Dual specificity mitogen-activated protein kinase kinase 7 (MAP kinase kinase 7) (MAPKK 7) (EC 2.7.12.2) (JNK-activating kinase 2) (MAPK/ERK kinase 7) (MEK 7) (Stress-activated protein kinase kinase 4) (SAPK kinase 4) (SAPKK-4) (SAPKK4) (c-Jun N-terminal kinase kinase 2) (JNK kinase 2) (JNKK 2)
1_MAASS 6_ LEQKL 11_ SRLEA 16_ KLKQE 21_ NREAR 26_ RRIDL 31_ NLDIS 36_ PQRPR 41_ PTLQL 46_ PLAND 51_ GGSRS 56_ PSSES 61_ SPQHP 66_ TPPAR 71_ PRHML 76_ GLPST 81_ LFTPR 86_ SMESI 91_ EIDQK 96_ LQEIM 101_ KQTGY 106_ LTIGG 111_ QRYQA 116_ EINDL 121_ ENLGE 126_ MGSGT 131_ CGQVW 136_ KMRFR 141_ KTGHV 146_ IAVKQ 151_ MRRSG 156_ NKEEN 161_ KRILM 166_ DLDVV 171_ LKSHD 176_ CPYIV 181_ QCFGT 186_ FITNT 191_ DVFIA 196_ MELMG 201_ TCAEK 206_ LKKRM 211_ QGPIP 216_ ERILG 221_ KMTVA 226_ IVKAL 231_ YYLKE 236_ KHGVI 241_ HRDVK 246_ PSNIL 251_ LDERG 256_ QIKLC 261_ DFGIS 266_ GRLVD 271_ SKAKT 276_ RSAGC 281_ AAYMA 286_ PERID 291_ PPDPT 296_ KPDYD 301_ IRADV 306_ WSLGI 311_ SLVEL 316_ ATGQF 321_ PYKNC 326_ KTDFE 331_ VLTKV 336_ LQEEP 341_ PLLPG 346_ HMGFS 351_ GDFQS 356_ FVKDC 361_ LTKDH 366_ RKRPK 371_ YNKLL 376_ EHSFI 381_ KRYET 386_ LEVDV 391_ ASWFK 396_ DVMAK 401_ TESPR 406_ TSGVL 411_SQPHL
1: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074)