Mixed lineage kinase domain-like protein (hMLKL)
1_MENLK 6_ HIITL 11_ GQVIH 16_ KRCEE 21_ MKYCK 26_ KQCRR 31_ LGHRV 36_ LGLIK 41_ PLEML 46_ QDQGK 51_ RSVPS 56_ EKLTT 61_ AMNRF 66_ KAALE 71_ EANGE 76_ IEKFS 81_ NRSNI 86_ CRFLT 91_ ASQDK 96_ ILFKD 101_ VNRKL 106_ SDVWK 111_ ELSLL 116_ LQVEQ 121_ RMPVS 126_ PISQG 131_ ASWAQ 136_ EDQQD 141_ ADEDR 146_ RAFQM 151_ LRRDN 156_ EKIEA 161_ SLRRL 166_ EINMK 171_ EIKET 176_ LRQYL 181_ PPKCM 186_ QEIPQ 191_ EQIKE 196_ IKKEQ 201_ LSGSP 206_ WILLR 211_ ENEVS 216_ TLYKG 221_ EYHRA 226_ PVAIK 231_ VFKKL 236_ QAGSI 241_ AIVRQ 246_ TFNKE 251_ IKTMK 256_ KFESP 261_ NILRI 266_ FGICI 271_ DETVT 276_ PPQFS 281_ IVMEY 286_ CELGT 291_ LRELL 296_ DREKD 301_ LTLGK 306_ RMVLV 311_ LGAAR 316_ GLYRL 321_ HHSEA 326_ PELHG 331_ KIRSS 336_ NFLVT 341_ QGYQV 346_ KLAGF 351_ ELRKT 356_ QTSMS 361_ LGTTR 366_ EKTDR 371_ VKSTA 376_ YLSPQ 381_ ELEDV 386_ FYQYD 391_ VKSEI 396_ YSFGI 401_ VLWEI 406_ ATGDI 411_ PFQGC 416_ NSEKI 421_ RKLVA 426_ VKRQQ 431_ EPLGE 436_ DCPSE 441_ LREII 446_ DECRA 451_ HDPSV 456_ RPSVD 461_ EILKK 466_LSTFS
1: Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Does not have protein kinase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following activation by ZBP1, MLKL is phosphorylated by RIPK3 in the nucleus, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol.following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (By similarity). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610)