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FLASH GENE

Symbol

MAPK14

contributors: mct/npt/pgu - updated : 19-03-2018

HGNC name	mitogen-activated protein kinase 14
HGNC id	6876

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	6p21.31      Physical location : 35.995.453 - 36.079.012
Synonym name	stress-activated protein kinase 2A
	CSAID (cytokine suppressive and anti-inflammatory drugs), binding protein 1
	p38 MAP kinase
	cytokine suppressive anti-inflammatory drug binding protein
	MAP kinase MXI2
	MAX-interacting protein 2
	p38alpha Exip
	stress-activated protein kinase 2A
Synonym symbol(s)	SAPK2A, p38MAPK, CSBP1, RK, p38, EXIP, Mxi2, CSBP2, PRKM14, PRKM15, CSPB1, p38ALPHA
EC.number	2.7.11.24

DNA

TYPE	functioning gene
SPECIAL FEATURE	head to head
STRUCTURE	83.56 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D6S1611 - D6S1645 - MAPK14 - D6S3801 - D6S291 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001315 12 splicing 4353 isoform 1 (longest) 41.4 360 - 1995 7696354 also called CSBP1 NM_139012 12 splicing 4353 isoform 2 - CSBP2 41.2 360 - 1995 7696354 NM_139013 10 splicing 1431 isoform 3 34 297 - 1995 7696354 loss of exon 10,11,11' playing a role in the signal transduction pathway different from other isoforms NM_139014 11 splicing 4274 isoform 4 35.3 307 - 1995 7696354

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine small intestine     highly Hearing/Equilibrium ear inner cochlea   highly Lymphoid/Immune thymus       highly Nervous brain         Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies	homolog to rattus Mapk14 (99,17 pc)
	homolog to murine Mapk14 (95,56 pc)

Homologene

FAMILY	protein kinase superfamily
	CMGC Ser/Thr protein kinase family
	MAP kinase subfamily

CATEGORY

chaperone/stress

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	serine/threonine kinase, may be playing a role in the early onset of apoptosis
	involved in hypertrophic differentiation of chondrocytes
	involved in cardiomyocyte proliferation and angiogenesis during development
	involved in Sp1 phosphorylation
	mediates IL1A-induced down-regulation of aggrecan gene expression in chondrocytes
	may be regulating the early secretory pathway
	substrates of this kinase include ATF2, MEF2C, MAX, CDC25B, p53, suggesting a role in stress related transcription and cell cycle regulation
	controls myogenesis by antagonizing the activation of the JNK proliferation-promoting pathway, before its direct effect on muscle differentiation-specific gene transcription (fundamental role in muscle formation)
	recruited to muscle-specific gene promoters during muscle development suggesting that indeed MAPK14 might play an important role at the chromatin
	role in activating CREB1 metabolic pathway in the events leading to erythroid differentiation)
	its activity promotes timely checkpoint satisfaction by indirectly influencing the motor proteins (e.g., Klp10, Klp67A) involved in regulating the dynamics of kinetochore microtubule ends
	in intestinal epithelial cells contributes to the host immune responses against enteric bacteria by the recruitment of immune cells
	MAPK14 recruitment to target genes appears to be a broad mechanism to regulate transcription
	its activity is not just necessary for gene promoter activation but might also be necessary for the nascent mRNA elongation of MAPK14-dependent genes
	regulates expression of osteoblast-specific genes by phosphorylation of osterix (SP7)
	maintains CDH1 expression by suppressing MAP3K7-NFKB signaling, thus impeding the induction of EMT in human primary mesothelial cells
	plays an important role in the regulation of hematopoietic stem cellself-renewal in vitro and inhibition of MAPK14 activation with a small molecule inhibitor may represent a novel approach to promote ex vivo expansion of hematopoietic stem cell
	controls prothrombin expression by regulated RNA 3prime end processing
	regulates G1-S transition in hypoxic cardiac fibroblasts
	MAPK14-signaling is a central pathway for the integration of instructive signals in dendritic cells for T(H)17 differentiation and inflammation
	MAPK14 and JNK pathways function downstream of ZAK during chondrogenesis
	unexpected role of MAPK14 in cell cycle regulation in response to Aurora B inhibition, by promoting the transcriptional elongation of the cell cycle inhibitor CDKN1A
	ARG2, MAPK14, and RPS6KB1 form a positive circuit which regulates endothelial senescence and cardiovascular aging
	mitophagy in mammalian cells predominantly occurs through an alternative autophagy pathway, requiring the MAPK1 and MAPK14 signaling pathways

CELLULAR PROCESS	cell cycle
	cell life, cell death/apoptosis
	nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

	pathway of redox-sensitive signaling via NOX4 and MAPK14 in endothelial cells
	MAPK14 pathway is an important contributor to the increased microglial production of proinflammatory cytokines induced by diverse stressors
	MAPK14-dependent protective pathway might be able to be selectively modulated to enhance cardio-protection while not interfering with the inhibition of the better-known detrimental MAPK14-dependent pathways

a component

INTERACTION

DNA

RNA

small molecule

protein	regulate TEAD1 and CEBPB transcriptional activity in the absence of environmental stress and suggests a role for MAPK14 in the expression of extracellular matrix components that maintain organ architecture
	SP7 (Osterix) is a novel substrate for MAPK14, and Ser-73 and Ser-77 are the regulatory sites phosphorylated by MAPK14
	MAPKAPK2 and MAPK14 function in concert to phosphorylate Keratin 8, Keratin 18, and Keratin 20 in intestinal epithelia
	interacting with MYCBP2 (modulates TRPV1 desensitization through MAPK14 signaling which presents not only a novel model for the modulation of TRPV1-mediated signals but also expands the role of MAPK14 in the regulation of activity-induced receptor internalization)
	interaction between phosphorylated MAPK14 and cleaved N-terminal ATF6 could results in a protective effect against the vicious cycle of oxidative stress-ER stress by induction of ER chaperones and ERAD components
	CDK5RAP3 binds MAPK14, alters its cellular localization, and inhibits basal and cytokine-stimulated MAPK14 activity
	interplay between MAPK14 phosphorylation and DNAJC3 upregulation has key roles in modulating ERP29-induced cell-growth arrest and survival
	SMAD7 and MAPK14 mitogen-activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGFB1 stimulation
	possible involvement of S100A12 in the development of osteoarthritis (OA) by up-regulating MMP13 and VEGFA via MAPK14 and NFKB1 pathways
	PDGFB-induced activation of MAPK14 was significantly suppressed by SERPINA12
	dual phosphorylation of PXN by JNK and MAPK14 is essential for T-cell activation, suggesting that NFATC1 is a functional target of the JNK/MAPK14 phosphorylated paxillin
	spatial regulation of MAPK14 by GADD45B/MAP3K4 negatively regulates the autophagic process
	OPRK1 activates MAPK14 through a phosphorylation and arrestin-dependent mechanism
	cascade of posttranslational modifications involving MAPK14, KAT5, and MAPKAPK5, three proteins that are essential for RAS-induced senescence
	role for MAPK14 in mediating cross-talk between apical Na(+) entry via SCNN1G and its basolateral exit via ATP1A1, which may allow principal cells to maintain intracellular Na(+) concentrations within narrow limits in collecting duct principal cells
	CASP3, CASP9, and MAPK14 interacted with SLIT1-ROBO2 signaling
	GSN induces cardiomyocyte hypertrophy and NPPB expression via MAPK14 signaling and GATA4 transcriptional factor activation
	IGF1 inhibits cells apoptosis in pulmonary artery smooth muscle cells (PASMC) by activating the MAPK14-NOS2 transduction pathway
	negative regulation of MAPK14 mediates the protective effects of SCD on ER homeostasis under distinct stress conditions
	FNDC5 activated MAPK14 in an AMPK-dependent manner
	TLR8, is involved in priming of human neutrophil ROS production by inducing the phosphorylation of NCF1 and MAPK14 and PIN1 is also involved in this process
	TNFAIP8L2 inhibited the phosphorylation of AKT1, while promoting the phosphorylation of MAPK14, but had no effect on NFKBIA and ERK pathway
	PGF may activate MMP9 via MAPK14 signaling pathway
	TNFSF18 could promote Th17 cell differentiation by MAPK14 and STAT3 signaling in autoimmune arthritis
	TNFAIP8L2 suppressed breast cancer tumorigenesis, growth and metastasis possibly via regulation of the AKT1 and MAPK14 signaling pathways
	CHRM3-induced activation of MAPK14 might contribute to the maintenance of epithelial barrier function through down-regulation of TNF signalling and activation of EGFR
	DSG2, beside its adhesion function, regulates intestinal barrier function via MAPK14 signalling
	PPP2CA regulated the stem cell factor (SCF)-induced activation of MAPK14/cofilin signaling pathway and subsequent migration of cardiac stem cells (CSCs) by interaction with MAPK14
	EXOC3 is involved in the enhancement of cell migration and suppression of apoptosis through the activation of HSPB1, HSPB2 or MAPK14 phosphorylation
	MAPK14 mediates epithelial-mesenchymal transition by regulating SUP20TH and SNAI1 in Head and Neck squamous cell carcinoma
	MAPK14 was required for phenotype changes of VSMCs induced by L3MBTL4 in hypertension

cell & other

REGULATION

activated by	stresses and proinflammatory cytokines
	phosphorylation by MAP kinase kinase or by its autophosphorylation triggered by the interaction with MAP3K7IP1
	suppression of SRC activity (stimulates muscle differentiation by activating MAPK14 uni-directionally)
	GAS1 that promotes myogenic differentiation through regulation of cell cycle arrest and is critical to activate MAPK14, most likely via association with CDON/Cadherin multiprotein complexes

Other

regulated by MKK3 and MKK6

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in myoblasts that are unable to differentiate and form multinucleated myotubes

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular atheroma cardiac FGF1/MAPK14 inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction cancer reproductive ovary pharmacological modulation of genes involved in cancer-specific homeostasis, such as MAPK14, might be exploited to design new therapeutic approaches to cancer treatment

ANIMAL & CELL MODELS

Mapk14 activity is markedly reduced in the livers of obese mice compared with lean mice