Description: Homo sapiens mitogen-activated protein kinase kinase 5 (MAP2K5), transcript variant 1, mRNA. 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]. Transcript (Including UTRs) Position: hg19 chr15:67,835,021-68,099,455 Size: 264,435 Total Exon Count: 22 Strand: + Coding Region Position: hg19 chr15:67,835,674-68,099,088 Size: 263,415 Coding Exon Count: 22
ID:MP2K5_HUMAN DESCRIPTION: RecName: Full=Dual specificity mitogen-activated protein kinase kinase 5; Short=MAP kinase kinase 5; Short=MAPKK 5; EC=2.7.12.2; 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.
Body Mass Index Elizabeth K Speliotes et al. Nature genetics 2010, Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index., Nature genetics.
[PubMed 20935630]
Body Mass Index Wanqing Wen et al. Nature genetics 2012, Meta-analysis identifies common variants associated with body mass index in east Asians., Nature genetics.
[PubMed 22344219]
Dehydroepiandrosterone Shih-Jen Hwang et al. BMC medical genetics 2007, A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study., BMC medical genetics.
[PubMed 17903292]
Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.
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.
ModBase Predicted Comparative 3D Structure on Q13163
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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.
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
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
