Human Gene MAP2K5 (ENST00000178640.10) Description and Page Index
  Description: Homo sapiens mitogen-activated protein kinase kinase 5 (MAP2K5), transcript variant 1, mRNA. (from RefSeq NM_145160)
RefSeq Summary (NM_145160): The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011].
Gencode Transcript: ENST00000178640.10
Gencode Gene: ENSG00000137764.20
Transcript (Including UTRs)
   Position: hg38 chr15:67,542,703-67,807,114 Size: 264,412 Total Exon Count: 22 Strand: +
Coding Region
   Position: hg38 chr15:67,543,336-67,806,750 Size: 263,415 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr15:67,542,703-67,807,114)mRNA (may differ from genome)Protein (448 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
PubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Dual specificity mitogen-activated protein kinase kinase 5; Short=MAP kinase kinase 5; Short=MAPKK 5; EC=; AltName: Full=MAPK/ERK kinase 5; Short=MEK 5;
FUNCTION: Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium.
SUBUNIT: Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI (By similarity). Interacts with Yersinia yopJ.
INTERACTION: P62993:GRB2; NbExp=2; IntAct=EBI-307294, EBI-401755; Q13164:MAPK7; NbExp=2; IntAct=EBI-307294, EBI-1213983;
TISSUE SPECIFICITY: Expressed in many adult tissues. Abundant in heart and skeletal muscle.
DOMAIN: Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the OPR domain. This domain also mediates interactions with SQSTM1 and PARD6A (By similarity).
PTM: Activated by phosphorylation on Ser/Thr by MAP kinase kinase kinases (By similarity).
PTM: Yersinia yopJ may acetylate Ser/Thr residues, preventing phosphorylation and activation, thus blocking the MAPK signaling pathway.
SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
SIMILARITY: Contains 1 OPR domain.
SIMILARITY: Contains 1 protein kinase domain.

-  MalaCards Disease Associations
  MalaCards Gene Search: MAP2K5
Diseases sorted by gene-association score: restless legs syndrome (12)

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

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.83 RPKM in Testis
Total median expression: 270.52 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 -222.30633-0.351 Picture PostScript Text
3' UTR -138.30364-0.380 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
IPR000270 - OPR_PB1
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00564 - PB1 domain
PF00069 - Protein kinase domain

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

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q13163
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
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  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:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0046872 metal ion binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000165 MAPK cascade
GO:0000187 activation of MAPK activity
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0007346 regulation of mitotic cell cycle
GO:0007507 heart development
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0023014 signal transduction by protein phosphorylation
GO:0030307 positive regulation of cell growth
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032147 activation of protein kinase activity
GO:0034115 negative regulation of heterotypic cell-cell adhesion
GO:0042981 regulation of apoptotic process
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045415 negative regulation of interleukin-8 biosynthetic process
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050679 positive regulation of epithelial cell proliferation
GO:0051247 positive regulation of protein metabolic process
GO:0060761 negative regulation of response to cytokine stimulus
GO:0070375 ERK5 cascade
GO:0071363 cellular response to growth factor stimulus
GO:0071499 cellular response to laminar fluid shear stress
GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis
GO:2000342 negative regulation of chemokine (C-X-C motif) ligand 2 production
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005819 spindle
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  BC008838 - Homo sapiens mitogen-activated protein kinase kinase 5, mRNA (cDNA clone MGC:14094 IMAGE:4100679), complete cds.
U25265 - Human MEK5 mRNA, complete cds.
AK315435 - Homo sapiens cDNA, FLJ96491, highly similar to Homo sapiens mitogen-activated protein kinase kinase 5 (MAP2K5), transcript variant A, mRNA.
U71087 - Human MAP kinase kinase MEK5b mRNA, complete cds.
U71088 - Homo sapiens MAP kinase kinase MEK5c mRNA, partial cds.
CU679141 - Synthetic construct Homo sapiens gateway clone IMAGE:100019451 5' read MAP2K5 mRNA.
AB385019 - Synthetic construct DNA, clone: pF1KB5026, Homo sapiens MAP2K5 gene for dual specificity mitogen-activated protein kinase kinase 5, complete cds, without stop codon, in Flexi system.
CR542229 - Homo sapiens full open reading frame cDNA clone RZPDo834G0225D for gene MAP2K5, mitogen-activated protein kinase kinase 5; complete cds, without stopcodon.
BT006780 - Homo sapiens mitogen-activated protein kinase kinase 5 mRNA, complete cds.
JF432129 - Synthetic construct Homo sapiens clone IMAGE:100073268 mitogen-activated protein kinase kinase 5 (MAP2K5) gene, encodes complete protein.
KJ891896 - Synthetic construct Homo sapiens clone ccsbBroadEn_01290 MAP2K5 gene, encodes complete protein.
KJ905297 - Synthetic construct Homo sapiens clone ccsbBroadEn_14809 MAP2K5 gene, encodes complete protein.
AK293459 - Homo sapiens cDNA FLJ57948 complete cds, highly similar to Dual specificity mitogen-activated protein kinase kinase 5 (EC
AK057521 - Homo sapiens cDNA FLJ32959 fis, clone TESTI2008237, highly similar to Dual specificity mitogen-activated protein kinase kinase 5 (EC
AK024766 - Homo sapiens cDNA: FLJ21113 fis, clone CAS05470, highly similar to HSU71087 Human MAP kinase kinase MEK5b mRNA.
JD150595 - Sequence 131619 from Patent EP1572962.
JD197010 - Sequence 178034 from Patent EP1572962.
JD056238 - Sequence 37262 from Patent EP1572962.
JD458469 - Sequence 439493 from Patent EP1572962.
JD105466 - Sequence 86490 from Patent EP1572962.
JD396110 - Sequence 377134 from Patent EP1572962.
JD135172 - Sequence 116196 from Patent EP1572962.
JD349099 - Sequence 330123 from Patent EP1572962.
JD508315 - Sequence 489339 from Patent EP1572962.
JD079946 - Sequence 60970 from Patent EP1572962.
JD397653 - Sequence 378677 from Patent EP1572962.
JD390087 - Sequence 371111 from Patent EP1572962.
JD254943 - Sequence 235967 from Patent EP1572962.
JD351199 - Sequence 332223 from Patent EP1572962.
JD390765 - Sequence 371789 from Patent EP1572962.
JD153923 - Sequence 134947 from Patent EP1572962.
JD397614 - Sequence 378638 from Patent EP1572962.
JD403607 - Sequence 384631 from Patent EP1572962.
JD133292 - Sequence 114316 from Patent EP1572962.
JD419356 - Sequence 400380 from Patent EP1572962.
AK092615 - Homo sapiens cDNA FLJ35296 fis, clone PROST2009208.
AK025177 - Homo sapiens cDNA: FLJ21524 fis, clone COL05921.
JD200330 - Sequence 181354 from Patent EP1572962.
JD417228 - Sequence 398252 from Patent EP1572962.
JD199073 - Sequence 180097 from Patent EP1572962.
JD446203 - Sequence 427227 from Patent EP1572962.
JD498703 - Sequence 479727 from Patent EP1572962.
JD501713 - Sequence 482737 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04540 - Gap junction
hsa04722 - Neurotrophin signaling pathway

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

Reactome (by CSHL, EBI, and GO)

Protein Q13163 (Reactome details) participates in the following event(s):

R-HSA-198733 ERK5 is activated
R-HSA-198765 Signalling to ERK5
R-HSA-187037 Signaling by NTRK1 (TRKA)
R-HSA-166520 Signaling by NTRKs
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B4DE43, MEK5, MKK5, MP2K5_HUMAN, NM_145160, PRKMK5, Q13163, Q92961, Q92962, uc002aqu.1, uc002aqu.2, uc002aqu.3, uc002aqu.4, uc002aqu.5
UCSC ID: uc002aqu.5
RefSeq Accession: NM_145160
Protein: Q13163 (aka MP2K5_HUMAN or MPK5_HUMAN)
CCDS: CCDS10224.1, CCDS42051.1

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