Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2)
1_MEYMS 6_ TGSDN 11_ KEEID 16_ LLIKH 21_ LNVSD 26_ VIDIM 31_ ENLYA 36_ SEEPA 41_ VYEPS 46_ LMTMC 51_ QDSNQ 56_ NDERS 61_ KSLLL 66_ SGQEV 71_ PWLSS 76_ VRYGT 81_ VEDLL 86_ AFANH 91_ ISNTA 96_ KHFYG 101_ QRPQE 106_ SGILL 111_ NMVIT 116_ PQNGR 121_ YQIDS 126_ DVLLI 131_ PWKLT 136_ YRNIG 141_ SDFIP 146_ RGAFG 151_ KVYLA 156_ QDIKT 161_ KKRMA 166_ CKLIP 171_ VDQFK 176_ PSDVE 181_ IQACF 186_ RHENI 191_ AELYG 196_ AVLWG 201_ ETVHL 206_ FMEAG 211_ EGGSV 216_ LEKLE 221_ SCGPM 226_ REFEI 231_ IWVTK 236_ HVLKG 241_ LDFLH 246_ SKKVI 251_ HHDIK 256_ PSNIV 261_ FMSTK 266_ AVLVD 271_ FGLSV 276_ QMTED 281_ VYFPK 286_ DLRGT 291_ EIYMS 296_ PEVIL 301_ CRGHS 306_ TKADI 311_ YSLGA 316_ TLIHM 321_ QTGTP 326_ PWVKR 331_ YPRSA 336_ YPSYL 341_ YIIHK 346_ QAPPL 351_ EDIAD 356_ DCSPG 361_ MRELI 366_ EASLE 371_ RNPNH 376_ RPRAA 381_ DLLKH 386_ EALNP 391_ PREDQ 396_ PRCQS 401_ LDSAL 406_ LERKR 411_ LLSRK 416_ ELELP 421_ ENIAD 426_ SSCTG 431_ STEES 436_ EMLKR 441_ QRSLY 446_ IDLGA 451_ LAGYF 456_ NLVRG 461_PPTLE
1: Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant