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MAPK15

gene
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Also known as ERK8ERK7

Summary

MAPK15 (mitogen-activated protein kinase 15, HGNC:24667) is a protein-coding gene on chromosome 8q24.3, encoding Mitogen-activated protein kinase 15 (Q8TD08). Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner.

Enables MAP kinase activity and chromatin binding activity. Involved in several processes, including dopamine uptake; protein localization to ciliary transition zone; and regulation of organelle organization. Located in several cellular components, including Golgi apparatus; autophagosome; and microtubule organizing center. Biomarker of breast cancer.

Source: NCBI Gene 225689 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 146 total
  • Druggable target: yes — 26 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_139021

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:24667
Approved symbolMAPK15
Namemitogen-activated protein kinase 15
Location8q24.3
Locus typegene with protein product
StatusApproved
AliasesERK8, ERK7
Ensembl geneENSG00000181085
Ensembl biotypeprotein_coding
OMIM618616
Entrez225689

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 21 protein_coding, 5 retained_intron

ENST00000338033, ENST00000395107, ENST00000395108, ENST00000461928, ENST00000475376, ENST00000484654, ENST00000528175, ENST00000533830, ENST00000883226, ENST00000883227, ENST00000883228, ENST00000883229, ENST00000883230, ENST00000883231, ENST00000883232, ENST00000883233, ENST00000883234, ENST00000883235, ENST00000883236, ENST00000883237, ENST00000883238, ENST00000883239, ENST00000883240, ENST00000883241, ENST00000883242, ENST00000920808

RefSeq mRNA: 1 — MANE Select: NM_139021 NM_139021

CCDS: CCDS6409

Canonical transcript exons

ENST00000338033 — 14 exons

ExonStartEnd
ENSE00001864719143716349143716443
ENSE00002434571143720230143720287
ENSE00002470495143718775143718905
ENSE00002477730143720703143720840
ENSE00003460081143719343143719482
ENSE00003519149143718212143718302
ENSE00003527988143721231143721411
ENSE00003537278143718993143719156
ENSE00003584250143722075143722458
ENSE00003585694143721549143721673
ENSE00003607133143718047143718076
ENSE00003634164143721000143721105
ENSE00003642158143717694143717792
ENSE00003656692143721752143721880

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 99.81.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2862 / max 90.5241, expressed in 364 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
914181.2862364

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right uterine tubeUBERON:000130299.81gold quality
olfactory segment of nasal mucosaUBERON:000538696.59gold quality
left testisUBERON:000453394.80gold quality
right testisUBERON:000453494.61gold quality
left lobe of thyroid glandUBERON:000112093.71gold quality
left uterine tubeUBERON:000130393.69gold quality
right lobe of thyroid glandUBERON:000111993.32gold quality
thyroid glandUBERON:000204691.58gold quality
right lungUBERON:000216790.97gold quality
metanephros cortexUBERON:001053390.88gold quality
testisUBERON:000047389.70gold quality
lower esophagus mucosaUBERON:003583488.67gold quality
adenohypophysisUBERON:000219688.33gold quality
skin of abdomenUBERON:000141687.04gold quality
ventricular zoneUBERON:000305385.92gold quality
skin of legUBERON:000151185.88gold quality
upper lobe of left lungUBERON:000895285.84gold quality
pituitary glandUBERON:000000785.43gold quality
esophagus mucosaUBERON:000246984.61gold quality
body of pancreasUBERON:000115083.82gold quality
upper lobe of lungUBERON:000894883.72gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047383.67gold quality
endocervixUBERON:000045882.14gold quality
zone of skinUBERON:000001481.07gold quality
minor salivary glandUBERON:000183080.32gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099179.70gold quality
anterior cingulate cortexUBERON:000983578.74gold quality
esophagusUBERON:000104377.82gold quality
vaginaUBERON:000099677.75gold quality
tibial nerveUBERON:000132377.63gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes10.25
E-GEOD-98556no11.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TGFB1I1

miRNA regulators (miRDB)

16 targeting MAPK15, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-486-3P99.5166.821901
HSA-MIR-766-5P99.4767.912225
HSA-MIR-127599.4767.902749
HSA-MIR-751599.3168.221795
HSA-MIR-319698.9663.91326
HSA-MIR-4755-3P98.7765.591915
HSA-MIR-4700-5P98.6367.431915
HSA-MIR-4722-5P98.4666.341611
HSA-MIR-6816-5P98.4664.35364
HSA-MIR-317998.2265.901445
HSA-MIR-4768-3P98.1666.022330
HSA-MIR-444398.0266.251928
HSA-MIR-808997.7466.211698
HSA-MIR-4667-5P97.6166.671683
HSA-MIR-4640-5P97.4266.331543
HSA-MIR-4726-5P97.2465.671299

Literature-anchored findings (GeneRIF, showing 22)

  • ERK8, a new member of the mitogen-activated protein kinase family. (PMID:11875070)
  • The activity of ERK8 in transfected HEK-293 cells depends on the relative rates of ERK8 autophosphorylation and dephosphorylation by one or more members of the PPP family of protein serine/threonine phosphatases. (PMID:16336213)
  • Erk8 has a role as a novel effector of RET/PTC3 and, therefore, RET biological functions (PMID:16484222)
  • human ERK8 has a role as a negative regulator of human GRalpha, acting through Hic-5 (PMID:16624805)
  • Regulation of the activity and expression of DERK8 by DNA damage are reported. (PMID:19166846)
  • Extracellular signal-regulated kinase 8-mediated c-Jun phosphorylation increases tumorigenesis of human colon cancer (PMID:20395206)
  • Data show that ERK8 prevents HDM2-mediated PCNA destruction by inhibiting the association of PCNA with HDM2, and implicate ERK8 in the regulation of genomic stability. (PMID:20733054)
  • a novel function for ERK8 as a bona fide ERRalpha corepressor, involved in control of its cellular localization by nuclear exclusion, and suggest a key role for this MAP kinase in the regulation of the biological activities of this nuclear receptor. (PMID:21190936)
  • ATG8-like proteins (MAP1LC3B, GABARAP and GABARAPL1) are novel interactors of MAPK15/ERK8, a MAP kinase involved in cell proliferation and transformation. (PMID:22948227)
  • Data suggest that the model coulb be a tool for the development of specific ERK8 kinase inhibitors. (PMID:23326322)
  • ERK8 appears as a constitutive brake on N-Acetylgalactosaminyltransferase relocalisation, and the loss of its expression could drive cancer aggressivity through increased cell motility. (PMID:24618899)
  • The present study suggests that MAPK15 overexpression may contribute to the malignant transformation of gastric mucosa by prolonging the stability of c-Jun. (PMID:26035356)
  • depletion of endogenous MAPK15 expression inhibited BCR-ABL1-dependent cell proliferation, in vitro (PMID:26291129)
  • In HeLa cells, phosphorylation of HuR by ERK8 prevents it from binding to PDCD4 mRNA and allows miR-21-mediated degradation of PDCD4. (PMID:26595526)
  • High MAPK15 expression is associated with male germ cell tumors. (PMID:26988910)
  • Our results describe a primary cilia-related role for this poorly studied member of the MAPK family in vivo, and indicate a broad requirement for MAPK15 in the formation of multiple ciliary classes across species. (PMID:29021280)
  • As multiple roles of MAPK15 were observed among these studies, therefore, it remains unclear whether MAPK15 acts as a proto-oncogene or tumor suppressor. Here, the recent literature on human MAPK15 and the resulting functions will be discussed. (PMID:30070699)
  • MAPK15 stimulates ULK1, is part of the ULK complex, colocalizes in autophagosomes, and is involved in autophagosome biogenesis. (PMID:30131341)
  • MAPK15-ULK1 signaling regulates mitophagy of airway epithelial cell in chronic obstructive pulmonary disease. (PMID:34224814)
  • MAPK15 protects from oxidative stress-dependent cellular senescence by inducing the mitophagic process. (PMID:35642724)
  • Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer. (PMID:38203280)
  • MAPK15 controls cellular responses to oxidative stress by regulating NRF2 activity and expression of its downstream target genes. (PMID:38555711)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriomapk15ENSDARG00000100822
mus_musculusMapk15ENSMUSG00000063704
rattus_norvegicusMapk15ENSRNOG00000009336
drosophila_melanogasterErk7FBGN0052703
caenorhabditis_elegansWBGENE00015478

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), MAPK7 (ENSG00000166484), SRPK3 (ENSG00000184343), MAPK11 (ENSG00000185386), MAPK12 (ENSG00000188130)

Protein

Protein identifiers

Mitogen-activated protein kinase 15 — Q8TD08 (reviewed: Q8TD08)

Alternative names: Extracellular signal-regulated kinase 7, Extracellular signal-regulated kinase 8

All UniProt accessions (1): Q8TD08

UniProt curated annotations — full annotation on UniProt →

Function. Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner. Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation. Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling. Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins. Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion. Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA. Regulates DA transporter (DAT) activity and protein expression via activation of RhoA. In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3’UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression. Also functions in a kinase activity-independent manner as a negative regulator of growth. Phosphorylates in vitro FOS and MBP. During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos. Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity.

Subunit / interactions. Interacts with CSK/c-Src, ABL1, RET and TGFB1I1. Interacts with GABARAP, MAP1LC3B and GABARAPL1; controls, in a kinase-dependent fashion, both basal and starvation-induced autophagy. Interacts with ESRRA; promotes re-localization of ESRRA to the cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA transcriptional activity. Interacts with PCNA; the interaction is chromatin binding- and kinase activity-dependent and prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2. Interacts with DVL2. Interacts with CLIC3; MAPK15 does not phosphorylate CLIC3.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Cell junction. Tight junction. Microtubule organizing center. Centrosome. Centriole. Cytoplasmic vesicle. Autophagosome. Golgi apparatus. Nucleus. Spindle.

Tissue specificity. Widely expressed with a maximal expression in lung and kidney.

Post-translational modifications. Autophosphorylated on Thr-175 and Tyr-177; activates the enzyme. Ubiquitinated. Ubiquitination may allow its tight kinase activity regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase.

Activity regulation. Activated by threonine and tyrosine phosphorylation. Inhibited by dual specificity phosphatases, such as DUSP1. Phosphorylation and activation in response to DNA damaging agents, serum stimulation. Constitutively activated when phosphorylated on Tyr-177. Activity depends on the relative rates of MAPK15 autophosphorylation and dephosphorylation by PTPN1.

Domain organisation. The N-terminal region (1-20) is the minimal region necessary for ubiquitination and further proteasomal degradation. The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Miscellaneous. Appears not to be a CSK- and RET-dependent activated kinase.

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

Isoforms (3)

UniProt IDNamesCanonical?
Q8TD08-11yes
Q8TD08-22, Erk8 delta
Q8TD08-33

RefSeq proteins (1): NP_620590* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR003527MAP_kinase_CSConserved_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site
IPR050117MAPKFamily

Pfam: PF00069

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 (36 total): mutagenesis site 13, splice variant 4, repeat 4, modified residue 3, region of interest 3, binding site 2, sequence variant 2, chain 1, domain 1, active site 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8TD08-F169.560.41

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): 137 (proton acceptor)

Ligand- & substrate-binding residues (2): 19–27; 42

Post-translational modifications (3): 175, 177, 449

Mutagenesis-validated functional residues (13):

PositionPhenotype
42not phosphorylated at thr-175 and tyr-177.
42loss of autophosphorylation and activity. does not increase dopamine transporter activity. impairs kinase activity. does
59does not increase dopamine transporter activity. impairs kinase activity.
155unable to induce the formation of autophagosomal structures. is able to bind to map1lc3b and to colocalize with this pro
175loss of autophosphorylation and activity. still heavily phosphorylated at tyr-177. does not rescues inhibition of o-glyc
177loss of autophosphorylation and activity. heavily phosphorylated at thr-175.
177does not rescue inhibition of o-glycosylation in mapk15-depleted cells; when associated with a-175.
265–269markedly decreases interaction with esrra. impairs interaction with esrra; when associated with a-281 and 284-a–a-285.
281–285markedly decreases interaction with esrra. impairs interaction with esrra; when associated with a-265 and 268-a–a-269.
300impairs interaction with pcna. associates with chromatin.
340–343impairs interaction with gabarap and map1lc3b. affects subcellular localization in autophagosome. does not induce autoph
390impairs chromatin binding; when associated with a-398. increases kinase activity; when associated with a-398.
398impairs chromatin binding; when associated with a-390. increases kinase activity; when associated with a-390.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 174 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_VESICLE_TARGETING, GOBP_TELOMERE_ORGANIZATION, GOBP_CHROMOSOME_SEPARATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE

GO Biological Process (18): obsolete regulation of COPII vesicle coating (GO:0003400), DNA damage response (GO:0006974), endoplasmic reticulum organization (GO:0007029), positive regulation of cell population proliferation (GO:0008284), regulation of autophagy (GO:0010506), negative regulation of cell migration (GO:0030336), positive regulation of telomere maintenance (GO:0032206), intracellular signal transduction (GO:0035556), positive regulation of transcription by RNA polymerase II (GO:0045944), protein autophosphorylation (GO:0046777), dopamine uptake (GO:0090494), regulation of cilium assembly (GO:1902017), protein localization to ciliary transition zone (GO:1904491), positive regulation of metaphase/anaphase transition of meiosis I (GO:1905188), positive regulation of spindle assembly (GO:1905832), MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468), cellular response to stress (GO:0033554)

GO Molecular Function (11): chromatin binding (GO:0003682), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), MAP kinase activity (GO:0004707), ATP binding (GO:0005524), kinase activity (GO:0016301), SH3 domain binding (GO:0017124), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (15): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), autophagosome (GO:0005776), Golgi apparatus (GO:0005794), centriole (GO:0005814), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), cytoplasmic vesicle (GO:0031410), ciliary basal body (GO:0036064), meiotic spindle (GO:0072687), spindle (GO:0005819), cytoskeleton (GO:0005856), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
intracellular membraneless organelle3
intracellular anatomical structure2
binding2
protein kinase activity2
intracellular membrane-bounded organelle2
cytoplasm2
microtubule organizing center2
cellular response to stress1
organelle organization1
endomembrane system organization1
cell population proliferation1
regulation of cell population proliferation1
positive regulation of cellular process1
autophagy1
regulation of catabolic process1
cell migration1
regulation of cell migration1
negative regulation of cell motility1
telomere maintenance1
regulation of telomere maintenance1
positive regulation of DNA metabolic process1
positive regulation of chromosome organization1
signal transduction1
regulation of transcription by RNA polymerase II1
transcription by RNA polymerase II1
positive regulation of DNA-templated transcription1
protein phosphorylation1
catecholamine uptake1
cilium assembly1
regulation of plasma membrane bounded cell projection assembly1
regulation of organelle assembly1
protein localization to cilium1
positive regulation of metaphase/anaphase transition of meiotic cell cycle1
regulation of metaphase/anaphase transition of meiosis I1
metaphase/anaphase transition of meiosis I1
spindle assembly1
positive regulation of cytoskeleton organization1
positive regulation of cell cycle process1
regulation of spindle assembly1

Protein interactions and networks

STRING

2918 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MAPK15CLIC3O95833969
MAPK15CLIC1O00299838
MAPK15CLIC2O15247828
MAPK15ADCY9O60503729
MAPK15TGFB1I1O43294646
MAPK15GABARAPO95166631
MAPK15TMEM276P0DTL5600
MAPK15MROH1Q8NDA8585
MAPK15ESRRAP11474555
MAPK15SACK1HQ6ZRV2495
MAPK15SRCP12931488
MAPK15ARHGAP39Q9C0H5482
MAPK15CPSF1Q10570474
MAPK15MAP1LC3BQ9GZQ8473
MAPK15SEC16AO15027432

IntAct

23 interactions, top by confidence:

ABTypeScore
CDK2CCNB1psi-mi:“MI:0914”(association)0.890
CDK2CCNB2psi-mi:“MI:0914”(association)0.860
MAPK15CDK2psi-mi:“MI:0915”(physical association)0.710
CDK2GMNNpsi-mi:“MI:0914”(association)0.640
HSP90AB1MAPK15psi-mi:“MI:0915”(physical association)0.560
MAPK15AKT1psi-mi:“MI:0915”(physical association)0.550
MAPK15AKT1psi-mi:“MI:2364”(proximity)0.550
AKT1MAPK15psi-mi:“MI:0915”(physical association)0.550
MAPK15CCT6Bpsi-mi:“MI:0915”(physical association)0.400
SGK1psi-mi:“MI:0914”(association)0.350
MAPK15TIMM8Apsi-mi:“MI:0914”(association)0.350
MAPK15HSPA8psi-mi:“MI:0914”(association)0.350
MAPK15ESYT2psi-mi:“MI:0914”(association)0.350
SPOPMAPK15psi-mi:“MI:2364”(proximity)0.270
MAPK15SPOPpsi-mi:“MI:2364”(proximity)0.270
EGFRMAPK15psi-mi:“MI:2364”(proximity)0.270
MAPK15PTPN11psi-mi:“MI:2364”(proximity)0.270
MAPK15PTENpsi-mi:“MI:2364”(proximity)0.270

BioGRID (67): MAPK15 (Affinity Capture-MS), MAPK15 (Affinity Capture-MS), MAPK15 (Affinity Capture-MS), MAPK15 (Affinity Capture-MS), NAMPT (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), MAPK15 (Affinity Capture-MS), CLIC3 (Affinity Capture-Western), MAPK15 (Affinity Capture-RNA), MAPK15 (Affinity Capture-RNA), CCT6B (Affinity Capture-MS), MAPK15 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS)

ESM2 similar proteins: A5PKJ4, B1AK53, B8Y466, D3ZG83, O14976, O54967, O60307, O70405, O75385, O96013, P0C865, P80192, P97756, Q02779, Q13164, Q17R13, Q2YDU3, Q3U1V8, Q3U214, Q3U2S4, Q3ULB5, Q3V016, Q4KMP7, Q4V793, Q5I1X5, Q5R8Z4, Q5TCX8, Q5U2X5, Q66HA1, Q66L42, Q6NZR5, Q6ZRS2, Q80XI6, Q80Y86, Q8BHL3, Q8BTW9, Q8C078, Q8CIP4, Q8N5S9, Q8TD08

Diamond homologs: A0AUV4, A8WYE4, B0WAU8, D2I3C6, D3ZBE5, E9Q0S6, F1LP90, F1MH24, F1SPM8, G5ECQ3, O13773, O14976, O34507, O43066, O75061, O75716, P0C1X8, P0C8M8, P20911, P32562, P34331, P38080, P40494, P50613, P51952, P51954, P51956, P51957, P53974, P56180, P57059, P97874, Q03147, Q04205, Q09170, Q0WQ57, Q15131, Q16W24, Q20845, Q23356

SIGNOR signaling

8 interactions.

AEffectBMechanism
MAPK15up-regulatesMAPK15phosphorylation
PPP2CAdown-regulatesMAPK15dephosphorylation
PTPN1down-regulatesMAPK15dephosphorylation
MAPK15“down-regulates activity”ELAVL1phosphorylation
17beta-estradiolup-regulatesMAPK15“chemical activation”
MAPK15up-regulatesJUNphosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance113
Likely benign9
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2729 predictions. Top by Δscore:

VariantEffectΔscore
8:143716440:GGGG:Gdonor_gain1.0000
8:143716441:GGGG:Gdonor_gain1.0000
8:143718211:GGA:Gacceptor_gain1.0000
8:143718301:GG:Gdonor_gain1.0000
8:143718301:GGGT:Gdonor_loss1.0000
8:143718302:GG:Gdonor_gain1.0000
8:143718303:G:GGdonor_gain1.0000
8:143718303:GT:Gdonor_loss1.0000
8:143718304:T:Adonor_loss1.0000
8:143718770:TGCAG:Tacceptor_loss1.0000
8:143718772:CA:Cacceptor_loss1.0000
8:143718773:A:AGacceptor_gain1.0000
8:143718773:AGA:Aacceptor_loss1.0000
8:143718774:G:GAacceptor_gain1.0000
8:143718774:G:GTacceptor_loss1.0000
8:143718774:GA:Gacceptor_gain1.0000
8:143718774:GAC:Gacceptor_gain1.0000
8:143718774:GACAC:Gacceptor_gain1.0000
8:143718902:GAAG:Gdonor_gain1.0000
8:143718904:AGG:Adonor_loss1.0000
8:143718905:GGTG:Gdonor_loss1.0000
8:143718989:GCA:Gacceptor_loss1.0000
8:143718991:A:AGacceptor_gain1.0000
8:143718991:A:ATacceptor_loss1.0000
8:143718991:AGCC:Aacceptor_gain1.0000
8:143718992:G:GTacceptor_gain1.0000
8:143718992:GC:Gacceptor_gain1.0000
8:143718992:GCC:Gacceptor_gain1.0000
8:143718992:GCCG:Gacceptor_gain1.0000
8:143718992:GCCGT:Gacceptor_gain1.0000

AlphaMissense

3476 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
8:143717753:G:CK42N0.996
8:143717753:G:TK42N0.996
8:143719039:A:TD155V0.994
8:143719040:C:AD155E0.993
8:143719040:C:GD155E0.993
8:143719039:A:CD155A0.989
8:143719365:T:AW202R0.989
8:143719365:T:CW202R0.989
8:143717746:C:AA40D0.987
8:143717769:T:CF48L0.986
8:143717771:T:AF48L0.986
8:143717771:T:GF48L0.986
8:143717715:G:CA30P0.983
8:143719367:G:CW202C0.983
8:143719367:G:TW202C0.983
8:143719368:A:CS203R0.983
8:143719370:T:AS203R0.983
8:143719370:T:GS203R0.983
8:143719039:A:GD155G0.982
8:143717749:T:AI41N0.980
8:143718898:A:TD137V0.979
8:143718898:A:CD137A0.977
8:143717745:G:CA40P0.975
8:143718895:G:CR136P0.975
8:143719037:T:GC154W0.975
8:143719359:G:CD200H0.975
8:143718899:C:AD137E0.973
8:143718899:C:GD137E0.973
8:143719038:G:CD155H0.973
8:143719360:A:TD200V0.973

dbSNP variants (sampled 300 via entrez): RS1000396823 (8:143720644 A>G), RS1001132300 (8:143719543 G>A,C), RS1002179257 (8:143717450 A>C,G), RS1002231735 (8:143717629 G>A,C), RS1002852047 (8:143719279 C>T), RS1003183845 (8:143718553 T>C,G), RS1003263169 (8:143722198 G>A,C), RS1003807828 (8:143720021 G>A), RS1004010480 (8:143714734 C>A), RS1006151943 (8:143721025 G>C,T), RS1006767500 (8:143716840 G>C), RS1006830854 (8:143722719 C>A), RS1007189429 (8:143722873 C>T), RS1007823961 (8:143718239 A>G), RS1008086154 (8:143719930 G>A)

Disease associations

OMIM: gene MIM:618616 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST001762_174Obesity-related traits2.000000e-06

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004626IGFBP-3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5198 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

26 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 145,780 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1287853FEDRATINIB43,554
CHEMBL1336SORAFENIB486,060
CHEMBL3301622GILTERITINIB42,395
CHEMBL576982QUIZARTINIB44,432
CHEMBL223360LINIFANIB33,925
CHEMBL300138ENZASTAURIN33,209
CHEMBL428690ALVOCIDIB327,781
CHEMBL603469LESTAURTINIB3
CHEMBL91829RUBOXISTAURIN377
CHEMBL103667DORAMAPIMOD21,681
CHEMBL1230609FORETINIB23,096
CHEMBL1738757REBASTINIB21,478
CHEMBL1944698ZOTIRACICLIB22,915
CHEMBL3655762CYC-0652388
CHEMBL384304RG-547293
CHEMBL445813AT-751922,614
CHEMBL475251R-4062762
CHEMBL1084546PF-005622711399
CHEMBL1230607PHA-7938871299
CHEMBL1908397KW-24491622
CHEMBL296468BMS-3870321
CHEMBL4169078SRA-7371
CHEMBL4225966SEL-120 FREE BASE1
CHEMBL4439321ATUVECICLIB1
CHEMBL494089GSK-6906931
CHEMBL574738AST-4871

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Erk7 subfamily

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

LigandActionAffinityParameter
BS-194Inhibition6.48pIC50

Binding affinities (BindingDB)

9 measured of 9 human assays (9 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]ureaKD0.37 nM
StaurosporineKD1.7 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamideKD370 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)ureaKD450 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dioneKD700 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]ureaKD1400 nM
BMS-387072KD1800 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3bKD3100 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-oneKD5300 nM

ChEMBL bioactivities

88 potent at pChembl≥5 of 90 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.05IC500.9nMBISINDOLYLMALEIMIDE IX
8.72Ki1.9nMSTAUROSPORINE
8.59IC502.6nMSTAUROSPORINE
8.31Kd4.9nMLESTAURTINIB
8.30Kd5nMCHEMBL2048872
8.26Kd5.5nMSTAUROSPORINE
8.14IC507.3nMSTAUROSPORINE
8.10IC508.01nMSTAUROSPORINE
8.10IC507.9nMCHEMBL6144731
8.04IC509.1nMSTAUROSPORINE
7.98IC5010.4nMSTAUROSPORINE
7.89Kd12.86nMCHEMBL3752910
7.75Kd18nMRG-547
7.74Kd18.4nMCHEMBL5653589
7.58ED5026.04nMCHEMBL3752910
7.52Kd30nMERKi
7.50Kd32nMCHEMBL1082152
7.46Kd35nMSTAUROSPORINE
7.43ED5037.26nMCHEMBL5653589
7.34Kd46nMSORAFENIB
7.23IC5059.1nMBMS-387032
7.22IC5059.7nMCHEMBL5561973
7.16Kd69nMRG-547
7.14Kd73nMFORETINIB
7.12Kd76nMENZASTAURIN
7.10IC5079.1nMCHEMBL4587232
7.06Kd88nMRUBOXISTAURIN
7.05Kd90nMCHEMBL3688339
7.05Kd89nMCHEMBL379218
7.03Kd94nMAST-487
6.96IC50110nMCHEMBL4762609
6.95Kd113nMCHEMBL4465866
6.92Kd120nMBMS-387032
6.92Ki119.5nMALVOCIDIB
6.92Kd120nMAT-7519
6.89IC50130nMSRA-737
6.79IC50163.7nMALVOCIDIB
6.78Kd167nMK-252A
6.68Kd210nMTAE-684
6.58Kd263nMGILTERITINIB
6.58Kd264nMPHA-793887
6.57Kd270nMQUIZARTINIB
6.56Kd276nMREBASTINIB
6.51Kd306nMCHEMBL4576489
6.48Kd330nMALVOCIDIB
6.48IC50330nMCHEMBL1234833
6.47Kd340nMCHEMBL6108991
6.41IC50385.9nMCYC-065
6.40IC50400nMCHEMBL2430323
6.37Kd430nMCHEMBL1474834

PubChem BioAssay actives

62 with measured affinity, of 655 total; 45 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(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-one507940: Binding affinity to ERK8kd0.0049uM
(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-one1948635: Binding affinity to recombinant MAPK15 (unknown origin) assessed as dissociation constant by DSF assaykd0.0055uM
N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-4-(thieno[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide1360779: Inhibition of human ERK7 at 0.123 uM by Hotspot assayic500.0100uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148707: Binding affinity to human MAPK15 incubated for 45 mins by Kinobead based pull down assaykd0.0129uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone1425060: 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.kd0.0180uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148707: Binding affinity to human MAPK15 incubated for 45 mins by Kinobead based pull down assaykd0.0184uM
3-[3-(2,3-dihydroxypropylamino)phenyl]-4-(5-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione465266: Inhibition of ERK8kd0.0320uM
Sorafenib435405: Binding constant for ERK8 kinase domainkd0.0460uM
5,6-dibromo-4-(difluoromethyl)-1-(oxan-4-yl)-2-piperazin-1-ylbenzimidazole2070990: Inhibition of ERK8 (unknown origin) by ADP-Glo assayic500.0597uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide624715: Binding constant for ERK8 kinase domainkd0.0730uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione624715: Binding constant for ERK8 kinase domainkd0.0760uM
(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-dione435405: Binding constant for ERK8 kinase domainkd0.0880uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine624715: Binding constant for ERK8 kinase domainkd0.0890uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone1425060: 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.kd0.0900uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea435405: Binding constant for ERK8 kinase domainkd0.0940uM
2-(3,4-difluorophenyl)-1-[4-[(3-morpholin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino]piperidin-1-yl]ethanone1678990: Inhibition of human ERK8 (2 to 544 residues) incubated for 5 mins in presence of [gamma33P]ATP by scintillation counting analysisic500.1100uM
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]propanamide1526155: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MAPK15 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.1130uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide624715: Binding constant for ERK8 kinase domainkd0.1200uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide435405: Binding constant for ERK8 kinase domainkd0.1200uM
5-[[4-[[(2R)-morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridinyl]amino]pyrazine-2-carbonitrile2154699: Inhibition of human ERK8 in presence of ATP by by radiometric kinase assayic500.1300uM
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-carboxylate1425060: 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.kd0.1670uM
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-diamine624715: Binding constant for ERK8 kinase domainkd0.2100uM
Gilteritinib1425060: 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.kd0.2630uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide1425060: 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.kd0.2640uM
Quizartinib507940: Binding affinity to ERK8kd0.2700uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide1425060: 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.kd0.2760uM
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]propanamide1526155: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MAPK15 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.3060uM
(2S,3S)-3-[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]butane-1,2,4-triol604633: Inhibition of ERK8ic500.3300uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one435405: Binding constant for ERK8 kinase domainkd0.3300uM
N-[3-(3-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)phenyl]acetamide773186: Inhibition of human ERK8 in presence of 5 uM ATPic500.4000uM
6-(1,3-benzodioxol-5-yl)-N-methyl-N-[(2-methyl-1,3-thiazol-4-yl)methyl]quinazolin-4-amine594091: Binding affinity to human Erk8kd0.4300uM
Fedratinib624715: Binding constant for ERK8 kinase domainkd0.5100uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one624715: Binding constant for ERK8 kinase domainkd0.6400uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone769515: Binding affinity to ERK8 (unknown origin)kd0.6500uM
5-(6-bromo-5-methoxy-1H-indol-3-yl)-2-(1H-pyrrol-2-yl)-1,3-oxazole1541187: Inhibition of ERK8 (unknown origin) by [33P]-ATP filter binding kinase assayic501.0000uM
(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-decaene1425060: 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.kd1.0730uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone624715: Binding constant for ERK8 kinase domainkd1.1000uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide435405: Binding constant for ERK8 kinase domainkd1.1000uM
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-ol1425060: 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.kd1.2050uM
6,7-dibromo-5-methyl-2-piperazin-1-yl-1,3-diazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene2070990: Inhibition of ERK8 (unknown origin) by ADP-Glo assayic501.3440uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]methanesulfonamide1425060: 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.kd1.4660uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea435405: Binding constant for ERK8 kinase domainkd2.8000uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea435405: Binding constant for ERK8 kinase domainkd3.0000uM
N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine624715: Binding constant for ERK8 kinase domainkd4.5000uM
6-[(3,4-dichlorobenzoyl)amino]-N-(1,3-thiazol-2-yl)naphthalene-2-carboxamide1577088: Binding affinity to wild-type human partial length ERK8 (M1 to P437 residues) expressed in bacterial expression system measured after 1 hr by kinomescan methodkd5.3200uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidincreases expression, increases methylation2
bufotalindecreases expression1
bisphenol Adecreases methylation1
sodium arsenitedecreases expression1
nutlin 3affects cotreatment, increases expression1
4-methyl-N1-(3-phenylpropyl)benzene-1,2-diaminedecreases reaction, increases expression1
Resveratrolaffects cotreatment, decreases expression1
Air Pollutantsincreases expression, increases abundance1
Arsenicaffects cotreatment, increases expression1
Arsenicalsincreases methylation1
Atrazineincreases expression1
Benzo(a)pyreneincreases methylation, decreases methylation1
Capsaicinincreases expression1
Cisplatinaffects cotreatment, increases activity, increases response to substance, affects cleavage, affects reaction (+4 more)1
Copperaffects binding, increases expression1
Dactinomycinaffects cotreatment, increases expression1
Diethylhexyl Phthalatedecreases expression1
Estradiolaffects cotreatment, increases expression1
Lipopolysaccharidesincreases expression1
Plant Extractsaffects cotreatment, decreases expression1
Smokeincreases abundance, increases expression1
Tobacco Smoke Pollutiondecreases expression1
1-Methyl-4-phenylpyridiniumincreases expression1
Organoselenium Compoundsaffects binding, increases expression1
Acrylamidedecreases expression1

ChEMBL screening assays

228 unique, capped per target: 227 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1000625BindingInhibition of ERK8 at 1 uM relative to controlNovel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL4735376ADMETInhibition of wild-type human partial length ERK8 (M1 to P437 residues) expressed in bacterial expression system assessed as residual activity at 1 uM by Kinomescan method relative to controlDiscovery of indazole-pyridinone derivatives as a novel class of potent and selective MNK1/2 kinase inhibitors that protecting against endotoxin-induced septic shock. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

CellosaurusNameCategorySex
CVCL_SW91HAP1 MAPK15 (-)Cancer cell lineMale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 79

This page pulls from 79 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot