Serine/threonine-protein kinase NLK (EC 2.7.11.24) (Nemo-like kinase) (Protein LAK1)
1_MSLCG 6_ ARANA 11_ KMMAA 16_ YNGGT 21_ SAAAA 26_ GHHHH 31_ HHHHL 36_ PHLPP 41_ PHLHH 46_ HHHPQ 51_ HHLHP 56_ GSAAA 61_ VHPVQ 66_ QHTSS 71_ AAAAA 76_ AAAAA 81_ AAAML 86_ NPGQQ 91_ QPYFP 96_ SPAPG 101_ QAPGP 106_ AAAAP 111_ AQVQA 116_ AAAAT 121_ VKAHH 126_ HQHSH 131_ HPQQQ 136_ LDIEP 141_ DRPIG 146_ YGAFG 151_ VVWSV 156_ TDPRD 161_ GKRVA 166_ LKKMP 171_ NVFQN 176_ LVSCK 181_ RVFRE 186_ LKMLC 191_ FFKHD 196_ NVLSA 201_ LDILQ 206_ PPHID 211_ YFEEI 216_ YVVTE 221_ LMQSD 226_ LHKII 231_ VSPQP 236_ LSSDH 241_ VKVFL 246_ YQILR 251_ GLKYL 256_ HSAGI 261_ LHRDI 266_ KPGNL 271_ LVNSN 276_ CVLKI 281_ CDFGL 286_ ARVEE 291_ LDESR 296_ HMTQE 301_ VVTQY 306_ YRAPE 311_ ILMGS 316_ RHYSN 321_ AIDIW 326_ SVGCI 331_ FAELL 336_ GRRIL 341_ FQAQS 346_ PIQQL 351_ DLITD 356_ LLGTP 361_ SLEAM 366_ RTACE 371_ GAKAH 376_ ILRGP 381_ HKQPS 386_ LPVLY 391_ TLSSQ 396_ ATHEA 401_ VHLLC 406_ RMLVF 411_ DPSKR 416_ ISAKD 421_ ALAHP 426_ YLDEG 431_ RLRYH 436_ TCMCK 441_ CCFST 446_ STGRV 451_ YTSDF 456_ EPVTN 461_ PKFDD 466_ TFEKN 471_ LSSVR 476_ QVKEI 481_ IHQFI 486_ LEQQK 491_ GNRVP 496_ LCINP 501_ QSAAF 506_ KSFIS 511_ STVAQ 516_ PSEMP 521_PSPLV
1: Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989)