MAPK14 (mitogen-activated protein kinase 14)

Alias_names	CSPB1
	CSBP1
	CSBP2
Alias_symbol (synonym)	PRKM14
	p38
	Mxi2
	PRKM15
Other alias	EXIP
	RK
	SAPK2A
	p38ALPHA
HGNC (Hugo)	MAPK14
LocusID (NCBI)	1432
Atlas_Id	41292
Location	6p21.31  [Link to chromosome band 6p21]
Location_base_pair	Starts at 36027677 and ends at 36111236 bp from pter ( according to hg19-Feb_2009)  [Mapping MAPK14.png]
	Schematic representation of human chromosome 6 indicating the position of MAPK14 locus (p21.31) (red bar).

	MAPK14 gene locus. Representation of the MAPK14 gene organization indicating the position of the exons (coding region) and untranslated regions.
Description	The gene spans a region of 83.53 kb and the coding part is divided into 41 different exons. Larger transcripts contain 12 or 13 exons. (GATExplorer).
Transcription	9 types of transcripts have been described, although only 5 are protein coding transcripts. The larger 4319-nucleotide transcript encodes a protein of 360 amino acid residues. The first and last exons are partially untranslated.
Pseudogene	None described so far.

	MAPK14 protein domains. Schematic representation of MAPK14 protein indicating the position of its functional domains. 30-54: protein kinase ATP signature, ATP-binding region; 59-162: MAPK signature; 24-308: protein kinase domain.
Description	MAPK14 is a Ser/Thr kinase composed of 90 to 360 residues depending on the transcript variant.
	Crystal structure of MAPK14 at 2.3 A resolution. From PDB (access number: 1WFC).
Expression	p38alpha MAPK is ubiquitously expressed, being the p38 most abundant isoform.
Localisation	p38alpha is mainly present in the cytosol, but it can translocate to the nucleus. In addition, it can be localized in the mitochondria or in other subcellular compartments.
Function	p38alpha is mainly activated by various environmental stresses and proinflammatory cytokines, but many other extracellular signals, including growth factors, also lead to p38alpha activation. The canonical activation requires its phosphorylation in threonine and tyrosine residues by dual-specificity MAP kinase kinases (MKKs), MKK3, MKK6 and MKK4. Substrates of this kinase include transcription factors, such as ATF1, ATF2, ATF6, p53, MEF2 or C/EBPbeta and protein kinases, such as MAPKAP-K2 and MAPKAP-K3 (also known as MK-2 and MK-3), MSK-1, MNK-1/MNK-2 and other proteins. p38alpha MAPK is essential for embryonic development and it regulates different cellular functions such as proliferation, differentiation, cell death, adhesion, migration, as well as the response to stress and many metabolic pathways, among others. It does so through regulation of transcription, mRNA stability, chromatin remodelling, protein synthesis, etc. Concerning cell death, although p38alpha plays an important role as a pro-apoptotic signal, it can play a dual role, acting as either a mediator of cell survival or of cell death, depending on the cell type and the stimuli. Related with its function as a negative regulator of proliferation and a mediator of apoptosis, p38alpha acts as a tumor suppressor in the initial stages of a tumorigenic process, while at later stages it can promote metastasis.
	Signaling through p38alphaMAPK. Signaling through MAPK14 cascade and its role in the regulation of cellular functions. MAPK14 is involved in signaling pathways triggered by a variety of stimuli such as growth factors, oxidative stress, UV, cytokines and DNA damage. Depending on the stimulus, different receptors and intermediates (adaptors, GTPases or kinases) are activated leading to the activation of the p38alpha MAPK cascade. This cascade is initiated by activation of MAPKKKs, which phosphorylate and activate MAPKKs (MKK3/6/4), which in turn lead to activation of MAPK14 through dual phosphorylation in Tyr and Thr. Once phosphorylated, MAPK14 phosphorylates a number of cytosolic and nuclear substrates, including transcription factors, which lead to the control of many cellular responses.

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