MAP3K5

mitogen-activated protein kinase kinase kinase 5 | ASK1, MAPKKK5, MEKK5

Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

Biological processes 58 terms

ATP binding (GO:0005524)ATP binding (GO:0005524)IRE1-TRAF2-ASK1 complex (GO:1990604)JNK cascade (GO:0007254)JNK cascade (GO:0007254)JNK cascade (GO:0007254)JUN kinase kinase kinase activity (GO:0004706)MAP kinase kinase kinase activity (GO:0004709)MAP kinase kinase kinase activity (GO:0004709)MAP kinase kinase kinase activity (GO:0004709)MAP kinase kinase kinase activity (GO:0004709)MAPK cascade (GO:0000165)MAPK cascade (GO:0000165)MAPK cascade (GO:0000165)apoptotic signaling pathway (GO:0097190)apoptotic signaling pathway (GO:0097190)cellular response to amino acid starvation (GO:0034198)cellular response to hydrogen peroxide (GO:0070301)cellular senescence (GO:0090398)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytosol (GO:0005829)cytosol (GO:0005829)endoplasmic reticulum (GO:0005783)identical protein binding (GO:0042802)intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631)intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631)magnesium ion binding (GO:0000287)neuron apoptotic process (GO:0051402)neuron apoptotic process (GO:0051402)neuron apoptotic process (GO:0051402)neuron intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0036480)p38MAPK cascade (GO:0038066)p38MAPK cascade (GO:0038066)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of JNK cascade (GO:0046330)positive regulation of JNK cascade (GO:0046330)positive regulation of JNK cascade (GO:0046330)positive regulation of apoptotic process (GO:0043065)positive regulation of apoptotic process (GO:0043065)positive regulation of myoblast differentiation (GO:0045663)protein binding (GO:0005515)protein domain specific binding (GO:0019904)protein homodimerization activity (GO:0042803)protein kinase activity (GO:0004672)protein kinase activity (GO:0004672)protein kinase binding (GO:0019901)protein kinase complex (GO:1902911)protein phosphatase binding (GO:0019903)protein serine kinase activity (GO:0106310)protein serine/threonine kinase activity (GO:0004674)protein-containing complex (GO:0032991)response to endoplasmic reticulum stress (GO:0034976)response to endoplasmic reticulum stress (GO:0034976)stress-activated MAPK cascade (GO:0051403)

Expression (TPM)

TFs regulating MAP3K5 0 TFs

Transcription factors with Perturb-seq knockdown data for MAP3K5. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = MAP3K5 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

TF	Mean coef	Binding	Outlier	TF→Gene link

Rows:

Elements linked to MAP3K5

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of MAP3K5, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Element	Dist. to TSS	Link type	TFs
chr6:136,499,147–136,499,983	293.5 kb	Distal (>10kb) Multiome	207
chr6:136,526,121–136,527,142	266.5 kb	Distal (>10kb) Multiome	235
chr6:136,549,356–136,551,131	242.5 kb	Distal (>10kb) Multiome	722
chr6:136,791,271–136,793,463	124 bp	At TSS Multiome	880
chr6:136,822,046–136,823,437	29.7 kb	Distal (>10kb) Multiome	679
chr6:136,920,717–136,924,225	130.6 kb	Distal (>10kb) Multiome	498
chr6:136,956,824–136,957,720	164.1 kb	Distal (>10kb) Multiome	256
chr6:136,989,383–136,990,306	196.7 kb	Distal (>10kb) Multiome	295
chr6:137,001,359–137,002,211	208.8 kb	Distal (>10kb) Multiome	208
chr6:137,044,029–137,045,166	251.4 kb	Distal (>10kb) Multiome	428

Genome Browser

Genomic view of the MAP3K5 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.