Mitogen-activated protein kinase kinase kinase 5
ENZYME REGULATION: Contains an N-terminal autoinhibitory domain. Activated by phosphorylation at Thr-838, inhibited by phosphorylation at Ser-966 and Ser-1033. Binds to, and stabilizes MAP3K6 and is activated by MAP3K6 by phosphorylation on Thr-838.
SUBUNIT: Homodimer when inactive. Binds both upstream activators and downstream substrates in multimolecular complexes. Associates with and inhibited by HIV-1 Nef. Interacts with DAB2IP and PPM1L. Interacts with ARRB2. 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.
SUBCELLULAR LOCATION: Cytoplasm.
TISSUE SPECIFICITY: Abundantly expressed in heart and pancreas.
INDUCTION: By TNF. Inhibited by HIV-1 Nef.
PTM: Dephosphorylated and activated by PGAM5.
SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
SIMILARITY: Contains 1 protein kinase domain.
GENE SYNONYMS: ASK1 MAPKKK5 MEKK5.
COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.