MAPK13

Summary

MAPK13 (mitogen-activated protein kinase 13, HGNC:6875) is a protein-coding gene on chromosome 6p21.31, encoding Mitogen-activated protein kinase 13 (O15264). Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.

This gene encodes a member of the mitogen-activated protein (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. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 5603 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 67 total
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002754

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6875
Approved symbol	MAPK13
Name	mitogen-activated protein kinase 13
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	SAPK4, p38delta
Ensembl gene	ENSG00000156711
Ensembl biotype	protein_coding
OMIM	602899
Entrez	5603

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000211287, ENST00000373759, ENST00000373766, ENST00000476951, ENST00000490334, ENST00000874020, ENST00000874021, ENST00000939826, ENST00000954697, ENST00000954698

RefSeq mRNA: 1 — MANE Select: NM_002754 NM_002754

CCDS: CCDS4818

Canonical transcript exons

ENST00000211287 — 12 exons

Exon	Start	End
ENSE00000748253	36138365	36138444
ENSE00001322852	36136879	36136950
ENSE00001880346	36130513	36130701
ENSE00002279320	36139294	36144521
ENSE00002451069	36136656	36136770
ENSE00002492643	36136484	36136531
ENSE00003461628	36138879	36139055
ENSE00003541765	36132621	36132679
ENSE00003584682	36138702	36138780
ENSE00003597327	36135753	36135861
ENSE00003637736	36136019	36136048
ENSE00003681113	36131271	36131400

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7913 / max 457.1229, expressed in 1250 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67491	3.7950	922
67486	1.7894	333
67489	1.2741	295
67490	1.1871	234
67488	0.3136	96
67487	0.2760	80
67492	0.1562	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	95.52	gold quality
esophagus squamous epithelium	UBERON:0006920	95.07	gold quality
epithelium of esophagus	UBERON:0001976	94.48	gold quality
gingiva	UBERON:0001828	94.45	gold quality
squamous epithelium	UBERON:0006914	94.32	gold quality
mucosa of transverse colon	UBERON:0004991	94.08	gold quality
right adrenal gland	UBERON:0001233	93.95	gold quality
right adrenal gland cortex	UBERON:0035827	93.94	gold quality
lower esophagus mucosa	UBERON:0035834	93.83	gold quality
esophagus mucosa	UBERON:0002469	93.71	gold quality
gingival epithelium	UBERON:0001949	93.69	gold quality
left adrenal gland	UBERON:0001234	93.58	gold quality
ileal mucosa	UBERON:0000331	93.37	gold quality
penis	UBERON:0000989	93.18	gold quality
left adrenal gland cortex	UBERON:0035825	92.79	gold quality
adrenal cortex	UBERON:0001235	92.51	gold quality
parotid gland	UBERON:0001831	92.44	gold quality
mammalian vulva	UBERON:0000997	91.97	gold quality
sperm	CL:0000019	91.92	gold quality
duodenum	UBERON:0002114	91.72	gold quality
adrenal gland	UBERON:0002369	91.70	gold quality
oral cavity	UBERON:0000167	91.63	gold quality
skin of abdomen	UBERON:0001416	91.63	gold quality
skin of leg	UBERON:0001511	91.42	gold quality
colonic mucosa	UBERON:0000317	91.38	gold quality
cervix squamous epithelium	UBERON:0006922	91.21	gold quality
pharyngeal mucosa	UBERON:0000355	91.17	gold quality
upper arm skin	UBERON:0004263	91.15	gold quality
zone of skin	UBERON:0000014	91.05	gold quality
mouth mucosa	UBERON:0003729	90.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.61
E-MTAB-6142	no	56.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, TP53, ZHX2

miRNA regulators (miRDB)

161 targeting MAPK13, 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-188-3P	100.00	68.76	1240
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4493	99.90	66.48	977

Literature-anchored findings (GeneRIF, showing 30)

• Novel protein kinase C isoforms regulate human keratinocyte differentiation by activating a p38 delta mitogen-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (PMID:12080077)
• p38 has a role in mediating induction of VEGF mRNA expression by sodium arsenite (PMID:12482858)
• p38delta mitogen-activated protein kinase as a downstream carrier of the PKCdelta-dependent death signal in keratinocytes (PMID:15340077)
• sapk4 activation mediates apoptosis and neurodegeneration in infantile neuronal ceroid lipofuscinosis (PMID:16644870)
• activation of p38 isoforms by hypertonicity does not contribute to activation of TonEBP/OREBP because of opposing effects of p38alpha and p38delta. (PMID:18367666)
• These results suggest that, in SupT1-based cell lines, p38alpha, p38gamma and p38delta, but not p38beta, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells. (PMID:18559936)
• results indicate that p38delta is important for motility and invasion of CC cells, suggesting that p38delta may play an important role in CC metastasis. (PMID:19816939)
• Function of p38delta in regulating of epidermal keratinocyte differentiation, apoptosis and skin tumor development, is discussed. (PMID:20090411)
• Taken together, the data indicate that the respective stress-dependent action of p38 isoforms is responsible for the up-regulation of the gene expression of the chemokine BRAK/CXCL14. (PMID:20478268)
• Isoforms of p38MAPK gamma and delta contribute to differentiation of human AML cells induced by 1,25-dihydroxyvitamin D. (PMID:20804750)
• PRMT5 inhibits the PKCdelta- or 12-O-tetradecanoylphorbol-13-acetate-dependent increase in human involucrin expression, and PRMT5 dimethylates proteins in the p38delta complex. (PMID:22199349)
• SEPW1 silencing increases MKK4, which activates p38gamma, p38delta, and JNK2 to phosphorylate p53 on Ser-33 and cause a transient G(1) arrest. (PMID:22730327)
• MAPK13 is responsible for IL-13-driven mucus production in human airway epithelial cells. (PMID:23187130)
• DNA methylation alterations are widespread in melanoma; epigenetic silencing of MAPK13 contributes to melanoma progression (PMID:23590314)
• esophageal squamous cell carcinoma cell lines which are p38delta-negative grew more quickly than cell lines which express endogenous p38delta. (PMID:23722928)
• GSK3alpha, GSK3beta, and MAPK13 were found to be the most active tau kinases, phosphorylating tau at all four epitopes. (PMID:23798682)
• Data indicate that p38delta mediates oncogene-induced senescence through a p53- and p16(INK4A)-independent mechanism. (PMID:23878395)
• MAPK13 undergoes a larger interlobe configurational rearrangement upon activation compared with MAPK14. (PMID:25849390)
• p38delta expression was significantly higher in esophageal squamous cell carcinoma tissues compared with paired normal controls. No significant association was found for p38delta between its expression and other clinicopathological parameters. In Eca109 cells, p38delta can promote the cell growth and motility. p38delta overexpression promotes tumorigenesis in nude mice when p38delta was stably over-expressed and p38ga… (PMID:26666822)
• p38gamma and p38delta reprogram liver metabolism by modulating neutrophil infiltration and provide a potential target for NAFLD therapy (PMID:26843485)
• MAPK13 gene knockdown using siRNA reduced the aldehyde dehydrogenase high cell population and abrogated the tumor-initiating ability. (PMID:26969274)
• The p38delta mitogen-activated protein kinase was identified as a novel regulator of NLRP3 inflammasome activation in primary human macrophages, and thus, represents a potential target for modulation of atherosclerotic inflammation. (PMID:27417584)
• expression of claudin-11 in cutaneous squamous cell carcinoma cells depended on the activity of p38delta MAPK (PMID:27992079)
• Study proposes MAPK p38delta protein as a key factor in breast cancer. (PMID:28783172)
• Study identified p38alpha and p38delta as critical regulators of ASC oligomerization, inflammasome activation, and IL-1beta secretion in keratinocytes. Furthermore, data suggest that the nature of the mitogen-activated protein kinase regulating inflammasome activity exhibits a certain cell specificity, with p38 playing a predominant role in keratinocytes and Jun N-terminal kinase 1 in cells of myeloid origin. (PMID:29287762)
• The knockdown of MAPK13 also blocked the effect of miR23a5p in osteogenic differentiation of bone marrow-derived mesenchymal stem cells. (PMID:29344643)
• Mitogen-activated protein kinases p38gamma/p38delta deficiency protects against Candida albicans infection by increasing reactive oxygen species and iNOS enzyme production and thus the antifungal capacity of neutrophils and macrophages. (PMID:29661910)
• p38delta promotes micro-aggregate transport by phosphorylating SQSTM1, a major scaffold protein that assembles soluble ubiquitylated proteins into micro-aggregates. (PMID:29930081)
• These observations indicate that p38alpha probably blocks brown adipose tissue thermogenesis through p38delta inhibition. (PMID:29979672)
• MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer. (PMID:31695024)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapk13	ENSDARG00000058470
mus_musculus	Mapk13	ENSMUSG00000004864
rattus_norvegicus	Mapk13	ENSRNOG00000000515
drosophila_melanogaster	nmo	FBGN0011817
drosophila_melanogaster	CG8565	FBGN0030697
drosophila_melanogaster	p38c	FBGN0267339
drosophila_melanogaster	SRPK	FBGN0286813
caenorhabditis_elegans		WBGENE00002187
caenorhabditis_elegans		WBGENE00002188
caenorhabditis_elegans		WBGENE00003048
caenorhabditis_elegans		WBGENE00004055
caenorhabditis_elegans		WBGENE00004056
caenorhabditis_elegans		WBGENE00004980
caenorhabditis_elegans	gskl-2	WBGENE00007977
caenorhabditis_elegans		WBGENE00008200
caenorhabditis_elegans		WBGENE00013091
caenorhabditis_elegans	Y106G6E.1	WBGENE00013705

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), MAPK7 (ENSG00000166484), MAPK15 (ENSG00000181085), SRPK3 (ENSG00000184343), MAPK11 (ENSG00000185386), MAPK12 (ENSG00000188130)

Protein

Protein identifiers

Mitogen-activated protein kinase 13 — O15264 (reviewed: O15264)

Alternative names: Mitogen-activated protein kinase p38 delta, Stress-activated protein kinase 4

All UniProt accessions (4): O15264, A0A024RD04, A0A0S2Z542, Q5R3E6

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.

Subunit / interactions. Interacts with MAPK8IP2.

Tissue specificity. Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells.

Post-translational modifications. Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1.

Activity regulation. Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.

Domain organisation. 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 (2)

UniProt ID	Names	Canonical?
O15264-1	1	yes
O15264-2	2

RefSeq proteins (1): NP_002745* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR003527	MAP_kinase_CS	Conserved_site
IPR008352	MAPK_HOG-like	Family
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR038785	MAPK13	Family
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 (56 total): helix 18, strand 12, sequence conflict 5, turn 4, modified residue 4, sequence variant 3, splice variant 2, mutagenesis site 2, binding site 2, chain 1, domain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8X23	X-RAY DIFFRACTION	1.5
4YNO	X-RAY DIFFRACTION	1.7
5EKO	X-RAY DIFFRACTION	2
3COI	X-RAY DIFFRACTION	2.09
4EYJ	X-RAY DIFFRACTION	2.1
4EYM	X-RAY DIFFRACTION	2.35
4MYG	X-RAY DIFFRACTION	2.59
5EKN	X-RAY DIFFRACTION	2.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15264-F1	89.14	0.70

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): 150 (proton acceptor)

Ligand- & substrate-binding residues (2): 31–39; 54

Post-translational modifications (4): 47, 180, 182, 350

Mutagenesis-validated functional residues (2):

Position	Phenotype
180	loss of kinase activity.
182	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-171007	p38MAPK events
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-167044	Signalling to RAS
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168643	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-187687	Signalling to ERKs
R-HSA-194138	Signaling by VEGF
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 266 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_NOD1_2_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, JAEGER_METASTASIS_DN, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, ENK_UV_RESPONSE_KERATINOCYTE_UP, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (14): response to osmotic stress (GO:0006970), positive regulation of interleukin-6 production (GO:0032755), cellular response to UV (GO:0034644), intracellular signal transduction (GO:0035556), positive regulation of inflammatory response (GO:0050729), stress-activated MAPK cascade (GO:0051403), cellular response to hydrogen peroxide (GO:0070301), cellular response to interleukin-1 (GO:0071347), cellular response to sorbitol (GO:0072709), cellular response to anisomycin (GO:0072740), cellular response to sodium arsenite (GO:1903936), MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468), cellular response to stress (GO:0033554)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), MAP kinase activity (GO:0004707), ATP binding (GO:0005524), 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)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
Signalling to RAS	1
Signaling by VEGF	1
Signalling to ERKs	1
Immune System	1
Innate Immune System	1
Signaling by NTRKs	1
Signaling by NTRK1 (TRKA)	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	2
intracellular anatomical structure	2
MAPK cascade	2
protein kinase activity	2
cellular anatomical structure	2
response to abiotic stimulus	1
positive regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
response to UV	1
cellular response to light stimulus	1
signal transduction	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
stress-activated protein kinase signaling cascade	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to interleukin-1	1
cellular response to cytokine stimulus	1
cellular response to carbohydrate stimulus	1
response to sorbitol	1
response to anisomycin	1
cellular response to arsenic-containing substance	1
cellular response to salt	1
response to sodium arsenite	1
intracellular signaling cassette	1
phosphorylation	1
protein modification process	1
cellular response to stimulus	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1

Protein interactions and networks

STRING

4232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPK13	MAPK8IP2	Q13387	749
MAPK13	JUN	P05412	684
MAPK13	RCSD1	Q6JBY9	648
MAPK13	BCL2	P10415	616
MAPK13	CREB1	P16220	609
MAPK13	HSPB1	P04792	591
MAPK13	HSPB2	Q16082	584
MAPK13	TNF	P01375	583
MAPK13	HSPB3	Q12988	576
MAPK13	IL1B	P01584	571
MAPK13	MEF2A	Q02078	570
MAPK13	HIF1A	Q16665	568
MAPK13	DUSP16	Q9BY84	567
MAPK13	CAPZA1	P52907	559
MAPK13	TAB1	Q15750	558

IntAct

52 interactions, top by confidence:

A	B	Type	Score
MAPK12	MAPK13	psi-mi:“MI:0914”(association)	0.640
AKT1	MAPK13	psi-mi:“MI:0914”(association)	0.600
MAPK13	AKT1	psi-mi:“MI:0915”(physical association)	0.600
MAPK13	AKT1	psi-mi:“MI:2364”(proximity)	0.600
MAPK13	POTEF	psi-mi:“MI:0915”(physical association)	0.590
MAPK13	PRKD1	psi-mi:“MI:0915”(physical association)	0.590
PRKD1	MAPK13	psi-mi:“MI:0915”(physical association)	0.590
MAPK13	PRKD1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
MAPK13	FPR1	psi-mi:“MI:0915”(physical association)	0.500
FPR1	MAPK13	psi-mi:“MI:0914”(association)	0.500
MAPK13	ATF2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MAPK13	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
Pkd1	MAPK13	psi-mi:“MI:0915”(physical association)	0.400
STAT3	MAPK13	psi-mi:“MI:0915”(physical association)	0.400
MAPK13	GPX4	psi-mi:“MI:0915”(physical association)	0.370
SMAD4	MAPK13	psi-mi:“MI:0915”(physical association)	0.370
MAPK13	Plekhf2	psi-mi:“MI:0914”(association)	0.350
MAPK13	DDX3X	psi-mi:“MI:0914”(association)	0.350
MAPK13	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
MAPK12		psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (49): POTEF (Affinity Capture-MS), MAPK13 (Affinity Capture-MS), MAP3K4 (Co-localization), MAPKAPK3 (Co-localization), SQSTM1 (Biochemical Activity), MAPK13 (Affinity Capture-MS), POTEF (Affinity Capture-MS), MAPK13 (Proximity Label-MS), MAPT (Affinity Capture-Western), MAPT (Biochemical Activity), GYS1 (Biochemical Activity), MAPK13 (Proximity Label-MS), MAPK13 (Affinity Capture-Western), ATF2 (Biochemical Activity), FGF12 (Biochemical Activity)

ESM2 similar proteins: A0A194WDG1, A1CAF0, A1DES4, A2QN07, B0Y462, B0Y4X4, G4N374, O02812, O08911, O13352, O15264, O42376, O44408, O59854, O61443, O62618, P14681, P39745, P47811, P50750, P53778, P70618, Q00772, Q06060, Q0CIC7, Q16539, Q17446, Q1L5Z8, Q39026, Q3T0N5, Q40532, Q4WQR3, Q4WUN7, Q5J4W4, Q63538, Q750A9, Q84UI5, Q8MXI4, Q92398, Q95NE7

Diamond homologs: A0A1B5KW97, A0A1S3Z5Y0, A0A5B9GBF0, A1CAF0, A1CPG7, A1D2C9, A1DES4, A1IVT7, A2QN07, A2QRF6, A2XFC8, A3EZ53, A3EZ54, A3EZ55, A3LN91, A9S9Q8, A9T142, B0XR80, B0Y462, G1XJZ4, M1T7M3, O02812, O08911, O15264, O42376, O59853, O59854, O61443, O62618, O93982, P0C431, P0CP68, P0CP69, P32485, P42525, P47811, P47812, P53778, P70618, Q06060

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
TRIM27	up-regulates	MAPK13
MAP2K6	up-regulates	MAPK13	phosphorylation
MAPK13	“down-regulates activity”	EEF2K	phosphorylation
MAPK13	up-regulates	KRT8	phosphorylation
MAPK13	down-regulates	EEF2K	phosphorylation
MAPK13	down-regulates	PRKD1	phosphorylation
(-)-anisomycin	up-regulates	MAPK13	“chemical activation”
MAPK13	down-regulates	STMN1	phosphorylation
MAP2K3	“up-regulates activity”	MAPK13	phosphorylation
MAP2K6	“up-regulates activity”	MAPK13	phosphorylation
MAP2K7	“up-regulates activity”	MAPK13	phosphorylation
MAP2K4	“up-regulates activity”	MAPK13	phosphorylation
MAPK13	“down-regulates activity”	MAPT	phosphorylation
MAPK13	up-regulates	TP53	phosphorylation
TNFRSF17	up-regulates	MAPK13
MAPK13	down-regulates	CDC25B
MAPK13	“down-regulates activity”	RCSD1	phosphorylation
MAPK13	“down-regulates activity”	TP53BP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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)	5	35.2×	9e-05
Signaling by NTRKs	5	32.4×	9e-05
Signaling by Interleukins	5	11.5×	4e-03
Signaling by Receptor Tyrosine Kinases	6	11.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
intracellular signal transduction	8	9.5×	9e-04
positive regulation of gene expression	7	8.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1813 predictions. Top by Δscore:

Variant	Effect	Δscore
6:36130697:GTGTG:G	donor_gain	1.0000
6:36131269:A:AG	acceptor_gain	1.0000
6:36131269:AGCTC:A	acceptor_gain	1.0000
6:36131270:G:GG	acceptor_gain	1.0000
6:36131270:GCTCG:G	acceptor_gain	1.0000
6:36131397:GAAC:G	donor_gain	1.0000
6:36131398:AAC:A	donor_gain	1.0000
6:36131399:AC:A	donor_gain	1.0000
6:36131401:G:GG	donor_gain	1.0000
6:36132675:GACTT:G	donor_gain	1.0000
6:36132680:G:GG	donor_gain	1.0000
6:36135854:GCCT:G	donor_gain	1.0000
6:36135858:TAAGG:T	donor_loss	1.0000
6:36135859:AAGGT:A	donor_loss	1.0000
6:36135861:GG:G	donor_loss	1.0000
6:36136530:AGG:A	donor_loss	1.0000
6:36136531:GGTG:G	donor_loss	1.0000
6:36136532:G:C	donor_loss	1.0000
6:36136641:T:G	acceptor_gain	1.0000
6:36136646:T:TA	acceptor_gain	1.0000
6:36136648:T:TA	acceptor_gain	1.0000
6:36136653:T:G	acceptor_gain	1.0000
6:36136654:A:AG	acceptor_gain	1.0000
6:36136655:G:GT	acceptor_gain	1.0000
6:36136655:GA:G	acceptor_gain	1.0000
6:36136655:GAT:G	acceptor_gain	1.0000
6:36136655:GATT:G	acceptor_gain	1.0000
6:36136655:GATTC:G	acceptor_gain	1.0000
6:36136766:GACAG:G	donor_gain	1.0000
6:36136769:AGG:A	donor_loss	1.0000

AlphaMissense

2405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:36131313:G:C	K54N	1.000
6:36131313:G:T	K54N	1.000
6:36136663:A:T	D168V	1.000
6:36136664:T:A	D168E	1.000
6:36136664:T:G	D168E	1.000
6:36131306:C:A	A52D	0.999
6:36131311:A:G	K54E	0.999
6:36131348:C:A	A66D	0.999
6:36131363:G:C	R71P	0.999
6:36135857:T:C	L138P	0.999
6:36136047:G:T	R149M	0.999
6:36136485:A:C	D150A	0.999
6:36136485:A:G	D150G	0.999
6:36136485:A:T	D150V	0.999
6:36136486:C:A	D150E	0.999
6:36136486:C:G	D150E	0.999
6:36136488:T:C	L151P	0.999
6:36136499:A:G	N155D	0.999
6:36136501:C:A	N155K	0.999
6:36136501:C:G	N155K	0.999
6:36136662:G:C	D168H	0.999
6:36136663:A:C	D168A	0.999
6:36136663:A:G	D168G	0.999
6:36136669:G:A	G170E	0.999
6:36136672:T:C	L171P	0.999
6:36136714:C:T	T185I	0.999
6:36136722:T:C	Y188H	0.999
6:36136881:G:C	D205H	0.999
6:36136882:A:T	D205V	0.999
6:36136887:T:A	W207R	0.999

dbSNP variants (sampled 300 via entrez): RS1000013472 (6:36130277 G>A), RS1000203629 (6:36138311 G>A), RS1000254477 (6:36144860 A>G), RS1000302836 (6:36144672 C>G), RS1000940018 (6:36139615 T>C,G), RS1000947687 (6:36134193 G>A,C,T), RS1001105556 (6:36142921 G>C), RS1001135088 (6:36142767 A>G), RS1001170612 (6:36142125 G>A), RS1001357875 (6:36136191 C>A,T), RS1001429081 (6:36129552 A>C,G), RS1001705458 (6:36142492 G>A), RS1001907473 (6:36131441 T>A,C), RS1001970422 (6:36129769 T>C), RS1002451535 (6:36134830 A>T)

Disease associations

OMIM: gene MIM:602899 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_1820	Blood protein levels	1.000000e-11
GCST008362_156	Birth weight	2.000000e-13
GCST008363_50	Offspring birth weight	2.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094115 (PROTEIN FAMILY), CHEMBL2939 (SINGLE PROTEIN), CHEMBL3038503 (PROTEIN FAMILY), CHEMBL5465205 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465225 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 212,198 (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
CHEMBL267495	NALFURAFINE	4	310
CHEMBL5416410	DASATINIB	4	655
CHEMBL941	IMATINIB	4	111,611
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL119385	NEFLAMAPIMOD	2	1,603
CHEMBL363648	TAK-715	2	442
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL475251	R-406	2	762
CHEMBL3577124	LY-3009120	1	198
CHEMBL482767	SNS-314	1	336
CHEMBL574738	AST-487	1	451
CHEMBL585902	AMG-548	1	487

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — p38 subfamily

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
PF-03715455	Inhibition	7.64	pIC50
doramapimod	Inhibition	6.52	pIC50
MAPK13-IN-1	Inhibition	6.21	pIC50
compound 4e [PMID: 35546685]	Inhibition	5.39	pIC50

Binding affinities (BindingDB)

14 measured of 19 human assays (19 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CHEMBL142697	IC50	0.4 nM
Aminopyrazole inhibitor, 3576	IC50	7 nM
CHEMBL142187	IC50	20 nM
Aminopyrazole inhibitor, 3528	IC50	23 nM
Aminopyrazole inhibitor, 3451	IC50	25 nM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[5-(2-morpholin-4-ylethyl)-1,3-thiazol-2-yl]urea	IC50	27.5 nM	US-9187470: Anti-mucus drugs and uses therefor
Aminopyrazole inhibitor, 4326	IC50	55 nM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-(4-pyridin-4-yloxyphenyl)urea	IC50	280 nM	US-9187470: Anti-mucus drugs and uses therefor
1-(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)-3-(4-(pyridin-4-yloxy)phenyl)urea	IC50	620 nM	US-9187470: Anti-mucus drugs and uses therefor
(S)-2-(2-amino-3-phenylpropylamino)-3-methyl-5-(naphthalen-2-yl)-6-(pyridin-4-yl)pyrimidin-4(3H)-one	IC50	7740 nM	US-9187470: Anti-mucus drugs and uses therefor
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[2-(oxane-4-carbonyl)-1,3-dihydroisoindol-5-yl]urea	IC50	8650 nM	US-9187470: Anti-mucus drugs and uses therefor
3-(4-methylimidazol-1-yl)-N-(4-pyridin-4-yloxyphenyl)benzamide	IC50	10200 nM	US-9187470: Anti-mucus drugs and uses therefor
2-morpholin-4-yl-N-(4-pyridin-4-yloxyphenyl)pyridine-4-carboxamide	IC50	14900 nM	US-9187470: Anti-mucus drugs and uses therefor

ChEMBL bioactivities

1085 potent at pChembl≥5 of 1149 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.33	Ki	0.047	nM	CHEMBL194813
10.30	Ki	0.05	nM	CHEMBL363643
10.24	Ki	0.057	nM	CHEMBL196741
10.24	Ki	0.057	nM	CHEMBL197206
10.01	Kd	0.097	nM	DORAMAPIMOD
10.00	Kd	0.1	nM	CHEMBL318810
9.96	IC50	0.11	nM	CHEMBL305178
9.82	Ki	0.15	nM	CHEMBL195532
9.82	IC50	0.15	nM	CHEMBL545353
9.80	Ki	0.16	nM	CHEMBL197351
9.72	IC50	0.19	nM	CHEMBL303144
9.70	IC50	0.2	nM	CHEMBL356125
9.70	IC50	0.2	nM	CHEMBL357598
9.70	IC50	0.2	nM	CHEMBL69319
9.40	IC50	0.4	nM	CHEMBL142697
9.40	IC50	0.4	nM	CHEMBL142187
9.40	IC50	0.4	nM	CHEMBL92082
9.40	IC50	0.4	nM	CHEMBL446404
9.39	Ki	0.41	nM	CHEMBL274257
9.39	Ki	0.41	nM	CHEMBL198876
9.38	Ki	0.42	nM	CHEMBL274257
9.30	IC50	0.5	nM	CHEMBL327987
9.30	IC50	0.5	nM	CHEMBL119595
9.29	IC50	0.51	nM	CHEMBL219796
9.22	IC50	0.6	nM	CHEMBL328242
9.22	IC50	0.6	nM	CHEMBL331252
9.22	IC50	0.6	nM	CHEMBL161276
9.21	Ki	0.61	nM	CHEMBL382954
9.19	IC50	0.64	nM	CHEMBL2087507
9.19	IC50	0.65	nM	CHEMBL3220549
9.16	IC50	0.69	nM	CHEMBL219804
9.15	IC50	0.7	nM	CHEMBL92814
9.14	IC50	0.72	nM	CHEMBL2402001
9.13	IC50	0.74	nM	CHEMBL388582
9.12	IC50	0.75	nM	CHEMBL308939
9.10	IC50	0.8	nM	CHEMBL343682
9.10	IC50	0.8	nM	CHEMBL142289
9.10	IC50	0.8	nM	CHEMBL92082
9.10	IC50	0.8	nM	NEFLAMAPIMOD
9.10	Ki	0.8	nM	NEFLAMAPIMOD
9.09	IC50	0.82	nM	CHEMBL1738839
9.08	IC50	0.83	nM	CHEMBL2087515
9.04	IC50	0.91	nM	CHEMBL325211
9.01	Ki	0.97	nM	CHEMBL383137
9.01	IC50	0.97	nM	CHEMBL446404
9.00	IC50	1	nM	CHEMBL3220550
9.00	Kd	1	nM	CHEMBL420047
8.96	IC50	1.1	nM	CHEMBL358108
8.96	IC50	1.1	nM	CHEMBL142463
8.92	IC50	1.2	nM	CHEMBL92648

PubChem BioAssay actives

922 with measured affinity, of 2628 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
3-[[5-cyano-6-[2,2-dimethylpropyl(methyl)amino]-2-(methylamino)pyrimidin-4-yl]amino]-N-methoxy-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	<0.0001	uM
3-[[5-cyano-6-[2,2-dimethylpropyl(methyl)amino]-2-(4-methyl-1,4-diazepan-1-yl)pyrimidin-4-yl]amino]-N-methoxy-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0001	uM
3-[[5-cyano-6-[2,2-dimethylpropyl(methyl)amino]pyrimidin-4-yl]amino]-N-methoxy-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0001	uM
3-[[2-amino-5-cyano-6-[2,2-dimethylpropyl(methyl)amino]pyrimidin-4-yl]amino]-N-methoxy-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0001	uM
3-[[2-amino-5-cyano-6-(propan-2-ylamino)pyrimidin-4-yl]amino]-4-methyl-N-(1,2-oxazol-3-yl)benzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0001	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	127075: Binding affinity against human Mitogen-activated protein kinase p38 kinase evaluated by exchange curve	kd	0.0001	uM
4-[3-methyl-2-piperidin-4-yl-5-[3-(trifluoromethyl)phenyl]imidazol-4-yl]-N-[(1S)-1-phenylethyl]pyrimidin-2-amine	127106: Inhibition of Mitogen-activated protein kinase p38	ic50	0.0001	uM
N-[(1S)-1-phenylethyl]-4-[6-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]pyridazin-4-yl]pyrimidin-2-amine;dihydrochloride	127106: Inhibition of Mitogen-activated protein kinase p38	ic50	0.0001	uM
1-(3-tert-butyl-1-phenylpyrazol-5-yl)-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	1525522: Binding affinity to P38 mitogen activated protein kinase (unknown origin)	kd	0.0001	uM
3-[[2-amino-5-cyano-6-(cyclopentylamino)pyrimidin-4-yl]amino]-4-methyl-N-(1,2-oxazol-3-yl)benzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0002	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(piperidin-4-ylamino)-1,6-naphthyridin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0002	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(1-propan-2-ylpiperidin-4-yl)quinolin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0002	uM
4-[3-methyl-2-piperidin-4-yl-5-[3-(trifluoromethyl)phenyl]imidazol-4-yl]-N-[(1S)-1-phenylethyl]pyridin-2-amine	127243: Inhibition of Mitogen-activated protein kinase p38	ic50	0.0002	uM
2-[5-[2-(cyclopropylmethylamino)pyrimidin-4-yl]-4-(4-fluorophenyl)-1H-imidazol-2-yl]-N,N,5-trimethyl-1,3-dioxane-5-carboxamide	209043: Inhibition of p38-related TNF alpha release by human monocyte cell line (THP-1)	ic50	0.0002	uM
6-(4-fluorophenyl)-7-[2-[[(1S)-1-phenylethyl]amino]pyrimidin-4-yl]-2,3-dihydro-1H-pyrazolo[1,2-a]pyrazol-5-one	215246: Inhibition of LPS-stimulated p38-related TNF-alpha production in human peripheral blood mononuclear cells (PBMC)	ic50	0.0004	uM
N-[(1R)-1-phenylethyl]-4-[2-piperidin-4-yl-4-[3-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]pyrimidin-2-amine	92862: Inhibition of LPS-induced release of Tumor necrosis factor-alpha (TNF-alpha) from human whole blood	ic50	0.0004	uM
3-[[5-cyano-6-(cyclopentylamino)pyrimidin-4-yl]amino]-N-methoxy-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0004	uM
3-[[5-cyano-6-(propan-2-ylamino)pyrimidin-4-yl]amino]-4-methyl-N-(1,2-oxazol-3-yl)benzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0004	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)amino]-3,4-dihydroquinazolin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0004	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)amino]-1,6-naphthyridin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0004	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(piperidin-4-ylamino)-3,4-dihydroquinazolin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0005	uM
3-[2-[[(2S)-1-methoxypropan-2-yl]amino]-4-pyridinyl]-2-phenylimidazo[1,2-a]pyrimidin-7-amine	155458: Inhibition of LPS-induced p38-related TNF-alpha production in human peripheral blood mononuclear cells	ic50	0.0005	uM
5-(2,4-difluorophenyl)-1-(2,6-difluorophenyl)-7-(methylamino)-1,6-naphthyridin-2-one	274335: Inhibition of p38	ic50	0.0005	uM
N-[(1S)-1-phenylethyl]-4-[6-piperazin-1-yl-3-[3-(trifluoromethyl)phenyl]pyridazin-4-yl]pyrimidin-2-amine	127106: Inhibition of Mitogen-activated protein kinase p38	ic50	0.0006	uM
3-[[5-cyano-6-(propan-2-ylamino)pyrimidin-4-yl]amino]-N-methoxy-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0006	uM
5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-(1-propan-2-ylpiperidin-4-yl)-3,4-dihydroquinazolin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0006	uM
N-cyclopropyl-3-fluoro-4-methyl-5-[3-(1-methylcyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl]benzamide	685461: Inhibition of p38alpha	ic50	0.0006	uM
2-phenyl-3-[2-[[(1S)-1-phenylethyl]amino]pyrimidin-4-yl]imidazo[1,2-a]pyrimidin-7-amine	155458: Inhibition of LPS-induced p38-related TNF-alpha production in human peripheral blood mononuclear cells	ic50	0.0006	uM
1-(2,6-dichlorophenyl)-6-(2,4-difluorophenyl)sulfanyl-7-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]-3,4-dihydropyrido[3,2-d]pyrimidin-2-one	209193: Anti human TNF-alpha activity determined through TNF-alpha release was measured in the supernatants by ELISA	ic50	0.0007	uM
7-amino-5-(2,4-difluorophenyl)-1-(2,6-difluorophenyl)-1,6-naphthyridin-2-one	274335: Inhibition of p38	ic50	0.0007	uM
3,4-dihydro-1H-quinolin-2-one	286353: Inhibition of mitogen-activated protein kinase p38 at 2 uM ATP	ic50	0.0007	uM
N-[5-(cyclopropylcarbamoyl)-2-methylphenyl]-5-(6-methyl-3-pyridinyl)thiophene-2-carboxamide	758209: Inhibition of p38 MAPK-mediated TNFalpha production in LPS-induced human whole blood preincubated for 5 mins prior to LPS-treatment measured after 6 hrs by ELISA	ic50	0.0007	uM
N-[(1S)-1-phenylethyl]-4-[2-piperidin-4-yl-4-[3-(trifluoromethyl)phenyl]-1H-imidazol-5-yl]pyrimidin-2-amine	127243: Inhibition of Mitogen-activated protein kinase p38	ic50	0.0008	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,6-naphthyridin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0008	uM
3-[3-(3-chloro-4-pyridinyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl]-N-cyclopropyl-5-fluoro-4-methylbenzamide	685461: Inhibition of p38alpha	ic50	0.0008	uM
8-(2,6-dichlorophenyl)-4-(2,4-difluorophenyl)-7-oxido-2-piperidin-4-yl-1,7-naphthyridin-7-ium	1504524: Inhibition of MAPK p38 (unknown origin)	ic50	0.0008	uM
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	1525523: Inhibition of P38 mitogen activated protein kinase (unknown origin)	ki	0.0008	uM
5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-(1-propan-2-ylpiperidin-4-yl)-3,4-dihydroquinolin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0008	uM
2-(4-fluorophenyl)-4-phenylmethoxy-3-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-6-amine	222608: Inhibition of TNF-alpha production by lipopolysaccharide-stimulated human peripheral blood mononuclear cells	ic50	0.0009	uM
3-[[5-cyano-6-(propylamino)pyrimidin-4-yl]amino]-N-methoxy-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0010	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-naphthalen-1-ylurea	127076: Binding affinity for human recombinant Mitogen-activated protein kinase p38 in a fluorescent binding assay	kd	0.0010	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(1-propan-2-ylpiperidin-4-yl)amino]-1,6-naphthyridin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0011	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-1,6-naphthyridin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0011	uM
N-[4-[2-(4-fluoro-3-methylphenyl)imidazo[1,2-b]pyridazin-3-yl]-2-pyridinyl]-6-methylpyridine-3-carboxamide	1388757: Inhibition of MAPK p38 in human THP1 cells assessed as reduction in LPS-induced TNFalpha production preincubated for 60 mins followed by LPS addition measured after 4 hrs by HTRF assay	ic50	0.0012	uM
7-[5-(cyclopropylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(2,6-dichlorophenyl)-6-(2,4-difluorophenyl)sulfanyl-3,4-dihydropyrido[3,2-d]pyrimidin-2-one	209193: Anti human TNF-alpha activity determined through TNF-alpha release was measured in the supernatants by ELISA	ic50	0.0012	uM
5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(1-propan-2-ylpiperidin-4-yl)-1,6-naphthyridin-2-one	127092: Inhibition of p38 MAP kinase	ic50	0.0013	uM
1-(2,6-dichlorophenyl)-6-(2,4-difluorophenyl)sulfanyl-7-(5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-3,4-dihydropyrido[3,2-d]pyrimidin-2-one	209193: Anti human TNF-alpha activity determined through TNF-alpha release was measured in the supernatants by ELISA	ic50	0.0013	uM
N,N,N’-trimethyl-N’-[5-[2-[[(1S)-1-phenylethyl]amino]pyrimidin-4-yl]-6-[3-(trifluoromethyl)phenyl]pyridazin-3-yl]ethane-1,2-diamine	127106: Inhibition of Mitogen-activated protein kinase p38	ic50	0.0014	uM
2-(4-fluorophenyl)-4-[(3-methoxyphenyl)methoxy]-3-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-6-amine	222608: Inhibition of TNF-alpha production by lipopolysaccharide-stimulated human peripheral blood mononuclear cells	ic50	0.0015	uM
3-[[2-amino-5-cyano-6-(propan-2-ylamino)pyrimidin-4-yl]amino]-N-(2-ethylpyrazol-3-yl)-4-methylbenzamide	254526: Binding affinity for human p38 MAP kinase expressed in Escherichia coli using [gamma-33P]ATP; n=4	ki	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	6
Benzo(a)pyrene	affects methylation, increases expression	4
sodium arsenite	increases phosphorylation, increases abundance, increases expression, increases activity	3
Cadmium Chloride	increases abundance, increases phosphorylation, increases expression, affects cotreatment	3
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases expression, affects expression, increases abundance	2
Calcitriol	increases expression	2
Fluorouracil	increases expression	2
Quercetin	affects expression, increases expression	2
Tobacco Smoke Pollution	affects expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium bichromate	decreases expression	1
o,p’-DDT	decreases expression	1
afimoxifene	decreases response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
paricalcitol	affects cotreatment, increases expression	1
SB 203580	affects cotreatment, increases expression	1
U 0126	decreases reaction, increases phosphorylation	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1

ChEMBL screening assays

847 unique, capped per target: 792 binding, 54 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004015	Binding	Inhibition of human p38 MAPK	Hepatitis C virus NS5A is a direct substrate of casein kinase I-alpha, a cellular kinase identified by inhibitor affinity chromatography using specific NS5A hyperphosphorylation inhibitors. — J Biol Chem
CHEMBL4181658	ADMET	Inhibition of P38 (unknown origin)	Imidazo[1,2-a]pyridin-6-yl-benzamide analogs as potent RAF inhibitors. — Bioorg Med Chem Lett
CHEMBL697600	Functional	Inhibition of LPS-induced p38-related TNF alpha release from human monocytes	Pyrroles and other heterocycles as inhibitors of p38 kinase. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8Q6	Ubigene HCT 116 MAPK13 KO	Cancer cell line	Male
CVCL_D9JN	Ubigene HEK293 MAPK13 KO	Transformed cell line	Female
CVCL_SW87	HAP1 MAPK13 (-) 1	Cancer cell line	Male
CVCL_SW88	HAP1 MAPK13 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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