MAP3K2

Summary

MAP3K2 (mitogen-activated protein kinase kinase kinase 2, HGNC:6854) is a protein-coding gene on chromosome 2q14.3, encoding Mitogen-activated protein kinase kinase kinase 2 (Q9Y2U5). Component of a protein kinase signal transduction cascade.

The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate Ikappa B kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process.

Source: NCBI Gene 10746 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 72 total
• Druggable target: yes — 31 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001371910

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6854
Approved symbol	MAP3K2
Name	mitogen-activated protein kinase kinase kinase 2
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	MEKK2B
Ensembl gene	ENSG00000169967
Ensembl biotype	protein_coding
OMIM	609487
Entrez	10746

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000344908, ENST00000409947, ENST00000682094, ENST00000882622, ENST00000882623, ENST00000882624, ENST00000882625, ENST00000882626, ENST00000882627, ENST00000882628, ENST00000882629

RefSeq mRNA: 3 — MANE Select: NM_001371910 NM_001371910, NM_001371911, NM_006609

CCDS: CCDS46404

Canonical transcript exons

ENST00000682094 — 17 exons

Exon	Start	End
ENSE00001136891	127318169	127318317
ENSE00001136897	127322046	127322252
ENSE00001206624	127314754	127314883
ENSE00001206629	127317629	127317760
ENSE00001206644	127323902	127323994
ENSE00001206654	127325728	127325807
ENSE00001206669	127335870	127335969
ENSE00001232572	127326687	127326817
ENSE00001232690	127324174	127324241
ENSE00001232710	127329921	127330008
ENSE00001232717	127330392	127330505
ENSE00001232740	127337738	127337778
ENSE00001232824	127338932	127339050
ENSE00001529241	127343126	127343194
ENSE00001778162	127387452	127387975
ENSE00002508951	127308585	127308762
ENSE00003917029	127298668	127307804

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.8038 / max 1100.7359, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30526	37.6392	1821
30527	1.1646	778

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.59	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.59	gold quality
trabecular bone tissue	UBERON:0002483	98.45	gold quality
cauda epididymis	UBERON:0004360	97.87	gold quality
caput epididymis	UBERON:0004358	97.69	gold quality
corpus epididymis	UBERON:0004359	97.55	gold quality
epithelium of nasopharynx	UBERON:0001951	97.39	gold quality
nipple	UBERON:0002030	97.38	gold quality
bronchial epithelial cell	CL:0002328	97.37	gold quality
pylorus	UBERON:0001166	96.97	gold quality
lower lobe of lung	UBERON:0008949	96.92	gold quality
saphenous vein	UBERON:0007318	96.89	gold quality
mammalian vulva	UBERON:0000997	96.87	gold quality
superficial temporal artery	UBERON:0001614	96.85	gold quality
mammary duct	UBERON:0001765	96.85	gold quality
skin of hip	UBERON:0001554	96.71	gold quality
jejunum	UBERON:0002115	96.71	gold quality
visceral pleura	UBERON:0002401	96.65	gold quality
oral cavity	UBERON:0000167	96.64	gold quality
superior surface of tongue	UBERON:0007371	96.49	gold quality
penis	UBERON:0000989	96.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.37	gold quality
cardia of stomach	UBERON:0001162	96.34	gold quality
pigmented layer of retina	UBERON:0001782	96.30	gold quality
upper leg skin	UBERON:0004262	96.26	gold quality
pericardium	UBERON:0002407	96.22	gold quality
palpebral conjunctiva	UBERON:0001812	96.15	gold quality
synovial joint	UBERON:0002217	96.11	gold quality
renal medulla	UBERON:0000362	95.85	gold quality
trigeminal ganglion	UBERON:0001675	95.57	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	13.36
E-GEOD-83139	no	2.76
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

473 targeting MAP3K2, 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-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
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-4768-5P	100.00	69.49	2861
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4668-3P	100.00	68.74	2635
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

Literature-anchored findings (GeneRIF, showing 34)

• MEKK2 is a potent activator of the c-Jun N-terminal kinase pathway in fibroblast-like synoviocytes in rheumatoid arthritis. (PMID:14734742)
• Unlike ERK5 and MEK5, their upstream activator MEKK2 is localized mainly in the cytosol of resting cells, and translocates into the nucleus upon EGF stimulation (PMID:15075238)
• MEKK2 is dimerized and activated by the novel protein Mip1. (PMID:15988011)
• Through interaction with MEKK2, XIAP functions in an ubiquitin ligase dependent manner to evoke a second wave of NF-kappaB activation, resulting in the modulation of NF-kappaB target gene expression. (PMID:18761086)
• 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)
• The ability of MEKK2 to discriminate tumor from normal cells was orthogonally confirmed. (PMID:19690195)
• Calcium regulation of EGF-induced ERK5 activation is mediated through interaction of MEKK2 with the adaptor protein Lad1. (PMID:20830310)
• Hepatitis B virus X protein enhances the growth of hepatoma cells through upregulation of MEKK2. (PMID:21804577)
• Data suggest that MEKK2 and MLK3 represent untargeted kinases in tumor biology for potential therapeutic development. (PMID:22139075)
• results strongly support a role for MEKK2 as a regulator of signaling that modulates breast tumor cell spread area and migration through control of focal adhesion stability (PMID:24491810)
• Restoration of miR17/20a in solid tumor cells enhances the natural killer cell antitumor activity by targeting Mekk2 (PMID:24801835)
• methylation of MAP3K2 by SMYD3 increases MAP kinase signalling and promotes the formation of Ras-driven carcinomas (PMID:24847881)
• Inhibitors of apoptosis proteins regulate myogenic differentiation by directly suppressing MEKK2/3-MEK5-ERK5 signaling. (PMID:24975362)
• EBV microRNA BART 18-5p targets MAP3K2 to facilitate persistence in vivo by inhibiting viral replication in B cells. (PMID:25012295)
• MEKK2 has a novel function as a regulator of ubiquitylation-dependent paxillin redistribution in breast tumour cells. (PMID:25190348)
• HBXIP activated ERK1/2 through up-regulating MEKK2. (PMID:25304384)
• SMYD3-mediated methylation of MAP3K2 increases mutant K-Ras-induced activation of ERK1/2. (Review) (PMID:25382779)
• Study found miR-186 expression significantly decreased in lung cancer tissues and cells and MAP3K2 expression increased in the same cancer tissues. Also, results confirmed that MAP3K2 is a target gene of miR-186 and both expression correlated with prognosis. (PMID:27498924)
• miR-34c-3p may regulate triple-negative breast cancer progression by directly targeting the 3’-untranslated region of mitogen-activated protein kinase kinase kinase 2 (MAP3K2). (PMID:28069384)
• Compound 1s displayed activity in cell-based assays in which it inhibited ERK5 pathway activation in cells and inhibited cell migration in a scratch assay. Thus, we have identified a scaffold that has promising potential to be developed into a highly selective and potent inhibitor of MEKK2. Information from these SAR studies provides specific guidance for the future design of MEKK2 inhibitor probes. (PMID:29309787)
• Degradation of mitogen-activated protein kinase kinase kinase 2 (MEKK2). (PMID:29549164)
• Expression of MEKK2 and MEKK3 inhibits medulloblastoma cell proliferation. (PMID:29662197)
• These results suggest that NDR2 may play important roles in IL-17-associated inflammation by promoting Smurf1-mediated MEKK2 ubiquitination and degradation. (PMID:30504095)
• these results indicated that miR36133p may have complicated roles in endothelial cells (ECs) under heat stress. miR36133p may serve an important role in the apoptosis of heattreated ECs, and this effect may be partly achieved by targeting MAP3K2. (PMID:31257536)
• circ-PITX1 exerted as a competing endogenous RNA (ceRNA) in glioblastoma by sponging miR-379-5p to elevate MAP3K2 expression (PMID:31493405)
• MIR205HG acts as a ceRNA to expedite cell proliferation and progression in lung squamous cell carcinoma via targeting miR-299-3p/MAP3K2 axis. (PMID:32513149)
• MEKK2 mediates aberrant ERK activation in neurofibromatosis type I. (PMID:33177525)
• Structural basis for antigen recognition by methylated lysine-specific antibodies. (PMID:33303630)
• Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers. (PMID:33627787)
• miR36133p/MAP3K2/p38/caspase3 pathway regulates the heatstressinduced apoptosis of endothelial cells. (PMID:34278472)
• CircRNA circBACH1 facilitates hepatitis B virus replication and hepatoma development by regulating the miR-200a-3p/MAP3K2 axis. (PMID:35352818)
• miRNA-338-3p inhibits the migration, invasion and proliferation of human lung adenocarcinoma cells by targeting MAP3K2. (PMID:35929837)
• CircHSPG2 knockdown attenuates hypoxia-induced apoptosis, inflammation, and oxidative stress in human AC16 cardiomyocytes by regulating the miR-1184/MAP3K2 axis. (PMID:36810972)
• Regulation of a Novel CircTRRAP/miR-761/MAP3K2 CeRNA Cascade in Inflammation, Apoptosis, and Oxidative Stress in Human AC16 Cardiomyocytes under Hypoxia Conditions. (PMID:37258120)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	map3k2	ENSDARG00000062884
mus_musculus	Map3k2	ENSMUSG00000024383
rattus_norvegicus	Map3k2	ENSRNOG00000014089
drosophila_melanogaster	lic	FBGN0261524
caenorhabditis_elegans		WBGENE00004758
caenorhabditis_elegans		WBGENE00018034
caenorhabditis_elegans		WBGENE00018035

Paralogs (8): MAP2K4 (ENSG00000065559), MAP2K7 (ENSG00000076984), MAP3K4 (ENSG00000085511), MAP2K2 (ENSG00000126934), NEK1 (ENSG00000137601), MAP2K5 (ENSG00000137764), MAP2K1 (ENSG00000169032), MAP3K3 (ENSG00000198909)

Protein

Protein identifiers

Mitogen-activated protein kinase kinase kinase 2 — Q9Y2U5 (reviewed: Q9Y2U5)

Alternative names: MAPK/ERK kinase kinase 2

All UniProt accessions (1): Q9Y2U5

UniProt curated annotations — full annotation on UniProt →

Function. Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7. Plays a role in caveolae kiss-and-run dynamics.

Subunit / interactions. Interacts with PKN2; the interaction activates PKN2 kinase activity in a MAP3K2-independent kinase activity. Self-associates. Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts (via the kinase catalytic domain) with STK38. Interacts with XIAP/BIRC4.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Autophosphorylated. Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation.

Activity regulation. Activated by phosphorylation on Thr-524.

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

RefSeq proteins (3): NP_001358839, NP_001358840, NP_006600 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000270	PB1_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR034879	PB1_MEKK2/3	Domain
IPR053793	PB1-like	Domain

Pfam: PF00069, PF00564

Enzyme classification (BRENDA):

• EC 2.7.12.2 — mitogen-activated protein kinase kinase (BRENDA: 38 organisms, 149 substrates, 134 inhibitors, 6 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0533	1
ERK2	0.0002	1
K52R-[ERK2]	0.0001	1
K53M-[P38ALPHA]	0.0002	1
P38ALPHA	0.0002	1

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 (46 total): sequence conflict 11, modified residue 10, strand 6, compositionally biased region 4, region of interest 4, sequence variant 3, domain 2, binding site 2, helix 2, chain 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
6LDW	X-RAY DIFFRACTION	1.6
5HQ8	X-RAY DIFFRACTION	1.72
2NPT	X-RAY DIFFRACTION	1.75
6LDY	X-RAY DIFFRACTION	1.77
6LDX	X-RAY DIFFRACTION	1.8
6LDV	X-RAY DIFFRACTION	1.9
9P6A	X-RAY DIFFRACTION	2.4
5EX0	X-RAY DIFFRACTION	2.7
2CU1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2U5-F1	68.27	0.39

Antibody-complex structures (SAbDab): 4 — 6LDV, 6LDW, 6LDX, 6LDY

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): 483 (proton acceptor)

Ligand- & substrate-binding residues (2): 362–371; 385

Post-translational modifications (10): 26, 153, 159, 164, 239, 297, 311, 331, 344, 349

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 333 (showing top): TAATAAT_MIR126, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, KEGG_MAPK_SIGNALING_PATHWAY, TTTGTAG_MIR520D, AAAGACA_MIR511, ATTCTTT_MIR186, BIOCARTA_MAPK_PATHWAY, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_DN, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, SENESE_HDAC1_TARGETS_UP, CUI_TCF21_TARGETS_2_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, HOXA4_Q2, chr2q14

GO Biological Process (4): intracellular signal transduction (GO:0035556), cellular response to mechanical stimulus (GO:0071260), MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468)

GO Molecular Function (11): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), MAP kinase kinase kinase activity (GO:0004709), ATP binding (GO:0005524), protein kinase binding (GO:0019901), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
protein kinase activity	2
signal transduction	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
intracellular signaling cassette	1
phosphorylation	1
protein modification process	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
kinase binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP3K2	LYN	P07948	753
MAP3K2	SMYD3	Q9H7B4	681
MAP3K2	SMURF1	Q9HCE7	648
MAP3K2	MAP2K5	Q13163	644
MAP3K2	MAPK7	Q13164	632
MAP3K2	SCARB2	Q14108	616
MAP3K2	CD36	P16671	616
MAP3K2	SCARB1	Q8WTV0	613
MAP3K2	TP53	P04637	523
MAP3K2	HSP90AA1	P07900	509
MAP3K2	HSP90AB1	P08238	507
MAP3K2	XIAP	P98170	489
MAP3K2	PITX1	P78337	477
MAP3K2	AKT1	P31749	460
MAP3K2	SMYD2	Q9NRG4	441

IntAct

73 interactions, top by confidence:

A	B	Type	Score
YWHAB	MAP3K2	psi-mi:“MI:0915”(physical association)	0.900
YWHAG	MAP3K2	psi-mi:“MI:0915”(physical association)	0.890
MAP2K5	MAPK7	psi-mi:“MI:0914”(association)	0.860
MAP3K2	YWHAE	psi-mi:“MI:0915”(physical association)	0.830
YWHAE	MAP3K2	psi-mi:“MI:0915”(physical association)	0.830
YWHAE	MAP3K2	psi-mi:“MI:0403”(colocalization)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
MAP3K2	MAP2K5	psi-mi:“MI:0915”(physical association)	0.800
SFN	MAP3K2	psi-mi:“MI:0915”(physical association)	0.690
MAP3K2	SFN	psi-mi:“MI:0915”(physical association)	0.690
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SMYD3	MAP3K2	psi-mi:“MI:0213”(methylation reaction)	0.560
SMYD3	MAP3K2	psi-mi:“MI:0407”(direct interaction)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
STUB1	MAP3K2	psi-mi:“MI:0915”(physical association)	0.520
MAP3K2	STUB1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (164): SFN (Affinity Capture-MS), MAP3K3 (Affinity Capture-MS), STX3 (Affinity Capture-MS), YWHAB (Affinity Capture-MS), YWHAE (Affinity Capture-MS), YWHAG (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), YWHAQ (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), CTNNB1 (Affinity Capture-MS), MAP3K2 (Affinity Capture-Western), CTNNB1 (Reconstituted Complex), CTNNB1 (Biochemical Activity), MAP3K2 (Affinity Capture-Western), MAP3K2 (Affinity Capture-Western)

ESM2 similar proteins: A2VDU3, A7E3S4, A8XJW8, E9PUQ8, F1QGZ6, O35346, O43318, O54748, P04049, P05625, P09560, P0C8E4, P11345, P11346, P27966, P33886, P34152, P34908, P42331, Q00944, Q04982, Q05397, Q07192, Q07292, Q08BR4, Q16760, Q21029, Q3UVC0, Q56R14, Q5R5M7, Q5RFL3, Q5U2Z7, Q61083, Q61084, Q61097, Q61UC4, Q62073, Q69Z98, Q6GPK9, Q6VAB6

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0LT89, B0XXN8, B5VNQ3, C4YRB7, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, H2L099, O00506, O14047, O14305, O22040, O22042, O24527, O54748, O61122, O61125, O81472, O95382, P0CY23, P0CY24, P23561, P27636, P28829

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MAP3K2	up-regulates	MAP2K5	phosphorylation
MAP3K2	up-regulates	MAP2K1	phosphorylation
MAP3K2	“up-regulates activity”	MAP2K4	phosphorylation
MAP3K2	up-regulates	MEK1/2	phosphorylation
MAP3K2	“down-regulates quantity”	PXN	phosphorylation
MAP3K2	“up-regulates quantity by stabilization”	STK38	phosphorylation
MAP3K2	“up-regulates activity”	MAP2K7	phosphorylation
MAP3K2	up-regulates	MAP2K5

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
Activation of BAD and translocation to mitochondria	7	152.3×	2e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	134.3×	3e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	134.3×	3e-12
Activation of BH3-only proteins	7	99.3×	3e-11
RHO GTPases activate PKNs	7	63.4×	7e-10
Intrinsic Pathway for Apoptosis	7	58.6×	1e-09
FOXO-mediated transcription	5	48.0×	1e-06
SARS-CoV-1-host interactions	8	40.2×	9e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	44.7×	2e-05
MAPK cascade	6	22.4×	3e-05
intracellular protein localization	8	20.4×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2613 predictions. Top by Δscore:

Variant	Effect	Δscore
2:127307800:CACTC:C	acceptor_gain	1.0000
2:127307802:CTC:C	acceptor_gain	1.0000
2:127307803:TC:T	acceptor_gain	1.0000
2:127307804:CC:C	acceptor_gain	1.0000
2:127307804:CCTGA:C	acceptor_loss	1.0000
2:127307805:CTGA:C	acceptor_loss	1.0000
2:127308580:CCTA:C	donor_loss	1.0000
2:127308581:CTA:C	donor_loss	1.0000
2:127308582:TA:T	donor_loss	1.0000
2:127308583:A:AC	donor_gain	1.0000
2:127308584:C:CA	donor_gain	1.0000
2:127308584:CCAG:C	donor_gain	1.0000
2:127308584:CCAGA:C	donor_gain	1.0000
2:127308602:T:TA	donor_gain	1.0000
2:127308758:TGCGC:T	acceptor_gain	1.0000
2:127308759:GCGC:G	acceptor_gain	1.0000
2:127308760:CGC:C	acceptor_gain	1.0000
2:127308760:CGCC:C	acceptor_gain	1.0000
2:127308761:GC:G	acceptor_gain	1.0000
2:127308761:GCCTA:G	acceptor_loss	1.0000
2:127308762:CC:C	acceptor_gain	1.0000
2:127308763:C:CC	acceptor_gain	1.0000
2:127308769:A:AC	acceptor_gain	1.0000
2:127314749:CTTA:C	donor_loss	1.0000
2:127314751:TA:T	donor_loss	1.0000
2:127314752:A:AC	donor_gain	1.0000
2:127314752:A:AG	donor_loss	1.0000
2:127314752:AC:A	donor_gain	1.0000
2:127314753:C:CT	donor_gain	1.0000
2:127314753:CC:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010255 (2:127325146 G>C), RS1000026907 (2:127368105 T>A), RS1000062610 (2:127324769 A>G), RS1000124559 (2:127342588 T>C), RS1000126169 (2:127370931 GAAGAA>G), RS1000258390 (2:127387264 G>A,C), RS1000294881 (2:127323172 C>T), RS1000304349 (2:127304682 A>G,T), RS1000329045 (2:127388875 G>A), RS1000332198 (2:127365899 T>C), RS1000379255 (2:127304637 TAG>T), RS1000435346 (2:127322851 T>C), RS1000492526 (2:127342808 T>C), RS1000499879 (2:127372284 T>C), RS1000521958 (2:127316419 G>A)

Disease associations

OMIM: gene MIM:609487 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006119_1	Protein C levels	6.000000e-12
GCST006119_5	Protein C levels	1.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004633	protein C measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5914 (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: 439,314 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL572881	MOTESANIB	3	4,642
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL3545396	BMS-690514	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL572878	TOZASERTIB	2
CHEMBL1908397	KW-2449	1
CHEMBL2140408	AMG-900	1
CHEMBL4289017	PF-03814735	1
CHEMBL494089	GSK-690693	1

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

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
URMC-099	Inhibition	6.18	pIC50

ChEMBL bioactivities

72 potent at pChembl≥5 of 72 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.62	Kd	2.4	nM	STAUROSPORINE
8.32	Kd	4.8	nM	LESTAURTINIB
8.03	Kd	9.4	nM	NINTEDANIB
7.72	Kd	19	nM	CHEMBL4554938
7.63	IC50	23.5	nM	STAUROSPORINE
7.52	Kd	30	nM	BOSUTINIB
7.48	IC50	33.2	nM	STAUROSPORINE
7.42	Kd	38	nM	CHEMBL4465866
7.39	Kd	41	nM	RUXOLITINIB
7.36	IC50	43.5	nM	STAUROSPORINE
7.28	Kd	53	nM	CHEMBL4576489
7.24	Kd	57	nM	SUNITINIB
7.16	Kd	69.98	nM	CHEMBL3752910
7.15	Kd	71	nM	DOVITINIB
7.14	Kd	73	nM	SU-014813
7.14	Kd	72	nM	CRIZOTINIB
7.14	Kd	72	nM	KW-2449
7.10	IC50	79.6	nM	CHEMBL4554938
7.07	Kd	86	nM	CHEMBL1908395
7.03	Kd	94	nM	R-406
7.00	ED50	100.2	nM	CHEMBL3752910
6.96	Kd	110	nM	TAE-684
6.85	Kd	140	nM	CHEMBL3416026
6.85	Kd	140	nM	MIDOSTAURIN
6.85	Kd	140	nM	DASATINIB
6.79	Kd	164	nM	PF-03814735
6.59	IC50	255	nM	CHEMBL4281823
6.56	Kd	277	nM	AT-9283
6.54	Kd	290	nM	PAZOPANIB
6.47	Kd	340	nM	GSK-690693
6.35	Kd	450	nM	NERATINIB
6.34	Kd	460	nM	CHEMBL3688339
6.27	Kd	536	nM	GILTERITINIB
6.24	Kd	580	nM	FEDRATINIB
6.20	Kd	630	nM	CHEMBL386051
6.19	Kd	650	nM	BOSUTINIB
6.18	IC50	661	nM	CHEMBL2436978
6.16	Kd	690	nM	CHEMBL2312304
6.15	Kd	710	nM	RUBOXISTAURIN
6.13	Kd	747	nM	Cerdulatinib Hydrochloride
6.06	Kd	870	nM	CHEMBL1241674
6.04	IC50	910	nM	SR-318
6.02	Kd	950	nM	CGP-52421
6.00	IC50	1000	nM	TP-030n
5.98	Kd	1054	nM	BMS-690514
5.96	Kd	1100	nM	TOZASERTIB
5.82	Kd	1501	nM	NINTEDANIB
5.72	Kd	1900	nM	FORETINIB
5.71	Kd	1966	nM	AMG-900
5.68	Kd	2100	nM	DASATINIB

PubChem BioAssay actives

69 with measured affinity, of 543 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(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	625062: Binding constant for MAP3K2 kinase domain	kd	0.0024	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	507598: Binding affinity to MAP3K2	kd	0.0048	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625062: Binding constant for MAP3K2 kinase domain	kd	0.0094	uM
4-[(2,9-dimethyl-8-oxo-6-thia-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-13-yl)amino]benzenesulfonamide	2189151: Binding affinity to MAP3K2 (unknown origin) assessed as dissociation constant	kd	0.0190	uM
Bosutinib	625062: Binding constant for MAP3K2 kinase domain	kd	0.0300	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526189: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MAP3K2 (unknown origin) (337 to 620 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0380	uM
Ruxolitinib	625062: Binding constant for MAP3K2 kinase domain	kd	0.0410	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526189: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MAP3K2 (unknown origin) (337 to 620 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0530	uM
Sunitinib	507598: Binding affinity to MAP3K2	kd	0.0570	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148691: Binding affinity to human MAP3K2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0700	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625062: Binding constant for MAP3K2 kinase domain	kd	0.0710	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625062: Binding constant for MAP3K2 kinase domain	kd	0.0720	uM
Crizotinib	625062: Binding constant for MAP3K2 kinase domain	kd	0.0720	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	625062: Binding constant for MAP3K2 kinase domain	kd	0.0730	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625062: Binding constant for MAP3K2 kinase domain	kd	0.0860	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625062: Binding constant for MAP3K2 kinase domain	kd	0.0940	uM
[(2R)-1-methoxypropan-2-yl] 2-[6-[[5-carbamoyl-4-(2-methoxyanilino)-2-pyridinyl]amino]-3-pyridinyl]acetate	2021296: Inhibition of MAP3K2 (unknown origin)	ic50	0.1000	uM
2-[6-[[5-carbamoyl-4-(2-methoxyanilino)-2-pyridinyl]amino]-3-pyridinyl]acetic acid	2021296: Inhibition of MAP3K2 (unknown origin)	ic50	0.1000	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	625062: Binding constant for MAP3K2 kinase domain	kd	0.1100	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	625062: Binding constant for MAP3K2 kinase domain	kd	0.1400	uM
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-(1H-indol-7-ylamino)-1,2,4-triazine-6-carboxamide	1199667: Competitive binding affinity to human MAP3K2	kd	0.1400	uM
Midostaurin	507598: Binding affinity to MAP3K2	kd	0.1400	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	1425046: 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	0.1640	uM
1-[5-(4-amino-7-ethylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethoxy)phenyl]ethanone	1415180: Inhibition of recombinant full length human MEKK2 using myelin basic protein as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis	ic50	0.2550	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1425046: 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	0.2770	uM
Pazopanib	625062: Binding constant for MAP3K2 kinase domain	kd	0.2900	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625062: Binding constant for MAP3K2 kinase domain	kd	0.3400	uM
Neratinib	625062: Binding constant for MAP3K2 kinase domain	kd	0.4500	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425046: 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	0.4600	uM
Gilteritinib	1425046: 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	0.5360	uM
Fedratinib	625062: Binding constant for MAP3K2 kinase domain	kd	0.5800	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625062: Binding constant for MAP3K2 kinase domain	kd	0.6300	uM
3-(1H-indol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine	775410: Inhibition of wild type human MEKK2 by high throughput ATP-[33P] radiolabeled assay	ic50	0.6610	uM
4-(cyclopentylamino)-2-[(2,5-dichlorophenyl)methylamino]-N-[3-(2-oxo-1,3-oxazolidin-3-yl)propyl]pyrimidine-5-carboxamide	1771920: Binding affinity to human MAP3K2 by KINOMEscan scanMAX assay	kd	0.6900	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	625062: Binding constant for MAP3K2 kinase domain	kd	0.7100	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1425046: 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	0.7470	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625062: Binding constant for MAP3K2 kinase domain	kd	0.8700	uM
5-amino-N-[[4-(3-cyclohexylpropylcarbamoyl)phenyl]methyl]-1-phenylpyrazole-4-carboxamide	1527587: Inhibition of ZAK (unknown origin) expressed in human HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition by NanoBRET assay	ic50	0.9100	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-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-4-yl]-N-methylbenzamide	507598: Binding affinity to MAP3K2	kd	0.9500	uM
(3R,4R)-4-amino-1-[[4-(3-methoxyanilino)pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol	1425046: 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	1.0540	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625062: Binding constant for MAP3K2 kinase domain	kd	1.1000	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625062: Binding constant for MAP3K2 kinase domain	kd	1.9000	uM
N-[4-[[3-(2-aminopyrimidin-4-yl)-2-pyridinyl]oxy]phenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine	1425046: 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	1.9660	uM
2-[1-[2-(5-chloro-2-fluorophenyl)-5-methyl-4-pyridinyl]-2-oxoimidazo[4,5-c]pyridin-3-yl]acetamide	1627771: Inhibition of MAP3K2 (unknown origin)	ic50	2.2000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625062: Binding constant for MAP3K2 kinase domain	kd	2.3000	uM
Erlotinib	625062: Binding constant for MAP3K2 kinase domain	kd	2.5000	uM
Gefitinib	625062: Binding constant for MAP3K2 kinase domain	kd	3.3000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	625062: Binding constant for MAP3K2 kinase domain	kd	3.8000	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-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-nonaene-16-carboxylate	1425046: 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	4.1180	uM
2,5-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573312: Binding affinity to MAP3K2 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	4.3960	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
Benzo(a)pyrene	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects expression, affects cotreatment	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	affects expression, affects cotreatment	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
entinostat	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
asparanin A	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Caffeine	increases phosphorylation	1
Chelating Agents	affects binding, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, increases expression	1
Succimer	affects cotreatment, increases expression	1

ChEMBL screening assays

220 unique, capped per target: 220 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1046146	Binding	Inhibition of MAPK3K2 at 3 uM	Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors. — J Med Chem

Cellosaurus cell lines

8 cell lines: 8 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1GF	Abcam A-549 MAP3K2 KO 2	Cancer cell line	Male
CVCL_B1WJ	Abcam HeLa MAP3K2 KO	Cancer cell line	Female
CVCL_B2NY	Abcam A-549 MAP3K2 KO 1	Cancer cell line	Male
CVCL_D7UA	Ubigene A-549 MAP3K2 KO	Cancer cell line	Male
CVCL_E0H8	Ubigene HeLa MAP3K2 KO	Cancer cell line	Female
CVCL_SW64	HAP1 MAP3K2 (-) 1	Cancer cell line	Male
CVCL_SW65	HAP1 MAP3K2 (-) 2	Cancer cell line	Male
CVCL_SW66	HAP1 MAP3K2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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