969	OSI-632	2	1,150
CHEMBL3039525	GOLVATINIB	2	535
CHEMBL384304	RG-547	2	93
CHEMBL402548	DANUSERTIB	2
CHEMBL495727	AT-9283	2
CHEMBL607707	PELITINIB	2
CHEMBL1908394	GSK-461364	1
CHEMBL1908397	KW-2449	1
CHEMBL2138625	AV-412 FREE BASE	1
CHEMBL3577124	LY-3009120	1
CHEMBL4289017	PF-03814735	1
CHEMBL482967	CYC-116	1
CHEMBL574738	AST-487	1

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs16886403	Efficacy	3	carboplatin;cisplatin;docetaxel;paclitaxel	Non-Small Cell Lung Carcinoma
rs726501	Efficacy	3	carboplatin;cisplatin;docetaxel;erlotinib;gefitinib;paclitaxel
rs96844	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs726501	MAP3K1	3	3.00	1	carboplatin;cisplatin;docetaxel;erlotinib;gefitinib;paclitaxel
rs16886403	MAP3K1	3	3.00	1	carboplatin;cisplatin;docetaxel;paclitaxel

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — STE11 family

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

Ligand	Action	Affinity	Parameter
E6201	Inhibition	7.51	pIC50

Binding affinities (BindingDB)

19 measured of 39 human assays (39 total across all organisms); most potent 19 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(4-Cyclopropyl-2-fluoroanilino)-3,4-difluoro-5-[[3-fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]benzamide	IC50	17 nM	US-11964950: Arylamide derivative having antitumor activity
4-cyano-2-(2-fluoro-4-iodoanilino)benzoic acid	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
4-cyano-2-(2-fluoro-4-iodoanilino)-N-methoxybenzamide	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
4-cyano-N-ethoxy-2-(2-fluoro-4-iodoanilino)benzamide	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
4-cyano-2-(2-fluoro-4-iodoanilino)-N-propoxybenzamide	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
4-cyano-N-(2-hydroxyethoxy)-2-(4-iodo-2-methylanilino)benzamide	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
4-cyano-N-(cyclopropylmethoxy)-2-(2-fluoro-4-iodoanilino)benzamide	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
4-cyano-N-(cyclopropylmethoxy)-2-(4-iodo-2-methylanilino)benzamide	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
N-(2-aminoethoxy)-4-cyano-2-(2-fluoro-4-iodoanilino)benzamide	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
2-(3-aminopropyl)-8-(2-fluoro-4-iodoanilino)-2,6-naphthyridin-1-one	IC50	825 nM	US-12378240: Naphthyridinone-aniline compounds for treatment of dermal disorders
8-(2-fluoro-4-iodoanilino)-2-hydroxy-2,6-naphthyridin-1-one	IC50	825 nM	US-12378240: Naphthyridinone-aniline compounds for treatment of dermal disorders
8-(2-fluoro-4-iodoanilino)-2-(2-hydroxyethoxy)-2,6-naphthyridin-1-one	IC50	825 nM	US-12378240: Naphthyridinone-aniline compounds for treatment of dermal disorders
8-(2-fluoro-4-iodoanilino)-2-(2-hydroxyethoxy)-3,4-dihydro-2,6-naphthyridin-1-one	IC50	825 nM	US-12378240: Naphthyridinone-aniline compounds for treatment of dermal disorders
2-ethoxy-8-(2-fluoro-4-iodoanilino)-3,4-dihydro-2,6-naphthyridin-1-one	IC50	825 nM	US-12378240: Naphthyridinone-aniline compounds for treatment of dermal disorders
8-(2-fluoro-4-iodoanilino)-3,4-dihydro-2H-2,6-naphthyridin-1-one	IC50	825 nM	US-12378240: Naphthyridinone-aniline compounds for treatment of dermal disorders
8-ethyl-5-oxo-2-[4-[[2-(trifluoromethyl)phenyl]carbamothioyl]piperazin-1-yl]pyrido[2,3-d]pyrimidine-6-carboxylic acid	IC50	825 nM	US-20250387379: ARYL-ANILINE AND HETEROARYL-ANILINE COMPOUNDS FOR TREATMENT OF SKIN CANCERS
5-acetyl-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-4-methylthiophene-3-carboxamide	IC50	825 nM	US-12466818: Thienyl-aniline compounds for treatment of dermal disorders
5-acetyl-N-[(2S)-2,3-dihydroxypropyl]-2-(2-fluoro-4-iodoanilino)-4-methylthiophene-3-carboxamide	IC50	825 nM	US-12466818: Thienyl-aniline compounds for treatment of dermal disorders
5-acetyl-N-[(2R)-2,3-dihydroxypropyl]-2-(2-fluoro-4-iodoanilino)-4-methylthiophene-3-carboxamide	IC50	825 nM	US-12466818: Thienyl-aniline compounds for treatment of dermal disorders

ChEMBL bioactivities

53 potent at pChembl≥5 of 55 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	IC50	8	nM	CHEMBL318804
7.51	IC50	31	nM	CHEMBL2216826
7.34	IC50	46	nM	CHEMBL1097700
7.01	IC50	98	nM	LY-3009120
7.01	Kd	97	nM	PELITINIB
6.97	Kd	107	nM	BOSUTINIB
6.97	Kd	106	nM	GSK-461364
6.87	Kd	135	nM	OSI-632
6.46	Kd	350	nM	STAUROSPORINE
6.41	IC50	391	nM	STAUROSPORINE
6.33	Kd	465	nM	REGORAFENIB
6.32	IC50	474	nM	STAUROSPORINE
6.31	Kd	493	nM	PONATINIB
6.31	IC50	485	nM	STAUROSPORINE
6.29	Kd	509	nM	DANUSERTIB
6.08	IC50	840	nM	CHEMBL5092087
5.98	Kd	1055	nM	CHEMBL3991933
5.96	Kd	1106	nM	GOLVATINIB
5.96	IC50	1100	nM	CHEMBL5087055
5.96	Kd	1100	nM	CRIZOTINIB
5.90	Kd	1263	nM	DASATINIB
5.90	Kd	1254	nM	SCH-900776
5.89	Kd	1278	nM	CUDC-101
5.85	Kd	1399	nM	AT-9283
5.82	Kd	1500	nM	GSK-461364
5.76	Kd	1743	nM	TESEVATINIB
5.75	Kd	1800	nM	AST-487
5.74	Kd	1806	nM	CHEMBL3990456
5.73	Kd	1867	nM	CRIZOTINIB
5.72	Kd	1891	nM	BARICITINIB
5.72	Kd	1925	nM	CHEMBL5653589
5.68	Kd	2090	nM	TOVORAFENIB
5.67	Kd	2130	nM	KW-2449
5.66	Kd	2184	nM	PF-03814735
5.66	Kd	2187	nM	CHEMBL2376648
5.65	Kd	2247	nM	ERLOTINIB
5.61	Kd	2447	nM	TG100-115
5.60	Kd	2500	nM	CHEMBL1241674
5.54	Kd	2900	nM	PAZOPANIB
5.48	ED50	3335	nM	CHEMBL5653589
5.46	Kd	3500	nM	RG-547
5.45	Kd	3534	nM	CHEMBL3752910
5.42	Kd	3783	nM	SORAFENIB
5.38	Kd	4131	nM	ICOTINIB
5.38	Kd	4200	nM	RUXOLITINIB
5.37	Kd	4300	nM	TAE-684
5.36	Kd	4400	nM	LESTAURTINIB
5.36	Kd	4400	nM	BOSUTINIB
5.21	ED50	6123	nM	CHEMBL3752910
5.10	Kd	7960	nM	AV-412 FREE BASE

PubChem BioAssay actives

52 with measured affinity, of 506 total; 44 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
4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile	102175: Inhibition of MEK-1 Kinase phosphorylation in LoVo cells	ic50	0.0080	uM
(4S,5S,6Z,9S,10R,12E)-16-(ethylamino)-9,10,18-trihydroxy-4,5-dimethyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	719901: Inhibition of MEKK1	ic50	0.0310	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0970	uM
1-(3,3-dimethylbutyl)-3-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea	1226900: Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue	ic50	0.0980	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1060	uM
Bosutinib	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1070	uM
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1350	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	625026: Binding constant for MAP3K1 kinase domain	kd	0.3500	uM
regorafenib anhydrous	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4650	uM
Ponatinib	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4930	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5090	uM
4-amino-7-methyl-2-[[5-methyl-1-[(3S)-oxolan-3-yl]pyrazol-4-yl]amino]-6-[(2R)-2-methylpyrrolidin-1-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile	1817520: Inhibition of MAP3K1 expressed in human PBMCs measured by KiNativ profiling analysis	ic50	0.8400	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.0550	uM
Crizotinib	625026: Binding constant for MAP3K1 kinase domain	kd	1.1000	uM
4-amino-7-methyl-2-[[5-methyl-1-[(3R)-oxolan-3-yl]pyrazol-4-yl]amino]-6-[(2R)-2-methylpyrrolidin-1-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile	1817520: Inhibition of MAP3K1 expressed in human PBMCs measured by KiNativ profiling analysis	ic50	1.1000	uM
1-N’-[2-fluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1060	uM
6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3R)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2540	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2630	uM
7-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyheptanamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2780	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.3990	uM
7-[[(3aS,6aR)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methoxy]-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.7430	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625026: Binding constant for MAP3K1 kinase domain	kd	1.8000	uM
2-amino-2-cyclohexyl-N-[2-(1-methylpyrazol-4-yl)-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]acetamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.8060	uM
Baricitinib	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.8910	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148689: Binding affinity to human MAP3K1 incubated for 45 mins by Kinobead based pull down assay	kd	1.9249	uM
Tovorafenib	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.0900	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.1300	uM
N-[2-[4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.1840	uM
6-amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyridazine-3-carboxamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.1870	uM
Erlotinib	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.2470	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.4470	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625026: Binding constant for MAP3K1 kinase domain	kd	2.5000	uM
Pazopanib	625026: Binding constant for MAP3K1 kinase domain	kd	2.9000	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	625026: Binding constant for MAP3K1 kinase domain	kd	3.5000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148689: Binding affinity to human MAP3K1 incubated for 45 mins by Kinobead based pull down assay	kd	3.5342	uM
Sorafenib	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.7830	uM
N-(3-ethynylphenyl)-2,5,8,11-tetraoxa-15,17-diazatricyclo[10.8.0.014,19]icosa-1(12),13,15,17,19-pentaen-18-amine	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	4.1310	uM
Ruxolitinib	625026: Binding constant for MAP3K1 kinase domain	kd	4.2000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625026: Binding constant for MAP3K1 kinase domain	kd	4.3000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507596: Binding affinity to MAP3K1	kd	4.4000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-[3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl]quinazolin-6-yl]prop-2-enamide	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	7.9600	uM
3-[[5-[3-(4-methoxyphenyl)benzimidazol-5-yl]-1,3,4-oxadiazol-2-yl]sulfanylmethyl]benzonitrile	1799156: GSK-3beta Kinase Inhibition Assay from Article 10.1016/j.bmc.2009.01.019: “Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.”	ic50	8.1000	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	8.1590	uM
Ribociclib	1425044: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	12.4730	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, decreases expression, affects expression	4
sodium arsenite	increases abundance, affects methylation, decreases expression	4
Valproic Acid	increases methylation, affects expression, decreases expression	4
Curcumin	increases expression, decreases expression, decreases reaction	3
pyrazolanthrone	decreases reaction, increases activity, increases response to substance, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, increases expression, decreases reaction	2
Quercetin	increases phosphorylation, increases expression	2
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
2-anisidine	decreases expression	1
tanshinone	decreases expression	1
sulindac sulfide	decreases expression	1
ochratoxin A	decreases expression	1
3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
SB 203580	decreases reaction, increases activity, increases response to substance	1
aspartyl-glutamyl-valyl-aspartal	decreases reaction, increases cleavage	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
3,5-bis(2-fluorobenzylidene)piperidin-4-one	decreases reaction, increases expression	1

ChEMBL screening assays

167 unique, capped per target: 165 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1031537	Binding	Inhibition of MEKK1	Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta. — Bioorg Med Chem
CHEMBL4811091	ADMET	Inhibition of human MEKK1 at 1 uM measured after 30 mins by [gamma-33P]-ATP assay	Preparation, biological & cheminformatics-based assessment of N2,N4-diphenylpyrimidine-2,4-diamine as potential Kinase-targeted antimalarials. — Bioorg Med Chem
CHEMBL709029	Functional	Inhibition of MEK-1 Kinase phosphorylation in LoVo cells	Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade. — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1WG	Abcam HeLa MAP3K1 KO	Cancer cell line	Female
CVCL_D8PX	Ubigene HCT 116 MAP3K1 KO	Cancer cell line	Male
CVCL_D9J8	Ubigene HEK293 MAP3K1 KO	Transformed cell line	Female
CVCL_E0H6	Ubigene HeLa MAP3K1 KO	Cancer cell line	Female
CVCL_SW52	HAP1 MAP3K1 (-) 1	Cancer cell line	Male
CVCL_SW53	HAP1 MAP3K1 (-) 2	Cancer cell line	Male
CVCL_SW54	HAP1 MAP3K1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
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