|Institutional Source||Beutler Lab|
|Gene Name||mitogen-activated protein kinase kinase kinase 8|
|Synonyms||Tpl2, Tpl-2, c-COT, Cot, Cot/Tpl2|
|Is this an essential gene?||Non essential (E-score: 0.000)|
|Stock #||R7348 (G1)|
|Chromosomal Location||4331327-4353015 bp(-) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||T to A at 4340561 bp|
|Amino Acid Change||Histidine to Leucine at position 251 (H251L)|
|Ref Sequence||ENSEMBL: ENSMUSP00000025078 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000025078] [ENSMUST00000173930]|
|Predicted Effect||probably damaging
AA Change: H251L
PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
AA Change: H251L
|Predicted Effect||probably benign
|Coding Region Coverage||
|Validation Efficiency||99% (80/81)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
PHENOTYPE: Mutant mice resist endotoxic shock. Their MHC II expression is enhanced. Macrophages' TNF-alpha response to viruses and to all TLR ligands is impaired. Macrophage and T-cell secretion of other cytokines in response to various TLR ligands or OVA is aberrant. Anti-OVA Ig classes are abnormally skewed. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Map3k8||
(F):5'- AAACACGTGGTCATCATCCTTG -3'
(R):5'- CCGGCATGAGAACATTGCTG -3'
(F):5'- AACACGTGGTCATCATCCTTGTATTG -3'
(R):5'- AGAACATTGCTGAGTTATATGGTGCC -3'