P47811 (MK14_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase 14
Short name=MAP kinase 14
Short name=MAPK 14
EC=2.7.11.24

Alternative name(s):
CRK1
Mitogen-activated protein kinase p38 alpha
Short name=MAP kinase p38 alpha

Gene names

Name:	Mapk14
Synonyms:	Crk1, Csbp1, Csbp2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	360 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Phosphorylates S100A9 at 'Thr-113' By similarity. Ref.11 Ref.12 Ref.13 Ref.15
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.28
Cofactor	Magnesium.
Enzyme regulation	Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and interleukin-1. Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for auto-activation and substrate recognition. Phosphorylated at Tyr-323 by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). SB203580 is an inhibitor of MAPK14. Ref.11 Ref.15 Ref.19
Subunit structure	Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR. This interaction retains MAPK14 in the cytoplasm and prevents nuclear accumulation. Interacts with SPAG9, SUPT20H and GADD45A. Interacts with CDC25B, CDC25C, DUSP1, DUSP10, DUSP16, NP60 and TAB1 By similarity. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B By similarity. Ref.10 Ref.12 Ref.14 Ref.15 Ref.16 Ref.28
Subcellular location	Cytoplasm. Nucleus Ref.10.
Tissue specificity	Macrophages, monocytes, T- and B-lymphocytes. Isoform 2 is specifically expressed in kidney and liver.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to inflammatory cytokines, environmental stress or growth factors, which activates the enzyme. Dual phosphorylation can also be mediated by TAB1-mediated autophosphorylation. TCR engagement in T-cells also leads to Tyr-323 phosphorylation by ZAP70. Dephosphorylated and inactivated by DUPS1, DUSP10 and DUSP16. Ref.15 Ref.19 Ref.28 Acetylated at Lys-53 and Lys-152 by KAT2B and EP300. Acetylation at Lys-53 increases the affinity for ATP and enhances kinase activity. Lys-53 and Lys-152 are deacetylated by HDAC3 By similarity. Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.
Biophysicochemical properties	Kinetic parameters: KM=212 µM for ATP (when both Thr-180 and Tyr-182 are phosphorylated) Ref.19 KM=1669 µM for ATP (when only Thr-180 is phosphorylated) KM=656 µM for EGFR peptide as a substrate (when both Thr-180 and Tyr-182 are phosphorylated) KM=2800 µM for EGFR peptide as a substrate (when only Thr-180 is phosphorylated) KM=2.03 µM for ATF2 as a substrate (when both Thr-180 and Tyr-182 are phosphorylated) KM=20.1 µM for ATF2 as a substrate (when only Thr-180 is phosphorylated)

Ontologies

Keywords
Biological process	Apoptosis Stress response Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage checkpoint Inferred from mutant phenotype PubMed 12937170. Source: MGI angiogenesis Inferred from mutant phenotype PubMed 10973481. Source: MGI apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cartilage condensation Inferred from mutant phenotype PubMed 17202865. Source: AgBase cell morphogenesis Inferred from genetic interaction PubMed 17686994. Source: MGI cellular response to ionizing radiation Inferred from electronic annotation. Source: Ensembl cellular response to vascular endothelial growth factor stimulus Inferred from electronic annotation. Source: Ensembl chondrocyte differentiation Inferred from mutant phenotype PubMed 17202865. Source: AgBase fatty acid oxidation Inferred from mutant phenotype PubMed 12802337. Source: MGI glucose metabolic process Inferred from mutant phenotype PubMed 12802337. Source: MGI lipopolysaccharide-mediated signaling pathway Inferred from direct assay PubMed 12872135. Source: MGI negative regulation of canonical Wnt signaling pathway Inferred from mutant phenotype PubMed 17202865. Source: AgBase osteoclast differentiation Inferred from mutant phenotype PubMed 15304486. Source: BHF-UCL p38MAPK cascade Inferred from direct assay PubMed 22847234. Source: UniProtKB peptidyl-serine phosphorylation Inferred from direct assay PubMed 15304486. Source: BHF-UCL positive regulation of erythrocyte differentiation Inferred from mutant phenotype Ref.12. Source: MGI positive regulation of myoblast differentiation Inferred from mutant phenotype PubMed 22847234. Source: UniProtKB positive regulation of myoblast fusion Inferred from mutant phenotype PubMed 22847234. Source: UniProtKB positive regulation of myotube differentiation Inferred from mutant phenotype PubMed 22847234. Source: UniProtKB positive regulation of protein import into nucleus Inferred from mutant phenotype PubMed 16954198. Source: MGI positive regulation of reactive oxygen species metabolic process Inferred from electronic annotation. Source: Ensembl positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.12. Source: MGI response to muramyl dipeptide Inferred from direct assay PubMed 15692051. Source: MGI signal transduction in response to DNA damage Inferred from electronic annotation. Source: Ensembl skeletal muscle tissue development Inferred from mutant phenotype PubMed 15890335. Source: MGI stress-induced premature senescence Inferred from electronic annotation. Source: Ensembl striated muscle cell differentiation Inferred from genetic interaction PubMed 20160094. Source: MGI transcription, DNA-templated Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein serine/threonine kinase signaling pathway Inferred from genetic interaction PubMed 18363966. Source: MGI vascular endothelial growth factor receptor signaling pathway Inferred from electronic annotation. Source: Ensembl
Cellular_component	cytosol Inferred from direct assay PubMed 11884367. Source: MGI mitochondrion Inferred from direct assay PubMed 11884367. Source: MGI nucleus Inferred from direct assay Ref.10. Source: UniProtKB spindle pole Inferred from direct assay PubMed 15509711. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DUSP9	Q99956	2	EBI-298727,EBI-3906678	From a different organism.
Lcp1	Q61233	5	EBI-298727,EBI-309345
Mapk11	Q9WUI1	10	EBI-298727,EBI-645081
Mapkapk2	P49138	2	EBI-298727,EBI-298776
Slc12a2	P55012	2	EBI-298727,EBI-621078
Stk39	Q9Z1W9	2	EBI-298727,EBI-444764

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P47811-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P47811-2)

Also known as: Piccolo;

The sequence of this isoform differs from the canonical sequence as follows:
     255-278: ARNYIQSLAQMPKMNFANVFIGAN → DAK
     279-360: Missing.

Isoform 3 (identifier: P47811-3)

The sequence of this isoform differs from the canonical sequence as follows:
     230-254: DQLKLILRLVGTPGAELLKKISSES → NQLQQIMRLTGTPPAYLINRMPSHE

Isoform 4 (identifier: P47811-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-77: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 360

359

Mitogen-activated protein kinase 14

PRO_0000186292

Regions

Domain

24 – 308

285

Protein kinase

Nucleotide binding

30 – 38

9

ATP By similarity

Region

106 – 111

6

Inhibitor-binding

Motif

180 – 182

3

TXY

Sites

Active site

168

1

Proton acceptor By similarity

Binding site

32

1

Inhibitor

Binding site

35

1

Inhibitor

Binding site

53

1

ATP By similarity

Binding site

53

1

Inhibitor

Binding site

71

1

Inhibitor

Binding site

109

1

Inhibitor; via amide nitrogen and carbonyl oxygen

Binding site

111

1

Inhibitor; via amide nitrogen

Binding site

168

1

Inhibitor

Binding site

169

1

Inhibitor; via carbonyl oxygen

Amino acid modifications

Modified residue

2

1

N-acetylserine By similarity

Modified residue

2

1

Phosphoserine By similarity

Modified residue

16

1

Phosphothreonine By similarity

Modified residue

53

1

N6-acetyllysine By similarity

Modified residue

152

1

N6-acetyllysine By similarity

Modified residue

180

1

Phosphothreonine; alternate Ref.17 Ref.18 Ref.19 Ref.21

Modified residue

180

1

Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and autocatalysis; alternate By similarity

Modified residue

182

1

Phosphotyrosine; alternate Ref.17 Ref.18 Ref.19 Ref.21

Modified residue

182

1

Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and autocatalysis; alternate By similarity

Modified residue

323

1

Phosphotyrosine; by ZAP70 By similarity

Natural variations

Alternative sequence

1 – 77

77

Missing in isoform 4.

VSP_022359

Alternative sequence

230 – 254

25

DQLKL…ISSES → NQLQQIMRLTGTPPAYLINR MPSHE in isoform 3.

VSP_007544

Alternative sequence

255 – 278

24

ARNYI…FIGAN → DAK in isoform 2.

VSP_004846

Alternative sequence

279 – 360

82

Missing in isoform 2.

VSP_007545

Experimental info

Mutagenesis

180

1

T → A: Phosphorylation blocked.

Mutagenesis

182

1

Y → F: Phosphorylation blocked.

Sequence conflict

98

1

E → G in AAF06348. Ref.7

Sequence conflict

107 – 108

2

HL → LS in AAF06348. Ref.7

Sequence conflict

115

1

N → R in AAF06348. Ref.7

Sequence conflict

124

1

D → G in AAF06348. Ref.7

Sequence conflict

159 – 162

4

NEDC → TQVI in AAF06348. Ref.7

Sequence conflict

166

1

I → L in AAF06348. Ref.7

Sequence conflict

202

1

Q → R in AAF06348. Ref.7

Sequence conflict

211 – 212

2

CI → GF in AAF06348. Ref.7

Sequence conflict

224

1

P → L in AAF06348. Ref.7

Sequence conflict

271

1

A → P in AAF06348. Ref.7

Sequence conflict

299

1

A → V in AAF06348. Ref.7

Sequence conflict

315

1

D → Y in AAF06348. Ref.7

Isoform 3:

Sequence conflict

238

1

L → M in BAA19741. Ref.2

Secondary structure

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360

Helix Strand Turn

Details...

Beta strand

8 – 13

6

Beta strand

16 – 21

6

Beta strand

24 – 32

9

Beta strand

34 – 43

10

Turn

44 – 47

4

Beta strand

48 – 57

10

Helix

62 – 77

16

Beta strand

87 – 90

4

Helix

96 – 98

3

Beta strand

103 – 107

5

Beta strand

111 – 113

3

Helix

114 – 119

6

Helix

124 – 143

20

Helix

153 – 155

3

Beta strand

156 – 158

3

Beta strand

164 – 166

3

Beta strand

172 – 175

4

Beta strand

176 – 182

7

Helix

185 – 188

4

Helix

191 – 193

3

Beta strand

197 – 199

3

Helix

204 – 218

15

Helix

228 – 239

12

Helix

244 – 247

4

Helix

253 – 260

8

Helix

270 – 273

4

Turn

274 – 276

3

Helix

279 – 288

10

Turn

293 – 295

3

Helix

299 – 303

5

Helix

306 – 308

3

Turn

309 – 311

3

Helix

314 – 316

3

Helix

326 – 329

4

Helix

334 – 346

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: DFB03EBCE97BB51A	FASTA	360	41,287
	10 20 30 40 50 60 MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGHRV AVKKLSRPFQ 70 80 90 100 110 120 SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 130 140 150 160 170 180 KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 190 200 210 220 230 240 GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG 250 260 270 280 290 300 TPGAELLKKI SSESARNYIQ SLAQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA 310 320 330 340 350 360 QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP PPLDQEEMES
	Isoform 2 (Piccolo) [UniParc]. Checksum: ABDF65DC32AF0387	FASTA	257	29,540
	10 20 30 40 50 60 MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGHRV AVKKLSRPFQ 70 80 90 100 110 120 SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 130 140 150 160 170 180 KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 190 200 210 220 230 240 GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG 250 TPGAELLKKI SSESDAK
	Isoform 3 [UniParc]. Checksum: F1F20352F76590BD	FASTA	360	41,487
	10 20 30 40 50 60 MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGHRV AVKKLSRPFQ 70 80 90 100 110 120 SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 130 140 150 160 170 180 KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 190 200 210 220 230 240 GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHIN QLQQIMRLTG 250 260 270 280 290 300 TPPAYLINRM PSHEARNYIQ SLAQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA 310 320 330 340 350 360 QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP PPLDQEEMES
	Isoform 4 [UniParc]. Checksum: 895D71CB69550519	FASTA	283	32,327
	10 20 30 40 50 60 MKHENVIGLL DVFTPARSLE EFNDVYLVTH LMGADLNNIV KCQKLTDDHV QFLIYQILRG 70 80 90 100 110 120 LKYIHSADII HRDLKPSNLA VNEDCELKIL DFGLARHTDD EMTGYVATRW YRAPEIMLNW 130 140 150 160 170 180 MHYNQTVDIW SVGCIMAELL TGRTLFPGTD HIDQLKLILR LVGTPGAELL KKISSESARN 190 200 210 220 230 240 YIQSLAQMPK MNFANVFIGA NPLAVDLLEK MLVLDSDKRI TAAQALAHAY FAQYHDPDDE 250 260 270 280 PVADPYDQSF ESRDLLIDEW KSLTYDEVIS FVPPPLDQEE MES

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells." Han J., Lee J.-D., Bibbs L., Ulevitch R.J. Science 265:808-811(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	Higashitsuji H., Fujita J. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Strain: C57BL/6. Tissue: Brain.
[3]	"Piccolo, a new alternative spliced form of p38/CSBP1/Mxi2 that is specifically expressed in kidney and liver." Faccio L., Fusco C., Zervos S.A. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: C57BL/6. Tissue: Kidney.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). Strain: C57BL/6J. Tissue: Bone marrow, Pituitary and Thymus.
[5]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Liver.
[7]	Yin Z., Li J., Sha J., Zhou Z., Lin M., Wang L. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-318 (ISOFORM 3). Tissue: Testis.
[8]	"Novel CDC2-related protein kinases produced in murine hematopoietic stem cells." Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V. Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 154-186. Strain: CBA. Tissue: Bone marrow.
[9]	"Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms." Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J., Davis R.J. Science 267:682-685(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[10]	"A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase." Blanco-Aparicio C., Torres J., Pulido R. J. Cell Biol. 147:1129-1136(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPRR, SUBCELLULAR LOCATION.
[11]	"Deficiency of the stress kinase p38alpha results in embryonic lethality: characterization of the kinase dependence of stress responses of enzyme-deficient embryonic stem cells." Allen M., Svensson L., Roach M., Hambor J., McNeish J., Gabel C.A. J. Exp. Med. 191:859-870(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION. Tissue: Embryonic stem cell.
[12]	"Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis." Tamura K., Sudo T., Senftleben U., Dadak A.M., Johnson R., Karin M. Cell 102:221-231(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT. Strain: C57BL/6J.
[13]	"MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts." Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P., Arthur J.S. Mol. Cell. Biol. 22:2871-2881(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF RPS6KA5/MSK1 AND RPS6KA4/MSK2.
[14]	"JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors." Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P. Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPAG9.
[15]	"The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38 activation pathway." Salvador J.M., Mittelstadt P.R., Belova G.I., Fornace A.J. Jr., Ashwell J.D. Nat. Immunol. 6:396-402(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GADD45A, PHOSPHORYLATION AT TYR-323, AUTOPHOSPHORYLATION, ENZYME REGULATION, FUNCTION.
[16]	"p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation." Zohn I.E., Li Y., Skolnik E.Y., Anderson K.V., Han J., Niswander L. Cell 125:957-969(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUPT20H.
[17]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY. Tissue: Mast cell.
[18]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY. Tissue: Liver.
[19]	"Enzymatic activity and substrate specificity of mitogen-activated protein kinase p38alpha in different phosphorylation states." Zhang Y.Y., Mei Z.Q., Wu J.W., Wang Z.X. J. Biol. Chem. 283:26591-26601(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-180 AND TYR-182, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[20]	"In the cellular garden of forking paths: how p38 MAPKs signal for downstream assistance." Shi Y., Gaestel M. Biol. Chem. 383:1519-1536(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[21]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY. Tissue: Brain.
[22]	"Mechanisms and functions of p38 MAPK signalling." Cuadrado A., Nebreda A.R. Biochem. J. 429:403-417(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ENZYME REGULATION, REVIEW ON FUNCTION.
[23]	"The structure of mitogen-activated protein kinase p38 at 2.1-A resolution." Wang Z., Harkins P.C., Ulevitch R.J., Han J., Cobb M.H., Goldsmith E.J. Proc. Natl. Acad. Sci. U.S.A. 94:2327-2332(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[24]	"Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b." Chang C.I., Xu B.E., Akella R., Cobb M.H., Goldsmith E.J. Mol. Cell 9:1241-1249(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH MEF2A AND MAP2K3.
[25]	"The development of monocyclic pyrazolone based cytokine synthesis inhibitors." Golebiowski A., Townes J.A., Laufersweiler M.J., Brugel T.A., Clark M.P., Clark C.M., Djung J.F., Laughlin S.K., Sabat M.P., Bookland R.G., VanRens J.C., De B., Hsieh L.C., Janusz M.J., Walter R.L., Webster M.E., Mekel M.J. Bioorg. Med. Chem. Lett. 15:2285-2289(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[26]	"The development of new isoxazolone based inhibitors of tumor necrosis factor-alpha (TNF-alpha) production." Laughlin S.K., Clark M.P., Djung J.F., Golebiowski A., Brugel T.A., Sabat M., Bookland R.G., Laufersweiler M.J., VanRens J.C., Townes J.A., De B., Hsieh L.C., Xu S.C., Walter R.L., Mekel M.J., Janusz M.J. Bioorg. Med. Chem. Lett. 15:2399-2403(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[27]	"Molecular basis of MAPK-activated protein kinase 2:p38 assembly." White A., Pargellis C.A., Studts J.M., Werneburg B.G., Farmer B.T. II Proc. Natl. Acad. Sci. U.S.A. 104:6353-6358(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-360 IN COMPLEX WITH MAPKAPK2.
[28]	"A distinct interaction mode revealed by the crystal structure of the kinase p38alpha with the MAPK binding domain of the phosphatase MKP5." Zhang Y.Y., Wu J.W., Wang Z.X. Sci. Signal. 4:RA88-RA88(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) IN COMPLEX WITH DUSP10, CATALYTIC ACTIVITY, DEPHOSPHORYLATION BY DUSP10, INTERACTION WITH DUSP10.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U10871 mRNA. Translation: AAA20888.1.
D83073 mRNA. Translation: BAA19741.1.
AF128892 mRNA. Translation: AAF34818.1.
AK151348 mRNA. Translation: BAE30324.1.
AK153025 mRNA. Translation: BAE31659.1.
AK089059 mRNA. Translation: BAC40726.1.
AK133684 mRNA. Translation: BAE21782.1.
CT009661 Genomic DNA. Translation: CAQ52036.1.
CT009661 Genomic DNA. Translation: CAQ52037.1.
BC012235 mRNA. Translation: AAH12235.1.
AF195850 mRNA. Translation: AAF06348.1.
X65067 mRNA. Translation: CAA46200.1.

PIR

I49066.

RefSeq

NP_001161980.1. NM_001168508.1.
NP_001161985.1. NM_001168513.1.
NP_001161986.1. NM_001168514.1.
NP_036081.1. NM_011951.3.

UniGene

Mm.311337.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LEW	X-ray	2.30	A	1-360	[»]
1LEZ	X-ray	2.30	A	1-360	[»]
1P38	X-ray	2.10	A	1-360	[»]
1YW2	X-ray	2.01	A	1-360	[»]
1YWR	X-ray	1.95	A	1-360	[»]
2EWA	X-ray	2.10	A	1-360	[»]
2GHL	X-ray	2.10	A	5-351	[»]
2GHM	X-ray	2.35	A	5-351	[»]
2GTM	X-ray	1.90	A	5-351	[»]
2GTN	X-ray	1.80	A	5-351	[»]
2OZA	X-ray	2.70	B	2-360	[»]
2PUU	X-ray	2.50	A	5-352	[»]
3P4K	X-ray	2.30	A	1-360	[»]
3P5K	X-ray	2.09	A	2-360	[»]
3P78	X-ray	2.30	A	2-360	[»]
3P79	X-ray	2.10	A	2-360	[»]
3P7A	X-ray	2.31	A	2-360	[»]
3P7B	X-ray	1.90	A	2-360	[»]
3P7C	X-ray	2.30	A	2-360	[»]
3PY3	X-ray	2.10	A	1-360	[»]
3TG1	X-ray	2.71	A	1-360	[»]
4KA3	X-ray	2.71	A	1-360	[»]
4LOO	X-ray	1.95	A	1-360	[»]
4LOP	X-ray	2.05	A/B/C/D	1-360	[»]
4LOQ	X-ray	2.32	A/B/C/D	1-360	[»]

ProteinModelPortal

P47811.

SMR

P47811. Positions 1-354.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

204969. 20 interactions.

DIP

DIP-31073N.

IntAct

P47811. 26 interactions.

MINT

MINT-1204448.

STRING

10090.ENSMUSP00000004990.

Chemistry

BindingDB

P47811.

ChEMBL

CHEMBL2111473.

PTM databases

PhosphoSite

P47811.

Proteomic databases

PaxDb

P47811.

PRIDE

P47811.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000004990; ENSMUSP00000004990; ENSMUSG00000053436.
ENSMUST00000062694; ENSMUSP00000061958; ENSMUSG00000053436.
ENSMUST00000114752; ENSMUSP00000110400; ENSMUSG00000053436.
ENSMUST00000114754; ENSMUSP00000110402; ENSMUSG00000053436.

GeneID

26416.

KEGG

mmu:26416.

UCSC

uc008brl.2. mouse.

Organism-specific databases

CTD

1432.

MGI

MGI:1346865. Mapk14.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00550000074271.

HOVERGEN

HBG014652.

InParanoid

B2KF38.

KO

K04441.

OMA

QALAHGY.

TreeFam

TF105100.

Enzyme and pathway databases

BRENDA

2.7.11.24. 3474.

Reactome

REACT_127416. Developmental Biology.
REACT_78136. Gene Expression.
REACT_88316. Metabolism of RNA.

SABIO-RK

P47811.

Gene expression databases

ArrayExpress

P47811.

Bgee

P47811.

CleanEx

MM_MAPK14.

Genevestigator

P47811.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR01773. P38MAPKINASE.

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. SSF56112. 1 hit.

PROSITE

PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P47811.

NextBio

304425.

PRO

P47811.

SOURCE

Search...

Entry information

Entry name

MK14_MOUSE

Accession

Primary (citable) accession number: P47811
Secondary accession number(s): B2KF37 , B2KF38, O08666, Q3U6R5, Q3UZS3, Q8C289, Q9JLV8, Q9QZ80

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	January 23, 2007
Last modified:	February 19, 2014
This is version 160 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program