MAPK7

Summary

MAPK7 (mitogen-activated protein kinase 7, HGNC:6880) is a protein-coding gene on chromosome 17p11.2, encoding Mitogen-activated protein kinase 7 (Q13164). Plays a role in various cellular processes such as proliferation, differentiation and cell survival.

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported.

Source: NCBI Gene 5598 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 129 total — 4 pathogenic
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6880
Approved symbol	MAPK7
Name	mitogen-activated protein kinase 7
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	BMK1, ERK5
Ensembl gene	ENSG00000166484
Ensembl biotype	protein_coding
OMIM	602521
Entrez	5598

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 14 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000299612, ENST00000308406, ENST00000395602, ENST00000395604, ENST00000443215, ENST00000482850, ENST00000486905, ENST00000490660, ENST00000570306, ENST00000571657, ENST00000572716, ENST00000572853, ENST00000572968, ENST00000573417, ENST00000573466, ENST00000579284, ENST00000581260, ENST00000603493, ENST00000885402, ENST00000885403, ENST00000885404, ENST00000885405, ENST00000885406, ENST00000925981

RefSeq mRNA: 4 — MANE Select: NM_002749 NM_002749, NM_139032, NM_139033, NM_139034

CCDS: CCDS11206, CCDS11207

Canonical transcript exons

ENST00000395604 — 7 exons

Exon	Start	End
ENSE00001820553	19378498	19378630
ENSE00002415357	19381781	19382466
ENSE00003557625	19383078	19383544
ENSE00003570187	19378896	19379132
ENSE00003573119	19379782	19379947
ENSE00003577147	19380608	19381686
ENSE00003610069	19382813	19382946

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 92.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3413 / max 89.2489, expressed in 1791 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159836	10.7337	1769
159834	1.8349	1118
159835	0.7482	438
159837	0.0245	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	92.14	gold quality
ganglionic eminence	UBERON:0004023	91.96	gold quality
stromal cell of endometrium	CL:0002255	91.73	gold quality
popliteal artery	UBERON:0002250	90.55	gold quality
tibial artery	UBERON:0007610	90.53	gold quality
sural nerve	UBERON:0015488	90.41	gold quality
ventricular zone	UBERON:0003053	90.11	gold quality
ectocervix	UBERON:0012249	90.04	gold quality
granulocyte	CL:0000094	89.84	gold quality
right ovary	UBERON:0002118	89.27	gold quality
aorta	UBERON:0000947	89.06	gold quality
skin of leg	UBERON:0001511	88.96	gold quality
cortical plate	UBERON:0005343	88.87	gold quality
left adrenal gland cortex	UBERON:0035825	88.85	gold quality
right adrenal gland cortex	UBERON:0035827	88.72	gold quality
left adrenal gland	UBERON:0001234	88.60	gold quality
left coronary artery	UBERON:0001626	88.55	gold quality
left uterine tube	UBERON:0001303	88.54	gold quality
esophagus mucosa	UBERON:0002469	88.41	gold quality
right adrenal gland	UBERON:0001233	88.31	gold quality
right coronary artery	UBERON:0001625	88.31	gold quality
right lung	UBERON:0002167	87.90	gold quality
esophagus	UBERON:0001043	87.78	gold quality
descending thoracic aorta	UBERON:0002345	87.70	gold quality
mucosa of stomach	UBERON:0001199	87.69	gold quality
skin of abdomen	UBERON:0001416	87.69	gold quality
left ovary	UBERON:0002119	87.69	gold quality
body of uterus	UBERON:0009853	87.63	gold quality
endocervix	UBERON:0000458	87.52	gold quality
thoracic aorta	UBERON:0001515	87.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.78

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
KLF2	Activation
KLF4	Activation

Upstream regulators (CollecTRI, top): KLF2, KLF4, MEF2A, MEF2C, NR4A2

miRNA regulators (miRDB)

21 targeting MAPK7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-3929	98.32	65.58	1026

Literature-anchored findings (GeneRIF, showing 40)

• BMK1 (ERK5) regulates squamous differentiation marker SPRR1B transcription in Clara-like H441 cells. (PMID:12091247)
• BMK1 has a role in EGF-mediated Cx43 gap junction uncoupling by association and Cx43 Ser- 255 phosphorylation (PMID:12637502)
• BMK1 activation and cell proliferation are regulated by alternatively spliced MEK5alpha and MEK5beta (PMID:14583600)
• Showed that in resting, as well as in EGF-stimulated Rat-1 cell, endogenous ERK5 is localized mainly in the nucleus. (PMID:15075238)
• ERK5 signaling is directed by the presence of its unique C-terminal tail (PMID:15548525)
• the ability to regulate the cellular abundance of ERK5 contributes to the oncogenic potential of Abl kinases (PMID:15608616)
• results place the Erk5 route as a new regulatory signaling pathway that affects multiple myeloma proliferation and apoptosis (PMID:15692064)
• Investigation of the mechanism of neurotrophin-3/TrkC-induced apoptosis has identified a role for both MEK5/ERK5 and MEF2 in cell death. (PMID:15994942)
• ERK5 regulates transcriptional responses of cell survival and quiescence critical for angiogenesis and T-cell function (PMID:16166637)
• Selective activation of the ERK5 cascade by transfection of constitutively active MEK5 and wildtype ERK5 induces a reporter gene driven by the IL-2 promoter while barely affecting CD69 expression. (PMID:16316418)
• The large C-terminal domain of ERK5 is not required for binding or activation of RSK by ERK5. (PMID:16626623)
• ERK5 and ERK1/2 differ in their mechanisms of gene regulation, and ERK5 may control hypoxia-responsive genes by a mechanism independent of HIF-1alpha expression control (PMID:16735500)
• ERK5-dependent activation of PPARgamma represents a major effector pathway mediating the anti-tumorigenic effects of Wnt 7a and Fzd 9 in non-small cell lung cancer cells (PMID:16835228)
• activation of ERK5 promotes basal dopamine cell survival and protects dopamine cells from oxidative stress (PMID:16941494)
• Data show that, when expressed in Saccharomyces cerevisiae, ERK5 is is an Hsp90 client (PMID:16950928)
• Sustained ERK5 activity and the E3 ligase UBR1 regulate the stability and subcellular localization of c-Fos. (PMID:17018293)
• Cell integrity MAPK (mitogen-activated protein kinase) function can be provided in yeast cells by either the native Slt2(Mpk1)p of yeast or by a heterologously expressed human ERK5. (PMID:17052197)
• These results suggest the existence of an ERK1/2-driven negative feed-back regulation of ERK5 signaling in epidermal growth factor-stimulated HK-2 cells, which is mediated by MKP-3, DUSP5 and/or MKP-1. (PMID:17131384)
• ERK5 probably mediates HOXB9 expression by repressing BMI1 in Hodgkin lymphoma cell lines (PMID:17148583)
• Activation of ERK5 in transgenic mice prevents pressure overload- and doxorubicin-mediated induction of phosphodiesterase 3A/inducible cAMP early repressor feedback loop, cardiac apoptosis, as well as subsequent cardiac dysfunction in vivo. (PMID:17272811)
• Aberrant extracellular signal-regulated kinase (ERK) 5 signaling in hippocampus of suicide subjects. (PMID:17342168)
• Study reports that extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinases, is activated at G2-M and required for timely mitotic entry. (PMID:17452529)
• These results identify a new target of the still largely mysterious Erk5 and suggest that Erk5 in mitosis may be a decisive step for the survival of proliferating cells. (PMID:17624732)
• phorbol ester stimulation and ERK5 silencing in MDA-MB 231 and MDA-MB 361 breast cancer cells indicated Ser910 targeting by ERK5 also in these cells (PMID:17692050)
• ERK5 modulates platelet-derived growth factor-dependent biologic activities in human hepatic stellate cells (PMID:17998143)
• even upon over-expression DUSP6 fails to inactivate ERK5, confirming that it is indeed an ERK1/2-specific DUSP (PMID:18280112)
• ERK5 is necessary for colony stimulating factor 1-induced macrophage proliferation. (PMID:18322228)
• High ERK5 but not of high ERK1 expression is associated with advanced tumor stage and the presence of lymph node metastases in oral squamous cell carcinoma (PMID:18472963)
• Erk5 is involved in agonist-induced mesangial cell contraction, proliferation and ECM accumulation and point to a multifunctional role of Erk5 in the pathophysiology of glomerular mesangial cells. (PMID:18567890)
• These results implicate a novel EGFR/Erk5/Slug pathway in the control of cytoskeleton organization and cell motility in keratinocytes treated with epidermal growth factor. (PMID:18716062)
• An increase in MAPK7 copy number was detected in 35 of 66 primary HCC tumors. Results suggest the ERK5 protein product of MAPK7 promotes the growth of HCC cells by regulating mitotic entry. (PMID:18973138)
• Activation of ERK5 in angiotensin II-induced hypertrophy of human aortic smooth muscle cells (PMID:19011954)
• Results describe a a novel mechanism by which vitronectin receptors and focal adhesion kinase could promote cancer metastasis via ERK5 activation. (PMID:19089993)
• ERK5 gene was up-regulated in HepG2/ADM cells, but down-regulated in BEL-7402/5-FU cells. (PMID:19304531)
• Metformin decreases angiogenesis via NF-kappaB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1. (PMID:19414528)
• Overexpression of Erk5 is an independent predictor of disease-free survival in breast cancer, and may represent a future therapeutic target. (PMID:19440538)
• MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover (PMID:19605361)
• Ang II activates ERK5 via the AT1/PKC/PKD pathway and revealed a critical role of ERK5 in Ang II-induced human aortic smooth muscle cells hypertrophy. (PMID:19666008)
• Data show that LPS acts via ERK1/2/5 signaling pathways to decrease alphaENaC transcription, reducing channel abundance, activity, and transepithelial Na(+) transport in H441 airway epithelial cells. (PMID:19823867)
• ERK5 is a miR-143 target in prostate cancer (PMID:19855844)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapk7	ENSDARG00000023110
mus_musculus	Mapk7	ENSMUSG00000001034
rattus_norvegicus	Mapk7	ENSRNOG00000047907
caenorhabditis_elegans		WBGENE00003402
caenorhabditis_elegans		WBGENE00017277

Paralogs (19): MAPK9 (ENSG00000050748), MAPK6 (ENSG00000069956), MOK (ENSG00000080823), NLK (ENSG00000087095), SRPK1 (ENSG00000096063), MAPK1 (ENSG00000100030), MAPK3 (ENSG00000102882), MAPK8 (ENSG00000107643), MAPK10 (ENSG00000109339), MAK (ENSG00000111837), MAPK14 (ENSG00000112062), CILK1 (ENSG00000112144), SRPK2 (ENSG00000135250), MAPK4 (ENSG00000141639), MAPK13 (ENSG00000156711), MAPK15 (ENSG00000181085), SRPK3 (ENSG00000184343), MAPK11 (ENSG00000185386), MAPK12 (ENSG00000188130)

Protein

Protein identifiers

Mitogen-activated protein kinase 7 — Q13164 (reviewed: Q13164)

Alternative names: Big MAP kinase 1, Extracellular signal-regulated kinase 5

All UniProt accessions (6): C9JUK9, Q13164, I3L0J8, J3KT50, J3KT61, S4R3I1

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.

Subunit / interactions. Interacts with MAP2K5. Forms oligomers. Interacts with MEF2A, MEF2C and MEF2D; the interaction phosphorylates the MEF2s and enhances transcriptional activity of MEF2A, MEF2C but not MEF2D. Interacts with SGK1. Preferentially interacts with PML isoform PML-4 but shows interaction also with its other isoforms: isoform PML-1, isoform PML-2, isoform PML-3 and isoform PML-6. Interacts (via N-terminal half) with HSP90AB1-CDC37 chaperone complex in resting cells; the interaction is MAP2K5-independent and prevents MAPK7 from ubiquitination and proteasomal degradation. Interacts with STUB1/CHIP; the interaction is enhanced in the presence of IGF1 or MAP2K5 and promotes STUB1/CHIP E3 ligase activity.

Subcellular location. Cytoplasm. Nucleus. PML body.

Tissue specificity. Expressed in many adult tissues. Abundant in heart, placenta, lung, kidney and skeletal muscle. Not detectable in liver.

Post-translational modifications. Dually phosphorylated on Thr-219 and Tyr-221, which activates the enzyme. Autophosphorylated in vitro on threonine and tyrosine residues when the C-terminal part of the kinase, which could have a regulatory role, is absent.

Activity regulation. Activated by tyrosine and threonine phosphorylation. Activated in response to hyperosmolarity, hydrogen peroxide, and epidermal growth factor (EGF).

Domain organisation. The second proline-rich region may interact with actin targeting the kinase to a specific location in the cell. The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q13164-1	1	yes
Q13164-2	2
Q13164-3	3
Q13164-4	4

RefSeq proteins (4): NP_002740, NP_620601, NP_620602, NP_620603 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR003527	MAP_kinase_CS	Conserved_site
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050117	MAPK	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.24 — mitogen-activated protein kinase (BRENDA: 48 organisms, 305 substrates, 720 inhibitors, 27 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.048–0.096	4
ATF2DELTA109	0.002–0.02	2
EGF RECEPTOR PEPTIDE	0.656–2.8	2
ERKSUB	0.127–1.2	2
MEK1ERK	0.0037–0.065	2
MEK2ERK	0.0056–0.03	2
ELKERK	0.0044	1
ERKMEK1	0.344	1
ERKMEK2	0.388	1
ERKSTE7	0.173	1
PROTEIN ATF2	0.0019	1
SCRAMMMEK2	0.096	1
STE7ERK	0.0006	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 (75 total): helix 22, strand 13, compositionally biased region 12, region of interest 6, turn 4, modified residue 3, splice variant 3, short sequence motif 2, binding site 2, sequence variant 2, initiator methionine 1, chain 1, domain 1, active site 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
5BYZ	X-RAY DIFFRACTION	1.65
4ZSG	X-RAY DIFFRACTION	1.79
2Q8Y	X-RAY DIFFRACTION	2
4ZSL	X-RAY DIFFRACTION	2.25
6HKN	X-RAY DIFFRACTION	2.33
9LTA	X-RAY DIFFRACTION	2.33
5O7I	X-RAY DIFFRACTION	2.38
6HKM	X-RAY DIFFRACTION	2.47
4ZSJ	X-RAY DIFFRACTION	2.48
7PUS	X-RAY DIFFRACTION	2.59
4IC7	X-RAY DIFFRACTION	2.6
5BYY	X-RAY DIFFRACTION	2.79
4B99	X-RAY DIFFRACTION	2.8
4IC8	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13164-F1	66.87	0.35

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): 182 (proton acceptor)

Ligand- & substrate-binding residues (2): 61–69; 84

Post-translational modifications (3): 2, 720, 733

Mutagenesis-validated functional residues (1):

Position	Phenotype
219–221	loss activation by map2k5.

Function

Pathways and Gene Ontology

Reactome pathways

43 pathways

ID	Pathway
R-HSA-198753	ERK/MAPK targets
R-HSA-198765	Signalling to ERK5
R-HSA-202670	ERKs are inactivated
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-881907	Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-8853659	RET signaling
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-166520	Signaling by NTRKs
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
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-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling

MSigDB gene sets: 277 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_REGULATION_OF_HETEROTYPIC_CELL_CELL_ADHESION, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (37): MAPK cascade (GO:0000165), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), cell differentiation (GO:0030154), calcineurin-NFAT signaling cascade (GO:0033173), negative regulation of heterotypic cell-cell adhesion (GO:0034115), negative regulation of smooth muscle cell apoptotic process (GO:0034392), intracellular signal transduction (GO:0035556), regulation of angiogenesis (GO:0045765), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of inflammatory response (GO:0050728), positive regulation of protein metabolic process (GO:0051247), negative regulation of response to cytokine stimulus (GO:0060761), cellular response to hydrogen peroxide (GO:0070301), negative regulation of calcineurin-NFAT signaling cascade (GO:0070885), cellular response to growth factor stimulus (GO:0071363), cellular response to laminar fluid shear stress (GO:0071499), cellular response to transforming growth factor beta stimulus (GO:0071560), negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902176), negative regulation of endothelial cell apoptotic process (GO:2000352), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), protein phosphorylation (GO:0006468), epidermal growth factor receptor signaling pathway (GO:0007173), positive regulation of macrophage chemotaxis (GO:0010759), positive regulation of telomere maintenance (GO:0032206), regulation of stress-activated MAPK cascade (GO:0032872), cellular response to stress (GO:0033554), cellular response to amino acid starvation (GO:0034198), negative regulation of apoptotic process (GO:0043066), stress-activated MAPK cascade (GO:0051403), regulation of cytoskeleton organization (GO:0051493), response to epidermal growth factor (GO:0070849), caveolin-mediated endocytosis (GO:0072584), regulation of Golgi inheritance (GO:0090170), positive regulation of macrophage proliferation (GO:0120041), intracellular signaling cassette (GO:0141124), regulation of early endosome to late endosome transport (GO:2000641)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), MAP kinase activity (GO:0004707), enzyme inhibitor activity (GO:0004857), ATP binding (GO:0005524), mitogen-activated protein kinase binding (GO:0051019), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatase binding (GO:0019902)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), PML body (GO:0016605), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), caveola (GO:0005901), focal adhesion (GO:0005925)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Toll-like Receptor Cascades	6
Toll Like Receptor 4 (TLR4) Cascade	2
Toll Like Receptor 2 (TLR2) Cascade	2
Nuclear Events (kinase and transcription factor activation)	1
MAPK targets/ Nuclear events mediated by MAP kinases	1
Signaling by NTRK1 (TRKA)	1
ERK/MAPK targets	1
Cellular Senescence	1
G alpha (q) signalling events	1
Axon guidance	1
Immune System	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Signaling by Receptor Tyrosine Kinases	1

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
catalytic activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
endosome	2
intracellular signaling cassette	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cellular developmental process	1
calcineurin-mediated signaling	1
negative regulation of cell-cell adhesion	1
heterotypic cell-cell adhesion	1
regulation of heterotypic cell-cell adhesion	1
regulation of cell-cell adhesion involved in gastrulation	1
negative regulation of muscle cell apoptotic process	1
smooth muscle cell apoptotic process	1
regulation of smooth muscle cell apoptotic process	1
signal transduction	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
positive regulation of macromolecule metabolic process	1
protein metabolic process	1
regulation of protein metabolic process	1
response to cytokine	1
negative regulation of response to stimulus	1

Protein interactions and networks

STRING

4060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPK7	RAPGEF3	O95398	977
MAPK7	AKAP6	Q13023	958
MAPK7	AKAP1	Q92667	841
MAPK7	MAP2K5	Q13163	840
MAPK7	MEF2A	Q02078	755
MAPK7	KLF2	Q9Y5W3	729
MAPK7	JUN	P05412	677
MAPK7	PPARG	P37231	638
MAPK7	MAP3K2	Q9Y2U5	632
MAPK7	MEF2C	Q06413	630
MAPK7	PDE4A	P27815	628
MAPK7	CREB1	P16220	592
MAPK7	TRAF6	Q9Y4K3	589
MAPK7	ADCY5	O95622	572
MAPK7	SMAD3	P84022	551

IntAct

94 interactions, top by confidence:

A	B	Type	Score
MAP2K5	MAPK7	psi-mi:“MI:0915”(physical association)	0.860
MAP2K5	MAPK7	psi-mi:“MI:0914”(association)	0.860
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
BRAF	MEN1	psi-mi:“MI:0914”(association)	0.600
MAPK7	BRAF	psi-mi:“MI:0915”(physical association)	0.600
MAPK7	BRAF	psi-mi:“MI:2364”(proximity)	0.600
MAPK7	PML	psi-mi:“MI:0915”(physical association)	0.570
PML	MAPK7	psi-mi:“MI:0915”(physical association)	0.570
PML	MAPK7	psi-mi:“MI:0217”(phosphorylation reaction)	0.570
MAPK7	PML	psi-mi:“MI:0403”(colocalization)	0.570
MAPK7	UBE2C	psi-mi:“MI:0915”(physical association)	0.560
UBE2C	MAPK7	psi-mi:“MI:0915”(physical association)	0.560
BTN2	MAPK7	psi-mi:“MI:0915”(physical association)	0.560
MAPK7	FAP7	psi-mi:“MI:0915”(physical association)	0.560
MAPK7	AIM7	psi-mi:“MI:0915”(physical association)	0.560
AIM7	MAPK7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (210): NFE2L2 (Affinity Capture-Western), MAPK7 (Affinity Capture-Western), MAPK7 (Reconstituted Complex), PRKCZ (Affinity Capture-Western), PRKCZ (Two-hybrid), MAPK7 (Biochemical Activity), UBE2C (Two-hybrid), MAPK7 (Affinity Capture-MS), MAPK7 (Co-fractionation), MAPK7 (Reconstituted Complex), GPSM3 (Two-hybrid), MAPK7 (Affinity Capture-MS), MAPK7 (Affinity Capture-MS), MAPK7 (Affinity Capture-MS), MAPK7 (Dosage Rescue)

ESM2 similar proteins: A4IFM7, A8C984, B6D5P1, B6D5P6, E9PT87, O08815, O54988, O55092, O70551, O88831, P00519, P00520, P00521, P07313, P0C865, P13234, P20689, P42684, P46087, Q13164, Q14028, Q16566, Q2KI23, Q32MK0, Q3SYS4, Q3UH66, Q3UIZ8, Q3ULB5, Q4JIM5, Q4KMM3, Q4V8B0, Q5R8Z4, Q5RDG7, Q5TGJ6, Q63553, Q6AYH9, Q6PDI6, Q80XI3, Q8BHL3, Q8BWQ5

Diamond homologs: A0A194WDG1, A0A1S3Z5Y0, A1CPG7, A1D2C9, A2QRF6, A2XFC8, A5PKJ4, A9S9Q8, A9T142, B0XR80, B0Y4X4, B0Y8W7, C4YGK0, G4N0Z0, G4N374, O13352, O23236, O42781, O61443, O94737, P0C865, P0CP66, P0CP67, P0CP68, P0CP69, P14681, P16892, P21708, P26696, P27361, P27638, P28482, P36005, P39745, P40417, P42525, P43068, P46196, P47811, P47812

SIGNOR signaling

45 interactions.

A	Effect	B	Mechanism
MAP2K5	up-regulates	MAPK7	phosphorylation
SL-327	down-regulates	MAPK7	“chemical inhibition”
U0126	down-regulates	MAPK7	“chemical inhibition”
MAPK7	up-regulates	SGK1	phosphorylation
“hydrogen peroxide”	up-regulates	MAPK7
2-(2-amino-3-methoxyphenyl)chromen-4-one	down-regulates	MAPK7	“chemical inhibition”
SRC	up-regulates	MAPK7
U0126	down-regulates	MAPK7
MAPK7	down-regulates	PML	phosphorylation
MAPK7	up-regulates	MEF2D	phosphorylation
MAPK7	up-regulates	MEF2A	phosphorylation
MAPK7	“down-regulates activity”	GJA1	phosphorylation
MAP2K5	“up-regulates activity”	MAPK7	phosphorylation
MAPK7	“up-regulates quantity by expression”	KLF2	“transcriptional regulation”
MAPK7	“up-regulates quantity by expression”	KLF4	“transcriptional regulation”
MAPK7	“up-regulates activity”	MAPK7	phosphorylation
DUSP6	“down-regulates activity”	MAPK7	dephosphorylation
MAPK7	“up-regulates activity”	PPARG	binding
BRAF	“up-regulates quantity”	MAPK7	phosphorylation
MAPK7	“up-regulates activity”	NEUROG1	phosphorylation
MAPK7	“down-regulates activity”	PML	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
Signaling by NTRK1 (TRKA)	6	31.1×	8e-06
Signaling by NTRKs	6	28.6×	9e-06
Signaling by Receptor Tyrosine Kinases	9	12.2×	8e-06
Diseases of signal transduction by growth factor receptors and second messengers	6	9.0×	2e-03
Signaling by Interleukins	5	8.4×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	28.8×	2e-04
MAPK cascade	5	17.8×	1e-03
protein stabilization	9	14.0×	8e-06
protein folding	5	12.0×	4e-03
positive regulation of ERK1 and ERK2 cascade	5	9.9×	7e-03
heart development	5	9.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	111
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
427639	NM_002749.4(MAPK7):c.886G>A (p.Ala296Thr)	Pathogenic
427640	NM_002749.4(MAPK7):c.1760C>T (p.Pro587Leu)	Pathogenic
427641	NM_002749.4(MAPK7):c.1943C>T (p.Pro648Leu)	Pathogenic
980114	GRCh37/hg19 17p11.2(chr17:16761814-20330062)x3	Pathogenic

SpliceAI

1091 predictions. Top by Δscore:

Variant	Effect	Δscore
17:19379178:G:GT	donor_gain	1.0000
17:19379777:CTCAG:C	acceptor_loss	1.0000
17:19379779:CAG:C	acceptor_loss	1.0000
17:19379780:A:AG	acceptor_gain	1.0000
17:19379781:G:GA	acceptor_gain	1.0000
17:19379781:GGCCA:G	acceptor_gain	1.0000
17:19379904:G:GT	donor_gain	1.0000
17:19379943:TCTGT:T	donor_gain	1.0000
17:19379944:CTGT:C	donor_gain	1.0000
17:19379944:CTGTG:C	donor_loss	1.0000
17:19379946:GT:G	donor_gain	1.0000
17:19379947:TG:T	donor_loss	1.0000
17:19379948:G:GG	donor_gain	1.0000
17:19379948:GT:G	donor_loss	1.0000
17:19379949:T:G	donor_loss	1.0000
17:19380603:TCCA:T	acceptor_loss	1.0000
17:19380604:CCA:C	acceptor_loss	1.0000
17:19380605:CA:C	acceptor_loss	1.0000
17:19380606:A:AC	acceptor_loss	1.0000
17:19380606:A:AG	acceptor_gain	1.0000
17:19380607:G:GA	acceptor_gain	1.0000
17:19380607:GC:G	acceptor_gain	1.0000
17:19380607:GCT:G	acceptor_gain	1.0000
17:19380607:GCTA:G	acceptor_gain	1.0000
17:19380607:GCTAC:G	acceptor_gain	1.0000
17:19381917:G:GT	donor_gain	1.0000
17:19382942:GA:G	donor_gain	1.0000
17:19382944:TGGG:T	donor_loss	1.0000
17:19382945:GG:G	donor_gain	1.0000
17:19382946:GG:G	donor_gain	1.0000

AlphaMissense

5244 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:19379045:T:C	F49L	1.000
17:19379047:T:A	F49L	1.000
17:19379047:T:G	F49L	1.000
17:19379084:G:C	G62R	1.000
17:19379084:G:T	G62C	1.000
17:19379085:G:A	G62D	1.000
17:19379085:G:T	G62V	1.000
17:19379090:G:A	G64R	1.000
17:19379090:G:C	G64R	1.000
17:19379090:G:T	G64W	1.000
17:19379091:G:A	G64E	1.000
17:19379091:G:T	G64V	1.000
17:19379096:T:C	Y66H	1.000
17:19379099:G:A	G67R	1.000
17:19379099:G:C	G67R	1.000
17:19379100:G:A	G67E	1.000
17:19379100:G:T	G67V	1.000
17:19379106:T:A	V69E	1.000
17:19379114:G:C	A72P	1.000
17:19379115:C:A	A72D	1.000
17:19379793:G:C	A82P	1.000
17:19379794:C:A	A82D	1.000
17:19379797:T:A	I83N	1.000
17:19379797:T:G	I83S	1.000
17:19379799:A:C	K84Q	1.000
17:19379799:A:G	K84E	1.000
17:19379800:A:T	K84M	1.000
17:19379801:G:C	K84N	1.000
17:19379801:G:T	K84N	1.000
17:19379806:T:C	I86T	1.000

dbSNP variants (sampled 300 via entrez): RS1000223798 (17:19377717 C>A,G,T), RS1000495556 (17:19376658 C>A,G), RS1000777898 (17:19376243 A>C), RS1001125878 (17:19382331 T>A), RS1001271279 (17:19380129 C>G,T), RS1001975579 (17:19375856 G>A), RS1002425257 (17:19381500 A>G), RS1002507308 (17:19376644 A>T), RS1002623953 (17:19376251 T>C), RS1002646746 (17:19376759 C>A), RS1002698679 (17:19382049 C>T), RS1003572716 (17:19380258 CA>C), RS1004002502 (17:19379680 G>A,C), RS1004101952 (17:19379426 C>G,T), RS1004201275 (17:19379565 C>A,T)

Disease associations

OMIM: gene MIM:602521 | disease phenotypes: MIM:181800

GenCC curated gene-disease

Mondo (1): scoliosis, isolated, susceptibility to, 1 (MONDO:0008419)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007600_26	Alzheimer’s disease	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4523619 (PROTEIN FAMILY), CHEMBL5332 (SINGLE PROTEIN), CHEMBL5465236 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 169,418 (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
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL384304	RG-547	2	93
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL445813	AT-7519	2	2,614
CHEMBL513909	BI-2536	2	895
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1084546	PF-00562271	1	399
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
CHEMBL3128043	PF-03758309	1	233
CHEMBL4289017	PF-03814735	1	537

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — ERK subfamily

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
AX15836	Inhibition	8.1	pIC50
BAY-885	Inhibition	7.46	pIC50
BIX02189	Inhibition	7.23	pIC50
XMD8-92	Inhibition	7.1	pKd
XMD17-109	Inhibition	6.79	pIC50
BIX02188	Inhibition	6.09	pIC50
DCLK1-IN-1	Inhibition	5.74	pIC50

Binding affinities (BindingDB)

15 measured of 15 human assays (15 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
FIIN-1	KD	2.8 nM
FRIN-1	KD	3.1 nM
4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-8-methyl-1,3,5,8-tetrazatetracyclo[8.6.1.02,7.014,17]heptadeca-2,4,6,10,12,14(17)-hexaen-9-one	IC50	5 nM	US-9676792: Pyrimido-diazepinone compounds and methods of treating disorders
2-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)-5,11-dimethyl-5H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one	KD	19 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
5-ethyl-2-[[5-(4-hydroxypiperidin-1-yl)-2-pyridinyl]amino]-11-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	KD	50 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
2-((4-(4-hydroxypiperidin-1-yl)-2-methoxyphenyl)amino-5,11-dimethyl-5H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one	KD	57 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
2-((2-ethoxy-4-(4-hydroxypiperidin-1-yl)phenyl)amino)-5,11-dimethyl-5H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one	KD	80 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
4-[[(3R,7S)-2-cyclopentyl-9-methyl-8-oxo-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),10,12-trien-13-yl]amino]benzamide	KD	320 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
11-cyclopentyl-2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	IC50	339 nM	US-9676792: Pyrimido-diazepinone compounds and methods of treating disorders
(3R,7S)-2-cyclopentyl-9-methyl-13-(quinolin-6-ylamino)-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),10,12-trien-8-one	KD	550 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
2-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)-11-methyl-5H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one	KD	670 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
BMS-387072	KD	1800 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

291 potent at pChembl≥5 of 305 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	IC50	5	nM	CHEMBL5175191
8.30	IC50	5	nM	CHEMBL5188920
8.30	IC50	5	nM	CHEMBL5555328
8.22	IC50	6	nM	CHEMBL5186248
8.22	IC50	6	nM	CHEMBL5573086
8.15	IC50	7	nM	CHEMBL5197199
8.15	IC50	7	nM	CHEMBL5198962
8.10	IC50	8	nM	CHEMBL4541479
8.10	IC50	8	nM	CHEMBL5172952
8.05	IC50	9	nM	CHEMBL5574029
8.05	IC50	9	nM	CHEMBL5569331
8.05	IC50	9	nM	CHEMBL5571189
8.00	IC50	10.1	nM	CHEMBL1673042
8.00	IC50	10	nM	CHEMBL5566766
7.96	IC50	11	nM	CHEMBL4757477
7.89	IC50	13	nM	CHEMBL5175007
7.89	IC50	13	nM	CHEMBL5202924
7.89	IC50	12.9	nM	CHEMBL2381340
7.85	IC50	14	nM	CHEMBL5173346
7.85	IC50	14	nM	CHEMBL5175760
7.82	IC50	15	nM	CHEMBL6177472
7.80	IC50	16	nM	CHEMBL5208879
7.77	IC50	17	nM	CHEMBL4438379
7.77	IC50	17	nM	CHEMBL6174449
7.72	Kd	19	nM	CHEMBL1673039
7.72	IC50	19	nM	CHEMBL5180089
7.70	IC50	20	nM	CHEMBL4541479
7.70	IC50	20	nM	CHEMBL5197199
7.70	IC50	20	nM	CHEMBL6173856
7.68	IC50	21	nM	CHEMBL6177135
7.66	IC50	22	nM	CHEMBL5208123
7.60	IC50	25	nM	CHEMBL5193573
7.60	IC50	25	nM	CHEMBL6168986
7.58	IC50	26.5	nM	CHEMBL6144731
7.57	IC50	27.1	nM	CHEMBL5422839
7.55	IC50	28	nM	CHEMBL6169652
7.51	IC50	31	nM	CHEMBL5186248
7.46	IC50	35	nM	BAY-885
7.43	IC50	37	nM	CHEMBL5179461
7.38	Kd	42	nM	AT-7519
7.37	IC50	43	nM	CHEMBL5173346
7.37	IC50	43	nM	ZOTIRACICLIB
7.37	Kd	43	nM	ZOTIRACICLIB
7.32	Kd	48	nM	TAE-684
7.30	Kd	50	nM	CHEMBL3984135
7.29	IC50	51	nM	CHEMBL4469661
7.28	IC50	52.3	nM	CHEMBL1673046
7.27	IC50	54	nM	CHEMBL4550589
7.24	Kd	57	nM	CHEMBL1673040
7.24	IC50	58	nM	CHEMBL5175760

PubChem BioAssay actives

265 with measured affinity, of 968 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
4-(3,6-dichloro-2-fluorobenzoyl)-N-[6-[(4-methylpiperazin-1-yl)methyl]-3-pyridinyl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0050	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[6-(piperazin-1-ylmethyl)-3-pyridinyl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0050	uM
[2-amino-4-(trifluoromethoxy)phenyl]-[4-[6-fluoro-2-(3-methoxy-1-bicyclo[1.1.1]pentanyl)-1H-imidazo[4,5-b]pyridin-7-yl]piperidin-1-yl]methanone	2094783: Inhibition of ERK5 in human SN12C cells assessed as luciferase activity by Bright-Glo luminescence assay	ic50	0.0050	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[6-[(1-methylpiperidin-4-yl)methyl]-3-pyridinyl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0060	uM
[2-amino-4-(trifluoromethoxy)phenyl]-[4-[6-fluoro-2-(oxan-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]piperidin-1-yl]methanone	2094783: Inhibition of ERK5 in human SN12C cells assessed as luciferase activity by Bright-Glo luminescence assay	ic50	0.0060	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[2-[(4-methylpiperazin-1-yl)methyl]pyrimidin-5-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0070	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[1-(piperidin-4-ylmethyl)pyrazol-4-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0070	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[2-(piperazin-1-ylmethyl)pyrimidin-5-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0080	uM
2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methyl-11-methylsulfonylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1567606: Inhibition of ERK5 in human HeLa cells by KiNativ profiling method	ic50	0.0080	uM
[4-[6-fluoro-2-(4-methoxycyclohexyl)-1H-imidazo[4,5-b]pyridin-7-yl]piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone	2094783: Inhibition of ERK5 in human SN12C cells assessed as luciferase activity by Bright-Glo luminescence assay	ic50	0.0090	uM
[2-amino-4-(trifluoromethoxy)phenyl]-[4-[6-fluoro-2-(2-methoxypropan-2-yl)-1H-imidazo[4,5-b]pyridin-7-yl]piperidin-1-yl]methanone	2094783: Inhibition of ERK5 in human SN12C cells assessed as luciferase activity by Bright-Glo luminescence assay	ic50	0.0090	uM
[2-amino-4-(trifluoromethoxy)phenyl]-[4-[6-fluoro-2-(4-methoxycyclohexyl)-1H-imidazo[4,5-b]pyridin-7-yl]piperidin-1-yl]methanone	2094783: Inhibition of ERK5 in human SN12C cells assessed as luciferase activity by Bright-Glo luminescence assay	ic50	0.0090	uM
[4-[6-fluoro-2-(3-methoxy-1-bicyclo[1.1.1]pentanyl)-1H-imidazo[4,5-b]pyridin-7-yl]piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone	2094783: Inhibition of ERK5 in human SN12C cells assessed as luciferase activity by Bright-Glo luminescence assay	ic50	0.0100	uM
2-(2-methoxy-4-piperazin-1-ylanilino)-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	2015867: Inhibition of ERK5 (unknown origin) by ADP-Glo kinase assay	ic50	0.0101	uM
2-[2-ethoxy-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)anilino]-5,11-dimethylpyrido[4,3-b][1,4]benzodiazepin-6-one	1719439: Inhibition of ERK5 (unknown origin)	ic50	0.0110	uM
11-cyclopentyl-2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	2015867: Inhibition of ERK5 (unknown origin) by ADP-Glo kinase assay	ic50	0.0129	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-(2-piperazin-1-ylpyrimidin-5-yl)-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0130	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-(6-piperazin-1-yl-3-pyridinyl)-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0130	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[6-(1-methylpiperidin-4-yl)oxy-3-pyridinyl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0140	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[2-[(1-methylpiperidin-4-yl)amino]pyrimidin-5-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0140	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[1-[(1-methylpiperidin-4-yl)methyl]pyrazol-4-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0160	uM
[4-(7-morpholin-4-ylpyrido[3,2-d]pyrimidin-4-yl)piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone	1535166: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0170	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-(1-piperidin-4-ylpyrazol-4-yl)-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0190	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0220	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[6-[methyl-(1-methylpiperidin-4-yl)amino]-3-pyridinyl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0250	uM
ethyl 7-[4-[4-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-3-methoxyphenyl]piperazin-1-yl]heptanoate	2015867: Inhibition of ERK5 (unknown origin) by ADP-Glo kinase assay	ic50	0.0271	uM
[2-amino-4-(trifluoromethoxy)phenyl]-[4-[7-(4-methylpiperazin-1-yl)pyrido[3,2-d]pyrimidin-4-yl]piperidin-1-yl]methanone	1535166: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0350	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0370	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624888: Binding constant for ERK5 kinase domain	kd	0.0420	uM
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene	1987334: Inhibition of ERK5 (unknown origin)	ic50	0.0430	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	624888: Binding constant for ERK5 kinase domain	kd	0.0480	uM
[2-amino-4-(trifluoromethoxy)phenyl]-[4-(7-methoxyquinazolin-4-yl)piperidin-1-yl]methanone	1535166: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0510	uM
2-[2-ethoxy-4-(4-hydroxypiperidin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	2015867: Inhibition of ERK5 (unknown origin) by ADP-Glo kinase assay	ic50	0.0523	uM
[4-[7-(4-methylpiperazin-1-yl)pyrido[3,2-d]pyrimidin-4-yl]piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone	1535166: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0540	uM
3-[N-[3-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-N,N-dimethyl-1H-indole-6-carboxamide	1567602: Inhibition of GST-tagged ERK5 (unknown origin) expressed in baculovirus expression system incubated for 90 mins by HTS assay	ic50	0.0590	uM
(2S,4R)-1-[(2S)-2-[7-[4-[4-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-3-methoxyphenyl]piperazin-1-yl]heptanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2015867: Inhibition of ERK5 (unknown origin) by ADP-Glo kinase assay	ic50	0.0624	uM
[4-[7-[3-(dimethylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-4-yl]piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone	1535166: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0640	uM
Fedratinib	624888: Binding constant for ERK5 kinase domain	kd	0.0660	uM
11-ethyl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652718: Inhibition of ERK5 in human HeLa cells assessed as reduction in EGF-induced ERK5 autophosphorylation pretreated for 1 hr followed by EGF stimulation and measured after 17 mins by 32p kinase assay	ic50	0.0660	uM
(2S,4R)-1-[(2S)-2-[8-[4-[4-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-3-methoxyphenyl]piperazin-1-yl]octanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2015867: Inhibition of ERK5 (unknown origin) by ADP-Glo kinase assay	ic50	0.0671	uM
[4-[7-(3-hydroxy-3-methylpyrrolidin-1-yl)pyrido[3,2-d]pyrimidin-4-yl]piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone	1535166: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0680	uM
4-(2-chloro-6-fluorobenzoyl)-N-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-1H-pyrrole-2-carboxamide	1909509: Inhibition of ERK5 (unknown origin) using K-5FAM-LVEPLTPSGEAPNQ-COOH as substrate incubated for 2 hrs in presence of ATP by IMAP-FP assay	ic50	0.0720	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-(1-methylpyrazol-4-yl)-1H-pyrrole-2-carboxamide	1909536: Inhibition of ERK5 (1 to 492 residues) in HEK293 cells assessed as paradoxical activation of ERK5 transcriptional activity incubated for 20 hrs by dual luciferase reporter assay	ic50	0.0770	uM
11-cyclobutyl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652718: Inhibition of ERK5 in human HeLa cells assessed as reduction in EGF-induced ERK5 autophosphorylation pretreated for 1 hr followed by EGF stimulation and measured after 17 mins by 32p kinase assay	ic50	0.0790	uM
11-cyclopentyl-2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	2170509: Inhibition of EGF-stimulated ERK5 autophosphorylation in human HeLa cells preincubated with compound for 1 hrs followed by EGF stimulation for 17 mins by SDS-PAGE analysis	ec50	0.0800	uM
2-[(4-ethoxycyclohexyl)amino]-5,11-dimethylpyrido[4,3-b][1,4]benzodiazepin-6-one	1719444: Inhibition of recombinant human ERK5 using myelin basic protein as substrate by [gamm33P]ATP based HotSpot radiometric assay	ic50	0.0810	uM
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652718: Inhibition of ERK5 in human HeLa cells assessed as reduction in EGF-induced ERK5 autophosphorylation pretreated for 1 hr followed by EGF stimulation and measured after 17 mins by 32p kinase assay	ic50	0.0870	uM
11-butan-2-yl-2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1987334: Inhibition of ERK5 (unknown origin)	ic50	0.0880	uM
2-[(4-hydroxycyclohexyl)amino]-5,11-dimethylpyrido[4,3-b][1,4]benzodiazepin-6-one	1719439: Inhibition of ERK5 (unknown origin)	ic50	0.0890	uM
[4-(7-methoxypyrido[3,2-d]pyrimidin-4-yl)piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone	1535166: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0980	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases reaction, increases phosphorylation, decreases expression, increases expression	4
BIX 02189	decreases phosphorylation, increases reaction, decreases reaction, increases phosphorylation	2
Cycloheximide	decreases reaction, increases expression, affects cotreatment	2
Hydrogen Peroxide	decreases expression, affects expression, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects cotreatment	2
bisphenol F	increases expression, affects cotreatment	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
palytoxin	increases activity, increases phosphorylation, decreases reaction, increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
polydatin	decreases reaction, increases phosphorylation	1
KN 62	decreases reaction, increases phosphorylation	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
pterostilbene	increases expression, increases phosphorylation, affects reaction	1
platycodin D	increases phosphorylation, decreases reaction	1
STO 609	decreases reaction, increases phosphorylation	1
dorsomorphin	decreases reaction, increases phosphorylation	1
BIX 02188	decreases activity, increases response to substance	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
XMD 8-92	decreases reaction, increases phosphorylation	1
Resveratrol	increases phosphorylation	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases phosphorylation, affects cotreatment	1
Air Pollutants	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	affects expression	1
Chelating Agents	affects binding, increases expression	1

ChEMBL screening assays

260 unique, capped per target: 260 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4344513	Binding	Inhibition of ERK1/5 in human MKN74 cells assessed as reduction in c-MYC phosphorylation at S62 residue at 0.5 uM measured up to 24 hrs by Western blot analysis	Discovery of a Novel Dual-Target Inhibitor of ERK1 and ERK5 That Induces Regulated Cell Death to Overcome Compensatory Mechanism in Specific Tumor Types. — J Med Chem

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1WR	Abcam HeLa MAPK7 KO	Cancer cell line	Female
CVCL_B7Y6	Abcam Raji MAPK7 KO	Cancer cell line	Male
CVCL_B9YW	Abcam THP-1 MAPK7 KO	Cancer cell line	Male
CVCL_C7AM	Abcam PC-3 MAPK7 KO	Cancer cell line	Male
CVCL_D7UL	Ubigene A-549 MAPK7 KO	Cancer cell line	Male
CVCL_D8Q8	Ubigene HCT 116 MAPK7 KO	Cancer cell line	Male
CVCL_E0HI	Ubigene HeLa MAPK7 KO	Cancer cell line	Female
CVCL_SW97	HAP1 MAPK7 (-) 1	Cancer cell line	Male
CVCL_SW98	HAP1 MAPK7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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