MAPK14
mitogen-activated protein kinase 14, the group of Mitogen-activated protein kinases
Basic information
Region (hg38): 6:36027781-36111236
Previous symbols: [ "CSPB1", "CSBP1", "CSBP2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (2 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPK14 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 3 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 2 | 0 | 1 |
Variants in MAPK14
This is a list of pathogenic ClinVar variants found in the MAPK14 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-36059341-A-G | not specified | Uncertain significance (Jun 22, 2023) | ||
| 6-36073707-A-G | not specified | Uncertain significance (Oct 10, 2023) | ||
| 6-36100215-G-A | not specified | Uncertain significance (Jan 31, 2023) | ||
| 6-36100230-C-G | not specified | Uncertain significance (Dec 08, 2023) | ||
| 6-36107507-A-G | not specified | Likely benign (Jan 22, 2024) | ||
| 6-36107549-C-T | Benign (Jul 19, 2018) | |||
| 6-36108391-G-A | not specified | Uncertain significance (Nov 07, 2023) | ||
| 6-36108401-T-G | not specified | Uncertain significance (Oct 30, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAPK14 | protein_coding | protein_coding | ENST00000229795 | 12 | 83526 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.375 | 0.625 | 125739 | 0 | 9 | 125748 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.31 | 71 | 204 | 0.348 | 0.0000105 | 2379 |
| Missense in Polyphen | 10 | 72.431 | 0.13806 | 875 | ||
| Synonymous | -0.351 | 78 | 74.2 | 1.05 | 0.00000410 | 664 |
| Loss of Function | 3.39 | 5 | 22.2 | 0.225 | 0.00000113 | 254 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000618 | 0.0000615 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000656 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF- induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14- mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF- kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'. {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Influenza A - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;VEGF Signaling Pathway;Fc Epsilon Receptor I Signaling in Mast Cells;EGF-Core;JAK-STAT-Core;TGF-Core;Regulation of toll-like receptor signaling pathway;Physiological and Pathological Hypertrophy of the Heart;Angiogenesis;Energy Metabolism;MicroRNAs in cardiomyocyte hypertrophy;IL-1 signaling pathway;Angiogenesis overview;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Leptin signaling pathway;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Follicle Stimulating Hormone (FSH) signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Prolactin Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;AGE-RAGE pathway;Corticotropin-releasing hormone signaling pathway;Parkinsons Disease Pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Cardiac Progenitor Differentiation;Alpha 6 Beta 4 signaling pathway;Amyotrophic lateral sclerosis (ALS);JAK-STAT;Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;Kit receptor signaling pathway;Rac1-Pak1-p38-MMP-2 pathway;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Hepatitis C and Hepatocellular Carcinoma;TGF-beta Signaling Pathway;Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;MAPK Signaling Pathway;RIG-I-like Receptor Signaling;Canonical and Non-Canonical TGF-B signaling;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Protein alkylation leading to liver fibrosis;p38 MAPK Signaling Pathway;Oxidative Stress;MAPK Cascade;EMT transition in Colorectal Cancer;EGF-EGFR Signaling Pathway;Insulin Signaling;Interferon type I signaling pathways;Senescence and Autophagy in Cancer;T-Cell antigen Receptor (TCR) Signaling Pathway;Estrogen signaling pathway;Serotonin HTR1 Group and FOS Pathway;Monoamine Transport;Toll-like Receptor Signaling Pathway;Developmental Biology;RAGE;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Neutrophil degranulation;Signal Transduction;Gene expression (Transcription);Signaling by Interleukins;bioactive peptide induced signaling pathway;links between pyk2 and map kinases;il12 and stat4 dependent signaling pathway in th1 development;gata3 participate in activating the th2 cytokine genes expression;human cytomegalovirus and map kinase pathways;transcription factor creb and its extracellular signals;p38 mapk signaling pathway;regulation of eif-4e and p70s6 kinase;tsp-1 induced apoptosis in microvascular endothelial cell;regulation of map kinase pathways through dual specificity phosphatases;il-10 anti-inflammatory signaling pathway;signal transduction through il1r;tnf/stress related signaling;the 41bb-dependent immune response;VEGFA-VEGFR2 Pathway;nfkb activation by nontypeable hemophilus influenzae;bcr signaling pathway;keratinocyte differentiation;toll-like receptor pathway;mapkinase signaling pathway;Generic Transcription Pathway;Prolactin;Cytokine Signaling in Immune system;map kinase inactivation of smrt corepressor;Toll Like Receptor 9 (TLR9) Cascade;Alpha6Beta4Integrin;Oxidative Stress Induced Senescence;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;KSRP (KHSRP) binds and destabilizes mRNA;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Cellular Senescence;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Cellular responses to stress;RNA Polymerase II Transcription;Metabolism of RNA;TCR;Innate Immune System;Immune System;p73 transcription factor network;KitReceptor;BMP2 signaling TAK1;ATF-2 transcription factor network;Fibroblast growth factor-1;Nuclear Events (kinase and transcription factor activation);Signal amplification;BCR;IL-1 p38;CRH;TGF-beta super family signaling pathway canonical;IL1;TLR p38;p38MAPK events;Signalling to RAS;Platelet activation, signaling and aggregation;Cellular responses to external stimuli;CDO in myogenesis;Myogenesis;IL-7 signaling;Signalling to ERKs;Signaling by NTRK1 (TRKA);TGF_beta_Receptor;activated TAK1 mediates p38 MAPK activation;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);Signaling by NTRKs;ERK/MAPK targets;EGFR1;Activation of the AP-1 family of transcription factors;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Glucocorticoid receptor regulatory network;ADP signalling through P2Y purinoceptor 1;fmlp induced chemokine gene expression in hmc-1 cells;Hemostasis;MyD88 dependent cascade initiated on endosome;BCR signaling pathway;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;IL2;VEGFR3 signaling in lymphatic endothelium;EPO signaling;Regulation of TP53 Activity through Phosphorylation;IL2-mediated signaling events;Gastrin;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Signaling by VEGF;Angiopoietin receptor Tie2-mediated signaling;Rapid glucocorticoid signaling;IL4;EPO signaling pathway;IL5;Leptin;Activation of PPARGC1A (PGC-1alpha) by phosphorylation;TGF-beta signaling TAK1;Mitochondrial biogenesis;IL6;TLR ECSIT MEKK1 p38;TNFalpha;Regulation of mRNA stability by proteins that bind AU-rich elements;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;VEGF;Platelet sensitization by LDL;Platelet homeostasis;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;RANKL;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Signaling mediated by p38-alpha and p38-beta;RAC1 signaling pathway;CD40/CD40L signaling;CDC42 signaling events;Retinoic acid receptors-mediated signaling;Regulation of p38-alpha and p38-beta;CXCR3-mediated signaling events;p38 MAPK signaling pathway;Regulation of Androgen receptor activity;FAS (CD95) signaling pathway;p38 signaling mediated by MAPKAP kinases;Role of Calcineurin-dependent NFAT signaling in lymphocytes;IL4-mediated signaling events;Regulation of retinoblastoma protein;Trk receptor signaling mediated by the MAPK pathway;IL6-mediated signaling events;Endothelins;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;IL12-mediated signaling events;Atypical NF-kappaB pathway;p53 pathway;S1P2 pathway;TSLP;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.917
Intolerance Scores
- loftool
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.64
Haploinsufficiency Scores
- pHI
- 0.948
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.677
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mapk14
- Phenotype
- immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- mapk14a
- Affected structure
- retinal ganglion cell
- Phenotype tag
- abnormal
- Phenotype quality
- occurrence
Gene ontology
- Biological process
- DNA damage checkpoint;activation of MAPK activity;cell morphogenesis;cartilage condensation;angiogenesis;placenta development;chondrocyte differentiation;positive regulation of cytokine secretion involved in immune response;glucose metabolic process;regulation of transcription by RNA polymerase II;apoptotic process;chemotaxis;signal transduction;cell surface receptor signaling pathway;transmembrane receptor protein serine/threonine kinase signaling pathway;skeletal muscle tissue development;regulation of gene expression;positive regulation of gene expression;positive regulation of macrophage chemotaxis;positive regulation of myotube differentiation;peptidyl-serine phosphorylation;fatty acid oxidation;regulation of ossification;osteoclast differentiation;positive regulation of cyclase activity;lipopolysaccharide-mediated signaling pathway;response to muramyl dipeptide;intracellular signal transduction;cellular response to vascular endothelial growth factor stimulus;response to muscle stretch;p38MAPK cascade;positive regulation of protein import into nucleus;signal transduction in response to DNA damage;neutrophil degranulation;positive regulation of blood vessel endothelial cell migration;positive regulation of erythrocyte differentiation;positive regulation of myoblast differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of glucose import;vascular endothelial growth factor receptor signaling pathway;striated muscle cell differentiation;positive regulation of muscle cell differentiation;positive regulation of cardiac muscle cell proliferation;3'-UTR-mediated mRNA stabilization;cellular response to lipopolysaccharide;cellular response to lipoteichoic acid;cellular response to organic substance;cellular response to tumor necrosis factor;cellular response to ionizing radiation;negative regulation of canonical Wnt signaling pathway;positive regulation of brown fat cell differentiation;stress-induced premature senescence;cellular response to virus;regulation of synaptic membrane adhesion;regulation of cytokine production involved in inflammatory response;positive regulation of myoblast fusion;regulation of signal transduction by p53 class mediator;positive regulation of metallopeptidase activity;positive regulation of reactive oxygen species metabolic process;positive regulation of interleukin-12 secretion
- Cellular component
- spindle pole;extracellular region;nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;nuclear speck;secretory granule lumen;glutamatergic synapse;ficolin-1-rich granule lumen
- Molecular function
- protein serine/threonine kinase activity;MAP kinase activity;MAP kinase kinase activity;protein binding;ATP binding;enzyme binding;protein phosphatase binding;mitogen-activated protein kinase p38 binding;NFAT protein binding