Human Gene MAPK4 (uc002lev.3)
  Description: Homo sapiens mitogen-activated protein kinase 4 (MAPK4), mRNA.
RefSeq Summary (NM_002747): Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014].
Transcript (Including UTRs)
   Position: hg19 chr18:48,086,484-48,258,196 Size: 171,713 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg19 chr18:48,190,329-48,256,224 Size: 65,896 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr18:48,086,484-48,258,196)mRNA (may differ from genome)Protein (587 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: MK04_HUMAN
DESCRIPTION: RecName: Full=Mitogen-activated protein kinase 4; Short=MAP kinase 4; Short=MAPK 4; EC=2.7.11.24; AltName: Full=Extracellular signal-regulated kinase 4; Short=ERK-4; AltName: Full=MAP kinase isoform p63; Short=p63-MAPK;
FUNCTION: Atypical MAPK protein. Phosphorylates microtubule- associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity).
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium (By similarity).
ENZYME REGULATION: Activated by phosphorylation at Ser-186.
SUBUNIT: Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5 (By similarity).
SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). Note=Translocates to the cytoplasm following interaction with MAPKAPK5 (By similarity).
TISSUE SPECIFICITY: High expression in heart and brain.
DOMAIN: The FRIEDE motif is required for docking MAPKAPK5 (By similarity).
DOMAIN: In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.
PTM: Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.
SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
SIMILARITY: Contains 1 protein kinase domain.
SEQUENCE CAUTION: Sequence=CAA42411.1; Type=Frameshift; Positions=Several;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MAPK4ID41293ch18q21.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: MAPK4
Diseases sorted by gene-association score: pulmonary immaturity (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 30.37 RPKM in Brain - Caudate (basal ganglia)
Total median expression: 253.21 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -384.391000-0.384 Picture PostScript Text
3' UTR -659.181972-0.334 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
IPR008350 - MAPK_ERK3/4
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
PF07714 - Protein tyrosine kinase

SCOP Domains:
56112 - Protein kinase-like (PK-like)

ModBase Predicted Comparative 3D Structure on P31152
FrontTopSide
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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  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:0004707 MAP kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019901 protein kinase binding
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0000165 MAPK cascade
GO:0006468 protein phosphorylation
GO:0007049 cell cycle
GO:0010468 regulation of gene expression
GO:0016310 phosphorylation
GO:0071310 cellular response to organic substance

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  BC050299 - Homo sapiens mitogen-activated protein kinase 4, mRNA (cDNA clone MGC:44705 IMAGE:5303135), complete cds.
AK293818 - Homo sapiens cDNA FLJ50121 complete cds, highly similar to Homo sapiens mitogen-activated protein kinase 4 (MAPK4), mRNA.
BC040493 - Homo sapiens cDNA clone IMAGE:5301938.
AK295058 - Homo sapiens cDNA FLJ57847 complete cds, highly similar to Homo sapiens mitogen-activated protein kinase 4 (MAPK4), mRNA.
X59727 - H.sapiens 63 kDa protein kinase related to rat ERK3.
BC117216 - Homo sapiens mitogen-activated protein kinase 4, mRNA (cDNA clone MGC:150825 IMAGE:40125767), complete cds.
BC143769 - Homo sapiens cDNA clone IMAGE:9052283.
KJ891892 - Synthetic construct Homo sapiens clone ccsbBroadEn_01286 MAPK4 gene, encodes complete protein.
HQ258629 - Synthetic construct Homo sapiens clone IMAGE:100073183 mitogen-activated protein kinase 4 (MAPK4) gene, encodes complete protein.
AK303601 - Homo sapiens cDNA FLJ56195 complete cds, highly similar to Homo sapiens mitogen-activated protein kinase 4 (MAPK4), mRNA.
BX648603 - Homo sapiens mRNA; cDNA DKFZp686G10213 (from clone DKFZp686G10213).
JD205606 - Sequence 186630 from Patent EP1572962.
JD381949 - Sequence 362973 from Patent EP1572962.
JD168146 - Sequence 149170 from Patent EP1572962.
JD078157 - Sequence 59181 from Patent EP1572962.
JD453704 - Sequence 434728 from Patent EP1572962.
JD071598 - Sequence 52622 from Patent EP1572962.
JD413554 - Sequence 394578 from Patent EP1572962.
JD215471 - Sequence 196495 from Patent EP1572962.
JD420640 - Sequence 401664 from Patent EP1572962.
JD191706 - Sequence 172730 from Patent EP1572962.
JD391186 - Sequence 372210 from Patent EP1572962.
JD393777 - Sequence 374801 from Patent EP1572962.
JD434376 - Sequence 415400 from Patent EP1572962.
JD236907 - Sequence 217931 from Patent EP1572962.
JD494436 - Sequence 475460 from Patent EP1572962.
JD160647 - Sequence 141671 from Patent EP1572962.
JD261443 - Sequence 242467 from Patent EP1572962.
JD290046 - Sequence 271070 from Patent EP1572962.
JD136730 - Sequence 117754 from Patent EP1572962.
JD192544 - Sequence 173568 from Patent EP1572962.
JD239774 - Sequence 220798 from Patent EP1572962.
JD126885 - Sequence 107909 from Patent EP1572962.
JD269811 - Sequence 250835 from Patent EP1572962.
JD121777 - Sequence 102801 from Patent EP1572962.
JD259055 - Sequence 240079 from Patent EP1572962.
JD560196 - Sequence 541220 from Patent EP1572962.
JD264887 - Sequence 245911 from Patent EP1572962.
JD153791 - Sequence 134815 from Patent EP1572962.
JD492653 - Sequence 473677 from Patent EP1572962.
JD337025 - Sequence 318049 from Patent EP1572962.
JD258298 - Sequence 239322 from Patent EP1572962.
JD290444 - Sequence 271468 from Patent EP1572962.
JD051532 - Sequence 32556 from Patent EP1572962.
JD366947 - Sequence 347971 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_mapkPathway - MAPKinase Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein P31152 (Reactome details) participates in the following event(s):

R-HSA-5687086 PAK1,2,3 phosphorylates MAPK6,4
R-HSA-5687091 p-S MAPK6,4 binds MAPKAPK5
R-HSA-5687094 p-S MAPK6,4 phosphorylate MAPKAPK5
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ERK4, MK04_HUMAN, NM_002747, NP_002738, P31152, PRKM4
UCSC ID: uc002lev.3
RefSeq Accession: NM_002747
Protein: P31152 (aka MK04_HUMAN)
CCDS: CCDS42437.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_002747.3
exon count: 6CDS single in 3' UTR: no RNA size: 4736
ORF size: 1764CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3104.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.