MAPK13 (mitogen-activated protein kinase 13)

Alias_names	PRKM13
Alias_symbol (synonym)	SAPK4
	p38delta
Other alias	MGC99536
HGNC (Hugo)	MAPK13
LocusID (NCBI)	5603
Atlas_Id	41291
Location	6p21.31  [Link to chromosome band 6p21]
Location_base_pair	Starts at 36130484 and ends at 36144524 bp from pter ( according to hg19-Feb_2009)  [Mapping MAPK13.png]
	MAPK13 genomic context (chromosome 6, location 6p21.31).

	Genomic organization of MAPK13 gene on chromosome 6p21.31. The boxes indicate coding regions (exon 1-12) of the gene.
Description	The MAPK13 entire gene spans 9.58 Kb on the short arm of chromosome 6. It contains 12 exons.
Transcription	The MAPK13 gene encodes a 365 amino-acid protein of about 40 KDa. No splice variants have been reported.
Pseudogene	No human or mouse pseudogene known.

Note	p38delta (MAPK13), also known as Stress-activated protein kinase 4 (SAPK4) belongs to the p38 subfamily of MAPKs. The p38MAPK subfamily is composed by four members encoded by different genes, which share high sequence homologues and are designated as p38alpha (MAPK14, or SAPK2a), p38beta (MAPK11 or SAPK2b), p38gamma (MAPK12 or SAPK3) and p38delta (MAPK13 or SAPK4). They are about 60% identical in their amino acid sequence but differ in their expression patterns, substrate specificities and sensitivities to chemical inhibitors (Iñesta-Vaquera et al., 2008). All p38 MAPKs are strongly activated in vivo by environmental stresses and inflammatory cytokines, and less by serum and growth factors.
	Schematic representation of the p38delta (MAPK13) protein structure. Kinase Domain, catalytic kinase domain; TGY, sequence motif containing the regulatory phosphorylation residues.
Description	p38delta (MAPK13) is a Serine/Threonine protein kinase of 365 amino acids with a predicted molecular mass of 40 kDa. It possesses the conserved amino acid domains (I-XI) characteristic of protein kinases (Goedert et al., 1997). The Thr180 and Tyr182 residues in subdomain VIII are in an equivalent position to the TXY sequence in known MAPKs. The activation of p38delta (MAPK13) occurs via dual phosphorilation of its TGY motif, in the activation loop, by MKK3 and MKK6, although it is preferentially activated by MKK3 in mouse embryonic fibroblasts (Remy et al., 2009).
Expression	p38delta (MAPK13) mRNA is widely expressed with high levels of expression in testes, pancreas, kidney and small intestine.
Localisation	p38delta (MAPK13) localizes to the cytoplasm and nucleus of cultured cells.
Function	p38delta (MAPK13) phosphorylates typical p38 MAPK substrates such as the transcription factors ATF2, Elk-1 or SAP1. However, it cannot phosphorylate MAPKAPK2 or MAPKAPK3, which are good substrates for other p38 MAPK isoforms (Cuenda et al., 1997; Goedert et al., 1997). p38delta possibly plays a role in cytoskeleton regulation as it has been reported to phosphorylate the cytoplasmic protein stathmin, which has been linked to regulation of microtubule dynamics (Parker et al., 1998). Microtubule-associated protein Tau is another protein substrate of p38delta (Goedert et al., 1997; Feijoo et al., 2005; Yoshida and Goedert, 2006). In addition p38delta plays a role in the regulation of protein translation by phosphorylating and inactivating the eukaryotic elongation factor 2 (eEF2) kinase (Knebel et al., 2001; Knebel et al., 2002). p38delta also plays a key role in the regulation of insulin secretion as well as in the survival of pancreatic beta cells, since p38delta catalyzes an inhibitory phosphorylation of the protein kinase D1 (PDK1), which controls insuline exocytosis in pancreatic beta cells (Sumara et al., 2009). p38delta has been suggested to play an important role in inducing keratinocyte differentiation by regulating the expression of involucrin, which is a protein expressed during keratinocyte differentiation (Eckert et al., 2003). Activation of exogenously expressed p38delta by differentiation-inducing agents such as a bioactive green tea polyphenol (EGCG), okadaic acid (OA) or the phorbol ester TPA, correlated with increased involucrin promoter activity in keratinocytes via increased activity at AP1, Sp1 and C/EBP sites (Balasubramanian et al., 2002; Efimova et al., 2003). The mechanisms by which p38delta may regulates keratinocyte differentiation is still unknown, although it has been reported that in keratinocytes expressing exogenous p38delta this forms a complex with ERK1/ERK2 (Efimova et al., 2003; Eckert et al., 2004). Additional data supporting the idea that p38delta may play a role in keratinocyte differentiation come from a study carried out in lesional psoriasis skin (Johansen et al., 2005). It has been shown that the activity of p38alpha, p38beta and p38delta are augmented in lesional psoriasis skin compared with nonlesional psoriasis skin (Johansen et al., 2005). Alternatively, it has been also claimed that p38delta may have a dual role in keratinocytes contributing not only to the differentiation process, but also to their apoptosis in a PKCdelta dependent manner, and in response to OA or H2O2 (Efimova et al., 2004; Kraft et al., 2007).
Homology	p38delta (MAPK13) shows 70% identity with p38gamma (MAPK12), 60% sequence identity with p38alpha (MAPK14) and p38beta (MAPK11), 45% identity with HOG1 from S. cerevisiae, 47% identity with human SAP kinase-1 (JNK1) and 42% identity with p42 MAPkinase (ERK2).

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