Human Gene MAPKAPK2 (ENST00000367103.4_6) from GENCODE V47lift37

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Description: MAPK activated protein kinase 2, transcript variant 2 (from RefSeq NM_032960.4)
Gencode Transcript: ENST00000367103.4_6
Gencode Gene: ENSG00000162889.11_8
Transcript (Including UTRs)
Position: hg19 chr1:206,858,250-206,907,626 Size: 49,377 Total Exon Count: 10 Strand: +
Coding Region
Position: hg19 chr1:206,858,575-206,906,063 Size: 47,489 Coding Exon Count: 10

Page Index	Sequence and Links	UniProtKB Comments	Primers	CTD	Gene Alleles
RNA-Seq Expression	Microarray Expression	RNA Structure	Protein Structure	Other Species	GO Annotations
mRNA Descriptions	Pathways	Other Names	Model Information	Methods

Data last updated at UCSC: 2024-08-22 23:36:26

Sequence and Links to Tools and Databases

Genomic Sequence (chr1:206,858,250-206,907,626)			mRNA (may differ from genome)		Protein (400 aa)
Gene Sorter	Genome Browser	Other Species FASTA	VisiGene	Gene interactions	Table Schema
AlphaFold	BioGPS	Ensembl	Entrez Gene	ExonPrimer	GeneCards
HGNC	MGI	OMIM	PubMed	Reactome	UniProtKB
Wikipedia	BioGrid CRISPR DB

Comments and Description Text from UniProtKB


	ID: MAPK2_HUMAN DESCRIPTION: RecName: Full=MAP kinase-activated protein kinase 2; Short=MAPK-activated protein kinase 2; Short=MAPKAP kinase 2; Short=MAPKAP-K2; Short=MAPKAPK-2; Short=MK-2; Short=MK2; EC=2.7.11.1; FUNCTION: Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat- shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Activated following phosphorylation by p38- alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors. SUBUNIT: Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with PHC2. INTERACTION: Q00613:HSF1; NbExp=5; IntAct=EBI-993299, EBI-719620; P04792:HSPB1; NbExp=2; IntAct=EBI-993299, EBI-352682; Q16539:MAPK14; NbExp=2; IntAct=EBI-993299, EBI-73946; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm. TISSUE SPECIFICITY: Expressed in all tissues examined. PTM: Sumoylation inhibits the protein kinase activity. PTM: Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-222, Ser-272 and Thr-334. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SIMILARITY: Contains 1 protein kinase domain.

Primer design for this transcript

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Comparative Toxicogenomics Database (CTD)


	The following chemicals interact with this gene C093642 SB 203580 C017947 sodium arsenite D008070 Lipopolysaccharides D013012 Sorbitol C015001 arsenite D001554 Benzene D019256 Cadmium Chloride D006861 Hydrogen Peroxide C522498 (4-(5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl)pyridin-2-yl)-(1-phenylethyl)amine C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl more ... click here to view the complete list

Common Gene Haplotype Alleles


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RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)


	Highest median expression: 60.51 RPKM in Heart - Left Ventricle Total median expression: 1386.36 RPKM View in GTEx track of Genome Browser View at GTEx portal View GTEx Body Map

Microarray Expression Data


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mRNA Secondary Structure of 3' and 5' UTRs

Region	Fold Energy	Bases	Energy/Base	Display As
5' UTR	-221.50	325	-0.682	Picture	PostScript	Text
3' UTR	-639.30	1563	-0.409	Picture	PostScript	Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

Protein Domain and Structure Information

InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF06293 - Lipopolysaccharide kinase (Kdo/WaaP) family
PF07714 - Protein tyrosine and serine/threonine kinase

SCOP Domains:
101447 - Formin homology 2 domain (FH2 domain)
55831 - Thymidylate synthase/dCMP hydroxymethylase
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1KWP - X-ray MuPIT

1NXK - X-ray MuPIT

1NY3 - X-ray MuPIT

2JBO - X-ray MuPIT

2JBP - X-ray MuPIT

2OKR - X-ray MuPIT

2ONL - X-ray MuPIT

2OZA - X-ray MuPIT

2P3G - X-ray MuPIT

2PZY - X-ray MuPIT

3A2C - X-ray MuPIT

3FPM - X-ray MuPIT

3FYJ - X-ray MuPIT

3FYK - X-ray MuPIT

3GOK - X-ray MuPIT

3KA0 - X-ray MuPIT

3KC3 - X-ray MuPIT

3KGA - X-ray MuPIT

3M2W - X-ray MuPIT

3M42 - X-ray MuPIT

3R2B - X-ray MuPIT

3R2Y - X-ray MuPIT

3R30 - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P49137


Front	Top	Side

The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

Orthologous Genes in Other Species

Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.

Mouse	Rat	Zebrafish	D. melanogaster	C. elegans	S. cerevisiae
No ortholog	No ortholog	No ortholog	No ortholog	No ortholog	No ortholog
Gene Details	Gene Details		Gene Details
Gene Sorter	Gene Sorter		Gene Sorter
	RGD	Ensembl

Gene Ontology (GO) Annotations with Structured Vocabulary


	Molecular Function: GO:0000166 nucleotide binding GO:0004672 protein kinase activity GO:0004674 protein serine/threonine kinase activity GO:0004683 calmodulin-dependent protein kinase activity GO:0004871 signal transducer activity GO:0005515 protein binding GO:0005516 calmodulin binding GO:0005524 ATP binding GO:0009931 calcium-dependent protein serine/threonine kinase activity GO:0016301 kinase activity GO:0016740 transferase activity GO:0051019 mitogen-activated protein kinase binding Biological Process: GO:0000165 MAPK cascade GO:0000187 activation of MAPK activity GO:0002224 toll-like receptor signaling pathway GO:0006468 protein phosphorylation GO:0006691 leukotriene metabolic process GO:0006954 inflammatory response GO:0006974 cellular response to DNA damage stimulus GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0032496 response to lipopolysaccharide GO:0032675 regulation of interleukin-6 production GO:0032680 regulation of tumor necrosis factor production GO:0034097 response to cytokine GO:0035924 cellular response to vascular endothelial growth factor stimulus GO:0038066 p38MAPK cascade GO:0042535 positive regulation of tumor necrosis factor biosynthetic process GO:0043488 regulation of mRNA stability GO:0044351 macropinocytosis GO:0046777 protein autophosphorylation GO:0048010 vascular endothelial growth factor receptor signaling pathway GO:0048255 mRNA stabilization GO:0048839 inner ear development GO:0070935 3'-UTR-mediated mRNA stabilization GO:1900034 regulation of cellular response to heat Cellular Component: GO:0005634 nucleus GO:0005654 nucleoplasm GO:0005737 cytoplasm GO:0005813 centrosome GO:0005829 cytosol GO:0070062 extracellular exosome

Descriptions from all associated GenBank mRNAs


	U12779 - Human MAP kinase activated protein kinase 2 mRNA, complete cds. JD336473 - Sequence 317497 from Patent EP1572962. BC036060 - Homo sapiens mitogen-activated protein kinase-activated protein kinase 2, mRNA (cDNA clone MGC:33670 IMAGE:5296259), complete cds. JD406191 - Sequence 387215 from Patent EP1572962. BC052584 - Homo sapiens mitogen-activated protein kinase-activated protein kinase 2, mRNA (cDNA clone MGC:59706 IMAGE:6267183), complete cds. JD100680 - Sequence 81704 from Patent EP1572962. JD390062 - Sequence 371086 from Patent EP1572962. AB590627 - Synthetic construct DNA, clone: pFN21AE0686, Homo sapiens MAPKAPK2 gene for mitogen-activated protein kinase-activated protein kinase 2, without stop codon, in Flexi system. KJ897987 - Synthetic construct Homo sapiens clone ccsbBroadEn_07381 MAPKAPK2 gene, encodes complete protein. X75346 - H.sapiens mRNA for MAP kinase activated protein kinase. AK307499 - Homo sapiens cDNA, FLJ97447. JD124564 - Sequence 105588 from Patent EP1572962. JD042409 - Sequence 23433 from Patent EP1572962. JD493227 - Sequence 474251 from Patent EP1572962. JD150586 - Sequence 131610 from Patent EP1572962.

Biochemical and Signaling Pathways


	BioCarta from NCI Cancer Genome Anatomy Project h_p38mapkPathway - p38 MAPK Signaling Pathway h_mapkPathway - MAPKinase Signaling Pathway h_hsp27Pathway - Stress Induction of HSP Regulation Reactome (by CSHL, EBI, and GO) Protein P49137 (Reactome details) participates in the following event(s): R-HSA-187688 p38 MAPK phosphorylates MAPKAPK2, MAPKAPK3 R-HSA-4793911 MAPKAPK2 phosphorylates HSF1 R-HSA-429016 ALOX5 is phosphorylated by MAPKAP2 R-HSA-450463 MK2 phosphorylates ZFP36 (Tristetraproline, TTP) R-HSA-450474 MK2 phosphorylates BRF1 R-HSA-199917 MAPKAPK2 phosphorylates CREB at Serine 133 R-HSA-450257 Nuclear export of human p38 MAPK mediated by its substrate MAPKAPK2 or 3 R-HSA-450222 Active p38 MAPK phosphorylates MAPKAPK2 or 3 R-HSA-450333 Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK2 or MAPKAPK3 R-HSA-171007 p38MAPK events R-HSA-4420097 VEGFA-VEGFR2 Pathway R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA R-HSA-199920 CREB phosphorylation R-HSA-167044 Signalling to RAS R-HSA-194138 Signaling by VEGF R-HSA-3371556 Cellular response to heat stress R-HSA-450302 activated TAK1 mediates p38 MAPK activation R-HSA-2142753 Arachidonic acid metabolism R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-198725 Nuclear Events (kinase and transcription factor activation) R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases R-HSA-2559580 Oxidative Stress Induced Senescence R-HSA-187687 Signalling to ERKs R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-2262752 Cellular responses to stress R-HSA-450294 MAP kinase activation R-HSA-8978868 Fatty acid metabolism R-HSA-8953854 Metabolism of RNA R-HSA-187037 Signaling by NTRK1 (TRKA) R-HSA-2559583 Cellular Senescence R-HSA-162582 Signal Transduction R-HSA-8953897 Cellular responses to external stimuli R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-448424 Interleukin-17 signaling R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975871 MyD88 cascade initiated on plasma membrane R-HSA-556833 Metabolism of lipids R-HSA-166520 Signaling by NTRKs R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-449147 Signaling by Interleukins R-HSA-166166 MyD88-independent TLR4 cascade R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade R-HSA-1430728 Metabolism R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade R-HSA-168249 Innate Immune System R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-168256 Immune System

Other Names for This Gene


	Alternate Gene Symbols: ENST00000367103.1, ENST00000367103.2, ENST00000367103.3, MAPK2_HUMAN, NM_032960, P49137, Q5SY30, Q5SY41, Q8IYD6, uc318fqk.1, uc318fqk.2 UCSC ID: ENST00000367103.4_6 RefSeq Accession: NM_032960.4 Protein: P49137 (aka MAPK2_HUMAN or MKK2_HUMAN)

Gene Model Information


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Methods, Credits, and Use Restrictions


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