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Subcellular location: Cytoplasm. Endoplasmic reticulum. Note=Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] : 2CLQ (3D) [IMAGE] Seco
Subunit: Homodimer when inactive. Binds both upstream activators and downstream substrates in multimolecular complexes. Associates with and inhibited by HIV-1 Nef. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF. This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis. Interacts with SOCS1 which recognizes phosphorylation of Tyr-718 and induces MAP3K5/ASK1 degradation in endothelial cells. Interacts with the 14-3-3 family proteins such as YWHAB, YWHAE, YWHAQ, YWHAH, YWHAZ and SFN. Interacts with ARRB2, BIRC2, DAB2IP, IGF1R, MAP3K6/ASK2, PGAM5, PIM1, PPP5C, SOCS1, STUB1, TRAF2, TRAF6 and TXN. Interacts with ERN1 in a TRAF2-dependent manner. Interacts with calcineurin subunit PPP3R1 and with PPM1L (By similarity). Interacts (via N-terminus) with RAF1 and this interaction inhibits the proapoptotic function of MAP3K5
Tissue specificity: Abundantly expressed in heart and pancreas
Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily Contains 1 protein kinase domain
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