mitogen-activated protein kinase kinase kinase 5 (MAP3K5, MAPK/ERK kinase kinase 5, MEKK5, apoptosis signal-regulating kinase 1, ASK-1, ASK1, MAPKKK5)

Function

• activates SEK1-JNK & MKK3/MKK6-p38 signaling cascades
• activated by TNF & activates JNK/SAPK
• component of a protein kinase signal transduction cascade
• phosphorylates & activates MAP2K4 & MAP2K6, which in turn activate the JNK & p38 MAP kinases, respectively
• overexpression induces apoptotic cell death
• contains an N-terminal autoinhibitory domain
• activated by phosphorylation at Thr-838
• inhibited by phosphorylation at Ser-966 & Ser-1033
• binds to, & stabilizes MAP3K6 & is activated by MAP3K6 by phosphorylation on Thr-838
• binds both upstream activators & downstream substrates in multimolecular complexes
• associates with & inhibited by HIV-1 Nef
• interacts with DAB2IP

ATP + a protein <--> ADP + a phosphoprotein

Cofactor: Mg+2

Structure

• homodimer when inactive
• belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
• contains 1 protein kinase domain

Expression

• abundantly expressed in heart & pancreas
• induced by TNF-alpha
• inhibited by HIV-1 Nef.

More general terms

• MAP3K/MEKK

Database

• UniProt: http://www.uniprot.org/uniprot/Q99683.html
• OMIM: https://mirror.omim.org/entry/602448
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4217