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Protein: M3K5_HUMAN

Mitogen-activated protein kinase kinase kinase 5

FUNCTION: Component of a protein kinase signal transduction cascade. Phosphorylates and activates MAP2K4 and MAP2K6, which in turn activate the JNK and p38 MAP kinases, respectively. Overexpression induces apoptotic cell death. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. more...

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.


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.


COPYRIGHT: Protein annotation is derived from the UniProt Consortium ( Distributed under the Creative Commons Attribution-NoDerivs License.



  • Homo sapiens

Gene Symbol:

  • MAP3K5


  • MEK kinase 5
  • MAPK/ERK kinase kinase 5
  • Apoptosis signal-regulating kinase 1
  • MEKK 5
  • ASK-1

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